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Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

Posted in Biological Networks, Cancer Genomics, Clinical Genomics, Evidence-based decision-making, Nobel Prize Winners, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, Single Cell Genomics, Transcriptomics, Translational Research, Translational Science, tagged Advancing Precision Medicine, biomedical collaboration, gene expression profiling, genomics, HIF-1a, international consortium, liquid biopsy, mutational specrum, nobel leureates, oncogenes, Personalized and Precision Medicine & Genomic Research, Transcriptomics, Warburg Effect on October 3, 2025| Leave a Comment »

Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

Reporter: Stephen J. Williams, PhD

Leaders in Pharmaceutical Business Intellegence will be covering this conference LIVE over X.com at

using the following meeting hashtags

#AdvancingPM #precisionmedicine #WINSYMPO2025

Agenda Track 1: WIN Symposium

WIN SYMPOSIUM

Co-Chairs

Wafik S. El-Deiry, MD, PhD, FACP, Chair, WIN Consortium, Director, Legorreta Cancer Center Brown University, Director, Joint Program in Cancer Biology, Brown University and Brown University Health; Associate Dean, Oncologic Sciences, Warren Alpert Medical School, Brown University; Attending Physician, Hematology/Oncology, Brown University Health Mencoff Family University; Professor of Medical Science, Professor of Pathology and Laboratory Medicine, Brown University; Professor, American Cancer Society Research Professor

Razelle Kurzrock, MD, FACP, Chief Medical Officer, WIN Consortium; Professor of Medicine, Associate Director, Clinical Research, Linda T. and John A. Mellowes Chair of Precision Oncology, MCW Cancer Center and Linda T. & John A. Mellowes Center for Genomic Sciences and Precision Medicine

MULTI-OMICS

Chair

Arutha Kulasinghe, PhD, Associate Professor, Frazer Institute, University of Queensland; Founding Scientific Director, Queensland Spatial Biology Centre

8:40 – 9:00

Welcome and Introduction

Dr. El-Diery welcomes all to this joint symposium with Advancing Precision Medicine and the Win Consortium, which he is currently the head of. More in the WIN Consortium: (Worldwide Innovation Network Consortium in Precision Oncology). The WIN Network is involved in setting up internationalclinical tumor board collaboration

Source: https://winconsortium.org/

WIN was formed on the premise that we can accomplish more together than each organization can achieve working alone. We aim to improve cancer patients’ survival and quality of life. View WIN’s history and unique attributes:

Clinical trials, projects and publications

WIN members collaboratively design and carry out global studies designed to achieve breakthroughs for patients worldwide. Our distinguished Scientific Advisory Board oversees WIN studies. Current trials include:

View a summary of the WIN Consortium here:

Click to access Brochure_WIN_v24.0_2025_08_13__.pdf

They guide WIN’s strategic, operational, and scientific direction.

OrganizationThe WIN Consortium is organized in the following groups who collectively work together to achieve WIN’s common goals

Nigel Russell, Founder and CEO, Advancing Precision Medicine

Christopher P. Molineaux, President & Chief Executive Officer, Life Science Pennsylvania

Life Sciences Pennsylvania (LSPA) is the statewide trade association for the commonwealth’s life sciences industry. Founded in 1989, LSPA works to ensure Pennsylvania has a business and public policy climate that makes the commonwealth the most attractive location to open and operate a life sciences company. Our membership is comprised of organizations statewide, representing the entire ecosystem of the life sciences: research institutions, biotechnology, medical device, diagnostic, pharmaceutical, and investment entities, along with service providers who support the industry. Together, we unify Pennsylvania’s innovators to make the Commonwealth a global life sciences leader.

As president & CEO of Life Sciences Pennsylvania, Christopher Molineaux serves as the chief advocate and spokesman for the life sciences industry that calls Pennsylvania home. Molineaux oversees the strategic direction for the association, assuring Life Sciences Pennsylvania continues to be the catalyst that makes Pennsylvania the top location for life sciences companies.

Molineaux brings to Life Sciences Pennsylvania more than 25 years of experience in the bio-pharmaceutical and health care industries, with front-line experience in developing and executing strategies to navigate a shifting economic and political environment.

9:00-9:40

Keynote Lecture – WIN Consortium

Targeting the Achilles’ Heel of Cancer: Synthetic Lethality and Hypoxia in Precision Oncology

William G. Kaelin, Jr, MD, 2019 Nobel Laureate, Sidney Farber Professor, Harvard Medical School and Dana-Farber Cancer Institute

William Kaelin was born in New York City. He studied chemistry and mathematics at Duke University in Durham, North Carolina, and received his doctor of medicine degree there in 1982. He then did his residency at Johns Hopkins University in Baltimore, Maryland. In 2002 he became a professor at Harvard Medical School in Cambridge, Massachusetts.

Work

Animals need oxygen for the conversion of food into useful energy. The importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown. William Kaelin, Peter Ratcliffe, and Gregg Semenza discovered how cells can sense and adapt to changing oxygen availability. During the 1990s they identified a molecular machinery that regulates the activity of genes in response to varying levels of oxygen. The discoveries may lead to new treatments of anemia, cancer and many other diseases.

TRACK 1 204BC

WIN SYMPOSIUM

MULTI-OMICS

9:40 – 10:40

SESSION 1

From Base Pairs To Better Care:

AI and Omics in Precision Oncology

9:40-10:00

Multi-Omic Profiling and Clinical Decision Support in Precision Oncology

David Spetzler, PhD, MBA, MS, President, Caris Life Sciences

10:00-10:20

Integrating Omics and AI for Next-Gen Precision Oncology

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer Center; Professor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR)

10:20-10:40

Real-World Data and AI in Precision Oncology: Making Data Work for Patients – Q&A

MODERATOR: Jeff Elton, PhD, Vice Chairman, Founding CEO
ConcertAI

PANELISTS: David Spetzler, PhD, MBA, MS, President, Caris Life Sciences

0:40 – 11:10

Break and Exhibits

TRACK 1 204BC

TRACK 2 204A

WIN SYMPOSIUM

MULTI-OMICS

11:10 – 1:10

SESSION 2

The Evolution of Precision Oncology:

Integrating MRD, AI, and Beyond

11:10-12:00

Precision Cancer Consortium

Gabriele Allegri, MBA, Vice President, Global Commercial Precision Medicine, Johnson & Johnson Innovative Medicine

Shruti Mathur, MS, Pharma Diagnostic Strategy Leader, Global Product Strategy (GPS), Genentech

Daryl Pritchard, PhD, Interim President, Personalized Medicine Coalition

SESSION 3

The Shifting Landscape:

Tumor Plasticity and Resistance

12:00-12:20

Mathematical and Evolutionary Modeling in Precision Radiation Oncology

Jacob Scott, MD, DPhil, Professor and Staff Physician-Scientist, CWRU School of Medicine and Cleveland Clinic

12:20-12:40

Plasticity and Persistence: The Role of EMT in Cancer Progression and Therapy Resistance

Sendurai A. Mani, PhD, Professor of Pathology and Laboratory Medicine, Brown University; Associate Director of Translational Oncology, Brown University Legorreta Cancer Center

12:40-1:00

Targeting Molecularly Defined Subsets: Challenges in Translational Oncology

Benedito A. Carneiro, MD, MS, Director, Clinical Research
Director, Cancer Drug Development; Associate Director, Division of Hematology/Oncology
Legorreta Cancer Center, Brown University Health

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Nobel Prize in Chemistry 2024 to David Baker, Demis Hassabis and John M. Jumper

Posted in Amino acids, Gene Therapy & Gene Editing Development, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Genomics Pharmacy, Interviews with Scientific Leaders, mRNA Therapeutics, Mutagenesis, Nobel Prize Winners, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, Precision Cancer Medicine, Proteins, Proteomics, Single Cell Genomics, Single-cell sequencing, Variation in human protein-coding regions on October 9, 2024| Leave a Comment »

Nobel Prize in Chemistry 2024 to David Baker, Demis Hassabis and John M. Jumper

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 10/22/2024

ProteinMPNN, which is now available free on the open-source software repository GitHub, will give researchers the tools to make unlimited new designs. “The challenge, of course … is what are you going to design?” Baker says.

Hallucinating symmetric protein assemblies

Authors Info & Affiliations

Science

15 Sep 2022

Vol 378, Issue 6615

56-61

DOI: 10.1126/science.add1964

https://www.science.org/doi/10.1126/science.add1964

Robust deep learning–based protein sequence design using ProteinMPNN

Authors Info & Affiliations

Science

15 Sep 2022

Vol 378, Issue 6615

49-56

DOI: 10.1126/science.add2187

https://www.science.org/doi/10.1126/science.add2187

UPDATED on 10/13/2024

In a second Nobel win for AI, the Royal Swedish Academy of Sciences has awarded half the 2024 prize in chemistry to Demis Hassabis, the cofounder and CEO of Google DeepMind, and John M. Jumper, a director at the same company, for their work on using artificial intelligence to predict the structures of proteins. The other half goes to David Baker, a professor of biochemistry at the University of Washington, for his work on computational protein design. The winners will share a prize pot of 11 million Swedish kronor ($1 million).

The potential impact of this research is enormous. Proteins are fundamental to life, but understanding what they do involves figuring out their structure—a very hard puzzle that once took months or years to crack for each type of protein. By cutting down the time it takes to predict a protein’s structure, computational tools such as those developed by this year’s award winners are helping scientists gain a greater understanding of how proteins work and opening up new avenues of research and drug development. The technology could unlock more efficient vaccines, speed up research on cures for cancer, or lead to completely new materials.

Hassabis and Jumper created AlphaFold, which in 2020 solved a problem scientists have been wrestling with for decades: predicting the three-dimensional structure of a protein from a sequence of amino acids. The AI tool has since been used to predict the shapes of all proteins known to science.

Their latest model, AlphaFold 3, can predict the structures of DNA, RNA, and molecules like ligands, which are essential to drug discovery. DeepMind has also released the source code and database of its results to scientists for free.

“I’ve dedicated my career to advancing AI because of its unparalleled potential to improve the lives of billions of people,” said Demis Hassabis. “AlphaFold has already been used by more than two million researchers to advance critical work, from enzyme design to drug discovery. I hope we’ll look back on AlphaFold as the first proof point of AI’s incredible potential to accelerate scientific discovery,” he added.

Baker has created several AI tools for designing and predicting the structure of proteins, such as a family of programs called Rosetta. In 2022, his lab created an open-source AI tool called ProteinMPNN that could help researchers discover previously unknown proteins and design entirely new ones. It helps researchers who have an exact protein structure in mind find amino acid sequences that fold into that shape.

Most recently, in late September, Baker’s lab announced it had developed custom molecules that allow scientists to precisely target and eliminate proteins associated with diseases in living cells.

“[Proteins] evolved over the course of evolution to solve the problems that organisms faced during evolution. But we face new problems today, like covid. If we could design proteins that were as good at solving new problems as the ones that evolved during evolution are at solving old problems, it would be really, really powerful,” Baker told MIT Technology Review in 2022.

SOURCE

https://www.technologyreview.com/2024/10/09/1105335/google-deepmind-wins-joint-nobel-prize-in-chemistry-for-protein-prediction-ai/?utm_source=engagement_email&utm_medium=email&utm_campaign=wklysun&utm_term=10.13.24.nonsubs_eng_Numb&mc_cid=1b5c56f9aa&mc_eid=49896ad6f8

10/9/2024

David Baker “for computational protein design”

born 1962 in Seattle, WA, USA. PhD 1989 from University of California, Berkeley, CA, USA. Professor at University of Washington, Seattle, WA, USA and Investigator, Howard Hughes Medical Institute, USA.

University of Washington, Seattle, WA, USA
Howard Hughes Medical Institute, USA

Demis Hassabis “for protein structure prediction”

born 1976 in London, UK. PhD 2009 from University College London, UK. CEO of Google DeepMind, London, UK.

Google DeepMind, London, UK

John M. Jumper “for protein structure prediction”

born 1985 in Little Rock, AR, USA. PhD 2017 from University of Chicago, IL, USA. Senior Research Scientist at Google DeepMind, London, UK.

Google DeepMind, London, UK

The Nobel Prize in Chemistry 2024 is about proteins, life’s ingenious chemical tools. David Baker has succeeded with the almost impossible feat of building entirely new kinds of proteins. Demis Hassabis and John Jumper have developed an AI model to solve a 50-year-old problem: predicting proteins’ complex structures. These discoveries hold enormous potential.

“One of the discoveries being recognised this year concerns the construction of spectacular proteins. The other is about fulfilling a 50-year-old dream: predicting protein structures from their amino acid sequences. Both of these discoveries open up vast possibilities,” says Heiner Linke, Chair of the Nobel Committee for Chemistry.

Proteins generally consist of 20 different amino acids, which can be described as life’s building blocks. In 2003, David Baker succeeded in using these blocks to design a new protein that was unlike any other protein. Since then, his research group has produced one imaginative protein creation after another, including proteins that can be used as pharmaceuticals, vaccines, nanomaterials and tiny sensors.

The second discovery concerns the prediction of protein structures. In proteins, amino acids are linked together in long strings that fold up to make a three-dimensional structure, which is decisive for the protein’s function. Since the 1970s, researchers had tried to predict protein structures from amino acid sequences, but this was notoriously difficult. However, four years ago, there was a stunning breakthrough.

In 2020, Demis Hassabis and John Jumper presented an AI model called AlphaFold2. With its help, they have been able to predict the structure of virtually all the 200 million proteins that researchers have identified. Since their breakthrough, AlphaFold2 has been used by more than two million people from 190 countries. Among a myriad of scientific applications, researchers can now better understand antibiotic resistance and create images of enzymes that can decompose plastic.

Life could not exist without proteins. That we can now predict protein structures and design our own proteins confers the greatest benefit to humankind.

@@@@

This year’s Nobel Prize laureates in chemistry Demis Hassabis and John Jumper have developed an AI model to solve a 50-year-old problem: predicting proteins’ complex structures.

In 2020, Hassabis and Jumper presented an AI model called AlphaFold2. With its help, they have been able to predict the structure of virtually all the 200 million proteins that researchers have identified. Since their breakthrough, AlphaFold2 has been used by more than two million people from 190 countries. Among a myriad of scientific applications, researchers can now better understand antibiotic resistance and create images of enzymes that can decompose plastic.

Read more about their story: https://bit.ly/4diKiJ2

SOURCE

https://www.linkedin.com/company/nobelprize/posts/?feedView=all

Reference

Scientific background: Computational protein design and protein structure prediction (pdf)

SOURCE

https://www.nobelprize.org/prizes/chemistry/2024/press-release/

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2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation

Posted in Biological Networks, Gene Regulation and Evolution, Cell Biology, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Clinical & Translational, Clinical Genomics, Cytoskeleton, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Gene Regulation, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Expression, Interviews with Scientific Leaders, Meta-analysis of transcriptome data, mRNA Therapeutics, Nobel Prize Winners, Single Cell Genomics, Single-cell sequencing, Variation in human protein-coding regions on October 8, 2024| Leave a Comment »

2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation

Reporter: Aviva Lev-Ari, PhD, RN

Updated 10/22/2024

The revolution in our understanding of transcriptional regulation and dark regions of the genome

The genome of higher eukaryotes are comprised of multiple exonic and intronic regions, with coding and noncoding DNA respectively. Much of the DNA sequence between exonic regions of genes, the sequences encoding the amino acids of a polypeptide, was considered either promoter regions regulating an exonic sequence or ‘junk DNA’, which had merely separated exons and their regulatory elements. It was not considered that this dark DNA or junk DNA was important in regulating transcription of genes. It was felt that most gene regulation occurred in promoter regions by response element factors which bound to specific sequences within these regions.

MicroRNA (miRNA), originally discovered in Caenorhabditis elegans, is found in most eukaryotes, including humans [1–3]. It is predicted that miRNA account for 1-5% of the human genome and regulate at least 30% of protein-coding genes [4–8]. To date, 940 distinct miRNAs molecules have been identified within the human genome [9–12] (http://microrna.sanger.ac.uk accessed July 20, 2010). Although little is currently known about the specific targets and biological functions of miRNA molecules thus far, it is evident that miRNA plays a crucial role in the regulation of gene expression controlling diverse cellular and metabolic pathways.

MiRNA are small, evolutionary conserved, single-stranded, non-coding RNA molecules that bind target mRNA to prevent protein production by one of two distinct mechanisms. Mature miRNA is generated through two-step cleavage of primary miRNA (pri-miRNA), which incorporates into the effector complex RNA-induced silencing complex (RISC). The miRNA functions as a guide by base-pairing with target mRNA to negatively regulate its expression. The level of complementarity between the guide and mRNA target determines which silencing mechanism will be employed; cleavage of target messenger RNA (mRNA) with subsequent degradation or translation inhibition

Fig. (1). MicroRNA maturation and function.

Figure. miRNA maturation and function. Source: Macfarlane LA, Murphy PR. MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics. 2010 Nov;11(7):537-61. doi: 10.2174/138920210793175895.

The following is an interview in the journal Journal of Cellular Biology with Dr, Victor Ambros on his discovery of miRNA.

Source: Ambros V. Victor Ambros: the broad scope of microRNAs. Interview by Caitlin Sedwick. J Cell Biol. 2013 May 13;201(4):492-3. doi: 10.1083/jcb.2014pi. PMID: 23671307; PMCID: PMC3653358.

Once, we thought we understood all there was to know about how gene expression is regulated: A cell can tinker with the expression level of a given protein’s messenger RNA by modifying the activity, abundance, and type of transcription factors in the nucleus or with the RNA’s stability once it is made. But then came a surprising story about a short RNA in C. elegans called lin-4, which didn’t encode a protein but prevented expression of the protein encoded by another gene, lin-14, through antisense binding to lin-14 mRNA (1, 2). Today, we know that lin-4 was just the first example of a large number of small RNAs, called microRNAs, which regulate the expression of various other proteins in a similar way.

Victor Ambros, whose lab published that first story about lin-4, has been studying microRNAs (3, 4) and their regulation (5, 6) ever since, pushing forward our understanding of this powerful mechanism. We called him at his office at the University of Massachusetts Medical School to get some perspective on microRNAs and his career and to learn about some of the latest developments in his lab.

“That shared discovery is one of the most precious moments in my career.”

FROM FARM TO LAB TABLE

How did you end up doing a PhD with David Baltimore?

I was the first scientist in my family. My dad was an immigrant from Poland. He came to the States just after World War II and met my mom. They got married, moved to a farm in Vermont, and started farming. My siblings and I grew up amongst the cows and pigs and helped with the haying and cutting corn, stuff like that.

When I was about nine, I got interested in science, and after that I always wanted to be a scientist. I was an amateur astronomer; I built a telescope and started to imagine that I could actually do astronomy or physics as an occupation. But I quickly changed my mind when I reached college, in part because I realized that my math skills weren’t really up to the task of being a physicist and also because I discovered molecular biology and genetics and just fell in love with both subjects. David taught one of the advanced biology classes I took as an undergraduate at MIT, and that probably had some influence on my decision to work with him. After college, I worked as a technician in David’s lab for a year. I liked it a lot and stayed on in his lab when I entered graduate school at MIT. I was lucky because I had gotten a little bit of traction on a project and continued on that as a grad student, so I ended up finishing grad school fairly efficiently.

Had you any idea at the time what the nature of the lin-4 mutant was?

The assumption was that it was a protein product. I mean, nobody ever thought that there would be any other kind of regulator. There really wasn’t any reason to imagine that there were any other kinds of molecules necessary, other than proteins, to carry out everything that’s done in a cell—especially with regard to the regulation of gene expression. The complexity of gene regulation by proteins alone was so enormous that I never imagined—and nobody I knew imagined—that we needed to look for new kinds of regulatory molecules. The realization that lin-4 was antisense to the 3′-untranslated region of lin-14 was totally the result of communication between Gary and me. That shared discovery is one of the most precious moments in my career. But at the time I didn’t realize that this might be the first example of a general mechanism for regulating gene expression because I was prone to thinking that whatever I was studying in the worm was not generally applicable. It wasn’t until genome sequences were made available that the prevalence of this mechanism became clear.

THE RIGHT CONTEXT

You’ve moved to studying processes that modulate microRNA function…

One protein we’ve studied is called Nhl-2. It’s an example of an emerging class of proteins that can modulate, positively or negatively, the RNA-induced silencing complex (RISC) that inhibits mRNAs targeted by microRNAs. This class of genes may have either general effects on RISC activity or, in some cases, more specific effects. One area of interest in the lab right now is trying to understand the specific outcomes for the regulation of particular microRNAs. Do they always interact with all their targets, or is their activity on some targets promoted or inhibited at the expense of other targets? Can their interaction with certain targets be modified depending on context? We’re using genetic and genomic approaches to identify new modulatory cofactors.

Watch Video

Victor Ambros was born in 1953 in Hanover, New Hampshire, USA. He received his PhD from Massachusetts Institute of Technology (MIT), Cambridge, MA, in 1979 where he also did postdoctoral research 1979-1985. He became a Principal Investigator at Harvard University, Cambridge, MA in 1985. He was Professor at Dartmouth Medical School from 1992-2007 and he is now Silverman Professor of Natural Science at the University of Massachusetts Medical School, Worcester, MA.

Gary Ruvkun was born in Berkeley, California, USA in 1952. He received his PhD from Harvard University in 1982. He was a postdoctoral fellow at Massachusetts Institute of Technology (MIT), Cambridge, MA, 1982-1985. He became a Principal Investigator at Massachusetts General Hospital and Harvard Medical School in 1985, where he is now Professor of Genetics.

This year’s Nobel Prize honors two scientists for their discovery of a fundamental principle governing how gene activity is regulated.

The information stored within our chromosomes can be likened to an instruction manual for all cells in our body. Every cell contains the same chromosomes, so every cell contains exactly the same set of genes and exactly the same set of instructions. Yet, different cell types, such as muscle and nerve cells, have very distinct characteristics. How do these differences arise? The answer lies in gene regulation, which allows each cell to select only the relevant instructions. This ensures that only the correct set of genes is active in each cell type.

Victor Ambros and Gary Ruvkun were interested in how different cell types develop. They discovered microRNA, a new class of tiny RNA molecules that play a crucial role in gene regulation. Their groundbreaking discovery revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms, including humans. It is now known that the human genome codes for over one thousand microRNAs. Their surprising discovery revealed an entirely new dimension to gene regulation. MicroRNAs are proving to be fundamentally important for how organisms develop and function.

Ambros and Ruvkun were interested in genes that control the timing of activation of different genetic programs, ensuring that various cell types develop at the right time. They studied two mutant strains of worms, lin-4 and lin-14, that displayed defects in the timing of activation of genetic programs during development. The laureates wanted to identify the mutated genes and understand their function. Ambros had previously shown that the lin-4 gene appeared to be a negative regulator of the lin-14 gene. However, how the lin-14 activity was blocked was unknown. Ambros and Ruvkun were intrigued by these mutants and their potential relationship and set out to resolve these mysteries.

Ambros and Ruvkun performed further experiments showing that the lin-4 microRNA turns off lin-14 by binding to the complementary sequences in its mRNA, blocking the production of lin-14 protein. A new principle of gene regulation, mediated by a previously unknown type of RNA, microRNA, had been discovered! The results were published in 1993 in two articles in the journal Cell.

Ruvkun cloned let-7, a second gene encoding a microRNA. The gene is conserved in evolution, and it is now known that microRNA regulation is universal among multicellular organisms.

Andrew Z. Fire and Craig C. Mello, awarded the Nobel Prize in 2006, described RNA interference, where specific mRNA-molecules are inactivated by adding double-stranded RNA to cells.

Mutations in one of the proteins required for microRNA production result in the DICER1 syndrome, a rare but severe syndrome linked to cancer in various organs and tissues.

Reference

http://Scientific background: For the discovery of microRNA and its role in post-transcriptional gene regulation

SOURCE

https://www.nobelprize.org/prizes/medicine/2024/press-release/

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Genetic variation causes human lupus, systemic lupus erythematosus (SLE)

Posted in Autoimmune Inflammatory DIseases, CRISPR/Cas9 & Gene Editing, Genome Biology, Genomic Endocrinology, Inflammatory Pathophysiology, RNA Biology, Signaling & Cell Circuits, Single Cell Genomics, Single-cell sequencing, Systemic Inflammatory Response Related Disorders, Variation in human protein-coding regions on February 23, 2023| Leave a Comment »

Genetic variation causes human lupus, systemic lupus erythematosus (SLE)

Reporter: Aviva Lev-Ari, PhD, RN

TLR7 gain-of-function genetic variation causes human lupus

Abstract

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease^{1,2,3,4,5,6,7}, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA⁸,⁹ and binds to guanosine^10,11,–¹². We identified a de novo, previously undescribed missense TLR7^Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7^Y264H variant selectively increased sensing of guanosine and 2′,3′-cGMP^10,11,12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c⁺ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7^Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

SOURCE

Brown, G.J., Cañete, P.F., Wang, H. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349–356 (2022). https://doi.org/10.1038/s41586-022-04642-z

Scientists finally discover the cause of lupus

[Feb. 20, 2023: Alice Deeley, The Francis Crick Institute]

An international team of researchers has identified DNA mutations in a gene that senses viral RNA, as a cause of the autoimmune disease lupus, with the finding paving the way for the development of new treatments.

Lupus is a chronic autoimmune disease which causes inflammation in organs and joints, affects movement and the skin, and causes fatigue. In severe cases, symptoms can be debilitating and complications can be fatal.

In their genetic analysis, carried out at the Centre for Personalised Immunology at the Australian National University, the researchers found a single point mutation in the TLR7 gene. Via referrals from the US and the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, they identified other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team used CRISPR gene-editing to introduce it into mice. These mice went on to develop the disease and showed similar symptoms, providing evidence that the TLR7 mutation was the cause. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

“While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The work may also help explain why lupus is about 10 times more frequent in females than in males. As TLR7 sits on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

“There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

SOURCE

https://www-thebrighterside-news.cdn.ampproject.org/c/s/www.thebrighterside.news/amp/2202023-scientists-finally-discover-the-cause-of-lupus

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

Posted in BioPrinting in Regenerative Medicine, Cell Level, Cell Processing System in Cell Therapy Process Development, Gene Therapy & Gene Editing Development, Genetics & Innovations in Treatment, Genome Biology, MicroEngineering Cell-Tissue & Systems, mRNA Therapeutics, Mutagenesis, Regenerative Biology and Medicine, Single Cell Genomics, Single-cell sequencing, Tissue Engineering, Variation in human protein-coding regions on February 26, 2021| Leave a Comment »

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

The 2021 Virtual World Medical Innovation Forum will focus on the growing impact of gene and cell therapy.

Senior healthcare leaders from all over look to shape and debate the area of gene and cell therapy. Our shared belief: no matter the magnitude of change, responsible healthcare is centered on a shared commitment to collaborative innovation–industry, academia, and practitioners working together to improve patients’ lives.

About the World Medical Innovation Forum

Mass General Brigham is pleased to present the World Medical Innovation Forum (WMIF) virtual event Wednesday, May 19 – Friday, May 21. This interactive web event features expert discussions of gene and cell therapy (GCT) and its potential to change the future of medicine through its disease-treating and potentially curative properties. The agenda features 150+ executive speakers from the healthcare industry, venture, startups, life sciences manufacturing, consumer health and the front lines of care, including many Harvard Medical School-affiliated researchers and clinicians. The annual in-person Forum will resume live in Boston in 2022. The World Medical Innovation Forum is presented by Mass General Brigham Innovation, the global business development unit supporting the research requirements of 7,200 Harvard Medical School faculty and research hospitals including Massachusetts General, Brigham and Women’s, Massachusetts Eye and Ear, Spaulding Rehab and McLean Hospital. Follow us on Twitter: twitter.com/@MGBInnovation

Accelerating the Future of Medicine with Gene and Cell Therapy What Comes Next

https://worldmedicalinnovation.org/wp-content/uploads/2021/05/2021-WMIF-White-Paper-1.0.pdf

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

#WMIF2021

@MGBInnovation

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

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will be in virtual attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine

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Among them, books on Gene and Cell Therapy include the following:

Topics for May 19 – 21 include:

Impact on Patient Care – Therapeutic and Potentially Curative GCT Developments

GCT Delivery, Manufacturing – What’s Next

GCT Platform Development

Oncolytic Viruses – Cancer applications, start-ups

Regenerative Medicine/Stem Cells

Future of CAR-T

M&A Shaping GCT’s Future

Market Priorities

Venture Investing in GCT

China’s GCT Juggernaut

Disease and Patient Focus: Benign blood disorders, diabetes, neurodegenerative diseases

Click here for the current WMIF agenda

Plus:

Fireside Chats: 1:1 interviews with industry CEOs/C-Suite leaders including Novartis Gene Therapies, ThermoFisher, Bayer AG, FDA

First Look: 18 briefings on emerging GCT research from Mass General Brigham scientists

Virtual Poster Session: 40 research posters and presenters on potential GCT discoveries from Mass General Brigham

Announcement of the Disruptive Dozen, 12 GCT technologies likely to break through in the next few years

AGENDA

Wednesday, May 19, 2021

8:00 AM – 8:10 AM

Opening Remarks

Welcome and the vision for Gene and Cell Therapy and why it is a top Mass General Brigham priority.

