Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
microRNA (miRNA) miR-483-5p has a key role in preventing stress-related anxiety by acting on its target gene Pgap2 that curbs the development of this type of anxiety
Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress.
Named for ACGT co-founder, Edward Netter, the award recognizes a researcher who has made unparalleled and groundbreaking contributions to the field of cell and gene therapy for cancer. Dr. Mackall is a leader in advancing cell and gene therapies for the treatment of solid tumors, with a major focus on children’s cancers.
In addition to being an ACGT research fellow and a member of ACGT’s Scientific Advisory Council, Dr. Mackall is the Ernest and Amelia Gallo Family professor of Pediatrics and Medicine at Stanford University, the founding director of the Stanford Center for Cancer Cell Therapy, associate director of the Stanford Cancer Institute, leader of the Cancer Immunotherapy Program and director of the Parker Institute for Cancer Immunotherapy. She has led numerous groundbreaking clinical trials to treat children with sarcomas and brain cancers.
“There is exciting progress happening in the field of cancer cell and gene therapy,” said Kevin Honeycutt, CEO and president of ACGT. “We continue to see the FDA approve cell and gene therapy treatments for blood cancers, while research for solid tumors is now progressing to clinical trials. These successes are linked to the funding of ACGT, and Dr. Crystal Mackall is one of the best examples of a researcher who refused to accept the status-quo of standard cancer treatment and committed to developing novel cell and gene therapies for children with difficult-to-treat tumors. ACGT is proud that Dr. Mackall is an ACGT Research Fellow, a member of ACGT’s Scientific Advisory Council, and the newest recipient of the Edward Netter Leadership Award.”
The ACGT Awards Luncheon will celebrate the non-profit organization’s 20th anniversary and usher in a new decade as the only nonprofit dedicated exclusively to funding cancer cell and gene therapy research. ACGT funds innovative scientists and biotechnology companies working to harness the power of cell and gene therapy to transform how cancer is treated and to drive momentum toward a cure.
The Edward Netter Leadership Award will be presented to Dr. Mackall by Carl June, MD, of the University of Pennsylvania, who received the honor at ACGT’s 2019 Awards Gala. ACGT grant funding enabled Dr. June to research and develop cell and gene therapies that led to the first FDA approvals of CAR T-cell therapies for cancer.
For more than 20 years, Alliance for Cancer Gene Therapy has funded research that is bringing innovative treatment options to people living with deadly cancers – treatments that save lives and offer new hope to all cancer patients. Alliance for Cancer Gene Therapy funds researchers who are pioneering the potential of cancer cell and gene therapy – talented visionaries whose scientific advancements are driving the development of groundbreaking treatments for ovarian, prostate, sarcoma, glioblastoma, melanoma and pancreatic cancers. One hundred percent of all public funds raised by Alliance for Cancer Gene Therapy directly support research and programs. For more information, visit acgtfoundation.org, call (203) 358-5055, or join the Alliance for Cancer Gene Therapy community on Facebook, Twitter, LinkedIn, Instagram and YouTube @acgtfoundation.
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Other Related Articles in this Open Access Scientific Journal Include
Read key takeaways from the 2022 World Medical Innovation Forum in this report from the Bank of America Institute. #WMIF2022
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What are the 12 emerging #GeneAndCellTherapy technologies with the greatest potential to transform #healthcare? Read our report for key takeaways from #WMIF2022. @MassGenBrigham
Read key takeaways from the 2022 World Medical Innovation Forum in this report from the Bank of America Institute. #WMIF2022
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The Disruptive Dozen 12 #GCT Breakthroughs that are revolutionizing Healthcare
Liz Everett Krisberg, Head of the Bank of America Institute
The Disruptive Dozen 12 GCT breakthroughs that are revolutionizing healthcare 05 May 2022 Key Takeaways • Gene and cell therapy (GCT) is widely recognized as a transformational opportunity in medicine, with the potential to stop or slow the effects of disease by targeting it at the genetic level. • The “Disruptive Dozen” identifies 12 emerging GCT technologies with the greatest potential to transform healthcare over the next several years • These breakthroughs range from restoration of sight and increasing the supply of donor organs, to treating brain cancer, hearing loss and autoimmune diseases that currently lack few or any treatment alternatives. Gene and cell therapy (GCT) technologies are transforming medicine and the approach to severe diseases like cancer, hereditary conditions including Huntington Disease and Sickle Cell, as well as rare disorders that currently have no treatment alternatives. GCT has the potential to stop or slow the effects of disease by targeting it at the genetic level, either replacing, inactivating or modifying the genetic material or by transferring live or intact cells into a patient to treat or cure disease. Even in cases where the GCT approach does not fully cure a condition, GCT has the potential to be life changing. This is because GCT treatments are often “one and done,” only requiring a single administration, which may enable a patient to manage their disease without onerous ongoing treatment cycles. While some of the first GCT applications were focused on rare and orphan diseases, recent advancements show tremendous potential opportunity for use cases with more broad applications. Beyond the messenger ribonucleic acid or mRNA vaccines that protect against infectious disease including COVID-19, GCT technologies exhibit promise to address prevalent chronic diseases such as diabetes and hearing loss, as well as central nervous system (CNS) disorders and Alzheimer’s. This week, Bank of America joined Mass General Brigham to present the World Medical Innovation Forum in Boston, where over 1,000 clinical experts, industry leaders and investors explored how to advance GCT technologies that may lead to breakthrough medical advancements and solutions. We highlight the twelve emerging GCT technologies – the “Disruptive Dozen” – with the greatest potential to impact and transform healthcare in the next several years. These breakthroughs range from restoration of sight and increasing the supply of donor organs, to treating brain cancer, hearing loss and autoimmune diseases. Restoring sight by mending broken genes Roughly 200 genes are directly linked to vision disorders. In the last several years, groundbreaking new gene therapies have emerged that can compensate for faulty genes in the eye by adding new, healthy copies — a molecular fix that promises to restore sight to those who have lost it. The approach, known as CRISPR-Cas-9 gene editing, could open the door to treating genetic forms of vision loss that are not suited to conventional gene therapy, and a host of other medical conditions. A clinical trial is now underway to evaluate a CRISPR-Cas 9 gene-editing therapy for a severe form of childhood blindness for which there currently are no treatments. Although this treatment is still experimental, it is already historic — it is the first medicine based on CRISPR-Cas-9 to be delivered in vivo, or inside a patient’s body. Similar gene-editing therapies are also under development that correct genes within blood cells. A gene editing solution to increase the supply of donor organs In the U.S. alone, more than 100,000 people need a life-saving organ transplant. But the supply of donor organs is quite limited, and every day, patients die waiting for a donor organ. One way to address this crisis is xenotransplantation — harvesting organs from animals and placing them into human patients. Advances in gene editing technology make it possible to remove, insert, or replace genes with relative ease and precision. This molecular engineering can sidestep the human immune system, which is highly adept at recognizing foreign tissues and triggering rejection. Over the last 20 years, scientists have been working to devise successful gene editing strategies that will render pig organs compatible with humans. The field has taken another major step forward in the past year: transplanting gene-edited pig organs, including the heart and kidney, into humans. While extensive clinical testing is needed before xenotransplantation becomes a reality, that future now seems within reach. I NSTI TUTE Accessible version 2 05 May 2022 I NSTI TUTE Cell therapies to conquer common forms