Introducer:

Scott Sperling

Co-President, Thomas H. Lee Partners
Chairman of the Board of Directors, PHS

Presenter:

Anne Klibanski, MD

CEO, Mass General Brigham

3,000 people joined 5/19 morning

30 sessions: Lab to Clinic, academia, industry, investment community

May 22,23,24, 2022 – in Boston, in-person 2022 WMIF on CGT

8:10 AM – 8:30 AM

The Grand Challenge of Widespread GCT Patient Benefits

Co-Chairs identify the key themes of the Forum – set the stage for top GCT opportunities, challenges, and where the field might take medicine in the future.

Moderator:

Susan Hockfield, PhD

President Emerita and Professor of Neuroscience, MIT

GCT – poised to deliver therapies

Inflection point as Panel will present

Doctors and Patients – Promise for some patients

Barriers for Cell & Gene

Access for patients to therapies like CGT

Speakers:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic virus triple threat: Toxic, immunological, combine with anti cancer therapies

Polygenic therapy – multiple genes involved, plug-play,

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Ravi Thadhani, MD

CAO, Mass General Brigham
Professor, Medicine and Faculty Dean, HMS

Role of academia special to spear head the Polygenic therapy – multiple genes involved, plug-play,

Access critical, relations with Industry

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

Pharmacology Gene-Drug, Interface academic centers and industry

many CGT drugs emerged in Academic center

8:35 AM – 8:50 AM

FIRESIDE

Gene and Cell Therapy 2.0 – What’s Next as We Realize their Potential for Patients

Dave Lennon, PhD

President, Novartis Gene Therapies

Hope that CGT emerging, how the therapies work, neuro, muscular, ocular, genetic diseases of liver and of heart revolution for the industry 900 IND application 25 approvals Economic driver Skilled works, VC disease. Modality one time intervention, long duration of impart, reimbursement, ecosystem to be built around CGT

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Moderator:

Julian Harris, MD

Partner, Deerfield

Promise of CGT realized, what part?

FDA role and interaction in CGT

Manufacturing aspects which is critical

Speaker:

Dave Lennon, PhD

President, Novartis Gene Therapies

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Q&A

8:55 AM – 9:10 AM

8:55 AM – 9:20 AM

The Patient and GCT

GCT development for rare diseases is driven by patient and patient-advocate communities. Understanding their needs and perspectives enables biomarker research, the development of value-driving clinical trial endpoints and successful clinical trials. Industry works with patient communities that help identify unmet needs and collaborate with researchers to conduct disease natural history studies that inform the development of biomarkers and trial endpoints. This panel includes patients who have received cutting-edge GCT therapy as well as caregivers and patient advocates.

Moderator:

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

What is the Power of One – the impact that a patient can have on their own destiny by participating in Clinical Trials Contacting other participants in same trial can be beneficial

Speakers:

Jack Hogan

Patient, MEE

Jeanette Hogan

Parent of Patient, MEE

Jim Holland

CEO, Backcountry.com

Parkinson patient Constraints by regulatory on participation in clinical trial advance stage is approved participation Patients to determine the level of risk they wish to take Information dissemination is critical

Barbara Lavery

Chief Program Officer, ACGT Foundation

Advocacy agency beginning of work Global Genes educational content and out reach to access the information

Patient has the knowledge of the symptoms and recording all input needed for diagnosis by multiple clinicians Early application for CGT

Dan Tesler

Clinical Trial Patient, BWH/DFCC

Experimental Drug clinical trial patient participation in clinical trial is very important to advance the state of science

Sarah Beth Thomas, RN

Professional Development Manager, BWH

Outcome is unknown, hope for good, support with resources all advocacy groups,

Q&A

9:25 AM – 9:40 AM

9:25 AM – 9:45 AM

FIRESIDE

GCT Regulatory Framework | Why Different?

Moderator:

Vicki Sato, PhD

Chairman of the Board, Vir Biotechnology

Diversity of approaches

Process at FDA generalize from 1st entry to rules more generalizable

Speaker:

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research, FDA

Last Spring it became clear that something will work a vaccine by June 2020 belief that enough candidates the challenge manufacture enough and scaling up FDA did not predicted the efficacy of mRNA vaccine vs other approaches expected to work

Recover Work load for the pandemic will wean & clear, Gene Therapies IND application remained flat in the face of the pandemic Rare diseases urgency remains Consensus with industry advisory to get input gene therapy Guidance T-Cell therapy vs Regulation best thinking CGT evolve speedily flexible gained by Guidance

Immune modulators, Immunotherapy Genome editing can make use of viral vectors future technologies nanoparticles and liposome encapsulation

Q&A

9:50 AM – 10:05 AM

9:50 AM – 10:15 AM

Building a GCT Platform for Mainstream Success

This panel of GCT executives, innovators and investors explore how to best shape a successful GCT strategy. Among the questions to be addressed:

How are GCT approaches set around defining and building a platform?
Is AAV the leading modality and what are the remaining challenges?
What are the alternatives?
Is it just a matter of matching modalities to the right indications?

Moderator:

Jean-François Formela, MD

Partner, Atlas Venture

Established core components of the Platform

Speakers:

Katherine High, MD

President, Therapeutics, AskBio

Three drugs approved in Europe in the Gene therapy space

Regulatory Infrastructure exists for CGT drug approval – as new class of therapeutics

Participants investigators, regulators, patients i. e., MDM

Hemophilia in male most challenging

Human are natural hosts for AV safety signals

Dave Lennon, PhD

President, Novartis Gene Therapies

big pharma has portfolios of therapeutics not one drug across Tx areas: cell, gene iodine therapy

collective learning infrastructure features manufacturing at scale early in development Acquisitions strategy for growth # applications for scaling

Rick Modi

CEO, Affinia Therapeutics

Copy, paste EDIT from product A to B novel vectors leverage knowledge varient of vector, coder optimization choice of indication is critical exploration on larger populations Speed to R&D and Speed to better gene construct get to clinic with better design vs ASAP

Data sharing clinical experience with vectors strategies patients selection, vector selection, mitigation, patient type specific

Louise Rodino-Klapac, PhD

EVP, Chief Scientific Officer, Sarepta Therapeutics

AAV based platform 15 years in development same disease indication vs more than one indication stereotype, analytics as hurdle 1st was 10 years 2nd was 3 years

Safety to clinic vs speed to clinic, difference of vectors to trust

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:45 AM

AAV Success Studies | Retinal Dystrophy | Spinal Muscular Atrophy

Recent AAV gene therapy product approvals have catalyzed the field. This new class of therapies has shown the potential to bring transformative benefit to patients. With dozens of AAV treatments in clinical studies, all eyes are on the field to gauge its disruptive impact.

The panel assesses the largest challenges of the first two products, the lessons learned for the broader CGT field, and the extent to which they serve as a precedent to broaden the AAV modality.

Is AAV gene therapy restricted to genetically defined disorders, or will it be able to address common diseases in the near term?
Lessons learned from these first-in-class approvals.
Challenges to broaden this modality to similar indications.
Reflections on safety signals in the clinical studies?

Moderator:

Joan Miller, MD

Chief, Ophthalmology, MEE
Cogan Professor & Chair of Ophthalmology, HMS

Retina specialist, Luxturna success FMA condition cell therapy as solution

Lessons learned

Safety

Speakers:

Ken Mills

CEO, RegenXBio

Tissue types additional administrations, tech and science, address additional diseases, more science for photoreceptors a different tissue type underlying pathology novelties in last 10 years

Cell therapy vs transplant therapy no immunosuppression

Eric Pierce, MD, PhD

Director, Ocular Genomics Institute, MEE
Professor of Ophthalmology, HMS

Laxterna success to be replicated platform, paradigms measurement visual improved

More science is needed to continue develop vectors reduce toxicity,

AAV can deliver different cargos reduce adverse events improve vectors

Ron Philip

Chief Operating Officer, Spark Therapeutics

The first retinal gene therapy, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), was approved by the FDA in 2017.

Meredith Schultz, MD

Executive Medical Director, Lead TME, Novartis Gene Therapies

Impact of cell therapy beyond muscular dystrophy, translational medicine, each indication, each disease, each group of patients build platform unlock the promise

Monitoring for Safety signals real world evidence remote markers, home visits, clinical trial made safer, better communication of information

Q&A

10:50 AM – 11:05 AM

10:45 AM – 10:55 AM

Break

10:55 AM – 11:05 AM

FIRST LOOK

Control of AAV pharmacology by Rational Capsid Design

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

AAV a complex driver in Pharmacology durable, vector of choice, administer in vitro, gene editing tissue specificity, pharmacokinetics side effects and adverse events manufacturability site variation diversify portfolios,

Pathway for rational AAV rational design, curated smart variant libraries, AAV sequence screen multiparametric , data enable liver (de-) targeting unlock therapeutics areas: cochlea

Q&A

11:05 AM – 11:25 AM

11:05 AM – 11:15 AM

FIRST LOOK

Enhanced gene delivery and immunoevasion of AAV vectors without capsid modification

Casey Maguire, PhD

Associate Professor of Neurology, MGH & HMS

Virus Biology: Enveloped (e) or not

enveloped for gene therapy eAAV platform technology: tissue targets and Indications commercialization of eAAV

Q&A

11:15 AM – 11:35 AM

11:20 AM – 11:45 AM

HOT TOPICS

AAV Delivery

This panel will address the advances in the area of AAV gene therapy delivery looking out the next five years. Questions that loom large are: How can biodistribution of AAV be improved? What solutions are in the wings to address immunogenicity of AAV? Will patients be able to receive systemic redosing of AAV-based gene therapies in the future? What technical advances are there for payload size? Will the cost of manufacturing ever become affordable for ultra-rare conditions? Will non-viral delivery completely supplant viral delivery within the next five years?What are the safety concerns and how will they be addressed?

Moderators:

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

Speakers:

Jennifer Farmer

CEO, Friedreich’s Ataxia Research Alliance

Ataxia requires therapy targeting multiple organ with one therapy, brain, spinal cord, heart several IND, clinical trials in 2022

Mathew Pletcher, PhD

SVP, Head of Gene Therapy Research and Technical Operations, Astellas

Work with diseases poorly understood, collaborations needs example of existing: DMD is a great example explain dystrophin share placedo data

Continue to explore large animal guinea pig not the mice, not primates (ethical issues) for understanding immunogenicity and immune response

Manny Simons, PhD

CEO, Akouos

AAV Therapy for the fluid of the inner ear, CGT for the ear vector accessible to surgeons translational work on the inner ear for gene therapy right animal model

Biology across species nerve ending in the cochlea

engineer out of the caspid, lowest dose possible, get desired effect by vector use, 2022 new milestones

Q&A

11:50 AM – 12:05 PM

11:50 AM – 12:15 PM

M&A | Shaping GCT Innovation

The GCT M&A market is booming – many large pharmas have made at least one significant acquisition. How should we view the current GCT M&A market? What is its impact of the current M&A market on technology development? Are these M&A trends new are just another cycle? Has pharma strategy shifted and, if so, what does it mean for GCT companies? What does it mean for patients? What are the long-term prospects – can valuations hold up?

Moderator:

Adam Koppel, MD, PhD

Managing Director, Bain Capital Life Sciences

What acquirers are looking for??

What is the next generation vs what is real where is the industry going?

Speakers:

Debby Baron,

Worldwide Business Development, Pfizer

CGT is an important area Pfizer is active looking for innovators, advancing forward programs of innovation with the experience Pfizer has internally

Scalability and manufacturing regulatory conversations, clinical programs safety in parallel to planning getting drug to patients

Kenneth Custer, PhD

Vice President, Business Development and Lilly New Ventures, Eli Lilly and Company

Marianne De Backer, PhD

Head of Strategy, Business Development & Licensing, and Member of the Executive Committee, Bayer

Absolute Leadership in Gene editing, gene therapy, via acquisition and strategic alliance

Operating model of the acquired company discussed , company continue independence

Sean Nolan

Board Chairman, Encoded Therapeutics & Affinia

Executive Chairman, Jaguar Gene Therapy & Istari Oncology

As acquiree multiple M&A: How the acquirer looks at integration and cultures of the two companies

Traditional integration vs jump start by external acquisition

AAV – epilepsy, next generation of vectors

Q&A

12:20 PM – 12:35 PM

12:15 PM – 12:25 PM

FIRST LOOK

Gene Therapies for Neurological Disorders: Insights from Motor Neuron Disorders

Merit Cudkowicz, MD

Chief of Neurology, MGH

ALS – Man 1in 300, Women 1 in 400, next decade increase 7%

10% ALS is heredity 160 pharma in ALS space, diagnosis is late 1/3 of people are not diagnosed, active community for clinical trials Challenges: disease heterogeneity cases of 10 years late in diagnosis. Clinical Trials for ALS in Gene Therapy targeting ASO1 protein therapies FUS gene struck youngsters

Q&A

12:25 PM – 12:45 PM

12:25 PM – 12:35 PM

FIRST LOOK

Gene Therapy for Neurologic Diseases

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

Cerebral Vascular disease – ACTA2 179H gene smooth muscle cell proliferation disorder

no surgery or drug exist –

Cell therapy for ACTA2 Vasculopathy in the brain and control the BP and stroke – smooth muscle intima proliferation. Viral vector deliver aiming to change platform to non-viral delivery rare disease , gene editing, other mutations of ACTA2 gene target other pathway for atherosclerosis

Q&A

12:35 PM – 12:55 PM

12:35 PM – 1:15 PM

Lunch

1:15 PM – 1:40 PM

Oncolytic Viruses in Cancer | Curing Melanoma and Beyond

Oncolytic viruses represent a powerful new technology, but so far an FDA-approved oncolytic (Imlygic) has only occurred in one area – melanoma and that what is in 2015. This panel involves some of the protagonists of this early success story. They will explore why and how Imlygic became approved and its path to commercialization. Yet, no other cancer indications exist for Imlygic, unlike the expansion of FDA-approved indication for immune checkpoint inhibitors to multiple cancers. Why? Is there a limitation to what and which cancers can target? Is the mode of administration a problem?

No other oncolytic virus therapy has been approved since 2015. Where will the next success story come from and why? Will these therapies only be beneficial for skin cancers or other easily accessible cancers based on intratumoral delivery?

The panel will examine whether the preclinical models that have been developed for other cancer treatment modalities will be useful for oncolytic viruses. It will also assess the extent pre-clinical development challenges have slowed the development of OVs.

Moderator:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Challenges of manufacturing at Amgen what are they?

Speakers:

Robert Coffin, PhD

Chief Research & Development Officer, Replimune

2002 in UK promise in oncolytic therapy GNCSF

Phase III melanoma 2015 M&A with Amgen

oncolytic therapy remains non effecting on immune response

data is key for commercialization

do not belief in systemic therapy achieve maximum immune response possible from a tumor by localized injection

Roger Perlmutter, MD, PhD

Chairman, Merck & Co.

response rates systemic therapy like PD1, Keytruda, OPTIVA well tolerated combination of Oncolytic with systemic

GMP critical for manufacturing

David Reese, MD

Executive Vice President, Research and Development, Amgen

Inter lesion injection of agent vs systemic therapeutics

cold tumors immune resistant render them immune susceptible

Oncolytic virus is a Mono therapy

addressing the unknown

Ann Silk, MD

Physician, Dana Farber-Brigham and Women’s Cancer Center
Assistant Professor of Medicine, HMS

Which person gets oncolytics virus if patient has immune suppression due to other indications

Safety of oncolytic virus greater than Systemic treatment

series biopsies for injected and non injected tissue and compare Suspect of hot tumor and cold tumors likely to have sme response to agent unknown all potential

Q&A

1:45 PM – 2:00 PM

1:45 PM – 2:10 PM

Market Interest in Oncolytic Viruses | Calibrating

There are currently two oncolytic virus products on the market, one in the USA and one in China. As of late 2020, there were 86 clinical trials 60 of which were in phase I with just 2 in Phase III the rest in Phase I/II or Phase II. Although global sales of OVs are still in the ramp-up phase, some projections forecast OVs will be a $700 million market by 2026. This panel will address some of the major questions in this area:

What regulatory challenges will keep OVs from realizing their potential? Despite the promise of OVs for treating cancer only one has been approved in the US. Why has this been the case? Reasons such have viral tropism, viral species selection and delivery challenges have all been cited. However, these are also true of other modalities. Why then have oncolytic virus approaches not advanced faster and what are the primary challenges to be overcome?

Will these need to be combined with other agents to realize their full efficacy and how will that impact the market?
Why are these companies pursuing OVs while several others are taking a pass?

Moderators:

Martine Lamfers, PhD

Visiting Scientist, BWH

Challenged in development of strategies

Demonstrate efficacy

Robert Martuza, MD

Consultant in Neurosurgery, MGH
William and Elizabeth Sweet Distinguished Professor of Neurosurgery, HMS

Modulation mechanism

Speakers:

Anlong Li, MD, PhD

Clinical Director, Oncology Clinical Development, Merck Research Laboratories

IV delivery preferred – delivery alternative are less aggereable

Jeffrey Infante, MD

Early development Oncolytic viruses, Oncology, Janssen Research & Development

oncologic virus if it will generate systemic effects the adoption will accelerate

What areas are the best efficacious

Direct effect with intra-tumor single injection with right payload

Platform approach Prime with 1 and Boost with 2 – not yet experimented with

Do not have the data at trial design for stratification of patients

Turn off strategy not existing yet

Loic Vincent, PhD

Head of Oncology Drug Discovery Unit, Takeda

R&D in collaboration with Academic

Vaccine platform to explore different payload

IV administration may not bring sufficient concentration to the tumor is administer in the blood stream

Classification of Patients by prospective response type id UNKNOWN yet, population of patients require stratification

Q&A

2:15 PM – 2:30 PM

2:10 PM – 2:20 PM

FIRST LOOK

Oncolytic viruses: turning pathogens into anticancer agents

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic therapy DID NOT WORK Pancreatic Cancer and Glioblastoma

Intra- tumoral heterogeniety hinders success

Solution: Oncolytic VIRUSES – Immunological “coldness”

GADD-34 20,000 GBM 40,000 pancreatic cancer

Q&A

2:25 PM – 2:40 PM

2:20 PM – 2:45 PM

Entrepreneurial Growth | Oncolytic Virus

In 2020 there were a total of 60 phase I trials for Oncolytic Viruses. There are now dozens of companies pursuing some aspect of OV technology. This panel will address:

How are small companies equipped to address the challenges of developing OV therapies better than large pharma or biotech?
Will the success of COVID vaccines based on Adenovirus help the regulatory environment for small companies developing OV products in Europe and the USA?
Is there a place for non-viral delivery and other immunotherapy companies to engage in the OV space? Would they bring any real advantages?

Moderator:

Reid Huber, PhD

Partner, Third Rock Ventures

Critical milestones to observe

Speakers:

Caroline Breitbach, PhD

VP, R&D Programs and Strategy, Turnstone Biologics

Trying Intra-tumor delivery and IV infusion delivery oncolytic vaccine pushing dose

translation biomarkers program

transformation tumor microenvironment

Brett Ewald, PhD

SVP, Development & Corporate Strategy, DNAtrix

Studies gets larger, kicking off Phase III multiple tumors

Paul Hallenbeck, PhD

President and Chief Scientific Officer, Seneca Therapeutics

Translation:

Stephen Russell, MD, PhD

CEO, Vyriad

Systemic delivery Oncolytic Virus IV delivery woman in remission

Collaboration with Regeneron

Data collection: Imageable reporter secretable reporter, gene expression

Field is intense systemic oncolytic delivery is exciting in mice and in human, response rates are encouraging combination immune stimulant, check inhibitors

Q&A

2:50 PM – 3:05 PM

2:45 PM – 3:00 PM

Break

3:00 PM – 3:25 PM

CAR-T | Lessons Learned | What’s Next

Few areas of potential cancer therapy have had the attention and excitement of CAR-T. This panel of leading executives, developers, and clinician-scientists will explore the current state of CAR-T and its future prospects. Among the questions to be addressed are:

Is CAR-T still an industry priority – i.e. are new investments being made by large companies? Are new companies being financed? What are the trends?
What have we learned from first-generation products, what can we expect from CAR-T going forward in novel targets, combinations, armored CAR’s and allogeneic treatment adoption?
Early trials showed remarkable overall survival and progression-free survival. What has been observed regarding how enduring these responses are?
Most of the approvals to date have targeted CD19, and most recently BCMA. What are the most common forms of relapses that have been observed?
Is there a consensus about what comes after these CD19 and BCMA trials as to additional targets in liquid tumors? How have dual-targeted approaches fared?

Moderator:
Marcela Maus, MD, PhD
- Director, Cellular Immunotherapy Program, Cancer Center, MGH
- Associate Professor, Medicine, HMS
Is CAR-T Industry priority
Speakers:
- Jakob Dupont, MD
Head of R&D, Atara BioTherapeutics
Phyno-type of the cells for hematologic cancers
solid tumor
inventory of Therapeutics for treating patients in the future
Progressive MS program
EBBT platform B-Cells and T-Cells

- Stefan Hendriks
  - Gobal Head, Cell & Gene, Novartis
  - yes, CGT is a strategy in the present and future
  - Journey started years ago
  - Confirmation the effectiveness of CAR-T therapies, 1 year response prolonged to 5 years 26 months
  - Patient not responding – a lot to learn
  - Patient after 8 months of chemo can be helped by CAR-T
- Christi Shaw
  - CEO, Kite
  - CAR-T is priority 120 companies in the space
  - Manufacturing consistency
  - Patients respond with better quality of life
  - Blood cancer – more work to be done

Q&A

3:30 PM – 3:45 PM

3:30 PM – 3:55 PM

HOT TOPICS

CAR-T | Solid Tumors Success | When?

The potential application of CAR-T in solid tumors will be a game-changer if it occurs. The panel explores the prospects of solid tumor success and what the barriers have been. Questions include:

How would industry and investor strategy for CAR-T and solid tumors be characterized? Has it changed in the last couple of years?
Does the lack of tumor antigen specificity in solid tumors mean that lessons from liquid tumor CAR-T constructs will not translate well and we have to start over?
Whether due to antigen heterogeneity, a hostile tumor micro-environment, or other factors are some specific solid tumors more attractive opportunities than others for CAR-T therapy development?
Given the many challenges that CAR-T faces in solid tumors, does the use of combination therapies from the start, for example, to mitigate TME effects, offer a more compelling opportunity.

Moderator:

Oladapo Yeku, MD, PhD

Clinical Assistant in Medicine, MGH

window of opportunities studies

Speakers:

Jennifer Brogdon

Executive Director, Head of Cell Therapy Research, Exploratory Immuno-Oncology, NIBR

2017 CAR-T first approval

M&A and research collaborations

TCR tumor specific antigens avoid tissue toxicity

Knut Niss, PhD

CTO, Mustang Bio

tumor hot start in 12 month clinical trial solid tumors , theraties not ready yet. Combination therapy will be an experimental treatment long journey checkpoint inhibitors to be used in combination maintenance Lipid tumor

Barbra Sasu, PhD

CSO, Allogene

T cell response at prostate cancer

tumor specific

cytokine tumor specific signals move from solid to metastatic cell type for easier infiltration

Where we might go: safety autologous and allogeneic

Jay Short, PhD

Chairman, CEO, Cofounder, BioAlta, Inc.

Tumor type is not enough for development of therapeutics other organs are involved in the periphery

difficult to penetrate solid tumors biologics activated in the tumor only, positive changes surrounding all charges, water molecules inside the tissue acidic environment target the cells inside the tumor and not outside

Combination staggered key is try combination

Q&A

4:00 PM – 4:15 PM

4:00 PM – 4:25 PM

GCT Manufacturing | Vector Production | Autologous and Allogeneic | Stem Cells | Supply Chain | Scalability & Management

The modes of GCT manufacturing have the potential of fundamentally reordering long-established roles and pathways. While complexity goes up the distance from discovery to deployment shrinks. With the likelihood of a total market for cell therapies to be over $48 billion by 2027, groups of products are emerging. Stem cell therapies are projected to be $28 billion by 2027 and non-stem cell therapies such as CAR-T are projected be $20 billion by 2027. The manufacturing challenges for these two large buckets are very different. Within the CAR-T realm there are diverging trends of autologous and allogeneic therapies and the demands on manufacturing infrastructure are very different. Questions for the panelists are:

Help us all understand the different manufacturing challenges for cell therapies. What are the trade-offs among storage cost, batch size, line changes in terms of production cost and what is the current state of scaling naïve and stem cell therapy treatment vs engineered cell therapies?
For cell and gene therapy what is the cost of Quality Assurance/Quality Control vs. production and how do you think this will trend over time based on your perspective on learning curves today?
Will point of care production become a reality? How will that change product development strategy for pharma and venture investors? What would be the regulatory implications for such products?
How close are allogeneic CAR-T cell therapies? If successful what are the market implications of allogenic CAR-T? What are the cost implications and rewards for developing allogeneic cell therapy treatments?

Moderator:

Michael Paglia

VP, ElevateBio

Speakers:

Dannielle Appelhans
- SVP TechOps and Chief Technical Officer, Novartis Gene Therapies
Thomas Page, PhD
- VP, Engineering and Asset Development, FUJIFILM Diosynth Biotechnologies
Rahul Singhvi, ScD
- CEO and Co-Founder, National Resilience, Inc.
Thomas VanCott, PhD
- Global Head of Product Development, Gene & Cell Therapy, Catalent
- 2/3 autologous 1/3 allogeneic CAR-T high doses and high populations scale up is not done today quality maintain required the timing logistics issues centralized vs decentralized allogeneic are health donors innovations in cell types in use improvements in manufacturing

Ropa Pike, Director, Enterprise Science & Partnerships, Thermo Fisher Scientific

Centralized biopharma industry is moving to decentralized models site specific license

Q&A

4:30 PM – 4:45 PM

4:30 PM – 4:40 PM

FIRST LOOK

CAR-T

Marcela Maus, MD, PhD

Director, Cellular Immunotherapy Program, Cancer Center, MGH
Assistant Professor, Medicine, HMS

Fit-to-purpose CAR-T cells: 3 lead programs

Tr-fill

CAR-T induce response myeloma and multiple myeloma GBM

27 patents on CAR-T

+400 patients treaded 40 Clinical Trials

Q&A

4:40 PM – 5:00 PM

4:40 PM – 4:50 PM

FIRST LOOK

Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy

Khalid Shah, PhD

Vice Chair, Neurosurgery Research, BWH
Director, Center for Stem Cell Therapeutics and Imaging, HMS

Solid tumors are the hardest to treat because: immunosuppressive, hypoxic, Acidic Use of autologous tumor cells self homing ThTC self targeting therapeutic cells Therapeutic tumor cells efficacy pre-clinical models GBM 95% metastesis ThTC translation to patient settings

Q&A

4:50 PM – 5:10 PM

4:50 PM – 5:00 PM

FIRST LOOK

Other Cell Therapies for Cancer

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

T-cell are made in bone marrow create cryogel can be an off-the-shelf product repertoire on T Receptor CCL19+ mesenchymal cells mimic Tymus cells –

inter-tymic injection. Non human primate validation

Q&A

5:00 PM – 5:20 PM

FIRESIDE

Fireside with Mikael Dolsten, MD, PhD

Introducer:

Jonathan Kraft

Moderator:

Daniel Haber, MD, PhD

Chair, Cancer Center, MGH
Isselbacher Professor of Oncology, HMS

Vaccine Status

Mikael Dolsten, MD, PhD

Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer

Deliver vaccine around the Globe, Israel, US, Europe.

3BIL vaccine in 2022 for all Global vaccination

Bio Ntech in Germany

Experience with Biologics immuneoncology & allogeneic antibody cells – new field for drug discovery

mRNA curative effort and cancer vaccine

Access to drugs developed by Pfizer to underdeveloped countries

Q&A

5:25 PM – 5:40 AM

5:20 PM – 5:30 PM

Closing Remarks

Thursday, May 20, 2021

8:00 AM – 8:25 AM

GCT | The China Juggernaut

China embraced gene and cell therapies early. The first China gene therapy clinical trial was in 1991. China approved the world’s first gene therapy product in 2003—Gendicine—an oncolytic adenovirus for the treatment of advanced head and neck cancer. Driven by broad national strategy, China has become a hotbed of GCT development, ranking second in the world with more than 1,000 clinical trials either conducted or underway and thousands of related patents. It has a booming GCT biotech sector, led by more than 45 local companies with growing IND pipelines.

In late 1990, a T cell-based immunotherapy, cytokine-induced killer (CIK) therapy became a popular modality in the clinic in China for tumor treatment. In early 2010, Chinese researchers started to carry out domestic CAR T trials inspired by several important reports suggested the great antitumor function of CAR T cells. Now, China became the country with the most registered CAR T trials, CAR T therapy is flourishing in China.

The Chinese GCT ecosystem has increasingly rich local innovation and growing complement of development and investment partnerships – and also many subtleties.

This panel, consisting of leaders from the China GCT corporate, investor, research and entrepreneurial communities, will consider strategic questions on the growth of the gene and cell therapy industry in China, areas of greatest strength, evolving regulatory framework, early successes and products expected to reach the US and world market.

Moderator:

Min Wu, PhD

Managing Director, Fosun Health Fund

What are the area of CGT in China, regulatory similar to the US

Speakers:

Alvin Luk, PhD

CEO, Neuropath Therapeutics

Monogenic rare disease with clear genomic target

Increase of 30% in patient enrollment

Regulatory reform approval is 60 days no delay

Pin Wang, PhD

CSO, Jiangsu Simcere Pharmaceutical Co., Ltd.

Similar starting point in CGT as the rest of the World unlike a later starting point in other biological

Richard Wang, PhD

CEO, Fosun Kite Biotechnology Co., Ltd

Possibilities to be creative and capitalize the new technologies for innovating drug

Support of the ecosystem by funding new companie allowing the industry to be developed in China

Autologous in patients differences cost challenge

Tian Xu, PhD

Vice President, Westlake University

ICH committee and Chinese FDA -r regulation similar to the US

Difference is the population recruitment, in China patients are active participants in skin disease

Active in development of transposome

Development of non-viral methods, CRISPR still in D and transposome

In China price of drugs regulatory are sensitive

Shunfei Yan, PhD

Investment Manager, InnoStar Capital

Indication driven: Hymophilia,

Allogogenic efficiency therapies

Licensing opportunities

Q&A

8:30 AM – 8:45 AM

8:30 AM – 8:55 AM

Impact of mRNA Vaccines | Global Success Lessons

The COVID vaccine race has propelled mRNA to the forefront of biomedicine. Long considered as a compelling modality for therapeutic gene transfer, the technology may have found its most impactful application as a vaccine platform. Given the transformative industrialization, the massive human experience, and the fast development that has taken place in this industry, where is the horizon? Does the success of the vaccine application, benefit or limit its use as a therapeutic for CGT?

How will the COVID success impact the rest of the industry both in therapeutic and prophylactic vaccines and broader mRNA lessons?
How will the COVID success impact the rest of the industry both on therapeutic and prophylactic vaccines and broader mRNA lessons?
Beyond from speed of development, what aspects make mRNA so well suited as a vaccine platform?
Will cost-of-goods be reduced as the industry matures?
How does mRNA technology seek to compete with AAV and other gene therapy approaches?

Moderator:

Lindsey Baden, MD

Director, Clinical Research, Division of Infectious Diseases, BWH
Associate Professor, HMS

In vivo delivery process regulatory cooperation new opportunities for same platform for new indication

Speakers:

Melissa Moore Chief Scientific Officer, Moderna Many years of mRNA pivoting for new diseases, DARPA, nucleic Acids global deployment of a manufacturing unit on site where the need arise Elan Musk funds new directions at Moderna How many mRNA can be put in one vaccine: Dose and tolerance to achieve efficacy 45 days for Personalized cancer vaccine one per patient Ron Renaud CEO, Translate Bio 1.6 Billion doses produced rare disease monogenic correct mRNA like CF multiple mutation infection disease and oncology applications Platform allowing to swap cargo reusing same nanoparticles address disease beyond Big Pharma options for biotech WHat strain of Flu vaccine will come back in the future when people do not use masks Kate Bingham, UK Vaccine Taskforce July 2020, AAV vs mRNA delivery across UK local centers administered both types supply and delivery uplift

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

HOT TOPICS

Benign Blood Disorders

Hemophilia has been and remains a hallmark indication for the CGT. Given its well-defined biology, larger market, and limited need for gene transfer to provide therapeutic benefit, it has been at the forefront of clinical development for years, however, product approval remains elusive. What are the main hurdles to this success? Contrary to many indications that CGT pursues no therapeutic options are available to patients, hemophiliacs have an increasing number of highly efficacious treatment options. How does the competitive landscape impact this field differently than other CGT fields? With many different players pursuing a gene therapy option for hemophilia, what are the main differentiators? Gene therapy for hemophilia seems compelling for low and middle-income countries, given the cost of currently available treatments; does your company see opportunities in this market?

Moderator:

Nancy Berliner, MD

Chief, Division of Hematology, BWH
H. Franklin Bunn Professor of Medicine, HMS

Speakers:

Theresa Heggie

CEO, Freeline Therapeutics

Safety concerns, high burden of treatment CGT has record of safety and risk/benefit adoption of Tx functional cure CGT is potent Tx relative small quantity of protein needs be delivered

Potency and quality less quantity drug and greater potency

risk of delivery unwanted DNA, capsules are critical

analytics is critical regulator involvement in potency definition

Close of collaboration is exciting

Gallia Levy, MD, PhD

Chief Medical Officer, Spark Therapeutics

Hemophilia CGT is the highest potential for Global access logistics in underdeveloped countries working with NGOs practicality of the Tx

Roche reached 120 Counties great to be part of the Roche Group

Amir Nashat, PhD

Managing Partner, Polaris Ventures

Suneet Varma

Global President of Rare Disease, Pfizer

Gene therapy at Pfizer small molecule, large molecule and CGT – spectrum of choice allowing Hemophilia patients to marry

1/3 internal 1/3 partnership 1/3 acquisitions

Learning from COVID-19 is applied for other vaccine development

review of protocols and CGT for Hemophelia

You can’t buy Time

With MIT Pfizer is developing a model for Hemopilia CGT treatment

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Treating Rett Syndrome through X-reactivation

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

200 disease X chromosome unlock for neurological genetic diseases: Rett Syndromeand other autism spectrum disorders female model vs male mice model

deliver protein to the brain

restore own missing or dysfunctional protein

Epigenetic not CGT – no exogent intervention Xist ASO drug

Female model

Q&A

9:35 AM – 9:55 AM

9:35 AM – 9:45 AM

FIRST LOOK

Rare but mighty: scaling up success in single gene disorders

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

Single gene disorder NGS enable diagnosis, DIagnosis to Treatment How to know whar cell to target, make it available and scale up Address gap: missing components Biomarkers to cell types lipid chemistry cell animal biology

crosswalk from bone marrow matter

New gene discovered that causes neurodevelopment of stagnant genes Examining new Biology cell type specific biomarkers

Q&A

9:45 AM – 10:05 AM

9:50 AM – 10:15 AM

HOT TOPICS

Diabetes | Grand Challenge

The American Diabetes Association estimates 30 million Americans have diabetes and 1.5 million are diagnosed annually. GCT offers the prospect of long-sought treatment for this enormous cohort and their chronic requirements. The complexity of the disease and its management constitute a grand challenge and highlight both the potential of GCT and its current limitations.

Islet transplantation for type 1 diabetes has been attempted for decades. Problems like loss of transplanted islet cells due to autoimmunity and graft site factors have been difficult to address. Is there anything different on the horizon for gene and cell therapies to help this be successful?
How is the durability of response for gene or cell therapies for diabetes being addressed? For example, what would the profile of an acceptable (vs. optimal) cell therapy look like?

Moderator:

Marie McDonnell, MD

Chief, Diabetes Section and Director, Diabetes Program, BWH
Lecturer on Medicine, HMS

Type 1 Diabetes cost of insulin for continuous delivery of drug

alternative treatments:

The Future: neuropotent stem cells

What keeps you up at night

Speakers:

Tom Bollenbach, PhD

Chief Technology Officer, Advanced Regenerative Manufacturing Institute

Data managment sterility sensors, cell survival after implantation, stem cells manufacturing, process development in manufacturing of complex cells

Data and instrumentation the Process is the Product

Manufacturing tight schedules

Manasi Jaiman, MD

Vice President, Clinical Development, ViaCyte
Pediatric Endocrinologist

continous glucose monitoring

Bastiano Sanna, PhD

EVP, Chief of Cell & Gene Therapies and VCGT Site Head, Vertex Pharmaceuticals

100 years from discovering Insulin, Insulin is not a cure in 2021 – asking patients to partner more

Produce large quantities of the Islet cells encapsulation technology been developed

Scaling up is a challenge

Rogerio Vivaldi, MD

CEO, Sigilon Therapeutics

Advanced made, Patient of Type 1 Outer and Inner compartments of spheres (not capsule) no immune suppression continuous secretion of enzyme Insulin independence without immune suppression

Volume to have of-the-shelf inventory oxegenation in location lymphatic and vascularization conrol the whole process modular platform learning from others

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:40 AM

FIRESIDE

Building A Unified GCT Strategy

Introducer:

John Fish

CEO, Suffolk
Chairman of Board Trustees, Brigham Health

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

Last year, what was it at Novartis

Speaker:

Jay Bradner, MD

President, NIBR

Keep eyes open, waiting the Pandemic to end and enable working back on all the indications

Portfolio of MET, Mimi Emerging Therapies

Learning from the Pandemic – operationalize the practice science, R&D leaders, new collaboratives at NIH, FDA, Novartis

Pursue programs that will yield growth, tropic diseases with Gates Foundation, Rising Tide pods for access CGT within Novartis Partnership with UPenn in Cell Therapy

Cost to access to IP from Academia to a Biotech CRISPR accessing few translations to Clinic

Protein degradation organization constraint valuation by parties in a partnership

Novartis: nuclear protein lipid nuclear particles, tamplate for Biotech to collaborate

Game changing: 10% of the Portfolio, New frontiers human genetics in Ophthalmology, CAR-T, CRISPR, Gene Therapy Neurological and payloads of different matter

Q&A

10:45 AM – 11:00 AM

10:40 AM – 10:50 AM

Break

10:50 AM – 11:00 AM

FIRST LOOK

Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy

Christine Seidman, MD

Director, Cardiovascular Genetics Center, BWH
Smith Professor of Medicine & Genetics, HMS

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

The 2021 Virtual World Medical Innovation Forum will focus on the growing impact of gene and cell therapy.

About the World Medical Innovation Forum

Accelerating the Future of Medicine with Gene and Cell Therapy What Comes Next

https://worldmedicalinnovation.org/wp-content/uploads/2021/05/2021-WMIF-White-Paper-1.0.pdf

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

#WMIF2021

@MGBInnovation

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

member_60221522 copy

will be in virtual attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine

https://lnkd.in/ekWGNqA

Among them, books on Gene and Cell Therapy include the following:

Topics for May 19 – 21 include:

Impact on Patient Care – Therapeutic and Potentially Curative GCT Developments

GCT Delivery, Manufacturing – What’s Next

GCT Platform Development

Oncolytic Viruses – Cancer applications, start-ups

Regenerative Medicine/Stem Cells

Future of CAR-T

M&A Shaping GCT’s Future

Market Priorities

Venture Investing in GCT

China’s GCT Juggernaut

Disease and Patient Focus: Benign blood disorders, diabetes, neurodegenerative diseases

Click here for the current WMIF agenda

Plus:

Fireside Chats: 1:1 interviews with industry CEOs/C-Suite leaders including Novartis Gene Therapies, ThermoFisher, Bayer AG, FDA

First Look: 18 briefings on emerging GCT research from Mass General Brigham scientists

Virtual Poster Session: 40 research posters and presenters on potential GCT discoveries from Mass General Brigham

Announcement of the Disruptive Dozen, 12 GCT technologies likely to break through in the next few years

AGENDA

Wednesday, May 19, 2021

8:00 AM – 8:10 AM

Opening Remarks

Welcome and the vision for Gene and Cell Therapy and why it is a top Mass General Brigham priority.

Introducer:

Scott Sperling

Co-President, Thomas H. Lee Partners
Chairman of the Board of Directors, PHS

Presenter:

Anne Klibanski, MD

CEO, Mass General Brigham

3,000 people joined 5/19 morning

30 sessions: Lab to Clinic, academia, industry, investment community

May 22,23,24, 2022 – in Boston, in-person 2022 WMIF on CGT

8:10 AM – 8:30 AM

The Grand Challenge of Widespread GCT Patient Benefits

Co-Chairs identify the key themes of the Forum – set the stage for top GCT opportunities, challenges, and where the field might take medicine in the future.

Moderator:

Susan Hockfield, PhD

President Emerita and Professor of Neuroscience, MIT

GCT – poised to deliver therapies

Inflection point as Panel will present

Doctors and Patients – Promise for some patients

Barriers for Cell & Gene

Access for patients to therapies like CGT

Speakers:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic virus triple threat: Toxic, immunological, combine with anti cancer therapies

Polygenic therapy – multiple genes involved, plug-play,

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Ravi Thadhani, MD

CAO, Mass General Brigham
Professor, Medicine and Faculty Dean, HMS

Role of academia special to spear head the Polygenic therapy – multiple genes involved, plug-play,

Access critical, relations with Industry

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

Pharmacology Gene-Drug, Interface academic centers and industry

many CGT drugs emerged in Academic center

8:35 AM – 8:50 AM

FIRESIDE

Gene and Cell Therapy 2.0 – What’s Next as We Realize their Potential for Patients

Dave Lennon, PhD

President, Novartis Gene Therapies

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Moderator:

Julian Harris, MD

Partner, Deerfield

Promise of CGT realized, what part?

FDA role and interaction in CGT

Manufacturing aspects which is critical

Speaker:

Dave Lennon, PhD

President, Novartis Gene Therapies

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Q&A

8:55 AM – 9:10 AM

8:55 AM – 9:20 AM

The Patient and GCT

Moderator:

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

What is the Power of One – the impact that a patient can have on their own destiny by participating in Clinical Trials Contacting other participants in same trial can be beneficial

Speakers:

Jack Hogan

Patient, MEE

Jeanette Hogan

Parent of Patient, MEE

Jim Holland

CEO, Backcountry.com

Barbara Lavery

Chief Program Officer, ACGT Foundation

Advocacy agency beginning of work Global Genes educational content and out reach to access the information

Patient has the knowledge of the symptoms and recording all input needed for diagnosis by multiple clinicians Early application for CGT

Dan Tesler

Clinical Trial Patient, BWH/DFCC

Experimental Drug clinical trial patient participation in clinical trial is very important to advance the state of science

Sarah Beth Thomas, RN

Professional Development Manager, BWH

Outcome is unknown, hope for good, support with resources all advocacy groups,

Q&A

9:25 AM – 9:40 AM

9:25 AM – 9:45 AM

FIRESIDE

GCT Regulatory Framework | Why Different?

Moderator:

Vicki Sato, PhD

Chairman of the Board, Vir Biotechnology

Diversity of approaches

Process at FDA generalize from 1st entry to rules more generalizable

Speaker:

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research, FDA

Immune modulators, Immunotherapy Genome editing can make use of viral vectors future technologies nanoparticles and liposome encapsulation

Q&A

9:50 AM – 10:05 AM

9:50 AM – 10:15 AM

Building a GCT Platform for Mainstream Success

This panel of GCT executives, innovators and investors explore how to best shape a successful GCT strategy. Among the questions to be addressed:

How are GCT approaches set around defining and building a platform?
Is AAV the leading modality and what are the remaining challenges?
What are the alternatives?
Is it just a matter of matching modalities to the right indications?

Moderator:

Jean-François Formela, MD

Partner, Atlas Venture

Established core components of the Platform

Speakers:

Katherine High, MD

President, Therapeutics, AskBio

Three drugs approved in Europe in the Gene therapy space

Regulatory Infrastructure exists for CGT drug approval – as new class of therapeutics

Participants investigators, regulators, patients i. e., MDM

Hemophilia in male most challenging

Human are natural hosts for AV safety signals

Dave Lennon, PhD

President, Novartis Gene Therapies

big pharma has portfolios of therapeutics not one drug across Tx areas: cell, gene iodine therapy

collective learning infrastructure features manufacturing at scale early in development Acquisitions strategy for growth # applications for scaling

Rick Modi

CEO, Affinia Therapeutics

Data sharing clinical experience with vectors strategies patients selection, vector selection, mitigation, patient type specific

Louise Rodino-Klapac, PhD

EVP, Chief Scientific Officer, Sarepta Therapeutics

AAV based platform 15 years in development same disease indication vs more than one indication stereotype, analytics as hurdle 1st was 10 years 2nd was 3 years

Safety to clinic vs speed to clinic, difference of vectors to trust

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:45 AM

AAV Success Studies | Retinal Dystrophy | Spinal Muscular Atrophy

The panel assesses the largest challenges of the first two products, the lessons learned for the broader CGT field, and the extent to which they serve as a precedent to broaden the AAV modality.

Is AAV gene therapy restricted to genetically defined disorders, or will it be able to address common diseases in the near term?
Lessons learned from these first-in-class approvals.
Challenges to broaden this modality to similar indications.
Reflections on safety signals in the clinical studies?

Moderator:

Joan Miller, MD

Chief, Ophthalmology, MEE
Cogan Professor & Chair of Ophthalmology, HMS

Retina specialist, Luxturna success FMA condition cell therapy as solution

Lessons learned

Safety

Speakers:

Ken Mills

CEO, RegenXBio

Tissue types additional administrations, tech and science, address additional diseases, more science for photoreceptors a different tissue type underlying pathology novelties in last 10 years

Cell therapy vs transplant therapy no immunosuppression

Eric Pierce, MD, PhD

Director, Ocular Genomics Institute, MEE
Professor of Ophthalmology, HMS

Laxterna success to be replicated platform, paradigms measurement visual improved

More science is needed to continue develop vectors reduce toxicity,

AAV can deliver different cargos reduce adverse events improve vectors

Ron Philip

Chief Operating Officer, Spark Therapeutics

The first retinal gene therapy, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), was approved by the FDA in 2017.

Meredith Schultz, MD

Executive Medical Director, Lead TME, Novartis Gene Therapies

Impact of cell therapy beyond muscular dystrophy, translational medicine, each indication, each disease, each group of patients build platform unlock the promise

Monitoring for Safety signals real world evidence remote markers, home visits, clinical trial made safer, better communication of information

Q&A

10:50 AM – 11:05 AM

10:45 AM – 10:55 AM

Break

10:55 AM – 11:05 AM

FIRST LOOK

Control of AAV pharmacology by Rational Capsid Design

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

Pathway for rational AAV rational design, curated smart variant libraries, AAV sequence screen multiparametric , data enable liver (de-) targeting unlock therapeutics areas: cochlea

Q&A

11:05 AM – 11:25 AM

11:05 AM – 11:15 AM

FIRST LOOK

Enhanced gene delivery and immunoevasion of AAV vectors without capsid modification

Casey Maguire, PhD

Associate Professor of Neurology, MGH & HMS

Virus Biology: Enveloped (e) or not

enveloped for gene therapy eAAV platform technology: tissue targets and Indications commercialization of eAAV

Q&A

11:15 AM – 11:35 AM

11:20 AM – 11:45 AM

HOT TOPICS

AAV Delivery

Moderators:

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

Speakers:

Jennifer Farmer

CEO, Friedreich’s Ataxia Research Alliance

Ataxia requires therapy targeting multiple organ with one therapy, brain, spinal cord, heart several IND, clinical trials in 2022

Mathew Pletcher, PhD

SVP, Head of Gene Therapy Research and Technical Operations, Astellas

Work with diseases poorly understood, collaborations needs example of existing: DMD is a great example explain dystrophin share placedo data

Continue to explore large animal guinea pig not the mice, not primates (ethical issues) for understanding immunogenicity and immune response

Manny Simons, PhD

CEO, Akouos

AAV Therapy for the fluid of the inner ear, CGT for the ear vector accessible to surgeons translational work on the inner ear for gene therapy right animal model

Biology across species nerve ending in the cochlea

engineer out of the caspid, lowest dose possible, get desired effect by vector use, 2022 new milestones

Q&A

11:50 AM – 12:05 PM

11:50 AM – 12:15 PM

M&A | Shaping GCT Innovation

Moderator:

Adam Koppel, MD, PhD

Managing Director, Bain Capital Life Sciences

What acquirers are looking for??

What is the next generation vs what is real where is the industry going?

Speakers:

Debby Baron,

Worldwide Business Development, Pfizer

CGT is an important area Pfizer is active looking for innovators, advancing forward programs of innovation with the experience Pfizer has internally

Scalability and manufacturing regulatory conversations, clinical programs safety in parallel to planning getting drug to patients

Kenneth Custer, PhD

Vice President, Business Development and Lilly New Ventures, Eli Lilly and Company

Marianne De Backer, PhD

Head of Strategy, Business Development & Licensing, and Member of the Executive Committee, Bayer

Absolute Leadership in Gene editing, gene therapy, via acquisition and strategic alliance

Operating model of the acquired company discussed , company continue independence

Sean Nolan

Board Chairman, Encoded Therapeutics & Affinia

Executive Chairman, Jaguar Gene Therapy & Istari Oncology

As acquiree multiple M&A: How the acquirer looks at integration and cultures of the two companies

Traditional integration vs jump start by external acquisition

AAV – epilepsy, next generation of vectors

Q&A

12:20 PM – 12:35 PM

12:15 PM – 12:25 PM

FIRST LOOK

Gene Therapies for Neurological Disorders: Insights from Motor Neuron Disorders

Merit Cudkowicz, MD

Chief of Neurology, MGH

ALS – Man 1in 300, Women 1 in 400, next decade increase 7%

Q&A

12:25 PM – 12:45 PM

12:25 PM – 12:35 PM

FIRST LOOK

Gene Therapy for Neurologic Diseases

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

Cerebral Vascular disease – ACTA2 179H gene smooth muscle cell proliferation disorder

no surgery or drug exist –

Q&A

12:35 PM – 12:55 PM

12:35 PM – 1:15 PM

Lunch

1:15 PM – 1:40 PM

Oncolytic Viruses in Cancer | Curing Melanoma and Beyond

Moderator:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Challenges of manufacturing at Amgen what are they?

Speakers:

Robert Coffin, PhD

Chief Research & Development Officer, Replimune

2002 in UK promise in oncolytic therapy GNCSF

Phase III melanoma 2015 M&A with Amgen

oncolytic therapy remains non effecting on immune response

data is key for commercialization

do not belief in systemic therapy achieve maximum immune response possible from a tumor by localized injection

Roger Perlmutter, MD, PhD

Chairman, Merck & Co.

response rates systemic therapy like PD1, Keytruda, OPTIVA well tolerated combination of Oncolytic with systemic

GMP critical for manufacturing

David Reese, MD

Executive Vice President, Research and Development, Amgen

Inter lesion injection of agent vs systemic therapeutics

cold tumors immune resistant render them immune susceptible

Oncolytic virus is a Mono therapy

addressing the unknown

Ann Silk, MD

Physician, Dana Farber-Brigham and Women’s Cancer Center
Assistant Professor of Medicine, HMS

Which person gets oncolytics virus if patient has immune suppression due to other indications

Safety of oncolytic virus greater than Systemic treatment

series biopsies for injected and non injected tissue and compare Suspect of hot tumor and cold tumors likely to have sme response to agent unknown all potential

Q&A

1:45 PM – 2:00 PM

1:45 PM – 2:10 PM

Market Interest in Oncolytic Viruses | Calibrating

Will these need to be combined with other agents to realize their full efficacy and how will that impact the market?
Why are these companies pursuing OVs while several others are taking a pass?

Moderators:

Martine Lamfers, PhD

Visiting Scientist, BWH

Challenged in development of strategies

Demonstrate efficacy

Robert Martuza, MD

Consultant in Neurosurgery, MGH
William and Elizabeth Sweet Distinguished Professor of Neurosurgery, HMS

Modulation mechanism

Speakers:

Anlong Li, MD, PhD

Clinical Director, Oncology Clinical Development, Merck Research Laboratories

IV delivery preferred – delivery alternative are less aggereable

Jeffrey Infante, MD

Early development Oncolytic viruses, Oncology, Janssen Research & Development

oncologic virus if it will generate systemic effects the adoption will accelerate

What areas are the best efficacious

Direct effect with intra-tumor single injection with right payload

Platform approach Prime with 1 and Boost with 2 – not yet experimented with

Do not have the data at trial design for stratification of patients

Turn off strategy not existing yet

Loic Vincent, PhD

Head of Oncology Drug Discovery Unit, Takeda

R&D in collaboration with Academic

Vaccine platform to explore different payload

IV administration may not bring sufficient concentration to the tumor is administer in the blood stream

Classification of Patients by prospective response type id UNKNOWN yet, population of patients require stratification

Q&A

2:15 PM – 2:30 PM

2:10 PM – 2:20 PM

FIRST LOOK

Oncolytic viruses: turning pathogens into anticancer agents

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic therapy DID NOT WORK Pancreatic Cancer and Glioblastoma

Intra- tumoral heterogeniety hinders success

Solution: Oncolytic VIRUSES – Immunological “coldness”

GADD-34 20,000 GBM 40,000 pancreatic cancer

Q&A

2:25 PM – 2:40 PM

2:20 PM – 2:45 PM

Entrepreneurial Growth | Oncolytic Virus

In 2020 there were a total of 60 phase I trials for Oncolytic Viruses. There are now dozens of companies pursuing some aspect of OV technology. This panel will address:

How are small companies equipped to address the challenges of developing OV therapies better than large pharma or biotech?
Will the success of COVID vaccines based on Adenovirus help the regulatory environment for small companies developing OV products in Europe and the USA?
Is there a place for non-viral delivery and other immunotherapy companies to engage in the OV space? Would they bring any real advantages?

Moderator:

Reid Huber, PhD

Partner, Third Rock Ventures

Critical milestones to observe

Speakers:

Caroline Breitbach, PhD

VP, R&D Programs and Strategy, Turnstone Biologics

Trying Intra-tumor delivery and IV infusion delivery oncolytic vaccine pushing dose

translation biomarkers program

transformation tumor microenvironment

Brett Ewald, PhD

SVP, Development & Corporate Strategy, DNAtrix

Studies gets larger, kicking off Phase III multiple tumors

Paul Hallenbeck, PhD

President and Chief Scientific Officer, Seneca Therapeutics

Translation:

Stephen Russell, MD, PhD

CEO, Vyriad

Systemic delivery Oncolytic Virus IV delivery woman in remission

Collaboration with Regeneron

Data collection: Imageable reporter secretable reporter, gene expression

Field is intense systemic oncolytic delivery is exciting in mice and in human, response rates are encouraging combination immune stimulant, check inhibitors

Q&A

2:50 PM – 3:05 PM

2:45 PM – 3:00 PM

Break

3:00 PM – 3:25 PM

CAR-T | Lessons Learned | What’s Next

Is CAR-T still an industry priority – i.e. are new investments being made by large companies? Are new companies being financed? What are the trends?
What have we learned from first-generation products, what can we expect from CAR-T going forward in novel targets, combinations, armored CAR’s and allogeneic treatment adoption?
Early trials showed remarkable overall survival and progression-free survival. What has been observed regarding how enduring these responses are?
Most of the approvals to date have targeted CD19, and most recently BCMA. What are the most common forms of relapses that have been observed?
Is there a consensus about what comes after these CD19 and BCMA trials as to additional targets in liquid tumors? How have dual-targeted approaches fared?

Moderator:
Marcela Maus, MD, PhD
- Director, Cellular Immunotherapy Program, Cancer Center, MGH
- Associate Professor, Medicine, HMS
Is CAR-T Industry priority
Speakers:
- Jakob Dupont, MD
Head of R&D, Atara BioTherapeutics
Phyno-type of the cells for hematologic cancers
solid tumor
inventory of Therapeutics for treating patients in the future
Progressive MS program
EBBT platform B-Cells and T-Cells

- Stefan Hendriks
  - Gobal Head, Cell & Gene, Novartis
  - yes, CGT is a strategy in the present and future
  - Journey started years ago
  - Confirmation the effectiveness of CAR-T therapies, 1 year response prolonged to 5 years 26 months
  - Patient not responding – a lot to learn
  - Patient after 8 months of chemo can be helped by CAR-T
- Christi Shaw
  - CEO, Kite
  - CAR-T is priority 120 companies in the space
  - Manufacturing consistency
  - Patients respond with better quality of life
  - Blood cancer – more work to be done

Q&A

3:30 PM – 3:45 PM

3:30 PM – 3:55 PM

HOT TOPICS

CAR-T | Solid Tumors Success | When?