of blindness The eye has been a proving ground for pioneering gene therapies and is also fueling new cell-based therapies than can restore sight, offering a functional cure by replacing critical cells that have been lost or injured. One approach involves stem cells from the retina that can give rise to light-sensitive cells, called photoreceptors, which are required for healthy vision. Scientists are harnessing retinal stem cells to develop treatments for incurable eye diseases, including retinitis pigmentosa. Because the immune system doesn’t patrol the eye as aggressively as other parts of the body, retinal stem cells from unrelated, healthy donors can be transplanted into patients with vision disorders. Other progress includes cell therapies that harness patients’ own cells, for example, from blood or skin, that can be converted into almost any cell type in the body, including retinal cells. Another novel treatment being tested utilizes stem cells from a patient’s healthy eye to repair the affected cornea of the other eye. Harnessing the power of RNA to treat brain cancer RNA is widely known for its helper functions, carrying messages from one part of a cell to another to make proteins. But scientists now recognize that RNA plays a more central role in biology and are tapping its hidden potential to create potent new therapies for a range of diseases, including a devastating form of brain cancer called glioblastoma. This cancer is extremely challenging to treat and highly adaptable. New approaches that either target RNA or mimic its activity could hold promise, including an intriguing class of RNA molecules called microRNAs. One team identified a trio of microRNAs that plays important roles in healthy neurons but is lost when brain cancer develops. These microRNAs can be stitched together into a single unit and delivered into the brain using a virus. Initial studies in mice reveal that this therapeutic can render tumors more vulnerable to existing treatments, including chemotherapy. Another team is also exploring a microRNA called miR-10b. Blocking its activity causes tumor cells to die. Now, scientists are working to develop a targeted therapeutic against miR-10b that can be tested in clinical trials. Realizing the promise of gene therapy for brain disorders Gene therapy holds enormous promise for serious and currently untreatable diseases, including those of the brain and central nervous system. But some big obstacles remain. For example, a commonly-used vehicle for gene therapy — a virus called AAV — cannot penetrate a major biological roadblock, the blood-brain barrier. Now, researchers are engineering new versions of AAV that can cross the blood-brain barrier. Using various molecular strategies, a handful of teams have modified the protein shell that surrounds the virus so it can gain entry and become broadly distributed within the brain. These modified viral vectors are now under development and could begin clinical testing within a few years. Scientists are also tinkering with the inner machinery of AAV to sidestep potential toxicities. With a safe, effective method for accessing the brain, researchers will be able to devise gene therapies for a range of neurological conditions, including neurodegenerative diseases, cancers, and devastating rare diseases that lack any treatment. A flexible, programmable approach to fighting viruses The COVID-19 pandemic has laid bare the tremendous need for rapidly deployable therapies to counteract emerging viruses. Scientists are now developing a novel form of anti-viral therapy that can be programmed to target a range of different viruses — from well-known human pathogens, such as hepatitis C, to those less familiar, such as the novel coronavirus SARS-CoV-2. This new approach harnesses a popular family of gene editing tools, known as CRISPR-Cas. While CRISPR-based systems have gained attention for their capacity to modify human genes, their original purpose in nature was to defend bacteria from viral infections. As a throwback to these early roots, scientists are now adapting CRISPR tools to tackle a variety of viruses that infect humans. Researchers are studying the potential of these programmable anti-viral agents in the context of several different viruses, including ones that pose significant threats to global health, such as SARS-CoV-2, hepatitis C, and HIV. On the move: Cell therapies to restore gut motility The human digestive tract — or “gut” — has its own nervous system. This second brain, known as the enteric nervous system, is comprised of neurons and support cells that carry out critical tasks, like moving food through the gut. When enteric neurons are missing or injured, gut motility can be impaired. Now, scientists are developing an innovative cell replacement therapy to treat diseases of gut motility. Donor cells can be isolated from a patient’s own gut or from a more readily available source, such as subcutaneous fat. These cells are then cultivated in the laboratory and coaxed to form the progenitors that give rise to enteric neurons. Researchers are also devising “off-the-shelf” approaches, which could create a supply of donor cells that are shielded from the immune system and can therefore be transplanted universally across different patients. Early research shows that transplanted enteric neurons can also take up residence in the brain. That means these forays in cell therapy for the gut could also