The potential application of CAR-T in solid tumors will be a game-changer if it occurs. The panel explores the prospects of solid tumor success and what the barriers have been. Questions include:

How would industry and investor strategy for CAR-T and solid tumors be characterized? Has it changed in the last couple of years?
Does the lack of tumor antigen specificity in solid tumors mean that lessons from liquid tumor CAR-T constructs will not translate well and we have to start over?
Whether due to antigen heterogeneity, a hostile tumor micro-environment, or other factors are some specific solid tumors more attractive opportunities than others for CAR-T therapy development?
Given the many challenges that CAR-T faces in solid tumors, does the use of combination therapies from the start, for example, to mitigate TME effects, offer a more compelling opportunity.

Moderator:

Oladapo Yeku, MD, PhD

Clinical Assistant in Medicine, MGH

window of opportunities studies

Speakers:

Jennifer Brogdon

Executive Director, Head of Cell Therapy Research, Exploratory Immuno-Oncology, NIBR

2017 CAR-T first approval

M&A and research collaborations

TCR tumor specific antigens avoid tissue toxicity

Knut Niss, PhD

CTO, Mustang Bio

Barbra Sasu, PhD

CSO, Allogene

T cell response at prostate cancer

tumor specific

cytokine tumor specific signals move from solid to metastatic cell type for easier infiltration

Where we might go: safety autologous and allogeneic

Jay Short, PhD

Chairman, CEO, Cofounder, BioAlta, Inc.

Tumor type is not enough for development of therapeutics other organs are involved in the periphery

Combination staggered key is try combination

Q&A

4:00 PM – 4:15 PM

4:00 PM – 4:25 PM

GCT Manufacturing | Vector Production | Autologous and Allogeneic | Stem Cells | Supply Chain | Scalability & Management

Help us all understand the different manufacturing challenges for cell therapies. What are the trade-offs among storage cost, batch size, line changes in terms of production cost and what is the current state of scaling naïve and stem cell therapy treatment vs engineered cell therapies?
For cell and gene therapy what is the cost of Quality Assurance/Quality Control vs. production and how do you think this will trend over time based on your perspective on learning curves today?
Will point of care production become a reality? How will that change product development strategy for pharma and venture investors? What would be the regulatory implications for such products?
How close are allogeneic CAR-T cell therapies? If successful what are the market implications of allogenic CAR-T? What are the cost implications and rewards for developing allogeneic cell therapy treatments?

Moderator:

Michael Paglia

VP, ElevateBio

Speakers:

Dannielle Appelhans
- SVP TechOps and Chief Technical Officer, Novartis Gene Therapies
Thomas Page, PhD
- VP, Engineering and Asset Development, FUJIFILM Diosynth Biotechnologies
Rahul Singhvi, ScD
- CEO and Co-Founder, National Resilience, Inc.
Thomas VanCott, PhD
- Global Head of Product Development, Gene & Cell Therapy, Catalent
- 2/3 autologous 1/3 allogeneic CAR-T high doses and high populations scale up is not done today quality maintain required the timing logistics issues centralized vs decentralized allogeneic are health donors innovations in cell types in use improvements in manufacturing

Ropa Pike, Director, Enterprise Science & Partnerships, Thermo Fisher Scientific

Centralized biopharma industry is moving to decentralized models site specific license

Q&A

4:30 PM – 4:45 PM

4:30 PM – 4:40 PM

FIRST LOOK

CAR-T

Marcela Maus, MD, PhD

Director, Cellular Immunotherapy Program, Cancer Center, MGH
Assistant Professor, Medicine, HMS

Fit-to-purpose CAR-T cells: 3 lead programs

Tr-fill

CAR-T induce response myeloma and multiple myeloma GBM

27 patents on CAR-T

+400 patients treaded 40 Clinical Trials

Q&A

4:40 PM – 5:00 PM

4:40 PM – 4:50 PM

FIRST LOOK

Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy

Khalid Shah, PhD

Vice Chair, Neurosurgery Research, BWH
Director, Center for Stem Cell Therapeutics and Imaging, HMS

Q&A

4:50 PM – 5:10 PM

4:50 PM – 5:00 PM

FIRST LOOK

Other Cell Therapies for Cancer

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

T-cell are made in bone marrow create cryogel can be an off-the-shelf product repertoire on T Receptor CCL19+ mesenchymal cells mimic Tymus cells –

inter-tymic injection. Non human primate validation

Q&A

5:00 PM – 5:20 PM

FIRESIDE

Fireside with Mikael Dolsten, MD, PhD

Introducer:

Jonathan Kraft

Moderator:

Daniel Haber, MD, PhD

Chair, Cancer Center, MGH
Isselbacher Professor of Oncology, HMS

Vaccine Status

Mikael Dolsten, MD, PhD

Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer

Deliver vaccine around the Globe, Israel, US, Europe.

3BIL vaccine in 2022 for all Global vaccination

Bio Ntech in Germany

Experience with Biologics immuneoncology & allogeneic antibody cells – new field for drug discovery

mRNA curative effort and cancer vaccine

Access to drugs developed by Pfizer to underdeveloped countries

Q&A

5:25 PM – 5:40 AM

5:20 PM – 5:30 PM

Closing Remarks

Thursday, May 20, 2021

8:00 AM – 8:25 AM

GCT | The China Juggernaut

The Chinese GCT ecosystem has increasingly rich local innovation and growing complement of development and investment partnerships – and also many subtleties.

Moderator:

Min Wu, PhD

Managing Director, Fosun Health Fund

What are the area of CGT in China, regulatory similar to the US

Speakers:

Alvin Luk, PhD

CEO, Neuropath Therapeutics

Monogenic rare disease with clear genomic target

Increase of 30% in patient enrollment

Regulatory reform approval is 60 days no delay

Pin Wang, PhD

CSO, Jiangsu Simcere Pharmaceutical Co., Ltd.

Similar starting point in CGT as the rest of the World unlike a later starting point in other biological

Richard Wang, PhD

CEO, Fosun Kite Biotechnology Co., Ltd

Possibilities to be creative and capitalize the new technologies for innovating drug

Support of the ecosystem by funding new companie allowing the industry to be developed in China

Autologous in patients differences cost challenge

Tian Xu, PhD

Vice President, Westlake University

ICH committee and Chinese FDA -r regulation similar to the US

Difference is the population recruitment, in China patients are active participants in skin disease

Active in development of transposome

Development of non-viral methods, CRISPR still in D and transposome

In China price of drugs regulatory are sensitive

Shunfei Yan, PhD

Investment Manager, InnoStar Capital

Indication driven: Hymophilia,

Allogogenic efficiency therapies

Licensing opportunities

Q&A

8:30 AM – 8:45 AM

8:30 AM – 8:55 AM

Impact of mRNA Vaccines | Global Success Lessons

How will the COVID success impact the rest of the industry both in therapeutic and prophylactic vaccines and broader mRNA lessons?
How will the COVID success impact the rest of the industry both on therapeutic and prophylactic vaccines and broader mRNA lessons?
Beyond from speed of development, what aspects make mRNA so well suited as a vaccine platform?
Will cost-of-goods be reduced as the industry matures?
How does mRNA technology seek to compete with AAV and other gene therapy approaches?

Moderator:

Lindsey Baden, MD

Director, Clinical Research, Division of Infectious Diseases, BWH
Associate Professor, HMS

In vivo delivery process regulatory cooperation new opportunities for same platform for new indication

Speakers:

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

HOT TOPICS

Benign Blood Disorders

Moderator:

Nancy Berliner, MD

Chief, Division of Hematology, BWH
H. Franklin Bunn Professor of Medicine, HMS

Speakers:

Theresa Heggie

CEO, Freeline Therapeutics

Safety concerns, high burden of treatment CGT has record of safety and risk/benefit adoption of Tx functional cure CGT is potent Tx relative small quantity of protein needs be delivered

Potency and quality less quantity drug and greater potency

risk of delivery unwanted DNA, capsules are critical

analytics is critical regulator involvement in potency definition

Close of collaboration is exciting

Gallia Levy, MD, PhD

Chief Medical Officer, Spark Therapeutics

Hemophilia CGT is the highest potential for Global access logistics in underdeveloped countries working with NGOs practicality of the Tx

Roche reached 120 Counties great to be part of the Roche Group

Amir Nashat, PhD

Managing Partner, Polaris Ventures

Suneet Varma

Global President of Rare Disease, Pfizer

Gene therapy at Pfizer small molecule, large molecule and CGT – spectrum of choice allowing Hemophilia patients to marry

1/3 internal 1/3 partnership 1/3 acquisitions

Learning from COVID-19 is applied for other vaccine development

review of protocols and CGT for Hemophelia

You can’t buy Time

With MIT Pfizer is developing a model for Hemopilia CGT treatment

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Treating Rett Syndrome through X-reactivation

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

200 disease X chromosome unlock for neurological genetic diseases: Rett Syndromeand other autism spectrum disorders female model vs male mice model

deliver protein to the brain

restore own missing or dysfunctional protein

Epigenetic not CGT – no exogent intervention Xist ASO drug

Female model

Q&A

9:35 AM – 9:55 AM

9:35 AM – 9:45 AM

FIRST LOOK

Rare but mighty: scaling up success in single gene disorders

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

crosswalk from bone marrow matter

New gene discovered that causes neurodevelopment of stagnant genes Examining new Biology cell type specific biomarkers

Q&A

9:45 AM – 10:05 AM

9:50 AM – 10:15 AM

HOT TOPICS

Diabetes | Grand Challenge

Islet transplantation for type 1 diabetes has been attempted for decades. Problems like loss of transplanted islet cells due to autoimmunity and graft site factors have been difficult to address. Is there anything different on the horizon for gene and cell therapies to help this be successful?
How is the durability of response for gene or cell therapies for diabetes being addressed? For example, what would the profile of an acceptable (vs. optimal) cell therapy look like?

Moderator:

Marie McDonnell, MD

Chief, Diabetes Section and Director, Diabetes Program, BWH
Lecturer on Medicine, HMS

Type 1 Diabetes cost of insulin for continuous delivery of drug

alternative treatments:

The Future: neuropotent stem cells

What keeps you up at night

Speakers:

Tom Bollenbach, PhD

Chief Technology Officer, Advanced Regenerative Manufacturing Institute

Data managment sterility sensors, cell survival after implantation, stem cells manufacturing, process development in manufacturing of complex cells

Data and instrumentation the Process is the Product

Manufacturing tight schedules

Manasi Jaiman, MD

Vice President, Clinical Development, ViaCyte
Pediatric Endocrinologist

continous glucose monitoring

Bastiano Sanna, PhD

EVP, Chief of Cell & Gene Therapies and VCGT Site Head, Vertex Pharmaceuticals

100 years from discovering Insulin, Insulin is not a cure in 2021 – asking patients to partner more

Produce large quantities of the Islet cells encapsulation technology been developed

Scaling up is a challenge

Rogerio Vivaldi, MD

CEO, Sigilon Therapeutics

Advanced made, Patient of Type 1 Outer and Inner compartments of spheres (not capsule) no immune suppression continuous secretion of enzyme Insulin independence without immune suppression

Volume to have of-the-shelf inventory oxegenation in location lymphatic and vascularization conrol the whole process modular platform learning from others

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:40 AM

FIRESIDE

Building A Unified GCT Strategy

Introducer:

John Fish

CEO, Suffolk
Chairman of Board Trustees, Brigham Health

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

Last year, what was it at Novartis

Speaker:

Jay Bradner, MD

President, NIBR

Keep eyes open, waiting the Pandemic to end and enable working back on all the indications

Portfolio of MET, Mimi Emerging Therapies

Learning from the Pandemic – operationalize the practice science, R&D leaders, new collaboratives at NIH, FDA, Novartis

Pursue programs that will yield growth, tropic diseases with Gates Foundation, Rising Tide pods for access CGT within Novartis Partnership with UPenn in Cell Therapy

Cost to access to IP from Academia to a Biotech CRISPR accessing few translations to Clinic

Protein degradation organization constraint valuation by parties in a partnership

Novartis: nuclear protein lipid nuclear particles, tamplate for Biotech to collaborate

Game changing: 10% of the Portfolio, New frontiers human genetics in Ophthalmology, CAR-T, CRISPR, Gene Therapy Neurological and payloads of different matter

Q&A

10:45 AM – 11:00 AM

10:40 AM – 10:50 AM

Break

10:50 AM – 11:00 AM

FIRST LOOK

Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy

Christine Seidman, MD

Director, Cardiovascular Genetics Center, BWH
Smith Professor of Medicine & Genetics, HMS

@@@@@

Hypertrophic and Dilated Cardiomyopaies ‘

10% receive heart transplant 12 years survival

Mutation puterb function

TTN: contribute 20% of dilated cardiomyopaty

Silence gene

pleuripotential cells deliver therapies

Q&A

11:00 AM – 11:20 AM

11:00 AM – 11:10 AM

FIRST LOOK

Unlocking the secret lives of proteins in health and disease

Anna Greka, MD, PhD

Medicine, BWH
Associate Professor, Medicine, HMS

Cyprus Island, kidney disease by mutation causing MUC1 accumulation and death BRD4780 molecule that will clear the misfolding proteins from the kidney organoids: pleuripotent stem cells small molecule developed for applications in the other cell types in brain, eye, gene mutation build mechnism for therapy clinical models transition from Academia to biotech

Q&A

11:10 AM – 11:30 AM

11:10 AM – 11:35 AM

Rare and Ultra Rare Diseases | GCT Breaks Through

One of the most innovative segments in all of healthcare is the development of GCT driven therapies for rare and ultra-rare diseases. Driven by a series of insights and tools and funded in part by disease focused foundations, philanthropists and abundant venture funding disease after disease is yielding to new GCT technology. These often become platforms to address more prevalent diseases. The goal of making these breakthroughs routine and affordable is challenged by a range of issues including clinical trial design and pricing.

What is driving the interest in rare diseases?
What are the biggest barriers to making breakthroughs ‘routine and affordable?’
What is the role of retrospective and prospective natural history studies in rare disease? When does the expected value of retrospective disease history studies justify the cost?
Related to the first question, what is the FDA expecting as far as controls in clinical trials for rare diseases? How does this impact the collection of natural history data?

Moderator:

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Speakers:

Leah Bloom, PhD

SVP, External Innovation and Strategic Alliances, Novartis Gene Therapies

Ultra rare (less than 100) vs rare difficulty to recruit patients and to follow up after treatment

Bobby Gaspar, MD, PhD

CEO, Orchard Therapeutics

Study of rare condition have transfer to other larger diseases – delivery of therapeutics genes, like immune disorders

Patient testimonials just to hear what a treatment can make

Emil Kakkis, MD, PhD

CEO, Ultragenyx

Do 100 patient study then have information on natural history to develop a clinical trial

Stuart Peltz, PhD

CEO, PTC Therapeutics

Rare disease, challenge for FDA approval and after market commercialization follow ups

Justification of cost for Rare disease – demonstration of Change is IP in value patients advocacy is helpful

Q&A

11:40 AM – 11:55 AM

11:40 AM – 12:00 PM

FIRESIDE

Partnering Across the GCT Spectrum

Moderator:

Erin Harris

Chief Editor, Cell & Gene

Perspective & professional tenure

Partnership in manufacturing what are the recommendations?

Hospital systems: Partnership Challenges

Speaker:

Marc Casper

CEO, ThermoFisher

25 years in Diagnostics last 20 years at ThermoFisher

products used in the Lab for CAR-T research and manufacture

CGT Innovations: FDA will have a high level of approval each year

How move from research to clinical trials to manufacturing Quicker process

Best practices in Partnerships: the root cause if acceleration to market service providers to deliver highest standards

Building capacity by acquisition to avoid the waiting time

Accelerate new products been manufactured

Collaborations with Academic Medical center i.e., UCSF in CGT joint funding to accelerate CGT to clinics’

Customers are extremely knowledgable, scale the capital investment made investment

150MIL a year to improve the Workflow

Q&A

12:05 PM – 12:20 PM

12:05 PM – 12:30 PM

CEO Panel | Anticipating Disruption | Planning for Widespread GCT

The power of GCT to cure disease has the prospect of profoundly improving the lives of patients who respond. Planning for a disruption of this magnitude is complex and challenging as it will change care across the spectrum. Leading chief executives shares perspectives on how the industry will change and how this change should be anticipated.

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

CGT becoming staple therapy what are the disruptors emerging

Speakers:

Lisa Dechamps

SVP & Chief Business Officer, Novartis Gene Therapies

Reimagine medicine with collaboration at MGH, MDM condition in children

The Science is there, sustainable processes and systems impact is transformational

Value based pricing, risk sharing Payers and Pharma for one time therapy with life span effect

Collaboration with FDA

Kieran Murphy

CEO, GE Healthcare

Diagnosis of disease to be used in CGT

2021 investment in CAR-T platform

Investment in several CGT frontier

Investment in AI, ML in system design new technologies

GE: Scale and Global distributions, sponsor companies in software

Waste in Industry – Healthcare % of GDP, work with MGH to smooth the workflow faster entry into hospital and out of Hospital

Telemedicine during is Pandemic: Radiologist needs to read remotely

Supply chain disruptions slow down all ecosystem

Production of ventilators by collaboration with GM – ingenuity

Scan patients outside of hospital a scanner in a Box

Christian Rommel, PhD

Head, Pharmaceuticals Research & Development, Bayer AG

CGT – 2016 and in 2020 new leadership and capability

Disease Biology and therapeutics

Regenerative Medicine: CGT vs repair building pipeline in ophthalmology and cardiovascular

During Pandemic: Deliver Medicines like Moderna, Pfizer – collaborations between competitors with Government Bayer entered into Vaccines in 5 days, all processes had to change access innovations developed over decades for medical solutions

Q&A

12:35 PM – 12:50 PM

12:35 PM – 12:55 PM

FIRESIDE

Building a GCT Portfolio

GCT represents a large and growing market for novel therapeutics that has several segments. These include Cardiovascular Disease, Cancer, Neurological Diseases, Infectious Disease, Ophthalmology, Benign Blood Disorders, and many others; Manufacturing and Supply Chain including CDMO’s and CMO’s; Stem Cells and Regenerative Medicine; Tools and Platforms (viral vectors, nano delivery, gene editing, etc.). Bayer’s pharma business participates in virtually all of these segments. How does a Company like Bayer approach the development of a portfolio in a space as large and as diverse as this one? How does Bayer approach the support of the production infrastructure with unique demands and significant differences from its historical requirements?

Moderator:

Shinichiro Fuse, PhD

Managing Partner, MPM Capital

Speaker:

Wolfram Carius, PhD

EVP, Pharmaceuticals, Head of Cell & Gene Therapy, Bayer AG

CGT will bring treatment to cure, delivery of therapies

Be a Leader repair, regenerate, cure

Technology and Science for CGT – building a portfolio vs single asset decision criteria development of IP market access patients access acceleration of new products

Bayer strategy: build platform for use by four domains

Gener augmentation

Autologeneic therapy, analytics

Gene editing

Oncology Cell therapy tumor treatment: What kind of cells – the jury is out

Of 23 product launch at Bayer no prediction is possible some high some lows

Q&A

1:00 PM – 1:15 PM

12:55 PM – 1:35 PM

Lunch

1:40 PM – 2:05 PM

GCT Delivery | Perfecting the Technology

Gene delivery uses physical, chemical, or viral means to introduce genetic material into cells. As more genetically modified therapies move closer to the market, challenges involving safety, efficacy, and manufacturing have emerged. Optimizing lipidic and polymer nanoparticles and exosomal delivery is a short-term priority. This panel will examine how the short-term and long-term challenges are being tackled particularly for non-viral delivery modalities.

Moderator:

Natalie Artzi, PhD

Assistant Professor, BWH

Targeting ligands,

Speakers:

Matthew Stanton, PhD

CSO, Generation Bio

Hepatocytes

Sonya Montgomery

CMO, Evox Therapeutics

Exosomes and proteins and mRNA

Accessing CNS by different administration modes

Laura Sepp-Lorenzino, PhD

Chief Scientific Officer, Executive Vice President, Intellia Therapeutics

CRISPR – program cell ex Vivo bacteria editing

CRISPS Cas9 delivery mechanism in VIVO

Gene cassettes delivered to Liver

Doug Williams, PhD

CEO, Codiak BioSciences

Exosomes Platform and Kit delivery into the lumen of the exosomes

Two candidates in Oncology drug molecule on the surface of the lumen of exosomes

Enhance a nature process

Multiple ligands simultaneously, multiple distinct cells using combinatorial in a system developed

Q&A

2:10 PM – 2:25 PM

2:05 PM – 2:10 PM

Invention Discovery Grant Announcement

IDG Announcement

Tool for translation research at MGB

Commercialization of Lab to Clinic

$70MM was invested by VC minority equity investments in early stage for 1.2MM internal funding by MGB – Academia and Industry – Bayer as Investor

Six Winners

Lydia Lynche, PhD

Peter Page, PhD

Pietr from MEE

2:10 PM – 2:20 PM

FIRST LOOK

Enhancing vesicles for therapeutic delivery of bioproducts

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

DNA, RNA, exosomes avoid random transgene integration

EVs – Extracellular Vesicles

Q&A

2:20 PM – 2:35 PM

2:20 PM – 2:30 PM

FIRST LOOK

Versatile polymer-based nanocarriers for targeted therapy and immunomodulation

Natalie Artzi, PhD

Assistant Professor, BWH

Epigenome

Nonviral (nucleic acid) delivery

Nanoparticle Toolbox : Cyclical Dinucleotides (CDN)

Nanoparticles for delivery of medicines Delivery route affect on therapeutic efficacy

Polymeric based nanocarriers for targeted therapy and immunomodulation

Q&A

2:30 PM – 2:45 PM

2:55 PM – 3:20 PM

HOT TOPICS

Gene Editing | Achieving Therapeutic Mainstream

Gene editing was recognized by the Nobel Committee as “one of gene technology’s sharpest tools, having a revolutionary impact on life sciences.” Introduced in 2011, gene editing is used to modify DNA. It has applications across almost all categories of disease and is also being used in agriculture and public health.

Today’s panel is made up of pioneers who represent foundational aspects of gene editing. They will discuss the movement of the technology into the therapeutic mainstream.

Successes in gene editing – lessons learned from late-stage assets (sickle cell, ophthalmology)
When to use what editing tool – pros and cons of traditional gene-editing v. base editing. Is prime editing the future? Specific use cases for epigenetic editing.
When we reach widespread clinical use – role of off-target editing – is the risk real? How will we mitigate? How practical is patient-specific off-target evaluation?

Moderator:

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

target alteration of genes for research and novele therapeutics for indications without alternative Tx

Chardonay Platform Specificity and safety

Speakers:

John Evans

CEO, Beam Therapeutics

CRISPR targets the Genome reaching the site open DNA single base change in the Genome sicle cell anemia, letter misspelled correction

turn off or activate or program the protein function genome modification tool immunology CAR-T nanoparticles to deliver locally

Delivery is the challenge ex Vivo, In Vivo innovations in nanoparticles to blood system, muscle

Lisa Michaels

EVP & CMO, Editas Medicine

Gene editing allows correction of genetic abnormalities

CRISPR editing the Genome in Vivo

Delivery specificity edit DNA of cells for Tx objective

Rachel Haurwitz, PhD

Caribou BioSciences, Off UC, Berkeley, CA

Innovation to delivery large quantities of DNA

Q&A

3:25 PM – 3:50 PM

3:25 PM – 3:50 PM

HOT TOPICS

Common Blood Disorders | Gene Therapy

There are several dozen companies working to develop gene or cell therapies for Sickle Cell Disease, Beta Thalassemia, and Fanconi Anemia. In some cases, there are enzyme replacement therapies that are deemed effective and safe. In other cases, the disease is only managed at best. This panel will address a number of questions that are particular to this class of genetic diseases:

What are the pros and cons of various strategies for treatment? There are AAV-based editing, non-viral delivery even oligonucleotide recruitment of endogenous editing/repair mechanisms. Which approaches are most appropriate for which disease?
How can companies increase the speed of recruitment for clinical trials when other treatments are available? What is the best approach to educate patients on a novel therapeutic?
How do we best address ethnic and socio-economic diversity to be more representative of the target patient population?
How long do we have to follow up with the patients from the scientific, patient’s community, and payer points of view? What are the current FDA and EMA guidelines for long-term follow-up?
Where are we with regards to surrogate endpoints and their application to clinically meaningful endpoints?
What are the emerging ethical dilemmas in pediatric gene therapy research? Are there challenges with informed consent and pediatric assent for trial participation?
Are there differences in reimbursement policies for these different blood disorders? Clearly durability of response is a big factor. Are there other considerations?

Moderator:

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

Speakers:

Samarth Kukarni, PhD

Nick Leschly

Chief Bluebird, Bluebird Bio

Mike McCune, MD, PhD

Head, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation

Q&A

3:55 PM – 4:15 PM

3:50 PM – 4:00 PM

FIRST LOOK

Gene Editing

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

ONE-seq enriched in specific populations for genetic variation

seq IP and commercialization

FIRST LOOK

RNA Therapy for Brain Cancer

Pierpaolo Peruzzi, MD, PhD

Neurosurgery, BWH; Assistant Professor of Neurosurgery, HMS

Targeting with RNA clusters enhances chemotheraphy in GBM

AAV delivery micro RNA – viral mediated and by exosomes (non viral)

Therapeutic impact in Brain Tumors 2-3 readiness

Q&A

4:00 PM – 4:20 PM

4:20 PM – 4:45 PM

HOT TOPICS

Gene Expression | Modulating with Oligonucleotide-Based Therapies

Oligonucleotide drugs have recently come into their own with approvals from companies such as Biogen, Alnylam, Novartis and others. This panel will address several questions:

How important is the delivery challenge for oligonucleotides? Are technological advancements emerging that will improve the delivery of oligonucleotides to the CNS or skeletal muscle after systemic administration?

Will oligonucleotides improve as a class that will make them even more effective? Are further advancements in backbone chemistry anticipated, for example.
Will oligonucleotide based therapies blaze trails for follow-on gene therapy products?
Are small molecules a threat to oligonucleotide-based therapies?
Beyond exon skipping and knock-down mechanisms, what other roles will oligonucleotide-based therapies take mechanistically — can genes be activating oligonucleotides? Is there a place for multiple mechanism oligonucleotide medicines?
Are there any advantages of RNAi-based oligonucleotides over ASOs, and if so for what use?

Moderator:

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

The 2021 Virtual World Medical Innovation Forum will focus on the growing impact of gene and cell therapy.

About the World Medical Innovation Forum

Accelerating the Future of Medicine with Gene and Cell Therapy What Comes Next

https://worldmedicalinnovation.org/wp-content/uploads/2021/05/2021-WMIF-White-Paper-1.0.pdf

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

#WMIF2021

@MGBInnovation

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

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will be in virtual attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine

https://lnkd.in/ekWGNqA

Among them, books on Gene and Cell Therapy include the following:

Topics for May 19 – 21 include:

Impact on Patient Care – Therapeutic and Potentially Curative GCT Developments

GCT Delivery, Manufacturing – What’s Next

GCT Platform Development

Oncolytic Viruses – Cancer applications, start-ups

Regenerative Medicine/Stem Cells

Future of CAR-T

M&A Shaping GCT’s Future

Market Priorities

Venture Investing in GCT

China’s GCT Juggernaut

Disease and Patient Focus: Benign blood disorders, diabetes, neurodegenerative diseases

Click here for the current WMIF agenda

Plus:

Fireside Chats: 1:1 interviews with industry CEOs/C-Suite leaders including Novartis Gene Therapies, ThermoFisher, Bayer AG, FDA

First Look: 18 briefings on emerging GCT research from Mass General Brigham scientists

Virtual Poster Session: 40 research posters and presenters on potential GCT discoveries from Mass General Brigham

Announcement of the Disruptive Dozen, 12 GCT technologies likely to break through in the next few years

AGENDA

Wednesday, May 19, 2021

8:00 AM – 8:10 AM

Opening Remarks

Welcome and the vision for Gene and Cell Therapy and why it is a top Mass General Brigham priority.

Introducer:

Scott Sperling

Co-President, Thomas H. Lee Partners
Chairman of the Board of Directors, PHS

Presenter:

Anne Klibanski, MD

CEO, Mass General Brigham

3,000 people joined 5/19 morning

30 sessions: Lab to Clinic, academia, industry, investment community

May 22,23,24, 2022 – in Boston, in-person 2022 WMIF on CGT

8:10 AM – 8:30 AM

The Grand Challenge of Widespread GCT Patient Benefits

Co-Chairs identify the key themes of the Forum – set the stage for top GCT opportunities, challenges, and where the field might take medicine in the future.

Moderator:

Susan Hockfield, PhD

President Emerita and Professor of Neuroscience, MIT

GCT – poised to deliver therapies

Inflection point as Panel will present

Doctors and Patients – Promise for some patients

Barriers for Cell & Gene

Access for patients to therapies like CGT

Speakers:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic virus triple threat: Toxic, immunological, combine with anti cancer therapies

Polygenic therapy – multiple genes involved, plug-play,

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Ravi Thadhani, MD

CAO, Mass General Brigham
Professor, Medicine and Faculty Dean, HMS

Role of academia special to spear head the Polygenic therapy – multiple genes involved, plug-play,

Access critical, relations with Industry

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

Pharmacology Gene-Drug, Interface academic centers and industry

many CGT drugs emerged in Academic center

8:35 AM – 8:50 AM

FIRESIDE

Gene and Cell Therapy 2.0 – What’s Next as We Realize their Potential for Patients

Dave Lennon, PhD

President, Novartis Gene Therapies

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Moderator:

Julian Harris, MD

Partner, Deerfield

Promise of CGT realized, what part?

FDA role and interaction in CGT

Manufacturing aspects which is critical

Speaker:

Dave Lennon, PhD

President, Novartis Gene Therapies

FDA works by indications and risks involved, Standards and expectations for streamlining manufacturing, understanding of process and products

payments over time payers and Innovators relations

Q&A

8:55 AM – 9:10 AM

8:55 AM – 9:20 AM

The Patient and GCT

Moderator:

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

What is the Power of One – the impact that a patient can have on their own destiny by participating in Clinical Trials Contacting other participants in same trial can be beneficial

Speakers:

Jack Hogan

Patient, MEE

Jeanette Hogan

Parent of Patient, MEE

Jim Holland

CEO, Backcountry.com

Barbara Lavery

Chief Program Officer, ACGT Foundation

Advocacy agency beginning of work Global Genes educational content and out reach to access the information

Patient has the knowledge of the symptoms and recording all input needed for diagnosis by multiple clinicians Early application for CGT

Dan Tesler

Clinical Trial Patient, BWH/DFCC

Experimental Drug clinical trial patient participation in clinical trial is very important to advance the state of science

Sarah Beth Thomas, RN

Professional Development Manager, BWH

Outcome is unknown, hope for good, support with resources all advocacy groups,

Q&A

9:25 AM – 9:40 AM

9:25 AM – 9:45 AM

FIRESIDE

GCT Regulatory Framework | Why Different?

Moderator:

Vicki Sato, PhD

Chairman of the Board, Vir Biotechnology

Diversity of approaches

Process at FDA generalize from 1st entry to rules more generalizable

Speaker:

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research, FDA

Immune modulators, Immunotherapy Genome editing can make use of viral vectors future technologies nanoparticles and liposome encapsulation

Q&A

9:50 AM – 10:05 AM

9:50 AM – 10:15 AM

Building a GCT Platform for Mainstream Success

This panel of GCT executives, innovators and investors explore how to best shape a successful GCT strategy. Among the questions to be addressed:

How are GCT approaches set around defining and building a platform?
Is AAV the leading modality and what are the remaining challenges?
What are the alternatives?
Is it just a matter of matching modalities to the right indications?

Moderator:

Jean-François Formela, MD

Partner, Atlas Venture

Established core components of the Platform

Speakers:

Katherine High, MD

President, Therapeutics, AskBio

Three drugs approved in Europe in the Gene therapy space

Regulatory Infrastructure exists for CGT drug approval – as new class of therapeutics

Participants investigators, regulators, patients i. e., MDM

Hemophilia in male most challenging

Human are natural hosts for AV safety signals

Dave Lennon, PhD

President, Novartis Gene Therapies

big pharma has portfolios of therapeutics not one drug across Tx areas: cell, gene iodine therapy

collective learning infrastructure features manufacturing at scale early in development Acquisitions strategy for growth # applications for scaling

Rick Modi

CEO, Affinia Therapeutics

Data sharing clinical experience with vectors strategies patients selection, vector selection, mitigation, patient type specific

Louise Rodino-Klapac, PhD

EVP, Chief Scientific Officer, Sarepta Therapeutics

AAV based platform 15 years in development same disease indication vs more than one indication stereotype, analytics as hurdle 1st was 10 years 2nd was 3 years

Safety to clinic vs speed to clinic, difference of vectors to trust

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:45 AM

AAV Success Studies | Retinal Dystrophy | Spinal Muscular Atrophy

The panel assesses the largest challenges of the first two products, the lessons learned for the broader CGT field, and the extent to which they serve as a precedent to broaden the AAV modality.

Is AAV gene therapy restricted to genetically defined disorders, or will it be able to address common diseases in the near term?
Lessons learned from these first-in-class approvals.
Challenges to broaden this modality to similar indications.
Reflections on safety signals in the clinical studies?

Moderator:

Joan Miller, MD

Chief, Ophthalmology, MEE
Cogan Professor & Chair of Ophthalmology, HMS

Retina specialist, Luxturna success FMA condition cell therapy as solution

Lessons learned

Safety

Speakers:

Ken Mills

CEO, RegenXBio

Tissue types additional administrations, tech and science, address additional diseases, more science for photoreceptors a different tissue type underlying pathology novelties in last 10 years

Cell therapy vs transplant therapy no immunosuppression

Eric Pierce, MD, PhD

Director, Ocular Genomics Institute, MEE
Professor of Ophthalmology, HMS

Laxterna success to be replicated platform, paradigms measurement visual improved

More science is needed to continue develop vectors reduce toxicity,

AAV can deliver different cargos reduce adverse events improve vectors

Ron Philip

Chief Operating Officer, Spark Therapeutics

The first retinal gene therapy, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), was approved by the FDA in 2017.

Meredith Schultz, MD

Executive Medical Director, Lead TME, Novartis Gene Therapies

Impact of cell therapy beyond muscular dystrophy, translational medicine, each indication, each disease, each group of patients build platform unlock the promise

Monitoring for Safety signals real world evidence remote markers, home visits, clinical trial made safer, better communication of information

Q&A

10:50 AM – 11:05 AM

10:45 AM – 10:55 AM

Break

10:55 AM – 11:05 AM

FIRST LOOK

Control of AAV pharmacology by Rational Capsid Design

Luk Vandenberghe, PhD

Grousbeck Family Chair, Gene Therapy, MEE
Associate Professor, Ophthalmology, HMS

Pathway for rational AAV rational design, curated smart variant libraries, AAV sequence screen multiparametric , data enable liver (de-) targeting unlock therapeutics areas: cochlea

Q&A

11:05 AM – 11:25 AM

11:05 AM – 11:15 AM

FIRST LOOK

Enhanced gene delivery and immunoevasion of AAV vectors without capsid modification

Casey Maguire, PhD

Associate Professor of Neurology, MGH & HMS

Virus Biology: Enveloped (e) or not

enveloped for gene therapy eAAV platform technology: tissue targets and Indications commercialization of eAAV

Q&A

11:15 AM – 11:35 AM

11:20 AM – 11:45 AM

HOT TOPICS

AAV Delivery

Moderators:

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

Speakers:

Jennifer Farmer

CEO, Friedreich’s Ataxia Research Alliance

Ataxia requires therapy targeting multiple organ with one therapy, brain, spinal cord, heart several IND, clinical trials in 2022

Mathew Pletcher, PhD

SVP, Head of Gene Therapy Research and Technical Operations, Astellas

Work with diseases poorly understood, collaborations needs example of existing: DMD is a great example explain dystrophin share placedo data

Continue to explore large animal guinea pig not the mice, not primates (ethical issues) for understanding immunogenicity and immune response

Manny Simons, PhD

CEO, Akouos

AAV Therapy for the fluid of the inner ear, CGT for the ear vector accessible to surgeons translational work on the inner ear for gene therapy right animal model

Biology across species nerve ending in the cochlea

engineer out of the caspid, lowest dose possible, get desired effect by vector use, 2022 new milestones

Q&A

11:50 AM – 12:05 PM

11:50 AM – 12:15 PM

M&A | Shaping GCT Innovation

Moderator:

Adam Koppel, MD, PhD

Managing Director, Bain Capital Life Sciences

What acquirers are looking for??

What is the next generation vs what is real where is the industry going?

Speakers:

Debby Baron,

Worldwide Business Development, Pfizer

CGT is an important area Pfizer is active looking for innovators, advancing forward programs of innovation with the experience Pfizer has internally

Scalability and manufacturing regulatory conversations, clinical programs safety in parallel to planning getting drug to patients

Kenneth Custer, PhD

Vice President, Business Development and Lilly New Ventures, Eli Lilly and Company

Marianne De Backer, PhD

Head of Strategy, Business Development & Licensing, and Member of the Executive Committee, Bayer

Absolute Leadership in Gene editing, gene therapy, via acquisition and strategic alliance

Operating model of the acquired company discussed , company continue independence

Sean Nolan

Board Chairman, Encoded Therapeutics & Affinia

Executive Chairman, Jaguar Gene Therapy & Istari Oncology

As acquiree multiple M&A: How the acquirer looks at integration and cultures of the two companies

Traditional integration vs jump start by external acquisition

AAV – epilepsy, next generation of vectors

Q&A

12:20 PM – 12:35 PM

12:15 PM – 12:25 PM

FIRST LOOK

Gene Therapies for Neurological Disorders: Insights from Motor Neuron Disorders

Merit Cudkowicz, MD

Chief of Neurology, MGH

ALS – Man 1in 300, Women 1 in 400, next decade increase 7%

Q&A

12:25 PM – 12:45 PM

12:25 PM – 12:35 PM

FIRST LOOK

Gene Therapy for Neurologic Diseases

Patricia Musolino, MD, PhD

Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
Assistant Professor of Neurology, HMS

Cerebral Vascular disease – ACTA2 179H gene smooth muscle cell proliferation disorder

no surgery or drug exist –

Q&A

12:35 PM – 12:55 PM

12:35 PM – 1:15 PM

Lunch

1:15 PM – 1:40 PM

Oncolytic Viruses in Cancer | Curing Melanoma and Beyond

Moderator:

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Challenges of manufacturing at Amgen what are they?

Speakers:

Robert Coffin, PhD

Chief Research & Development Officer, Replimune

2002 in UK promise in oncolytic therapy GNCSF

Phase III melanoma 2015 M&A with Amgen

oncolytic therapy remains non effecting on immune response

data is key for commercialization

do not belief in systemic therapy achieve maximum immune response possible from a tumor by localized injection

Roger Perlmutter, MD, PhD

Chairman, Merck & Co.

response rates systemic therapy like PD1, Keytruda, OPTIVA well tolerated combination of Oncolytic with systemic

GMP critical for manufacturing

David Reese, MD

Executive Vice President, Research and Development, Amgen

Inter lesion injection of agent vs systemic therapeutics

cold tumors immune resistant render them immune susceptible

Oncolytic virus is a Mono therapy

addressing the unknown

Ann Silk, MD

Physician, Dana Farber-Brigham and Women’s Cancer Center
Assistant Professor of Medicine, HMS

Which person gets oncolytics virus if patient has immune suppression due to other indications

Safety of oncolytic virus greater than Systemic treatment

series biopsies for injected and non injected tissue and compare Suspect of hot tumor and cold tumors likely to have sme response to agent unknown all potential

Q&A

1:45 PM – 2:00 PM

1:45 PM – 2:10 PM

Market Interest in Oncolytic Viruses | Calibrating

Will these need to be combined with other agents to realize their full efficacy and how will that impact the market?
Why are these companies pursuing OVs while several others are taking a pass?

Moderators:

Martine Lamfers, PhD

Visiting Scientist, BWH

Challenged in development of strategies

Demonstrate efficacy

Robert Martuza, MD

Consultant in Neurosurgery, MGH
William and Elizabeth Sweet Distinguished Professor of Neurosurgery, HMS

Modulation mechanism

Speakers:

Anlong Li, MD, PhD

Clinical Director, Oncology Clinical Development, Merck Research Laboratories

IV delivery preferred – delivery alternative are less aggereable

Jeffrey Infante, MD

Early development Oncolytic viruses, Oncology, Janssen Research & Development

oncologic virus if it will generate systemic effects the adoption will accelerate

What areas are the best efficacious

Direct effect with intra-tumor single injection with right payload

Platform approach Prime with 1 and Boost with 2 – not yet experimented with

Do not have the data at trial design for stratification of patients

Turn off strategy not existing yet

Loic Vincent, PhD

Head of Oncology Drug Discovery Unit, Takeda

R&D in collaboration with Academic

Vaccine platform to explore different payload

IV administration may not bring sufficient concentration to the tumor is administer in the blood stream

Classification of Patients by prospective response type id UNKNOWN yet, population of patients require stratification

Q&A

2:15 PM – 2:30 PM

2:10 PM – 2:20 PM

FIRST LOOK

Oncolytic viruses: turning pathogens into anticancer agents

Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
Harvey W. Cushing Professor of Neurosurgery, HMS

Oncolytic therapy DID NOT WORK Pancreatic Cancer and Glioblastoma

Intra- tumoral heterogeniety hinders success

Solution: Oncolytic VIRUSES – Immunological “coldness”

GADD-34 20,000 GBM 40,000 pancreatic cancer

Q&A

2:25 PM – 2:40 PM

2:20 PM – 2:45 PM

Entrepreneurial Growth | Oncolytic Virus

In 2020 there were a total of 60 phase I trials for Oncolytic Viruses. There are now dozens of companies pursuing some aspect of OV technology. This panel will address:

How are small companies equipped to address the challenges of developing OV therapies better than large pharma or biotech?
Will the success of COVID vaccines based on Adenovirus help the regulatory environment for small companies developing OV products in Europe and the USA?
Is there a place for non-viral delivery and other immunotherapy companies to engage in the OV space? Would they bring any real advantages?

Moderator:

Reid Huber, PhD

Partner, Third Rock Ventures

Critical milestones to observe

Speakers:

Caroline Breitbach, PhD

VP, R&D Programs and Strategy, Turnstone Biologics

Trying Intra-tumor delivery and IV infusion delivery oncolytic vaccine pushing dose

translation biomarkers program

transformation tumor microenvironment

Brett Ewald, PhD

SVP, Development & Corporate Strategy, DNAtrix

Studies gets larger, kicking off Phase III multiple tumors

Paul Hallenbeck, PhD

President and Chief Scientific Officer, Seneca Therapeutics

Translation:

Stephen Russell, MD, PhD

CEO, Vyriad

Systemic delivery Oncolytic Virus IV delivery woman in remission

Collaboration with Regeneron

Data collection: Imageable reporter secretable reporter, gene expression

Field is intense systemic oncolytic delivery is exciting in mice and in human, response rates are encouraging combination immune stimulant, check inhibitors

Q&A

2:50 PM – 3:05 PM

2:45 PM – 3:00 PM

Break

3:00 PM – 3:25 PM

CAR-T | Lessons Learned | What’s Next

Is CAR-T still an industry priority – i.e. are new investments being made by large companies? Are new companies being financed? What are the trends?
What have we learned from first-generation products, what can we expect from CAR-T going forward in novel targets, combinations, armored CAR’s and allogeneic treatment adoption?
Early trials showed remarkable overall survival and progression-free survival. What has been observed regarding how enduring these responses are?
Most of the approvals to date have targeted CD19, and most recently BCMA. What are the most common forms of relapses that have been observed?
Is there a consensus about what comes after these CD19 and BCMA trials as to additional targets in liquid tumors? How have dual-targeted approaches fared?

Moderator:
Marcela Maus, MD, PhD
- Director, Cellular Immunotherapy Program, Cancer Center, MGH
- Associate Professor, Medicine, HMS
Is CAR-T Industry priority
Speakers:
- Jakob Dupont, MD
Head of R&D, Atara BioTherapeutics
Phyno-type of the cells for hematologic cancers
solid tumor
inventory of Therapeutics for treating patients in the future
Progressive MS program
EBBT platform B-Cells and T-Cells

- Stefan Hendriks
  - Gobal Head, Cell & Gene, Novartis
  - yes, CGT is a strategy in the present and future
  - Journey started years ago
  - Confirmation the effectiveness of CAR-T therapies, 1 year response prolonged to 5 years 26 months
  - Patient not responding – a lot to learn
  - Patient after 8 months of chemo can be helped by CAR-T
- Christi Shaw
  - CEO, Kite
  - CAR-T is priority 120 companies in the space
  - Manufacturing consistency
  - Patients respond with better quality of life
  - Blood cancer – more work to be done

Q&A

3:30 PM – 3:45 PM

3:30 PM – 3:55 PM

HOT TOPICS

CAR-T | Solid Tumors Success | When?

The potential application of CAR-T in solid tumors will be a game-changer if it occurs. The panel explores the prospects of solid tumor success and what the barriers have been. Questions include:

How would industry and investor strategy for CAR-T and solid tumors be characterized? Has it changed in the last couple of years?
Does the lack of tumor antigen specificity in solid tumors mean that lessons from liquid tumor CAR-T constructs will not translate well and we have to start over?
Whether due to antigen heterogeneity, a hostile tumor micro-environment, or other factors are some specific solid tumors more attractive opportunities than others for CAR-T therapy development?
Given the many challenges that CAR-T faces in solid tumors, does the use of combination therapies from the start, for example, to mitigate TME effects, offer a more compelling opportunity.

Moderator:

Oladapo Yeku, MD, PhD

Clinical Assistant in Medicine, MGH

window of opportunities studies

Speakers:

Jennifer Brogdon

Executive Director, Head of Cell Therapy Research, Exploratory Immuno-Oncology, NIBR

2017 CAR-T first approval

M&A and research collaborations

TCR tumor specific antigens avoid tissue toxicity

Knut Niss, PhD

CTO, Mustang Bio

Barbra Sasu, PhD

CSO, Allogene

T cell response at prostate cancer

tumor specific

cytokine tumor specific signals move from solid to metastatic cell type for easier infiltration

Where we might go: safety autologous and allogeneic

Jay Short, PhD

Chairman, CEO, Cofounder, BioAlta, Inc.

Tumor type is not enough for development of therapeutics other organs are involved in the periphery

Combination staggered key is try combination

Q&A

4:00 PM – 4:15 PM

4:00 PM – 4:25 PM

GCT Manufacturing | Vector Production | Autologous and Allogeneic | Stem Cells | Supply Chain | Scalability & Management

Help us all understand the different manufacturing challenges for cell therapies. What are the trade-offs among storage cost, batch size, line changes in terms of production cost and what is the current state of scaling naïve and stem cell therapy treatment vs engineered cell therapies?
For cell and gene therapy what is the cost of Quality Assurance/Quality Control vs. production and how do you think this will trend over time based on your perspective on learning curves today?
Will point of care production become a reality? How will that change product development strategy for pharma and venture investors? What would be the regulatory implications for such products?
How close are allogeneic CAR-T cell therapies? If successful what are the market implications of allogenic CAR-T? What are the cost implications and rewards for developing allogeneic cell therapy treatments?

Moderator:

Michael Paglia

VP, ElevateBio

Speakers:

Dannielle Appelhans
- SVP TechOps and Chief Technical Officer, Novartis Gene Therapies
Thomas Page, PhD
- VP, Engineering and Asset Development, FUJIFILM Diosynth Biotechnologies
Rahul Singhvi, ScD
- CEO and Co-Founder, National Resilience, Inc.
Thomas VanCott, PhD
- Global Head of Product Development, Gene & Cell Therapy, Catalent
- 2/3 autologous 1/3 allogeneic CAR-T high doses and high populations scale up is not done today quality maintain required the timing logistics issues centralized vs decentralized allogeneic are health donors innovations in cell types in use improvements in manufacturing

Ropa Pike, Director, Enterprise Science & Partnerships, Thermo Fisher Scientific

Centralized biopharma industry is moving to decentralized models site specific license

Q&A

4:30 PM – 4:45 PM

4:30 PM – 4:40 PM

FIRST LOOK

CAR-T

Marcela Maus, MD, PhD

Director, Cellular Immunotherapy Program, Cancer Center, MGH
Assistant Professor, Medicine, HMS

Fit-to-purpose CAR-T cells: 3 lead programs

Tr-fill

CAR-T induce response myeloma and multiple myeloma GBM

27 patents on CAR-T

+400 patients treaded 40 Clinical Trials

Q&A

4:40 PM – 5:00 PM

4:40 PM – 4:50 PM

FIRST LOOK

Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy

Khalid Shah, PhD

Vice Chair, Neurosurgery Research, BWH
Director, Center for Stem Cell Therapeutics and Imaging, HMS

Q&A

4:50 PM – 5:10 PM

4:50 PM – 5:00 PM

FIRST LOOK

Other Cell Therapies for Cancer

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

T-cell are made in bone marrow create cryogel can be an off-the-shelf product repertoire on T Receptor CCL19+ mesenchymal cells mimic Tymus cells –

inter-tymic injection. Non human primate validation

Q&A

5:00 PM – 5:20 PM

FIRESIDE

Fireside with Mikael Dolsten, MD, PhD

Introducer:

Jonathan Kraft

Moderator:

Daniel Haber, MD, PhD

Chair, Cancer Center, MGH
Isselbacher Professor of Oncology, HMS

Vaccine Status

Mikael Dolsten, MD, PhD

Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer

Deliver vaccine around the Globe, Israel, US, Europe.

3BIL vaccine in 2022 for all Global vaccination

Bio Ntech in Germany

Experience with Biologics immuneoncology & allogeneic antibody cells – new field for drug discovery

mRNA curative effort and cancer vaccine

Access to drugs developed by Pfizer to underdeveloped countries

Q&A

5:25 PM – 5:40 AM

5:20 PM – 5:30 PM

Closing Remarks

Thursday, May 20, 2021

8:00 AM – 8:25 AM

GCT | The China Juggernaut

The Chinese GCT ecosystem has increasingly rich local innovation and growing complement of development and investment partnerships – and also many subtleties.

Moderator:

Min Wu, PhD

Managing Director, Fosun Health Fund

What are the area of CGT in China, regulatory similar to the US

Speakers:

Alvin Luk, PhD

CEO, Neuropath Therapeutics

Monogenic rare disease with clear genomic target

Increase of 30% in patient enrollment

Regulatory reform approval is 60 days no delay

Pin Wang, PhD

CSO, Jiangsu Simcere Pharmaceutical Co., Ltd.

Similar starting point in CGT as the rest of the World unlike a later starting point in other biological

Richard Wang, PhD

CEO, Fosun Kite Biotechnology Co., Ltd

Possibilities to be creative and capitalize the new technologies for innovating drug

Support of the ecosystem by funding new companie allowing the industry to be developed in China

Autologous in patients differences cost challenge

Tian Xu, PhD

Vice President, Westlake University

ICH committee and Chinese FDA -r regulation similar to the US

Difference is the population recruitment, in China patients are active participants in skin disease

Active in development of transposome

Development of non-viral methods, CRISPR still in D and transposome

In China price of drugs regulatory are sensitive

Shunfei Yan, PhD

Investment Manager, InnoStar Capital

Indication driven: Hemophilia,

Allogogenic efficiency therapies

Licensing opportunities

Q&A

8:30 AM – 8:45 AM

8:30 AM – 8:55 AM

Impact of mRNA Vaccines | Global Success Lessons

How will the COVID success impact the rest of the industry both in therapeutic and prophylactic vaccines and broader mRNA lessons?
How will the COVID success impact the rest of the industry both on therapeutic and prophylactic vaccines and broader mRNA lessons?
Beyond from speed of development, what aspects make mRNA so well suited as a vaccine platform?
Will cost-of-goods be reduced as the industry matures?
How does mRNA technology seek to compete with AAV and other gene therapy approaches?

Moderator:

Lindsey Baden, MD

Director, Clinical Research, Division of Infectious Diseases, BWH
Associate Professor, HMS

In vivo delivery process regulatory cooperation new opportunities for same platform for new indication

Speakers:

Melissa Moore Chief Scientific Officer, Moderna Many years of mRNA pivoting for new diseases, DARPA, Nucleic Acids global deployment of a manufacturing unit on site where the need arise. Elan Musk funds new directions at Moderna How many mRNA can be put in one vaccine: Dose and tolerance to achieve efficacy 45 days for Personalized cancer vaccine one per patient Ron Renaud CEO, Translate Bio 1.6 Billion doses produced rare disease monogenic correct mRNA like CF multiple mutation infection disease and oncology applications Platform allowing to swap cargo reusing same nanoparticles address disease beyond Big Pharma options for biotech WHat strain of Flu vaccine will come back in the future when people do not use masks Kate Bingham, UK Vaccine Taskforce July 2020, AAV vs mRNA delivery across UK local centers administered both types supply and delivery uplift

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

HOT TOPICS

Benign Blood Disorders

Moderator:

Nancy Berliner, MD

Chief, Division of Hematology, BWH
H. Franklin Bunn Professor of Medicine, HMS

Speakers:

Theresa Heggie

CEO, Freeline Therapeutics

Safety concerns, high burden of treatment CGT has record of safety and risk/benefit adoption of Tx functional cure CGT is potent Tx relative small quantity of protein needs be delivered

Potency and quality less quantity drug and greater potency

risk of delivery unwanted DNA, capsules are critical

analytics is critical regulator involvement in potency definition

Close of collaboration is exciting

Gallia Levy, MD, PhD

Chief Medical Officer, Spark Therapeutics

Hemophilia CGT is the highest potential for Global access logistics in underdeveloped countries working with NGOs practicality of the Tx

Roche reached 120 Counties great to be part of the Roche Group

Amir Nashat, PhD

Managing Partner, Polaris Ventures

Suneet Varma

Global President of Rare Disease, Pfizer

Gene therapy at Pfizer small molecule, large molecule and CGT – spectrum of choice allowing Hemophilia patients to marry

1/3 internal 1/3 partnership 1/3 acquisitions

Learning from COVID-19 is applied for other vaccine development

review of protocols and CGT for Hemophelia

You can’t buy Time

With MIT Pfizer is developing a model for Hemopilia CGT treatment

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Treating Rett Syndrome through X-reactivation

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

200 disease X chromosome unlock for neurological genetic diseases: Rett Syndrome and other autism spectrum disorders female model vs male mice model

deliver protein to the brain

restore own missing or dysfunctional protein

Epigenetic not CGT – no exogenous intervention Xist ASO drug

Female model

Q&A

9:35 AM – 9:55 AM

9:35 AM – 9:45 AM

FIRST LOOK

Rare but mighty: scaling up success in single gene disorders

Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH
Associate Professor, Neurology, HMS

Single gene disorder NGS enable diagnosis, Diagnosis to Treatment How to know whar cell to target, make it available and scale up Address gap: missing components Biomarkers to cell types lipid chemistry cell animal biology

crosswalk from bone marrow matter

New gene discovered that causes neurodevelopment of stagnant genes Examining new Biology cell type specific biomarkers

Q&A

9:45 AM – 10:05 AM

9:50 AM – 10:15 AM

HOT TOPICS

Diabetes | Grand Challenge

Islet transplantation for type 1 diabetes has been attempted for decades. Problems like loss of transplanted islet cells due to autoimmunity and graft site factors have been difficult to address. Is there anything different on the horizon for gene and cell therapies to help this be successful?
How is the durability of response for gene or cell therapies for diabetes being addressed? For example, what would the profile of an acceptable (vs. optimal) cell therapy look like?

Moderator:

Marie McDonnell, MD

Chief, Diabetes Section and Director, Diabetes Program, BWH
Lecturer on Medicine, HMS

Type 1 Diabetes cost of insulin for continuous delivery of drug

alternative treatments:

The Future: neuropotent stem cells

What keeps you up at night

Speakers:

Tom Bollenbach, PhD

Chief Technology Officer, Advanced Regenerative Manufacturing Institute

Data managment sterility sensors, cell survival after implantation, stem cells manufacturing, process development in manufacturing of complex cells

Data and instrumentation the Process is the Product

Manufacturing tight schedules

Manasi Jaiman, MD

Vice President, Clinical Development, ViaCyte
Pediatric Endocrinologist

continous glucose monitoring

Bastiano Sanna, PhD

EVP, Chief of Cell & Gene Therapies and VCGT Site Head, Vertex Pharmaceuticals

100 years from discovering Insulin, Insulin is not a cure in 2021 – asking patients to partner more

Produce large quantities of the Islet cells encapsulation technology been developed

Scaling up is a challenge

Rogerio Vivaldi, MD

CEO, Sigilon Therapeutics

Advanced made, Patient of Type 1 Outer and Inner compartments of spheres (not capsule) no immune suppression continuous secretion of enzyme Insulin independence without immune suppression

Volume to have of-the-shelf inventory oxygenation in location lymphatic and vascularization control the whole process modular platform learning from others

Q&A

10:20 AM – 10:35 AM

10:20 AM – 10:40 AM

FIRESIDE

Building A Unified GCT Strategy

Introducer:

John Fish

CEO, Suffolk
Chairman of Board Trustees, Brigham Health

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

Last year, what was it at Novartis

Speaker:

Jay Bradner, MD

President, NIBR

Keep eyes open, waiting the Pandemic to end and enable working back on all the indications

Portfolio of MET, Mimi Emerging Therapies

Learning from the Pandemic – operationalize the practice science, R&D leaders, new collaboratives at NIH, FDA, Novartis

Pursue programs that will yield growth, tropic diseases with Gates Foundation, Rising Tide pods for access CGT within Novartis Partnership with UPenn in Cell Therapy

Cost to access to IP from Academia to a Biotech CRISPR accessing few translations to Clinic

Protein degradation organization constraint valuation by parties in a partnership

Novartis: nuclear protein lipid nuclear particles, tamplate for Biotech to collaborate

Game changing: 10% of the Portfolio, New frontiers human genetics in Ophthalmology, CAR-T, CRISPR, Gene Therapy Neurological and payloads of different matter

Q&A

10:45 AM – 11:00 AM

10:40 AM – 10:50 AM

Break

10:50 AM – 11:00 AM

FIRST LOOK

Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy

Christine Seidman, MD
- Director, Cardiovascular Genetics Center, BWH
- Smith Professor of Medicine & Genetics, HMS

The Voice of Dr. Seidman – Her abstract is cited below

The ultimate opportunity presented by discovering the genetic basis of human disease is accurate prediction and disease prevention. To enable this achievement, genetic insights must enable the identification of at-risk

individuals prior to end-stage disease manifestations and strategies that delay or prevent clinical expression. Genetic cardiomyopathies provide a paradigm for fulfilling these opportunities. Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, diastolic dysfunction with normal or enhanced systolic performance and a unique histopathology: myocyte hypertrophy, disarray and fibrosis. Dilated cardiomyopathy (DCM) exhibits enlarged ventricular volumes with depressed systolic performance and nonspecific histopathology. Both HCM and DCM are prevalent clinical conditions that increase risk for arrhythmias, sudden death, and heart failure. Today treatments for HCM and DCM focus on symptoms, but none prevent disease progression. Human molecular genetic studies demonstrated that these pathologies often result from dominant mutations in genes that encode protein components of the sarcomere, the contractile unit in striated muscles. These data combined with the emergence of molecular strategies to specifically modulate gene expression provide unparalleled opportunities to silence or correct mutant genes and to boost healthy gene expression in patients with genetic HCM and DCM. Many challenges remain, but the active and vital efforts of physicians, researchers, and patients are poised to ensure success.