help pave a path toward cell therapies for the brain and spinal cord. CAR-T cell therapies take aim at autoimmune diseases CAR-T cells have emerged as powerful treatments for some forms of cancer, especially blood cancers. By harnessing the same underlying concept — rewiring patients’ own T cells to endow them with therapeutic properties — scientists are working to develop novel CAR-T therapies for a variety of autoimmune diseases. Several research teams are engineering CAR-T cells so they can seek out and destroy harmful immune cells, such as those that produce auto-antibodies — immune proteins that help coordinate the attack on the body’s own tissues. For example, one team is using CAR-T cells to destroy certain immune cells, called B cells, as a potential treatment for lupus, a serious autoimmune disease that mainly affects women. Scientists are also 05 May 2022 3 I NSTI TUTE developing CAR-T therapies that take aim at other rogue members of the immune system. These efforts could yield novel treatments for multiple sclerosis and type 1 diabetes. Regrowing cells in the inner ear to treat hearing loss In the U.S. alone, some 37 million people suffer from a hearing deficit. Currently, there are no drugs that can halt, prevent, or even reverse hearing loss. Scientists are working on a novel regenerative approach that could restore the cells in the inner ear required for normal hearing, offering hope to millions of patients who grapple with hearing loss. Healthy hearing requires specialized cells in the inner ear called hair cells, which have fine, hair-like projections. If the cells are damaged or lost, which often happens with age or after repeated exposure to loud sounds, the body cannot repair them. But researchers have discovered a potential workaround that can stimulate existing cells in the ear to proliferate and give rise to new hair cells. Scientists are now working to convert this molecular strategy, which is being studied in animal models, into a therapeutic that is safe and effective for hearing loss patients. New technologies for delivering gene therapies A formidable challenge in the field of gene therapy is delivery — getting gene-based therapeutics into the body and into the right target cells. Researchers are exploring the potential of new delivery methods that could expand the reach of gene therapy, including microneedles. When applied to the skin, a microneedle patch can penetrate the outermost layer with minimal pain and discomfort. This novel delivery method can readily access the legion of immune cells that reside in the skin — important targets for vaccines as well as for the treatment of various diseases, including cancer and autoimmune conditions. Another emerging technology involves an implantable device made of biodegradable materials. When placed inside the body, this device can provide localized, sustained release of therapeutics with few side effects. The approach is now being tested for the first time in cancer patients using standard chemotherapy drugs administered directly at tumor sites. In the future, this method could be customized for the delivery of gene therapy payloads, an advance that could revolutionize cancer treatment, particularly for difficult-to-treat forms like pancreatic cancer. Engineering cancer-killing cells that target solid tumors CAR-T cells are a revolutionary form of cell therapy that has yielded some remarkable cures of difficult-to-treat blood cancers. But the outcomes in other cancers have been lackluster. Now, scientists are enhancing this technology to enable new ways of treating solid tumors. One approach involves making CAR-T cells more like computers, relying on simple logic to decide which cells are cancer — and should be destroyed — and which cells are healthy and should be spared. By building several logic gates and combining them together, researchers are hoping to pave the way toward targeting new tumor types. Scientists are also devising other groundbreaking forms of cancer-killing cell therapy, including one that uses cancer cells themselves. This approach exploits a remarkable feature: once disseminated within the body, cancer cells can migrate back to the original tumor. Researchers are now harnessing this rehoming capability and, with the help of gene editing, turning tumor cells into potent cancer killers. An early version of this technology uses patients’ own cells. Now, the scientists are developing an off-the-shelf version that can be universally applied to patients. Reawakening the X-chromosome: a therapeutic strategy for devastating neurodevelopmental diseases The X chromosome is one of two sex-determining chromosomes in humans, and it carries hundreds of disease-causing genes. These diseases often affect males and females differently. In females, one X chromosome is naturally, and randomly, chosen and rendered inactive. Although X-inactivation was once thought to be permanent, scientists are uncovering ways to reverse it. Scientists are now exploiting this unusual biology to reawaken the dormant X chromosome — a strategy that could yield muchneeded treatments for a group of rare, yet devastating neurodevelopmental disorders, which predominantly affect females. This new approach could hold promise for females with Rett syndrome, a severe X-linked disorder. A similar strategy could also hold promise for other serious X-linked disorders, including fragile X syndrome and CDKL5 syndrome.
Other related articles published in this Open Access Online Scientific Journal include the following:
UPDATED on 5/7/2022
Tweets at #WMIF2022 by @pharma_BI & @AVIVA1950 and All Retweets of these Tweets – 2022 World Medical Innovation Forum, GENE & CELL THERAPY • MAY 2–4, 2022 • BOSTON
2022 World Medical Innovation Forum, GENE & CELL THERAPY • MAY 2–4, 2022 • BOSTON • IN-PERSON
Reporter: Aviva Lev-Ari, PhD, RN
World Medical Innovation Forum as we bring together global leaders to assess the latest opportunities and challenges, from the investment landscape to key technology developments to manufacturing and regulatory barriers. Gain first-hand insights on medicine’s ultimate game changer.
World Medical Innovation Forum will be held June 12 – 14 in Boston, MA. We hope you’ll join us for #WMIF2023!
From: “Rieck, Lucy (BOS-WSW)” <LRieck@webershandwick.com> Date: Tuesday, April 12, 2022 at 10:25 AM To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu> Subject: You’re Invited: Mass General Brigham’s World Medical Innovation Forum
Hi Aviva,
I’m reaching out to extend free registration for you or a colleague to the 8th annual World Medical Innovation Forum (WMIF), taking place May 2-4 at the Westin Copley Place in Boston. This year’s event, co-sponsored with Bank of America, will explore gene and cell therapies (GCT), including the latest opportunities and challenges – from the investment landscape to key technology developments to manufacturing and regulatory barriers.
The event will feature 200 speakers – including CEOs of leading companies in the GCT and biotech fields, investors, entrepreneurs, Harvard clinicians and scientists, government officials and other key influencers – who discover, invest in, and cultivate GCT breakthroughs. Notable speakers include:
Peter Marks: Director, Center for Biologics Evaluation and Research at the FDA
Brian Moynihan: CEO, Bank of America
Anne Klibansky: President & CEO, Mass General Brigham
Senior executives from biopharma and academic institutions of all sizes (including Novartis, BMS, Takeda, Verve, UPenn)
You can view the full list of speakers here and the program agenda here.
WMIF is hosted by the Mass General Brigham health system, which comprises 14 hospitals, including two world-renowned medical centers: Mass General and Brigham & Women’s. Since 2015, the Forum has brought together global leaders to assess medical breakthroughs, the investment landscape and technology developments that have the potential to transform the industry.
In addition to a packed agenda, the 2022 “Disruptive Dozen” – 12 breakthrough technologies most likely to have significant impact on gene and cell therapy in the next 18 months – will also be announced.
Please let me know if you would be interested in attending.
Understanding long-term Gene and Cell Therapy investment complexities requires a keen awareness of where the science and the markets are headed. That’s why “The Doctor is In” in these updates on the latest GCT technologies. Presented by Mass General Brigham clinicians and innovators from the front lines of care, the sessions are co-hosted by expert analysts from Bank of America and include interactive discussion and Q&A.
In this session, Dr. Eichler will discuss the impact of gene defects across the lifespan and how timing and delivery of new genetic therapies is transforming the field of neurogenetics.
In this session, hear from experts in their field as they discuss the need and importance of regenerative medicine for the advancement in the treatment of diseases such as diabetes, kidney disease and blood disorders.
In this session, Dr. Artzi will share how an integrative approach of combining materials science, chemistry, imaging, and biology enables targeted delivery of gene therapy.
In this session, Drs. Robert Green and Adam Shaywitz will discuss how the early detection and prevention of rare diseases is imminent and represents an enormous public health opportunity.
In this session, Dr. Poznansky will share how research and development of vaccines and immunotherapy are safely accelerated from research lab to the patient leveraging novel mechanisms.
This panel features industry leaders who will discuss what the future may hold for gene and cell therapy. Which applications are likely to have the greatest impact? What are the key hurdles to be overcome? What specific platforms and technologies may enable optimal solutions? In what disease areas? Learn more about these and other questions as the panelists discuss the future potential of GCT.