2:10 PM – 2:20 PM

FIRST LOOK

Enhancing vesicles for therapeutic delivery of bioproducts

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

DNA, RNA, exosomes avoid random transgene integration

EVs – Extracellular Vesicles

Q&A

2:20 PM – 2:35 PM

2:20 PM – 2:30 PM

FIRST LOOK

Versatile polymer-based nanocarriers for targeted therapy and immunomodulation

Natalie Artzi, PhD

Assistant Professor, BWH

Epigenome

Nonviral (nucleic acid) delivery

Nanoparticle Toolbox : Cyclical Dinucleotides (CDN)

Nanoparticles for delivery of medicines Delivery route affect on therapeutic efficacy

Polymeric based nanocarriers for targeted therapy and immunomodulation

Q&A

2:30 PM – 2:45 PM

2:55 PM – 3:20 PM

HOT TOPICS

Gene Editing | Achieving Therapeutic Mainstream

Today’s panel is made up of pioneers who represent foundational aspects of gene editing. They will discuss the movement of the technology into the therapeutic mainstream.

Successes in gene editing – lessons learned from late-stage assets (sickle cell, ophthalmology)
When to use what editing tool – pros and cons of traditional gene-editing v. base editing. Is prime editing the future? Specific use cases for epigenetic editing.
When we reach widespread clinical use – role of off-target editing – is the risk real? How will we mitigate? How practical is patient-specific off-target evaluation?

Moderator:

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

target alteration of genes for research and novele therapeutics for indications without alternative Tx

Chardonay Platform Specificity and safety

Speakers:

John Evans

CEO, Beam Therapeutics

CRISPR targets the Genome reaching the site open DNA single base change in the Genome sicle cell anemia, letter misspelled correction

turn off or activate or program the protein function genome modification tool immunology CAR-T nanoparticles to deliver locally

Delivery is the challenge ex Vivo, In Vivo innovations in nanoparticles to blood system, muscle

Lisa Michaels

EVP & CMO, Editas Medicine

Gene editing allows correction of genetic abnormalities

CRISPR editing the Genome in Vivo

Delivery specificity edit DNA of cells for Tx objective

Rachel Haurwitz, PhD

Caribou BioSciences, Off UC, Berkeley, CA

Innovation to delivery large quantities of DNA

Q&A

3:25 PM – 3:50 PM

3:25 PM – 3:50 PM

HOT TOPICS

Common Blood Disorders | Gene Therapy

What are the pros and cons of various strategies for treatment? There are AAV-based editing, non-viral delivery even oligonucleotide recruitment of endogenous editing/repair mechanisms. Which approaches are most appropriate for which disease?
How can companies increase the speed of recruitment for clinical trials when other treatments are available? What is the best approach to educate patients on a novel therapeutic?
How do we best address ethnic and socio-economic diversity to be more representative of the target patient population?
How long do we have to follow up with the patients from the scientific, patient’s community, and payer points of view? What are the current FDA and EMA guidelines for long-term follow-up?
Where are we with regards to surrogate endpoints and their application to clinically meaningful endpoints?
What are the emerging ethical dilemmas in pediatric gene therapy research? Are there challenges with informed consent and pediatric assent for trial participation?
Are there differences in reimbursement policies for these different blood disorders? Clearly durability of response is a big factor. Are there other considerations?

Moderator:

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

Speakers:

Samarth Kukarni, PhD

Nick Leschly

Chief Bluebird, Bluebird Bio

Mike McCune, MD, PhD

Head, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation

Q&A

3:55 PM – 4:15 PM

3:50 PM – 4:00 PM

FIRST LOOK

Gene Editing

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

ONE-seq enriched in specific populations for genetic variation

seq IP and commercialization

FIRST LOOK

RNA therapy for brain cancer

Pierpaolo Peruzzi, MD, PhD

Nuerosurgery, BWH
Assistant Professor of Neurosurgery, HMS

Targeting with RNA clusters enhances chemotheraphy in GBM

AAV delivery micro RNA – viral mediated and by exosomes (non viral)

Therapeutic impact in Brain Tumors 2-3 readiness

Q&A

4:00 PM – 4:20 PM

4:20 PM – 4:45 PM

HOT TOPICS

Gene Expression | Modulating with Oligonucleotide-Based Therapies

Oligonucleotide drugs have recently come into their own with approvals from companies such as Biogen, Alnylam, Novartis and others. This panel will address several questions:

Will oligonucleotides improve as a class that will make them even more effective? Are further advancements in backbone chemistry anticipated, for example.
Will oligonucleotide based therapies blaze trails for follow-on gene therapy products?
Are small molecules a threat to oligonucleotide-based therapies?
Beyond exon skipping and knock-down mechanisms, what other roles will oligonucleotide-based therapies take mechanistically — can genes be activating oligonucleotides? Is there a place for multiple mechanism oligonucleotide medicines?
Are there any advantages of RNAi-based oligonucleotides over ASOs, and if so for what use?

Moderator:
Jeannie Lee, MD, PhD
- Molecular Biologist, MGH
- Professor of Genetics, HMS
srRNA vs mRNA
Speakers:
- Bob Brown, PhD
  - CSO, EVP of R&D, Dicerna

small molecule vs capacity of nanoparticles to deliver therapeutics quantity for more molecule is much larger

- CNS delivery most difficult
- Brett Monia, PhD
  - CEO, Ionis

Alfred Sandrock, MD, PhD

EVP, R&D and CMO, Biogen

Q&A

4:55 PM – 5:15 PM

Friday, May 21, 2021

8:30 AM – 8:55 AM

Venture Investing | Shaping GCT Translation

What is occurring in the GCT venture capital segment? Which elements are seeing the most activity? Which areas have cooled? How is the investment market segmented between gene therapy, cell therapy and gene editing? What makes a hot GCT company? How long will the market stay frothy? Some review of demographics — # of investments, sizes, etc. Why is the market hot and how long do we expect it to stay that way? Rank the top 5 geographic markets for GCT company creation and investing? Are there academic centers that have been especially adept at accelerating GCT outcomes? Do the business models for the rapid development of coronavirus vaccine have any lessons for how GCT technology can be brought to market more quickly?

Moderator:

Meredith Fisher, PhD

Partner, Mass General Brigham Innovation Fund

Speakers:

David Berry, MD, PhD

CEO, Valo Health
General Partner, Flagship Pioneering

Robert Nelsen

Managing Director, Co-founder, ARCH Venture Partners

Kush Parmar, MD, PhD

Managing Partner, 5AM Ventures

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

Regenerative Medicine | Stem Cells

The promise of stem cells has been a highlight in the realm of regenerative medicine. Unfortunately, that promise remains largely in the future. Recent breakthroughs have accelerated these potential interventions in particular for treating neurological disease. Among the topics the panel will consider are:

Stem cell sourcing
Therapeutic indication growth
Genetic and other modification in cell production
Cell production to final product optimization and challenges
How to optimize the final product

Moderator:

Ole Isacson, MD, PhD

Director, Neuroregeneration Research Institute, McLean
Professor, Neurology and Neuroscience, HMS

Speakers:

Kapil Bharti, PhD

Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH

Joe Burns, PhD

VP, Head of Biology, Decibel Therapeutics

Erin Kimbrel, PhD

Executive Director, Regenerative Medicine, Astellas

Nabiha Saklayen, PhD

CEO and Co-Founder, Cellino

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Stem Cells

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Q&A

9:35 AM – 9:55 AM

9:35 AM – 10:00 AM

Capital Formation ’21-30 | Investing Modes Driving GCT Technology and Timing

The dynamics of venture/PE investing and IPOs are fast evolving. What are the drivers – will the number of investors grow will the size of early rounds continue to grow? How is this reflected in GCT target areas, company design, and biotech overall? Do patients benefit from these trends? Is crossover investing a distinct class or a little of both? Why did it emerge and what are the characteristics of the players? Will SPACs play a role in the growth of the gene and cell therapy industry. What is the role of corporate investment arms eg NVS, Bayer, GV, etc. – has a category killer emerged? Are we nearing the limit of what the GCT market can absorb or will investment capital continue to grow unabated?

Moderator:

Roger Kitterman

VP, Venture, Mass General Brigham

Speakers:

Ellen Hukkelhoven, PhD

Managing Director, Perceptive Advisors

Peter Kolchinsky, PhD

Founder and Managing Partner, RA Capital Management

Deep Nishar

Senior Managing Partner, SoftBank Investment Advisors

Oleg Nodelman

Founder & Managing Partner, EcoR1 Capital

Q&A

10:05 AM – 10:20 AM

10:00 AM – 10:10 AM

FIRST LOOK

New scientific and clinical developments for autologous stem cell therapy for Parkinson’s disease patients

Penelope Hallett, PhD

NRL, McLean
Assistant Professor Psychiatry, HMS

Q&A

10:10 AM – 10:30 AM

10:10 AM – 10:35 AM

HOT TOPICS

Neurodegenerative Clinical Outcomes | Achieving GCT Success

Can stem cell-based platforms become successful treatments for neurodegenerative diseases?

What are the commonalities driving GCT success in neurodegenerative disease and non-neurologic disease, what are the key differences?
Overcoming treatment administration challenges
GCT impact on degenerative stage of disease
How difficult will it be to titrate the size of the cell therapy effect in different neurological disorders and for different patients?
Demonstrating clinical value to patients and payers
Revised clinical trial models to address issues and concerns specific to GCT

Moderator:

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Speakers:

Erwan Bezard, PhD

INSERM Research Director, Institute of Neurodegenerative Diseases

Nikola Kojic, PhD

CEO and Co-Founder, Oryon Cell Therapies

Geoff MacKay

President & CEO, AVROBIO

Viviane Tabar, MD

Founding Investigator, BlueRock Therapeutics
Chair of Neurosurgery, Memorial Sloan Kettering

Q&A

10:40 AM – 10:55 AM

10:35 AM – 11:35 AM

Disruptive Dozen: 12 Technologies that Will Reinvent GCT

Nearly one hundred senior Mass General Brigham Harvard faculty contributed to the creation of this group of twelve GCT technologies that they believe will breakthrough in the next two years. The Disruptive Dozen identifies and ranks the GCT technologies that will be available on at least an experimental basis to have the chance of significantly improving health care.

11:35 AM – 11:45 AM

Concluding Remarks

The co-chairs convene to reflect on the insights shared over the three days. They will discuss what to expect at the in-person GCT focused May 2-4, 2022 World Medical Innovation Forum.

Christine Seidman, MD

Hypertrophic and Dilated Cardiomyopaies ‘

10% receive heart transplant 12 years survival

Mutation puterb function

TTN: contribute 20% of dilated cardiomyopaty

Silence gene

pleuripotential cells deliver therapies

Q&A

11:00 AM – 11:20 AM

11:00 AM – 11:10 AM

FIRST LOOK

Unlocking the secret lives of proteins in health and disease

Anna Greka, MD, PhD

Medicine, BWH
Associate Professor, Medicine, HMS

Q&A

11:10 AM – 11:30 AM

11:10 AM – 11:35 AM

Rare and Ultra Rare Diseases | GCT Breaks Through

What is driving the interest in rare diseases?
What are the biggest barriers to making breakthroughs ‘routine and affordable?’
What is the role of retrospective and prospective natural history studies in rare disease? When does the expected value of retrospective disease history studies justify the cost?
Related to the first question, what is the FDA expecting as far as controls in clinical trials for rare diseases? How does this impact the collection of natural history data?

Moderator:

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Speakers:

Leah Bloom, PhD

SVP, External Innovation and Strategic Alliances, Novartis Gene Therapies

Ultra rare (less than 100) vs rare difficulty to recruit patients and to follow up after treatment

Bobby Gaspar, MD, PhD

CEO, Orchard Therapeutics

Study of rare condition have transfer to other larger diseases – delivery of therapeutics genes, like immune disorders

Patient testimonials just to hear what a treatment can make

Emil Kakkis, MD, PhD

CEO, Ultragenyx

Do 100 patient study then have information on natural history to develop a clinical trial

Stuart Peltz, PhD

CEO, PTC Therapeutics

Rare disease, challenge for FDA approval and after market commercialization follow ups

Justification of cost for Rare disease – demonstration of Change is IP in value patients advocacy is helpful

Q&A

11:40 AM – 11:55 AM

11:40 AM – 12:00 PM

FIRESIDE

Partnering Across the GCT Spectrum

Moderator:

Erin Harris

Chief Editor, Cell & Gene

Perspective & professional tenure

Partnership in manufacturing what are the recommendations?

Hospital systems: Partnership Challenges

Speaker:

Marc Casper

CEO, ThermoFisher

25 years in Diagnostics last 20 years at ThermoFisher

products used in the Lab for CAR-T research and manufacture

CGT Innovations: FDA will have a high level of approval each year

How move from research to clinical trials to manufacturing Quicker process

Best practices in Partnerships: the root cause if acceleration to market service providers to deliver highest standards

Building capacity by acquisition to avoid the waiting time

Accelerate new products been manufactured

Collaborations with Academic Medical center i.e., UCSF in CGT joint funding to accelerate CGT to clinics’

Customers are extremely knowledgable, scale the capital investment made investment

150MIL a year to improve the Workflow

Q&A

12:05 PM – 12:20 PM

12:05 PM – 12:30 PM

CEO Panel | Anticipating Disruption | Planning for Widespread GCT

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

CGT becoming staple therapy what are the disruptors emerging

Speakers:

Lisa Dechamps

SVP & Chief Business Officer, Novartis Gene Therapies

Reimagine medicine with collaboration at MGH, MDM condition in children

The Science is there, sustainable processes and systems impact is transformational

Value based pricing, risk sharing Payers and Pharma for one time therapy with life span effect

Collaboration with FDA

Kieran Murphy

CEO, GE Healthcare

Diagnosis of disease to be used in CGT

2021 investment in CAR-T platform

Investment in several CGT frontier

Investment in AI, ML in system design new technologies

GE: Scale and Global distributions, sponsor companies in software

Waste in Industry – Healthcare % of GDP, work with MGH to smooth the workflow faster entry into hospital and out of Hospital

Telemedicine during is Pandemic: Radiologist needs to read remotely

Supply chain disruptions slow down all ecosystem

Production of ventilators by collaboration with GM – ingenuity

Scan patients outside of hospital a scanner in a Box

Christian Rommel, PhD

Head, Pharmaceuticals Research & Development, Bayer AG

CGT – 2016 and in 2020 new leadership and capability

Disease Biology and therapeutics

Regenerative Medicine: CGT vs repair building pipeline in ophthalmology and cardiovascular

Q&A

12:35 PM – 12:50 PM

12:35 PM – 12:55 PM

FIRESIDE

Building a GCT Portfolio

Moderator:

Shinichiro Fuse, PhD

Managing Partner, MPM Capital

Speaker:

Wolfram Carius, PhD

EVP, Pharmaceuticals, Head of Cell & Gene Therapy, Bayer AG

CGT will bring treatment to cure, delivery of therapies

Be a Leader repair, regenerate, cure

Technology and Science for CGT – building a portfolio vs single asset decision criteria development of IP market access patients access acceleration of new products

Bayer strategy: build platform for use by four domains

Gener augmentation

Autologeneic therapy, analytics

Gene editing

Oncology Cell therapy tumor treatment: What kind of cells – the jury is out

Of 23 product launch at Bayer no prediction is possible some high some lows

Q&A

1:00 PM – 1:15 PM

12:55 PM – 1:35 PM

Lunch

1:40 PM – 2:05 PM

GCT Delivery | Perfecting the Technology

Moderator:

Natalie Artzi, PhD

Assistant Professor, BWH

Speakers:

Geoff McDonough, MD

CEO, Generation Bio

Sonya Montgomery

CMO, Evox Therapeutics

Laura Sepp-Lorenzino, PhD

Chief Scientific Officer, Executive Vice President, Intellia Therapeutics

Doug Williams, PhD

CEO, Codiak BioSciences

Q&A

2:10 PM – 2:25 PM

2:05 PM – 2:10 PM

Invention Discovery Grant Announcement

2:10 PM – 2:20 PM

FIRST LOOK

Enhancing vesicles for therapeutic delivery of bioproducts

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

Q&A

2:20 PM – 2:35 PM

2:20 PM – 2:30 PM

FIRST LOOK

Versatile polymer-based nanocarriers for targeted therapy and immunomodulation

Natalie Artzi, PhD

Assistant Professor, BWH

Q&A

2:30 PM – 2:45 PM

2:55 PM – 3:20 PM

HOT TOPICS

Gene Editing | Achieving Therapeutic Mainstream

Today’s panel is made up of pioneers who represent foundational aspects of gene editing. They will discuss the movement of the technology into the therapeutic mainstream.

Successes in gene editing – lessons learned from late-stage assets (sickle cell, ophthalmology)
When to use what editing tool – pros and cons of traditional gene-editing v. base editing. Is prime editing the future? Specific use cases for epigenetic editing.
When we reach widespread clinical use – role of off-target editing – is the risk real? How will we mitigate? How practical is patient-specific off-target evaluation?

Moderator:

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

Speakers:

John Evans

CEO, Beam Therapeutics

Lisa Michaels

EVP & CMO, Editas Medicine

Q&A

3:25 PM – 3:50 PM

3:25 PM – 3:50 PM

HOT TOPICS

Common Blood Disorders | Gene Therapy

What are the pros and cons of various strategies for treatment? There are AAV-based editing, non-viral delivery even oligonucleotide recruitment of endogenous editing/repair mechanisms. Which approaches are most appropriate for which disease?
How can companies increase the speed of recruitment for clinical trials when other treatments are available? What is the best approach to educate patients on a novel therapeutic?
How do we best address ethnic and socio-economic diversity to be more representative of the target patient population?
How long do we have to follow up with the patients from the scientific, patient’s community, and payer points of view? What are the current FDA and EMA guidelines for long-term follow-up?
Where are we with regards to surrogate endpoints and their application to clinically meaningful endpoints?
What are the emerging ethical dilemmas in pediatric gene therapy research? Are there challenges with informed consent and pediatric assent for trial participation?
Are there differences in reimbursement policies for these different blood disorders? Clearly durability of response is a big factor. Are there other considerations?

Moderator:

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

Speakers:

Samarth Kukarni, PhD

Nick Leschly

Chief Bluebird, Bluebird Bio

Mike McCune, MD, PhD

Head, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation

Q&A

3:55 PM – 4:15 PM

3:50 PM – 4:00 PM

FIRST LOOK

Gene Editing

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

Q&A

4:00 PM – 4:20 PM

4:20 PM – 4:45 PM

HOT TOPICS

Gene Expression | Modulating with Oligonucleotide-Based Therapies

Oligonucleotide drugs have recently come into their own with approvals from companies such as Biogen, Alnylam, Novartis and others. This panel will address several questions:

Will oligonucleotides improve as a class that will make them even more effective? Are further advancements in backbone chemistry anticipated, for example.
Will oligonucleotide based therapies blaze trails for follow-on gene therapy products?
Are small molecules a threat to oligonucleotide-based therapies?
Beyond exon skipping and knock-down mechanisms, what other roles will oligonucleotide-based therapies take mechanistically — can genes be activating oligonucleotides? Is there a place for multiple mechanism oligonucleotide medicines?
Are there any advantages of RNAi-based oligonucleotides over ASOs, and if so for what use?

Moderator:

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

Speakers:

Bob Brown, PhD

CSO, EVP of R&D, Dicerna

Brett Monia, PhD

CEO, Ionis

Alfred Sandrock, MD, PhD

EVP, R&D and CMO, Biogen

Q&A

4:50 PM – 5:05 PM

4:45 PM – 4:55 PM

FIRST LOOK

RNA therapy for brain cancer

Pierpaolo Peruzzi, MD, PhD

Nuerosurgery, BWH
Assistant Professor of Neurosurgery, HMS

Q&A

4:55 PM – 5:15 PM

Friday, May 21, 2021

8:30 AM – 8:55 AM

Venture Investing | Shaping GCT Translation

Moderator:

Meredith Fisher, PhD

Partner, Mass General Brigham Innovation Fund

Strategies, success what changes are needed in the drug discovery process

Speakers:

David Berry, MD, PhD
- CEO, Valo Health
- General Partner, Flagship Pioneering

Bring disruptive frontier as a platform with reliable delivery CGT double knock out disease cure all change efficiency and scope human centric vs mice centered right scale of data converted into therapeutics acceleratetion

Innovation in drugs 60% fails in trial because of Toxicology system of the future deal with big diseases

Moderna is an example in unlocking what is inside us Microbiome and beyond discover new drugs epigenetics

Robert Nelsen
- Managing Director, Co-founder, ARCH Venture Partners

Manufacturing change is not a new clinical trial FDA need to be presented with new rethinking for big innovations Drug pricing cheaper requires systematization How to systematically scaling up systematize the discovery and the production regulatory innovations

Kush Parmar, MD, PhD
- Managing Partner, 5AM Ventures

Responsibility mismatch should be and what is “are”

Long term diseases Stack holders and modalities risk benefir for populations

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

Regenerative Medicine | Stem Cells

Stem cell sourcing
Therapeutic indication growth
Genetic and other modification in cell production
Cell production to final product optimization and challenges
How to optimize the final product

Moderator:
- Ole Isacson, MD, PhD
  - Director, Neuroregeneration Research Institute, McLean
  - Professor, Neurology and Neuroscience, MGH, HMS

Opportunities in the next generation of the tactical level Welcome the oprimism and energy level of all Translational medicine funding stem cells enormous opportunities

Speakers:
Kapil Bharti, PhD
- Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH
- first drug required to establish the process for that innovations design of animal studies not done before
- Off-th-shelf one time treatment becoming cure
- Intact tissue in a dish is fragile to maintain metabolism
Joe Burns, PhD
- VP, Head of Biology, Decibel Therapeutics
- Ear inside the scall compartments and receptors responsible for hearing highly differentiated tall ask to identify cell for anticipated differentiation
- multiple cell types and tissue to follow
Erin Kimbrel, PhD
- Executive Director, Regenerative Medicine, Astellas
- In the ocular space immunogenecity
- regulatory communication
- use gene editing for immunogenecity Cas1 and Cas2 autologous cells
- gene editing and programming big opportunities
Nabiha Saklayen, PhD
- CEO and Co-Founder, Cellino
- scale production of autologous cells foundry using semiconductor process in building cassettes
- solution for autologous cells

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Stem Cells

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS
Cell therapy for Parkinson to replace dopamine producing cells lost ability to produce dopamin
skin cell to become autologous cells reprograms to become cells producing dopamine
transplantation fibroblast cells metabolic driven process lower mutation burden
Quercetin inhibition elimination undifferentiated cells graft survival oxygenation increased

Q&A

9:35 AM – 9:55 AM

9:35 AM – 10:00 AM

Capital Formation ’21-30 | Investing Modes Driving GCT Technology and Timing

Moderator:

Roger Kitterman

VP, Venture, Mass General Brigham
Saturation reached or more investment is coming in CGT

Speakers:

Ellen Hukkelhoven, PhD

Managing Director, Perceptive Advisors
Cardiac area transduct cells
matching tools
10% success of phase 1 in drug development next phase matters more

Peter Kolchinsky, PhD

Founder and Managing Partner, RA Capital Management
Future proof for new comers disruptors
Ex Vivo gene therapy to improve funding products what tool kit belongs to
company insulation from next instability vs comapny stabilizing themselves along few years
Company interested in SPAC
cross over investment vs SPAC
Multi Omics in cancer early screening metastatic diseas will be wiped out

Deep Nishar

Senior Managing Partner, SoftBank Investment Advisors
Young field vs CGT started in the 80s
high payloads is a challenge
cost effective fast delivery to large populations
Mission oriented by the team and management
Multi Omics disease modality

Oleg Nodelman

Founder & Managing Partner, EcoR1 Capital
Invest in company next round of investment will be IPO
Help company raise money cross over investment vs SPAC
Innovating ideas from academia in need for funding

Q&A

10:05 AM – 10:20 AM

10:00 AM – 10:10 AM

FIRST LOOK

New scientific and clinical developments for autologous stem cell therapy for Parkinson’s disease patients

Penelope Hallett, PhD

NRL, McLean
Assistant Professor Psychiatry, HMS
Pharmacologic agent in existing cause another disorders locomo-movement related
efficacy Autologous cell therapy transplantation approach program T cells into dopamine generating neurons greater than Allogeneic cell transplantation

Q&A

10:10 AM – 10:30 AM

10:10 AM – 10:35 AM

HOT TOPICS

Neurodegenerative Clinical Outcomes | Achieving GCT Success

Can stem cell-based platforms become successful treatments for neurodegenerative diseases?

What are the commonalities driving GCT success in neurodegenerative disease and non-neurologic disease, what are the key differences?
Overcoming treatment administration challenges
GCT impact on degenerative stage of disease
How difficult will it be to titrate the size of the cell therapy effect in different neurological disorders and for different patients?
Demonstrating clinical value to patients and payers
Revised clinical trial models to address issues and concerns specific to GCT

Moderator:

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS
Neurogeneration REVERSAL or slowing down

Speakers:

Erwan Bezard, PhD

INSERM Research Director, Institute of Neurodegenerative Diseases
Cautious on reversal
Early intervantion versus late

Nikola Kojic, PhD

CEO and Co-Founder, Oryon Cell Therapies
Autologus cell therapy placed focal replacing missing synapses reestablishment of neural circuitary

Geoff MacKay

President & CEO, AVROBIO
Prevent condition to be manifested in the first place
clinical effect durable single infusion preventions of symptoms to manifest
Cerebral edema – stabilization
Gene therapy know which is the abnormal gene grafting the corrected one
More than biomarker as end point functional benefit not yet established

Viviane Tabar, MD

Founding Investigator, BlueRock Therapeutics
Chair of Neurosurgery, Memorial Sloan Kettering
Current market does not have delivery mechanism that a drug-delivery is the solution Trials would fail on DELIVERY
Immune suppressed patients during one year to avoid graft rejection Autologous approach of Parkinson patient genetically mutated reprogramed as dopamine generating neuron – unknowns are present
Circuitry restoration
Microenvironment disease ameliorate symptoms – education of patients on the treatment

Q&A

10:40 AM – 10:55 AM

10:35 AM – 11:35 AM

Disruptive Dozen: 12 Technologies that Will Reinvent GCT

11:35 AM – 11:45 AM

Concluding Remarks

The co-chairs convene to reflect on the insights shared over the three days. They will discuss what to expect at the in-person GCT focused May 2-4, 2022 World Medical Innovation Forum.

Speakers:

Bob Brown, PhD

CSO, EVP of R&D, Dicerna

Brett Monia, PhD

CEO, Ionis

Alfred Sandrock, MD, PhD

EVP, R&D and CMO, Biogen

Q&A

4:50 PM – 5:05 PM

4:45 PM – 4:55 PM

FIRST LOOK

RNA therapy for brain cancer

Pierpaolo Peruzzi, MD, PhD

Nuerosurgery, BWH
Assistant Professor of Neurosurgery, HMS

Q&A

4:55 PM – 5:15 PM

Friday, May 21, 2021

8:30 AM – 8:55 AM

Venture Investing | Shaping GCT Translation

Moderator:

Meredith Fisher, PhD

Partner, Mass General Brigham Innovation Fund

Speakers:

David Berry, MD, PhD

CEO, Valo Health
General Partner, Flagship Pioneering

Robert Nelsen

Managing Director, Co-founder, ARCH Venture Partners

Kush Parmar, MD, PhD

Managing Partner, 5AM Ventures

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

Regenerative Medicine | Stem Cells

Stem cell sourcing
Therapeutic indication growth
Genetic and other modification in cell production
Cell production to final product optimization and challenges
How to optimize the final product

Moderator:

Ole Isacson, MD, PhD

Director, Neuroregeneration Research Institute, McLean
Professor, Neurology and Neuroscience, HMS

Speakers:

Kapil Bharti, PhD

Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH

Joe Burns, PhD

VP, Head of Biology, Decibel Therapeutics

Erin Kimbrel, PhD

Executive Director, Regenerative Medicine, Astellas

Nabiha Saklayen, PhD

CEO and Co-Founder, Cellino

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Stem Cells

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Q&A

9:35 AM – 9:55 AM

9:35 AM – 10:00 AM

Capital Formation ’21-30 | Investing Modes Driving GCT Technology and Timing

Moderator:

Roger Kitterman

VP, Venture, Mass General Brigham

Speakers:

Ellen Hukkelhoven, PhD

Managing Director, Perceptive Advisors

Peter Kolchinsky, PhD

Founder and Managing Partner, RA Capital Management

Deep Nishar

Senior Managing Partner, SoftBank Investment Advisors

Oleg Nodelman

Founder & Managing Partner, EcoR1 Capital

Q&A

10:05 AM – 10:20 AM

10:00 AM – 10:10 AM

FIRST LOOK

New scientific and clinical developments for autologous stem cell therapy for Parkinson’s disease patients

Penelope Hallett, PhD

NRL, McLean
Assistant Professor Psychiatry, HMS

Q&A

10:10 AM – 10:30 AM

10:10 AM – 10:35 AM

HOT TOPICS

Neurodegenerative Clinical Outcomes | Achieving GCT Success

Can stem cell-based platforms become successful treatments for neurodegenerative diseases?

What are the commonalities driving GCT success in neurodegenerative disease and non-neurologic disease, what are the key differences?
Overcoming treatment administration challenges
GCT impact on degenerative stage of disease
How difficult will it be to titrate the size of the cell therapy effect in different neurological disorders and for different patients?
Demonstrating clinical value to patients and payers
Revised clinical trial models to address issues and concerns specific to GCT

Moderator:

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Speakers:

Erwan Bezard, PhD

INSERM Research Director, Institute of Neurodegenerative Diseases

Nikola Kojic, PhD

CEO and Co-Founder, Oryon Cell Therapies

Geoff MacKay

President & CEO, AVROBIO

Viviane Tabar, MD

Founding Investigator, BlueRock Therapeutics
Chair of Neurosurgery, Memorial Sloan Kettering

Q&A

10:40 AM – 10:55 AM

10:35 AM – 11:35 AM

Disruptive Dozen: 12 Technologies that Will Reinvent GCT

11:35 AM – 11:45 AM

Concluding Remarks

The co-chairs convene to reflect on the insights shared over the three days. They will discuss what to expect at the in-person GCT focused May 2-4, 2022 World Medical Innovation Forum.

Christine Seidman, MD

Hypertrophic and Dilated Cardiomyopaies ‘

10% receive heart transplant 12 years survival

Mutation puterb function

TTN: contribute 20% of dilated cardiomyopaty

Silence gene

pleuripotential cells deliver therapies

Q&A

11:00 AM – 11:20 AM

11:00 AM – 11:10 AM

FIRST LOOK

Unlocking the secret lives of proteins in health and disease

Anna Greka, MD, PhD

Medicine, BWH
Associate Professor, Medicine, HMS

Q&A

11:10 AM – 11:30 AM

11:10 AM – 11:35 AM

Rare and Ultra Rare Diseases | GCT Breaks Through

What is driving the interest in rare diseases?
What are the biggest barriers to making breakthroughs ‘routine and affordable?’
What is the role of retrospective and prospective natural history studies in rare disease? When does the expected value of retrospective disease history studies justify the cost?
Related to the first question, what is the FDA expecting as far as controls in clinical trials for rare diseases? How does this impact the collection of natural history data?

Moderator:

Susan Slaugenhaupt, PhD

Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
Professor, Neurology, HMS

Speakers:

Leah Bloom, PhD

SVP, External Innovation and Strategic Alliances, Novartis Gene Therapies

Ultra rare (less than 100) vs rare difficulty to recruit patients and to follow up after treatment

Bobby Gaspar, MD, PhD

CEO, Orchard Therapeutics

Study of rare condition have transfer to other larger diseases – delivery of therapeutics genes, like immune disorders

Patient testimonials just to hear what a treatment can make

Emil Kakkis, MD, PhD

CEO, Ultragenyx

Do 100 patient study then have information on natural history to develop a clinical trial

Stuart Peltz, PhD

CEO, PTC Therapeutics

Rare disease, challenge for FDA approval and after market commercialization follow ups

Justification of cost for Rare disease – demonstration of Change is IP in value patients advocacy is helpful

Q&A

11:40 AM – 11:55 AM

11:40 AM – 12:00 PM

FIRESIDE

Partnering Across the GCT Spectrum

Moderator:

Erin Harris

Chief Editor, Cell & Gene

Perspective & professional tenure

Partnership in manufacturing what are the recommendations?

Hospital systems: Partnership Challenges

Speaker:

Marc Casper

CEO, ThermoFisher

25 years in Diagnostics last 20 years at ThermoFisher

products used in the Lab for CAR-T research and manufacture

CGT Innovations: FDA will have a high level of approval each year

How move from research to clinical trials to manufacturing Quicker process

Best practices in Partnerships: the root cause if acceleration to market service providers to deliver highest standards

Building capacity by acquisition to avoid the waiting time

Accelerate new products been manufactured

Collaborations with Academic Medical center i.e., UCSF in CGT joint funding to accelerate CGT to clinics’

Customers are extremely knowledgable, scale the capital investment made investment

150MIL a year to improve the Workflow

Q&A

12:05 PM – 12:20 PM

12:05 PM – 12:30 PM

CEO Panel | Anticipating Disruption | Planning for Widespread GCT

Moderator:

Meg Tirrell

Senior Health and Science Reporter, CNBC

CGT becoming staple therapy what are the disruptors emerging

Speakers:

Lisa Dechamps

SVP & Chief Business Officer, Novartis Gene Therapies

Reimagine medicine with collaboration at MGH, MDM condition in children

The Science is there, sustainable processes and systems impact is transformational

Value based pricing, risk sharing Payers and Pharma for one time therapy with life span effect

Collaboration with FDA

Kieran Murphy

CEO, GE Healthcare

Diagnosis of disease to be used in CGT

2021 investment in CAR-T platform

Investment in several CGT frontier

Investment in AI, ML in system design new technologies

GE: Scale and Global distributions, sponsor companies in software

Waste in Industry – Healthcare % of GDP, work with MGH to smooth the workflow faster entry into hospital and out of Hospital

Telemedicine during is Pandemic: Radiologist needs to read remotely

Supply chain disruptions slow down all ecosystem

Production of ventilators by collaboration with GM – ingenuity

Scan patients outside of hospital a scanner in a Box

Christian Rommel, PhD

Head, Pharmaceuticals Research & Development, Bayer AG

CGT – 2016 and in 2020 new leadership and capability

Disease Biology and therapeutics

Regenerative Medicine: CGT vs repair building pipeline in ophthalmology and cardiovascular

Q&A

12:35 PM – 12:50 PM

12:35 PM – 12:55 PM

FIRESIDE

Building a GCT Portfolio

Moderator:

Shinichiro Fuse, PhD

Managing Partner, MPM Capital

Speaker:

Wolfram Carius, PhD

EVP, Pharmaceuticals, Head of Cell & Gene Therapy, Bayer AG

CGT will bring treatment to cure, delivery of therapies

Be a Leader repair, regenerate, cure

Technology and Science for CGT – building a portfolio vs single asset decision criteria development of IP market access patients access acceleration of new products

Bayer strategy: build platform for use by four domains

Gener augmentation

Autologeneic therapy, analytics

Gene editing

Oncology Cell therapy tumor treatment: What kind of cells – the jury is out

Of 23 product launch at Bayer no prediction is possible some high some lows

Q&A

1:00 PM – 1:15 PM

12:55 PM – 1:35 PM

Lunch

1:40 PM – 2:05 PM

GCT Delivery | Perfecting the Technology

Moderator:

Natalie Artzi, PhD

Assistant Professor, BWH

Speakers:

Geoff McDonough, MD

CEO, Generation Bio

Sonya Montgomery

CMO, Evox Therapeutics

Laura Sepp-Lorenzino, PhD

Chief Scientific Officer, Executive Vice President, Intellia Therapeutics

Doug Williams, PhD

CEO, Codiak BioSciences

Q&A

2:10 PM – 2:25 PM

2:05 PM – 2:10 PM

Invention Discovery Grant Announcement

2:10 PM – 2:20 PM

FIRST LOOK

Enhancing vesicles for therapeutic delivery of bioproducts

Xandra Breakefield, PhD

Geneticist, MGH, MGH
Professor, Neurology, HMS

Q&A

2:20 PM – 2:35 PM

2:20 PM – 2:30 PM

FIRST LOOK

Versatile polymer-based nanocarriers for targeted therapy and immunomodulation

Natalie Artzi, PhD

Assistant Professor, BWH

Q&A

2:30 PM – 2:45 PM

2:55 PM – 3:20 PM

HOT TOPICS

Gene Editing | Achieving Therapeutic Mainstream

Today’s panel is made up of pioneers who represent foundational aspects of gene editing. They will discuss the movement of the technology into the therapeutic mainstream.

Successes in gene editing – lessons learned from late-stage assets (sickle cell, ophthalmology)
When to use what editing tool – pros and cons of traditional gene-editing v. base editing. Is prime editing the future? Specific use cases for epigenetic editing.
When we reach widespread clinical use – role of off-target editing – is the risk real? How will we mitigate? How practical is patient-specific off-target evaluation?

Moderator:

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

Speakers:

John Evans

CEO, Beam Therapeutics

Lisa Michaels

EVP & CMO, Editas Medicine

Q&A

3:25 PM – 3:50 PM

3:25 PM – 3:50 PM

HOT TOPICS

Common Blood Disorders | Gene Therapy

What are the pros and cons of various strategies for treatment? There are AAV-based editing, non-viral delivery even oligonucleotide recruitment of endogenous editing/repair mechanisms. Which approaches are most appropriate for which disease?
How can companies increase the speed of recruitment for clinical trials when other treatments are available? What is the best approach to educate patients on a novel therapeutic?
How do we best address ethnic and socio-economic diversity to be more representative of the target patient population?
How long do we have to follow up with the patients from the scientific, patient’s community, and payer points of view? What are the current FDA and EMA guidelines for long-term follow-up?
Where are we with regards to surrogate endpoints and their application to clinically meaningful endpoints?
What are the emerging ethical dilemmas in pediatric gene therapy research? Are there challenges with informed consent and pediatric assent for trial participation?
Are there differences in reimbursement policies for these different blood disorders? Clearly durability of response is a big factor. Are there other considerations?

Moderator:

David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
Jordan Professor of Medicine, HMS

Speakers:

Samarth Kukarni, PhD

Nick Leschly

Chief Bluebird, Bluebird Bio

Mike McCune, MD, PhD

Head, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation

Q&A

3:55 PM – 4:15 PM

3:50 PM – 4:00 PM

FIRST LOOK

Gene Editing

J. Keith Joung, MD, PhD

Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
Professor of Pathology, HMS

Q&A

4:00 PM – 4:20 PM

4:20 PM – 4:45 PM

HOT TOPICS

Gene Expression | Modulating with Oligonucleotide-Based Therapies

Oligonucleotide drugs have recently come into their own with approvals from companies such as Biogen, Alnylam, Novartis and others. This panel will address several questions:

Will oligonucleotides improve as a class that will make them even more effective? Are further advancements in backbone chemistry anticipated, for example.
Will oligonucleotide based therapies blaze trails for follow-on gene therapy products?
Are small molecules a threat to oligonucleotide-based therapies?
Beyond exon skipping and knock-down mechanisms, what other roles will oligonucleotide-based therapies take mechanistically — can genes be activating oligonucleotides? Is there a place for multiple mechanism oligonucleotide medicines?
Are there any advantages of RNAi-based oligonucleotides over ASOs, and if so for what use?

Moderator:

Jeannie Lee, MD, PhD

Molecular Biologist, MGH
Professor of Genetics, HMS

Speakers:

Bob Brown, PhD

CSO, EVP of R&D, Dicerna

Brett Monia, PhD

CEO, Ionis

Alfred Sandrock, MD, PhD

EVP, R&D and CMO, Biogen

Q&A

4:50 PM – 5:05 PM

4:45 PM – 4:55 PM

FIRST LOOK

RNA therapy for brain cancer

Pierpaolo Peruzzi, MD, PhD

Nuerosurgery, BWH
Assistant Professor of Neurosurgery, HMS

Q&A

4:55 PM – 5:15 PM

Friday, May 21, 2021

Computer connection to the iCloud of WordPress.com FROZE completely at 10:30AM EST and no file update was possible. COVERAGE OF MAY 21, 2021 IS RECORDED BELOW FOLLOWING THE AGENDA BY COPY AN DPASTE OF ALL THE TWEETS I PRODUCED ON MAY 21, 2021

8:30 AM – 8:55 AM

Venture Investing | Shaping GCT Translation

Moderator:

Meredith Fisher, PhD

Partner, Mass General Brigham Innovation Fund

Speakers:

David Berry, MD, PhD

CEO, Valo Health
General Partner, Flagship Pioneering

Robert Nelsen

Managing Director, Co-founder, ARCH Venture Partners

Kush Parmar, MD, PhD

Managing Partner, 5AM Ventures

Q&A

9:00 AM – 9:15 AM

9:00 AM – 9:25 AM

Regenerative Medicine | Stem Cells

Stem cell sourcing
Therapeutic indication growth
Genetic and other modification in cell production
Cell production to final product optimization and challenges
How to optimize the final product

Moderator:

Ole Isacson, MD, PhD

Director, Neuroregeneration Research Institute, McLean
Professor, Neurology and Neuroscience, HMS

Speakers:

Kapil Bharti, PhD

Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH

Joe Burns, PhD

VP, Head of Biology, Decibel Therapeutics

Erin Kimbrel, PhD

Executive Director, Regenerative Medicine, Astellas

Nabiha Saklayen, PhD

CEO and Co-Founder, Cellino

Q&A

9:30 AM – 9:45 AM

9:25 AM – 9:35 AM

FIRST LOOK

Stem Cells

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Q&A

9:35 AM – 9:55 AM

9:35 AM – 10:00 AM

Capital Formation ’21-30 | Investing Modes Driving GCT Technology and Timing

Moderator:

Roger Kitterman

VP, Venture, Mass General Brigham

Speakers:

Ellen Hukkelhoven, PhD

Managing Director, Perceptive Advisors

Peter Kolchinsky, PhD

Founder and Managing Partner, RA Capital Management

Deep Nishar

Senior Managing Partner, SoftBank Investment Advisors

Oleg Nodelman

Founder & Managing Partner, EcoR1 Capital

Q&A

10:05 AM – 10:20 AM

10:00 AM – 10:10 AM

FIRST LOOK

New scientific and clinical developments for autologous stem cell therapy for Parkinson’s disease patients

Penelope Hallett, PhD

NRL, McLean
Assistant Professor Psychiatry, HMS

Q&A

10:10 AM – 10:30 AM

10:10 AM – 10:35 AM

HOT TOPICS

Neurodegenerative Clinical Outcomes | Achieving GCT Success

Can stem cell-based platforms become successful treatments for neurodegenerative diseases?

What are the commonalities driving GCT success in neurodegenerative disease and non-neurologic disease, what are the key differences?
Overcoming treatment administration challenges
GCT impact on degenerative stage of disease
How difficult will it be to titrate the size of the cell therapy effect in different neurological disorders and for different patients?
Demonstrating clinical value to patients and payers
Revised clinical trial models to address issues and concerns specific to GCT

Moderator:

Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH
William and Elizabeth Sweet, Professor of Neurosurgery, HMS

Speakers:

Erwan Bezard, PhD

INSERM Research Director, Institute of Neurodegenerative Diseases

Nikola Kojic, PhD

CEO and Co-Founder, Oryon Cell Therapies

Geoff MacKay

President & CEO, AVROBIO

Viviane Tabar, MD

Founding Investigator, BlueRock Therapeutics
Chair of Neurosurgery, Memorial Sloan Kettering

Q&A

10:40 AM – 10:55 AM

10:35 AM – 11:35 AM

Disruptive Dozen: 12 Technologies that Will Reinvent GCT

11:35 AM – 11:45 AM

Concluding Remarks

The co-chairs convene to reflect on the insights shared over the three days. They will discuss what to expect at the in-person GCT focused May 2-4, 2022 World Medical Innovation Forum.

ALL THE TWEETS PRODUCED ON MAY 21, 2021 INCLUDE THE FOLLOWING:

Aviva Lev-Ari

@AVIVA1950

#WMIF2021

@MGBInnovation

Erwan Bezard, PhD INSERM Research Director, Institute of Neurodegenerative Diseases Cautious on reversal

Aviva Lev-Ari

Nikola Kojic, PhD CEO and Co-Founder, Oryon Cell Therapies Autologus cell therapy placed focal replacing missing synapses reestablishment of neural circutary

Aviva Lev-Ari

Bob Carter, MD, PhD Chairman, Department of Neurosurgery, MGH William and Elizabeth Sweet, Professor of Neurosurgery, HMS Neurogeneration REVERSAL or slowing down?

Aviva Lev-Ari

Penelope Hallett, PhD NRL, McLean Assistant Professor Psychiatry, HMS efficacy Autologous cell therapy transplantation approach program T cells into dopamine genetating cells greater than Allogeneic cell transplantation

Aviva Lev-Ari

Penelope Hallett, PhD NRL, McLean Assistant Professor Psychiatry, HMS Pharmacologic agent in existing cause another disorders locomo-movement related

Aviva Lev-Ari

Roger Kitterman VP, Venture, Mass General Brigham Saturation reached or more investment is coming in CGT Multi OMICS and academia originated innovations are the most attractive areas

Aviva Lev-Ari

Roger Kitterman VP, Venture, Mass General Brigham Saturation reached or more investment is coming in CGT

Aviva Lev-Ari

Oleg Nodelman Founder & Managing Partner, EcoR1 Capital Invest in company next round of investment will be IPO 20% discount

Aviva Lev-Ari

Peter Kolchinsky, PhD Founder and Managing Partner, RA Capital Management Future proof for new comers disruptors Ex Vivo gene therapy to improve funding products what tool kit belongs to

Aviva Lev-Ari

Deep Nishar Senior Managing Partner, SoftBank Investment Advisors Young field vs CGT started in the 80s high payloads is a challenge

Aviva Lev-Ari

Bob Carter, MD, PhD MGH, HMS cells producing dopamine transplantation fibroblast cells metabolic driven process lower mutation burden Quercetin inhibition elimination undifferentiated cells graft survival oxygenation increased

Aviva Lev-Ari

Chairman, Department of Neurosurgery, MGH, Professor of Neurosurgery, HMS Cell therapy for Parkinson to replace dopamine producing cells lost ability to produce dopamine skin cell to become autologous cells reprogramed

Kapil Bharti, PhD Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH Off-th-shelf one time treatment becoming cure Intact tissue in a dish is fragile to maintain metabolism to become like semiconductors

Aviva Lev-Ari

Ole Isacson, MD, PhD Director, Neuroregeneration Research Institute, McLean Professor, Neurology and Neuroscience, MGH, HMS Opportunities in the next generation of the tactical level Welcome the oprimism and energy level of all

Aviva Lev-Ari

Erin Kimbrel, PhD Executive Director, Regenerative Medicine, Astellas In the ocular space immunogenecity regulatory communication use gene editing for immunogenecity Cas1 and Cas2 autologous cells

Aviva Lev-Ari

Nabiha Saklayen, PhD CEO and Co-Founder, Cellino scale production of autologous cells foundry using semiconductor process in building cassettes by optic physicists

Aviva Lev-Ari

Joe Burns, PhD VP, Head of Biology, Decibel Therapeutics Ear inside the scall compartments and receptors responsible for hearing highly differentiated tall ask to identify cell for anticipated differentiation control by genomics

Aviva Lev-Ari

Kapil Bharti, PhD Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH first drug required to establish the process for that innovations design of animal studies not done before

Aviva Lev-Ari

Meredith Fisher, PhD Partner, Mass General Brigham Innovation Fund Strategies, success what changes are needed in the drug discovery process@pharma_BI

Aviva Lev-Ari

Robert Nelsen Managing Director, Co-founder, ARCH Venture Partners Manufacturing change is not a new clinical trial FDA need to be presented with new rethinking for big innovations Drug pricing cheaper requires systematization

Aviva Lev-Ari

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Aviva Lev-Ari

David Berry, MD, PhD CEO, Valo Health GP, Flagship Pioneering Bring disruptive frontier platform reliable delivery CGT double knockout disease cure all change efficiency scope human centric vs mice centered right scale acceleration

Aviva Lev-Ari

Kush Parmar, MD, PhD Managing Partner, 5AM Ventures build it yourself, benefit for patients FIrst Look at MGB shows MEE innovation on inner ear worthy investment

Aviva Lev-Ari

Robert Nelsen Managing Director, Co-founder, ARCH Venture Partners Frustration with supply chain during the Pandemic, GMC anticipation in advance CGT rapidly prototype rethink and invest proactive investor .edu and Pharma

@pharma_BI

@AVIVA1950

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Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Posted in Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease, Resident-cell-based, Single Cell Genomics, Single-cell sequencing, Systemic Inflammatory Diseases as CVD Risk, Variation in human protein-coding regions on September 29, 2020| Leave a Comment »

Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

The Voice of Dr. Pearlman on potential clinical implications of the New Atlas:

Published on 9/24/2020 in Nature

Litviňuková, M., Talavera-López, C., Maatz, H. et al. Cells of the adult human heart. Nature (2020). https://doi.org/10.1038/s41586-020-2797-4

Abstract

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require deeper understanding of the healthy heart’s molecular processes. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using state-of-the-art analyses of large-scale single-cell and nuclei transcriptomes, we characterise six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes, and fibroblasts, revealing distinct atrial and ventricular subsets with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment we identify cardiac resident macrophages with inflammatory and protective transcriptional signatures. Further, inference of cell-cell interactions highlight different macrophage-fibroblast-cardiomyocyte networks between atria and ventricles that are distinct from skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a healthy reference for future studies.

Author information

Author notes

These authors contributed equally: Monika Litviňuková, Carlos Talavera-López, Henrike Maatz, Daniel Reichart

These authors jointly supervised this work: J. G. Seidman, Christine E. Seidman, Michela Noseda, Norbert Hubner, Sarah A. Teichmann

Affiliations

Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

Monika Litviňuková, Carlos Talavera-López, Krzysztof Polanski, Kenny Roberts, Liz Tuck, Eirini S. Fasouli, Hongbo Zhang, Omer Bayraktar & Sarah A. Teichmann

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany

Monika Litviňuková, Henrike Maatz, Catherine L. Worth, Eric L. Lindberg, Masatoshi Kanda, Giannino Patone & Norbert Hubner

EMBL – EBI, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

Carlos Talavera-López

Department of Genetics, Harvard Medical School, Boston, MA, United States

Daniel Reichart, Emily R. Nadelmann, Daniel M. DeLaughter, Hiroko Wakimoto, Joshua M. Gorham, J. G. Seidman & Christine E. Seidman

Dept Physics/Cavendish Laboratory, University of Cambridge, JJ Thompson Ave, Cambridge, CB3 0EH, United Kingdom

Sarah A. Teichmann

Department of Cardiology, University Heart & Vascular Center, University of Hamburg, Hamburg, Germany

Daniel Reichart

National Heart and Lung Institute, Imperial College London, London, United Kingdom

Michael Lee, Sara Samari, Joseph J. Boyle & Michela Noseda

British Heart Foundation Centre of Research Excellence and Centre of Regenerative Medicine, Imperial College London, London, United Kingdom

Michela Noseda

Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Centre, and Cambridge Biorepository for Translational Medicine, Cambridge, United Kingdom

Krishnaa T. Mahbubani & Kourosh Saeb-Parsy

Charité-Universitätsmedizin, Berlin, Germany

Norbert Hubner

Berlin Institute of Health (BIH), Berlin, Germany

Norbert Hubner

DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany

Barbara McDonough & Norbert Hubner

Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, United States

Barbara McDonough & Christine E. Seidman

Howard Hughes Medical Institute, Chevy Chase, MD, United States

Christine E. Seidman

Institute of Computational Biology (ICB), HMGU, Neuherberg, Germany

Matthias Heinig

Department of Informatics, Technische Universitaet Muenchen (TUM), Munich, Germany

Matthias Heinig

Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

Department of Histology and Embryology of Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, China

Hongbo Zhang

Department of Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan

Masatoshi Kanda

Corresponding authors

Correspondence to J. G. Seidman or Christine E. Seidman or Michela Noseda or Norbert Hubner or Sarah A. Teichmann.

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Articles on the Use of single cell analysis in COVID-19 research and A machine learning model that can Predict Base-editing Outcomes

Posted in Artificial Intelligence in Medicine - Application for Diagnosis, Gene Therapy & Gene Editing Development, Genome Biology, Single Cell Genomics on July 1, 2020| Leave a Comment »

Articles on the Use of single cell analysis in COVID-19 research and A machine learning model that can Predict Base-editing Outcomes

Reporter: Aviva Lev-Ari, PhD, RN

From: Richard Lumb <contact@frontlinegenomics.com>

Date: July 1, 2020 at 6:05:55 AM EDT

To: avivalev-ari@alum.berkeley.edu

Subject: FLG Newsletter: Single cell analysis in COVID-19 research, a machine learning model that can predict base-editing outcomes & much more

Reply-To: contact@frontlinegenomics.com

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Dear Aviva,

First of all, a big thank you to everyone who attended yesterday’s webinar on a new approach for exploring the dark genome. If you missed it, you can still watch it ‘on demand’ here.

In the last week, we’ve also launched two more webinar series. Both are free to attend and available live or on-demand:

Single Cell Online: A series of 4 webinars in July, starting on the 9th, focusing on unleashing the full power of single cell technologies. The series includes contributors from Novartis, Merck, Sanofi, Roche, the University of Gothenburg, MGI and Partek. Find out more and register here.

Driving FAIR in BioPharma: A series of 3 webinars in July and August, starting on the 21st July, exploring various use cases of FAIR data implementation to enable the potential of AI and ML in R&D. The series features contributors from AstraZeneca, Roche, Novartis, University of Oxford, ONTOFORCE, FDA, Eurofins and CDD. Click here to find out more and register.

Finally, this week on the website we have some fantastic content for you, including articles on the use of single cell analysis in COVID-19 research and a machine learning model that can predict base-editing outcomes. There’s also the latest DNA Today Podcasts focusing on infertility, featuring insights from genetic counsellors and the writer and producer of an explosive genetics mystery sci-fi movie called ANYA (check it out, it’s very thought provoking).

Stay safe everyone.

Kind Regards,

Rich

Richard Lumb PhD

Founder & CEO

Front Line Genomics

J202, The Biscuit Factory, 100 Drummond Rd, London, SE16 4DG.