Manufacturing quality and cost are critical for enabling rapid growth in GCT. Panelists will explore a variety of critical questions in this space. For example, are there historic parallels that can be drawn between GCT manufacturing and other groundbreaking technologies? How do key manufacturing concerns in GCT differ from those for more conventional pharmaceutical? What are the long-term opportunities for non-viral vectors? Will manufacturing capacity be a limiting factor in GCT growth over the next 5 to 10 years?
At the end of 2021, roughly 410 novel drugs had been approved in the past decade. On average, there were 40 approvals per year with over 150 of them being between 2018 and 2020. What has changed in the approval process and what is the vision of the future state? What will happen over the next 1–3 years? What does the new iteration of the Prescription Drug User Fees Act (PDUFA) need to do in this area and which fields show the greatest potential for innovation in CGT?
This panel will delve into clinical trials for GCT. How do these trials differ from those for conventional therapeutics? What are the key lessons learned from completed GCT trials? How is the regulatory landscape shifting and what will that mean for the future of GCT?
Dr. Bourla will share what Pfizer has learned from its leadership on mRNA and the development of the Covid vaccine that can be extrapolated to other R&D.
As we enter the third year of the coronavirus pandemic, the world is shifting to a new strategy: living with and managing COVID as a part of our everyday lives. What will the coming year look like? How will mitigation measures differ in this new phase? What about treatment strategies? Should we be bracing for another surge?
This panel will feature a discussion of global biotech clusters with a deep dive into the New England/Boston area. How does the capital availability, scale, and density of New England drive local growth in GCT? Also, the influx of large biopharmaceutical companies into the region has fueled global outcomes. What is the future impact of these investments and when will they peak? How will the biopharmaceutical landscape in New England appear in 2030?
The role of patients and their experiences are critical as the promise of GCT unfolds. This panel will discuss the patient experience and explore the challenges different patient populations face, both in rare diseases and more common conditions. Panelists will also discuss financial considerations, clinical trial access, and the role of advocacy groups in GCT.
As many countries begin to turn the corner on COVID-19, they face a resurgence of chronic illnesses, such as cancer and cardiovascular disease, that were not adequately addressed during the pandemic, and for which new treatments are urgently needed. Population aging – and the resulting increase in chronic diseases associated with aging – has compounded the challenge. There’s never been a greater need for biopharmaceutical innovation – or, fortunately, a greater ability to innovate. Amgen is investing in new discovery research capabilities that portend a revolution in drug design and development.
Understanding long-term Gene and Cell Therapy investment complexities requires a keen awareness of where the science and the markets are headed. That’s why “The Doctor is In” in these updates on the latest GCT technologies. Presented by Mass General Brigham clinicians and innovators from the front lines of care, the sessions are co-hosted by expert analysts from Bank of America and include interactive discussion and Q&A.
In this session, Dr. Vavvas will discuss examples of clinical trials in rare diseases and share insights into how clinical trials should be approached for rare and ultra-rare diseases and how study design is not a one-size fits all.
In this session, hear experts weigh in on the possibilities of cell therapy development and transplantation for the treatment of Parkinson’s Disease. What does the futures hold and how do we get there?
In this session, Dr. Nikiforow will provide insights into the world of gene therapy manufacturing and the complexities of scaling, costs and insurance reimbursement.
In this session, Dr. Marks will discuss the ins and outs of regulatory challenges for biological products and therapies in gene and cell therapy and the responsibility to assure safety and effectiveness.
Dark genome, accounting for ~98.5% of the human genome and containing the non-coding part, offers unprecedented opportunity to look for novel elements that could play a role in human health. This non-coding region consists of repeat elements, enhancers, regulatory sequences and non-coding RNAs. This session will explore this exciting new frontier in biology and how to translate this so called “junk” and previously ignored genome into potential novel therapeutics.
Panelists will discuss the life sciences capital markets environment with particular emphasis on private and public fundraising for GCT companies. What trends do panelists observe that will impact the availability and cost of capital for GCT? Are there novel fundraising structures that will serve GCT in the future?
As one of the foremost researchers of CAR-T cancer treatments, Dr. June will share what he believes is the next wave of cell-and-gene based oncology research and how his work set the stage for breakthrough developments in cancer.
Richard W. Vague Professor in Immunotherapy, Director, Center for Cellular Immunotherapies, Director, Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine
This panel will examine the role of academia in driving the promise of GCT. How does academic innovation contribute to the success of GCT? What are the risks and opportunities? Which models have proven most successful and what is the impact on clinical translation? How can these partnerships be accelerated?
Richard W. Vague Professor in Immunotherapy, Director, Center for Cellular Immunotherapies, Director, Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine
This panel will bring together gene and cell therapy leaders from across the world to discuss the latest opportunities and challenges in the field, from the investment landscape to key technology developments to manufacturing and regulatory barriers. These global experts will offer first-hand insights on the systemic complexity of this advancing field and its therapeutic promise.
Chronic inflammation in the brain is now recognized as a contributor to many neurodegenerative diseases, ranging from Parkinson’s disease to multiple sclerosis to Alzheimer’s disease. Are solutions to these historically intractable neurological diseases imminent or several years away? Are market-making platforms identifiable for neurological diseases? Are there novel genetic targets that can be explored? What are the prospects for cell therapies?
Cell therapies, ranging from CAR-T cells to stem-cell-based approaches, are emerging as a transformative therapeutic modality. Panelists will examine this emerging landscape and discuss a range of key topics. What drives differentiation in this space given the high number of competing technologies? How will the uptake of autologous cell therapies and allogeneic versions evolve? When will the regenerative medicine market mature?
This panel will explore how GCT technology could lead to disruptions in other areas of medicine, including surgery and medical devices, over the next several years. Could cell replacement therapy in diabetes advance enough to reduce the need for diabetes pumps or insulin? Will stem-cell-based methods for regenerating cartilage advance rapidly enough to disrupt the number of patients seeking hip and knee replacements? How is GCT driving innovations in surgical techniques?
What is the new generation of approaches to gene therapy manufacturing and delivery? What are the lessons learned from Covid and how can it be applied to custom disease response and the ability to custom design biologic organisms?
This panel will feature an in-depth discussion of the safety of gene and cell therapies. What are the unique safety concerns in this field, both acute and potential long-term risks? Which of these concerns are supported by clinical data versus the presumption of theoretical risk? What are the key issues for AAV-based gene therapies? Will redosing become feasible? What are the predominant safety concerns for in vivo versus ex vivo GCT modalities, including base editing?
The label “RNA” encompasses a wide array of biologically active agents spanning therapeutic modalities, vaccines, non-coding controls, and other forms. In this panel we will discuss a number of these forms, discuss examples of recent developments and illustrate why RNA developments represent a promising source of novel therapies and therapeutic approaches.
The Disruptive Dozen identifies and ranks the GCT technologies that Mass General Brigham faculty feel will break through over the next one to five years to significantly improve health care.
The recent publication in Nature Medicine on genetic risk prediction in pre-implementation embryos(1) has already engendered heated discussion.(2,3) Kumar et al.(1) advocate the integration of polygenic risk scores (PRS) derived from pre-implantation genetic testing (PGT) with standard monogenic prediction. The paper focuses primarily on BRCA1 (and breast cancer) and APC (and colon cancer). Genetic tests for inherited disorders such as Tay-Sachs disease and breast cancers caused by BRCA1 and BRCA2 have been approved, but these are potentially devastating conditions with relatively simple inheritance; in most counseling situations the risks are straightforward to calculate.
The limitation on the amount and quality of DNA available from early embryo biopsies has made it difficult to produce genomic profiles of embryos in the IVF situation. Kumar et al. genotyped more than one-hundred embryos at hundreds of thousands of nucleotide sites and combined these genotype data with whole genome sequences of the prospective parents to produce reconstructed embryo genomes. These genomes were compared with those of ten born siblings and polygenic risk scores (PRS) were calculated for twelve conditions related to diseases. The PRS were claimed to be 97–99 percent accurate.
The primary market for this procedure would be couples seeking IVF, and Kumar and his colleagues, most of whom are employees of biotech companies, show that it