T: +44 (0)208 191 8810

M: +44 (0)7739 251 898

E: richard@frontlinegenomics.com

W: www.frontlinegenomics.com

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Live Notes, Real Time Conference Coverage @AACR #AACR20: Tuesday June 23, 2020 3:00 PM-5:30 PM Educational Sessions

Posted in Artificial Intelligence - Breakthroughs in Theories and Technologies, Artificial Intelligence - General, Artificial Intelligence Applications in Health Care, Artificial Intelligence in CANCER, Artificial Intelligence in Health Care - Tools & Innovations, Artificial Intelligence in Medicine - Application for Diagnosis, Artificial Intelligence in Medicine - Applications in Therapeutics, Big Data, BioIT: BioInformatics, Biological Engineering, Biological Networks, Biological Networks, Gene Regulation and Evolution, Breast Cancer - impalpable breast lesions, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, cancer metabolism, Deep Learning in Pathology, Genomic Expression, Glioblastoma, Inflammasome, Intelligent Information Systems, Personalized and Precision Medicine & Genomic Research, Prostate Cancer: Monitoring vs Treatment, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, Single Cell Genomics, Single-cell sequencing, tumor microenvironment, tagged #AACR20, AACR, Artificial intelligence, Cancer Genomics, functional proteomics, Machine Learning, mass spectrometry, natural language processing, Proteomics, tumor microenvironment on June 24, 2020| Leave a Comment »

Live Notes, Real Time Conference Coverage AACR 2020: Tuesday June 23, 2020 3:00 PM-5:30 PM Educational Sessions

Reporter: Stephen J. Williams, PhD

Follow Live in Real Time using

#AACR20

@pharma_BI

@AACR

Register for FREE at https://www.aacr.org/

uesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session

Tumor Biology, Bioinformatics and Systems Biology

The Clinical Proteomic Tumor Analysis Consortium: Resources and Data Dissemination

This session will provide information regarding methodologic and computational aspects of proteogenomic analysis of tumor samples, particularly in the context of clinical trials. Availability of comprehensive proteomic and matching genomic data for tumor samples characterized by the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) program will be described, including data access procedures and informatic tools under development. Recent advances on mass spectrometry-based targeted assays for inclusion in clinical trials will also be discussed.

Amanda G Paulovich, Shankha Satpathy, Meenakshi Anurag, Bing Zhang, Steven A Carr

Methods and tools for comprehensive proteogenomic characterization of bulk tumor to needle core biopsies

Shankha Satpathy

TCGA has 11,000 cancers with >20,000 somatic alterations but only 128 proteins as proteomics was still young field
CPTAC is NCI proteomic effort
Chemical labeling approach now method of choice for quantitative proteomics
Looked at ovarian and breast cancers: to measure PTM like phosphorylated the sample preparation is critical

Data access and informatics tools for proteogenomics analysis

Bing Zhang

Raw and processed data (raw MS data) with linked clinical data can be extracted in CPTAC
Python scripts are available for bioinformatic programming

Pathways to clinical translation of mass spectrometry-based assays

Meenakshi Anurag

· Using kinase inhibitor pulldown (KIP) assay to identify unique kinome profiles

· Found single strand break repair defects in endometrial luminal cases, especially with immune checkpoint prognostic tumors

· Paper: JNCI 2019 analyzed 20,000 genes correlated with ET resistant in luminal B cases (selected for a list of 30 genes)

· Validated in METABRIC dataset

· KIP assay uses magnetic beads to pull out kinases to determine druggable kinases

· Looked in xenografts and was able to pull out differential kinomes

· Matched with PDX data so good clinical correlation

· Were able to detect ESR1 fusion correlated with ER+ tumors

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session

Survivorship

Artificial Intelligence and Machine Learning from Research to the Cancer Clinic

The adoption of omic technologies in the cancer clinic is giving rise to an increasing number of large-scale high-dimensional datasets recording multiple aspects of the disease. This creates the need for frameworks for translatable discovery and learning from such data. Like artificial intelligence (AI) and machine learning (ML) for the cancer lab, methods for the clinic need to (i) compare and integrate different data types; (ii) scale with data sizes; (iii) prove interpretable in terms of the known biology and batch effects underlying the data; and (iv) predict previously unknown experimentally verifiable mechanisms. Methods for the clinic, beyond the lab, also need to (v) produce accurate actionable recommendations; (vi) prove relevant to patient populations based upon small cohorts; and (vii) be validated in clinical trials. In this educational session we will present recent studies that demonstrate AI and ML translated to the cancer clinic, from prognosis and diagnosis to therapy.
NOTE: Dr. Fish’s talk is not eligible for CME credit to permit the free flow of information of the commercial interest employee participating.

Ron C. Anafi, Rick L. Stevens, Orly Alter, Guy Fish

Overview of AI approaches in cancer research and patient care

Rick L. Stevens

Deep learning is less likely to saturate as data increases
Deep learning attempts to learn multiple layers of information
The ultimate goal is prediction but this will be the greatest challenge for ML
ML models can integrate data validation and cross database validation
What limits the performance of cross validation is the internal noise of data (reproducibility)
Learning curves: not the more data but more reproducible data is important
Neural networks can outperform classical methods
Important to measure validation accuracy in training set. Class weighting can assist in development of data set for training set especially for unbalanced data sets

Discovering genome-scale predictors of survival and response to treatment with multi-tensor decompositions

Orly Alter

Finding patterns using SVD component analysis. Gene and SVD patterns match 1:1
Comparative spectral decompositions can be used for global datasets
Validation of CNV data using this strategy
Found Ras, Shh and Notch pathways with altered CNV in glioblastoma which correlated with prognosis
These predictors was significantly better than independent prognostic indicator like age of diagnosis

Identifying targets for cancer chronotherapy with unsupervised machine learning

Ron C. Anafi

Many clinicians have noticed that some patients do better when chemo is given at certain times of the day and felt there may be a circadian rhythm or chronotherapeutic effect with respect to side effects or with outcomes
ML used to determine if there is indeed this chronotherapy effect or can we use unstructured data to determine molecular rhythms?
Found a circadian transcription in human lung
Most dataset in cancer from one clinical trial so there might need to be more trials conducted to take into consideration circadian rhythms

Stratifying patients by live-cell biomarkers with random-forest decision trees

Guy Fish CEO Cellanyx Diagnostics

Some clinicians feel we may be overdiagnosing and overtreating certain cancers, especially the indolent disease
Platform published in 2018 paper (Clinical Proof-of-concept of a Novel Platform Utilizing Biopsy-derived Live Single Cells, Phenotypic Biomarkers, and Machine Learning Toward a Precision Risk Stratification Test for Prostate Cancer Grade Groups 1 and 2 (Gleason 3 + 3 and 3 + 4)
Problem: their information knowledgebase based on cultured cells
Their platform first used to stratify prostate cancer

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session

Tumor Biology, Molecular and Cellular Biology/Genetics, Bioinformatics and Systems Biology, Prevention Research

The Wound Healing that Never Heals: The Tumor Microenvironment (TME) in Cancer Progression

This educational session focuses on the chronic wound healing, fibrosis, and cancer “triad.” It emphasizes the similarities and differences seen in these conditions and attempts to clarify why sustained fibrosis commonly supports tumorigenesis. Importance will be placed on cancer-associated fibroblasts (CAFs), vascularity, extracellular matrix (ECM), and chronic conditions like aging. Dr. Dvorak will provide an historical insight into the triad field focusing on the importance of vascular permeability. Dr. Stewart will explain how chronic inflammatory conditions, such as the aging tumor microenvironment (TME), drive cancer progression. The session will close with a review by Dr. Cukierman of the roles that CAFs and self-produced ECMs play in enabling the signaling reciprocity observed between fibrosis and cancer in solid epithelial cancers, such as pancreatic ductal adenocarcinoma.

Harold F Dvorak, Sheila A Stewart, Edna Cukierman

The importance of vascular permeability in tumor stroma generation and wound healing

Harold F Dvorak

Aging in the driver’s seat: Tumor progression and beyond

Sheila A Stewart

Why won’t CAFs stay normal?

Edna Cukierman

Tuesday, June 23

3:00 PM – 5:00 PM EDT

RNA from the SARS-CoV-2 virus taking over the cells it infects: Virulence – Pathogen’s ability to infect a Resistant Host: The Imbalance between Controlling virus Replication versus Activation of the Adaptive Immune Response

Posted in Antibody Responses Predict Antigen Exposure, Apoptosis, Autophagy-Modulating Proteins, Cell Biology, Signaling & Cell Circuits, Coronavirus Gene Expression, COVID-19, Cytokine Receptor Structure, Genome Biology, Human Antibody Response, Human Circulating Antibody Repertoire, Human Naive B Cell Repertoire, Immunology, Immunotherapy, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, MHC Repertoires for Antigen Prediction, mRNA Therapeutics, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Serology tests for coronavirus antibodies, Single Cell Genomics, Single-cell sequencing, Synthetic Immunology: Hacking Immune Cells, Vaccinology, Variation in human protein-coding regions, Viral diseases, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV on May 23, 2020| Leave a Comment »

RNA from the SARS-CoV-2 virus taking over the cells it infects: Virulence – Pathogen’s ability to infect a Resistant Host: The Imbalance between Controlling Virus Replication versus Activation of the Adaptive Immune Response

Curator: Aviva Lev-Ari, PhD, RN – I added colors and bold face

UPDATED on 9/8/2020

What bats can teach us about developing immunity to Covid-19 | Free to read

Clive Cookson, Anna Gross and Ian Bott, London

https://www.ft.com/content/743ce7a0-60eb-482d-b1f4-d4de11182fa9?utm_source=Nature+Briefing&utm_campaign=af64422080-briefing-dy-20200908&utm_medium=email&utm_term=0_c9dfd39373-af64422080-43323101

UPDATED on 6/29/2020

Another duality and paradox in the Treatment of COVID-19 Patients in ICUs was expressed by Mike Yoffe, MD, PhD, David H. Koch Professor of Biology and Biological Engineering, Massachusetts Institute of Technology. Dr. Yaffe has a joint appointment in Acute Care Surgery, Trauma, and Surgical Critical Care, and in Surgical Oncology @BIDMC

on 6/29 at SOLUTIONS with/in/sight at Koch Institute @MIT

How Are Cancer Researchers Fighting COVID-19? (Part II)” Jun 29, 2020 11:30 AM EST

Mike Yoffe, MD, PhD

In COVID-19 patients: two life threatening conditions are seen in ICUs:

Blood Clotting – Hypercoagulability or Thrombophilia

Cytokine Storm – immuno-inflammatory response

The coexistence of 1 and 2 – HINDERS the ability to use effectively tPA as an anti-clotting agent while the cytokine storm is present.

Mike Yoffe’s related domain of expertise:

Signaling pathways and networks that control cytokine responses and inflammation

Misregulation of cytokine feedback loops, along with inappropriate activation of the blood clotting cascade causes dysregulation of cell signaling pathways in innate immune cells (neutrophils and macrophages), resulting in tissue damage and multiple organ failure following trauma or sepsis. Our research is focused on understanding the role of the p38-MK2 pathway in cytokine control and innate immune function, and on cross-talk between cytokines, clotting factors, and neutrophil NADPH oxidase-derived ROS in tissue damage, coagulopathy, and inflammation, using biochemistry, cell biology, and mouse knock-out/knock-in models. We recently discovered a particularly important link between abnormal blood clotting and the complement pathway cytokine C5a which causes excessive production of extracellular ROS and organ damage by neutrophils after traumatic injury.

SOURCE

https://www.bidmc.org/research/research-by-department/surgery/acute-care-surgery-trauma-and-surgical-critical-care/michael-b-yaffe

See

The Genome Structure of CORONAVIRUS, SARS-CoV-2

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/05/04/the-genome-structure-of-coronavirus-sars-cov-2-i-awaited-for-this-article-for-60-days/

Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Open Access Published:May 15, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.026

Highlights

SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response

Strong chemokine expression is consistent across in vitro, ex vivo, and in vivo models

Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19

Summary

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

Graphical Abstract

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Keywords

SARS-CoV-2

COVID-19

interferon

Coronavirus

transcriptomics

virus-host interactions

chemokines

IL6

ferret

Results

Defining the Transcriptional Response to SARS-CoV-2 Relative to Other Respiratory Viruses

To compare the transcriptional response of SARS-CoV-2 with other respiratory viruses, including MERS-CoV, SARS-CoV-1, human parainfluenza virus 3 (HPIV3), respiratory syncytial virus (RSV), and IAV, we first chose to focus on infection in a variety of respiratory cell lines (Figure 1). To this end, we collected poly(A) RNA from infected cells and performed RNA sequencing (RNA-seq) to estimate viral load. These data show that virus infection levels ranged from 0.1% to more than 50% of total RNA reads (Figure 1A).

Discussion

In the present study, we focus on defining the host response to SARS-CoV-2 and other human respiratory viruses in cell lines, primary cell cultures, ferrets, and COVID-19 patients. In general, our data show that the overall transcriptional footprint of SARS-CoV-2 infection was distinct in comparison with other highly pathogenic coronaviruses and common respiratory viruses such as IAV, HPIV3, and RSV. It is noteworthy that, despite a reduced IFN-I and -III response to SARS-CoV-2, we observed a consistent chemokine signature. One exception to this observation is the response to high-MOI infection in A549-ACE2 and Calu-3 cells, where replication was robust and an IFN-I and -III signature could be observed. In both of these examples, cells were infected at a rate to theoretically deliver two functional virions per cell in addition to any defective interfering particles within the virus stock that were not accounted for by plaque assays. Under these conditions, the threshold for PAMP may be achieved prior to the ability of the virus to evade detection through production of a viral antagonist. Alternatively, addition of multiple genomes to a single cell may disrupt the stoichiometry of viral components, which, in turn, may itself generate PAMPs that would not form otherwise. These ideas are supported by the fact that, at a low-MOI infection in A549-ACE2 cells, high levels of replication could also be achieved, but in the absence of IFN-I and -III induction. Taken together, these data suggest that, at low MOIs, the virus is not a strong inducer of the IFN-I and -III system, as opposed to conditions where the MOI is high.

Taken together, the data presented here suggest that the response to SARS-CoV-2 is imbalanced with regard to controlling virus replication versus activation of the adaptive immune response. Given this dynamic, treatments for COVID-19 have less to do with the IFN response and more to do with controlling inflammation. Because our data suggest that numerous chemokines and ILs are elevated in COVID-19 patients, future efforts should focus on U.S. Food and Drug Administration (FDA)-approved drugs that can be rapidly deployed and have immunomodulating properties.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Hoffmann et al.

CellMarch 05, 2020
- In Brief
- Full-Text
- PDF
Open Access
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2
Wang et al.

CellApril 09, 2020
- In Brief
- Full-Text
- PDF
Open Access
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
Monteil et al.

CellApril 24, 2020
- In Brief
- Full-Text
- PDF
Open Access
Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
Grifoni et al.

CellMay 14, 2020
- In Brief
- Full-Text
- PDF
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
Walls et al.

CellMarch 09, 2020
- In Brief
- Full-Text
- PDF
Open Access

SOURCE

https://www.cell.com/cell/fulltext/S0092-8674(20)30489-X

SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, So Nakagawa, Kei Sato

doi: https://doi.org/10.1101/2020.05.11.088179

Abstract

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasi-species with extended ORF3b that may exacerbate COVID-19 symptoms.

Highlights

ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist

SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog

The anti-IFN activity of ORF3b depends on the length of its C-terminus

An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases

Competing Interest Statement

The authors have declared no competing interest.

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

SOURCE

https://www.biorxiv.org/content/10.1101/2020.05.11.088179v1

‘It’s something I have never seen’: How the Covid-19 virus hijacks cells

By SHARON BEGLEY @sxbegle

MAY 21, 2020

RNA (in green) from the SARS-CoV-2 virus is shown taking over the cells it infects.ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

A deep dive into how the new coronavirus infects cells has found that it orchestrates a hostile takeover of their genes unlike any other known viruses do, producing what one leading scientist calls “unique” and “aberrant” changes.Recent studies show that in seizing control of genes in the human cells it invades, the virus changes how segments of DNA are read, doing so in a way that might explain why the elderly are more likely to die of Covid-19 and why antiviral drugs might not only save sick patients’ lives but also prevent severe disease if taken before infection.“It’s something I have never seen in my 20 years of” studying viruses, said virologist Benjamin tenOever of the Icahn School of Medicine at Mount Sinai, referring to how SARS-CoV-2, the virus that causes Covid-19, hijacks cells’ genomes.The “something” he and his colleagues saw is how SARS-CoV-2 blocks one virus-fighting set of genes but allows another set to launch, a pattern never seen with other viruses. Influenza and the original SARS virus (in the early 2000s), for instance, interfere with both arms of the body’s immune response — what tenOever dubs “call to arms” genes and “call for reinforcement” genes.The first group of genes produces interferons. These proteins, which infected cells release, are biological semaphores, signaling to neighboring cells to activate some 500 of their own genes that will slow down the virus’ ability to make millions of copies of itself if it invades them. This lasts seven to 10 days, tenOever said, controlling virus replication and thereby buying time for the second group of genes to act.This second set of genes produce their own secreted proteins, called chemokines, that emit a biochemical “come here!” alarm. When far-flung antibody-making B cells and virus-killing T cells sense the alarm, they race to its source. If all goes well, the first set of genes holds the virus at bay long enough for the lethal professional killers to arrive and start eradicating viruses.

“Most other viruses interfere with some aspect of both the call to arms and the call for reinforcements,” tenOever said. “If they didn’t, no one would ever get a viral illness”: The one-two punch would pummel any incipient infection into submission.

SARS-CoV-2, however, uniquely blocks one cellular defense but activates the other, he and his colleagues reported in a study published last week in Cell. They studied healthy human lung cells growing in lab dishes, ferrets (which the virus infects easily), and lung cells from Covid-19 patients. In all three, they found that within three days of infection, the virus induces cells’ call-for-reinforcement genes to produce cytokines. But it blocks their call-to-arms genes — the interferons that dampen the virus’ replication.

The result is essentially no brakes on the virus’s replication, but a storm of inflammatory molecules in the lungs, which is what tenOever calls an “unique” and “aberrant” consequence of how SARS-CoV-2 manipulates the genome of its target.

In another new study, scientists in Japan last week identified how SARS-CoV-2 accomplishes that genetic manipulation. Its ORF3b gene produces a protein called a transcription factor that has “strong anti-interferon activity,” Kei Sato of the University of Tokyo and colleagues found — stronger than the original SARS virus or influenza viruses. The protein basically blocks the cell from recognizing that a virus is present, in a way that prevents interferon genes from being expressed.

In fact, the Icahn School team found no interferons in the lung cells of Covid-19 patients. Without interferons, tenOever said, “there is nothing to stop the virus from replicating and festering in the lungs forever.”

That causes lung cells to emit even more “call-for-reinforcement” genes, summoning more and more immune cells. Now the lungs have macrophages and neutrophils and other immune cells “everywhere,” tenOever said, causing such runaway inflammation “that you start having inflammation that induces more inflammation.”

At the same time, unchecked viral replication kills lung cells involved in oxygen exchange. “And suddenly you’re in the hospital in severe respiratory distress,” he said.

In elderly people, as well as those with diabetes, heart disease, and other underlying conditions, the call-to-arms part of the immune system is weaker than in younger, healthier people, even before the coronavirus arrives. That reduces even further the cells’ ability to knock down virus replication with interferons, and imbalances the immune system toward the dangerous inflammatory response.

The discovery that SARS-CoV-2 strongly suppresses infected cells’ production of interferons has raised an intriguing possibility: that taking interferons might prevent severe Covid-19 or even prevent it in the first place, said Vineet Menachery of the University of Texas Medical Branch.

In a study of human cells growing in lab dishes, described in a preprint (not peer-reviewed or published in a journal yet), he and his colleagues also found that SARS-CoV-2 “prevents the vast amount” of interferon genes from turning on. But when cells growing in lab dishes received the interferon IFN-1 before exposure to the coronavirus, “the virus has a difficult time replicating.”

After a few days, the amount of virus in infected but interferon-treated cells was 1,000- to 10,000-fold lower than in infected cells not pre-treated with interferon. (The original SARS virus, in contrast, is insensitive to interferon.)

Ending the pandemic and preventing its return is assumed to require an effective vaccine to prevent infectionand antiviral drugs such as remdesivir to treat the very sick, but the genetic studies suggest a third strategy: preventive drugs.

It’s possible that treatment with so-called type-1 interferon “could stop the virus before it could get established,” Menachery said.

Giving drugs to healthy people is always a dicey proposition, since all drugs have side effects — something considered less acceptable than when a drug is used to treat an illness. “Interferon treatment is rife with complications,” Menachery warned. The various interferons, which are prescribed for hepatitis, cancers, and many other diseases, can cause flu-like symptoms.

But the risk-benefit equation might shift, both for individuals and for society, if interferons or antivirals or other medications are shown to reduce the risk of developing serious Covid-19 or even make any infection nearly asymptomatic.

Interferon “would be warning the cells the virus is coming,” Menachery said, so such pretreatment might “allow treated cells to fend off the virus better and limit its spread.” Determining that will of course require clinical trials, which are underway.

About the Author

Sharon Begley

Senior Writer, Science and Discovery

sharon.begley@statnews.com

@sxbegle

SOURCE

https://www.statnews.com/2020/05/21/coronavirus-hijacks-cells-in-unique-ways/?utm_source=STAT+Newsletters&utm_campaign=bee97f4883-Daily_Recap&utm_medium=email&utm_term=0_8cab1d7961-bee97f4883-150237109

Medicine in 2045 – Perspectives by World Thought Leaders in the Life Sciences & Medicine

Posted in Advanced Computing Platform, Artificial Intelligence - General, Big Data, BioBanking, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Cancer and Current Therapeutics, CAST - Alternative to CRISPR/Cas9, Computational Biology/Systems and Bioinformatics, CRISPR/Cas9 & Gene Editing, Diagnostic Immunology, Digital HealthCare – biotech & internet joint ventures, Disease Biology, DNA repair, Drug Delivery Platform Technology, Gene Editing Impact on Longevity, Genetics & Innovations in Treatment, Genome Biology, Genomic Testing: Methodology for Diagnosis, Health Care System by Country, Health Economics and Outcomes Research, HealthCare IT, Human Immune System in Health and in Disease, Immuno-Oncology & Genomics, Immunodiagnostics, Liquid Biopsy: Circulating Tumor Cells in Urine and Blood, Microfuidics, Single Cell Genomics, Variation in human protein-coding regions on December 9, 2019| Leave a Comment »

Medicine in 2045 – Perspectives by World Thought Leaders in the Life Sciences & Medicine

Reporter: Aviva Lev-Ari, PhD, RN

This report is based on an article in Nature Medicine | VOL 25 | December 2019 | 1800–1809 | http://www.nature.com/naturemedicine

Looking forward 25 years: the future of medicine.

Nat Med 25, 1804–1807 (2019) doi:10.1038/s41591-019-0693-y

Aviv Regev, PhD

Core member and chair of the faculty, Broad Institute of MIT and Harvard; director, Klarman Cell Observatory, Broad Institute of MIT and Harvard; professor of biology, MIT; investigator, Howard Hughes Medical Institute; founding co-chair, Human Cell Atlas.

millions of genome variants, tens of thousands of disease-associated genes, thousands of cell types and an almost unimaginable number of ways they can combine, we had to approximate a best starting point—choose one target, guess the cell, simplify the experiment.
In 2020, advances in polygenic risk scores, in understanding the cell and modules of action of genes through genome-wide association studies (GWAS), and in predicting the impact of combinations of interventions.
we need algorithms to make better computational predictions of experiments we have never performed in the lab or in clinical trials.
Human Cell Atlas and the International Common Disease Alliance—and in new experimental platforms: data platforms and algorithms. But we also need a broader ecosystem of partnerships in medicine that engages interaction between clinical experts and mathematicians, computer scientists and engineers

Feng Zhang, PhD

investigator, Howard Hughes Medical Institute; core member, Broad Institute of MIT and Harvard; James and Patricia Poitras Professor of Neuroscience, McGovern Institute for Brain Research, MIT.

fundamental shift in medicine away from treating symptoms of disease and toward treating disease at its genetic roots.
Gene therapy with clinical feasibility, improved delivery methods and the development of robust molecular technologies for gene editing in human cells, affordable genome sequencing has accelerated our ability to identify the genetic causes of disease.
1,000 clinical trials testing gene therapies are ongoing, and the pace of clinical development is likely to accelerate.
refine molecular technologies for gene editing, to push our understanding of gene function in health and disease forward, and to engage with all members of society

Elizabeth Jaffee, PhD

Dana and Albert “Cubby” Broccoli Professor of Oncology, Johns Hopkins School of Medicine; deputy director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

a single blood test could inform individuals of the diseases they are at risk of (diabetes, cancer, heart disease, etc.) and that safe interventions will be available.
developing cancer vaccines. Vaccines targeting the causative agents of cervical and hepatocellular cancers have already proven to be effective. With these technologies and the wealth of data that will become available as precision medicine becomes more routine, new discoveries identifying the earliest genetic and inflammatory changes occurring within a cell as it transitions into a pre-cancer can be expected. With these discoveries, the opportunities to develop vaccine approaches preventing cancers development will grow.

Jeremy Farrar, OBE FRCP FRS FMedSci

Director, Wellcome Trust.

shape how the culture of research will develop over the next 25 years, a culture that cares more about what is achieved than how it is achieved.
building a creative, inclusive and open research culture will unleash greater discoveries with greater impact.

John Nkengasong, PhD

Director, Africa Centres for Disease Control and Prevention.

To meet its health challenges by 2050, the continent will have to be innovative in order to leapfrog toward solutions in public health.
Precision medicine will need to take center stage in a new public health order— whereby a more precise and targeted approach to screening, diagnosis, treatment and, potentially, cure is based on each patient’s unique genetic and biologic make-up.

Eric Topol, MD

Executive vice-president, Scripps Research Institute; founder and director, Scripps Research Translational Institute.

In 2045, a planetary health infrastructure based on deep, longitudinal, multimodal human data, ideally collected from and accessible to as many as possible of the 9+ billion people projected to then inhabit the Earth.
enhanced capabilities to perform functions that are not feasible now.
AI machines’ ability to ingest and process biomedical text at scale—such as the corpus of the up-to-date medical literature—will be used routinely by physicians and patients.
the concept of a learning health system will be redefined by AI.

Linda Partridge, PhD

Professor, Max Planck Institute for Biology of Ageing.

Geroprotective drugs, which target the underlying molecular mechanisms of ageing, are coming over the scientific and clinical horizons, and may help to prevent the most intractable age-related disease, dementia.

Trevor Mundel, MD

President of Global Health, Bill & Melinda Gates Foundation.

finding new ways to share clinical data that are as open as possible and as closed as necessary.
moving beyond drug donations toward a new era of corporate social responsibility that encourages biotechnology and pharmaceutical companies to offer their best minds and their most promising platforms.
working with governments and multilateral organizations much earlier in the product life cycle to finance the introduction of new interventions and to ensure the sustainable development of the health systems that will deliver them.
deliver on the promise of global health equity.

Josep Tabernero, MD, PhD

Vall d’Hebron Institute of Oncology (VHIO); president, European Society for Medical Oncology (2018–2019).

genomic-driven analysis will continue to broaden the impact of personalized medicine in healthcare globally.
Precision medicine will continue to deliver its new paradigm in cancer care and reach more patients.
Immunotherapy will deliver on its promise to dismantle cancer’s armory across tumor types.
AI will help guide the development of individually matched
genetic patient screenings
the promise of liquid biopsy policing of disease?

Pardis Sabeti, PhD

Professor, Harvard University & Harvard T.H. Chan School of Public Health and Broad Institute of MIT and Harvard; investigator, Howard Hughes Medical Institute.

the development and integration of tools into an early-warning system embedded into healthcare systems around the world could revolutionize infectious disease detection and response.
But this will only happen with a commitment from the global community.

Els Toreele, PhD

Executive director, Médecins Sans Frontières Access Campaign

we need a paradigm shift such that medicines are no longer lucrative market commodities but are global public health goods—available to all those who need them.
This will require members of the scientific community to go beyond their role as researchers and actively engage in R&D policy reform mandating health research in the public interest and ensuring that the results of their work benefit many more people.
The global research community can lead the way toward public-interest driven health innovation, by undertaking collaborative open science and piloting not-for-profit R&D strategies that positively impact people’s lives globally.

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Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

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SESSION 1

From Base Pairs To Better Care:

AI and Omics in Precision Oncology

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SESSION 2

The Evolution of Precision Oncology:

Integrating MRD, AI, and Beyond

SESSION 3

The Shifting Landscape:

Tumor Plasticity and Resistance

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Nobel Prize in Chemistry 2024 to David Baker, Demis Hassabis and John M. Jumper

10/9/2024

David Baker “for computational protein design”

Demis Hassabis “for protein structure prediction”

John M. Jumper “for protein structure prediction”

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2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation

Fig. (1). MicroRNA maturation and function.

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Genetic variation causes human lupus, systemic lupus erythematosus (SLE)

Scientists finally discover the cause of lupus

Other related articles published in this Open Access Online Scientific Journal

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2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

Accelerating the Future of Medicine with Gene and Cell Therapy What Comes Next

Virtual | May 19–21, 2021

#WMIF2021

@MGBInnovation

will cover the event in Real Time

Founder LPBI 1.0 & LPBI 2.0

will be in virtual attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine

Among them, books on Gene and Cell Therapy include the following:

Topics for May 19 – 21 include:

AGENDA

Wednesday, May 19, 2021

Thursday, May 20, 2021

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

Accelerating the Future of Medicine with Gene and Cell Therapy What Comes Next

Virtual | May 19–21, 2021

#WMIF2021

@MGBInnovation

will cover the event in Real Time

Founder LPBI 1.0 & LPBI 2.0

will be in virtual attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine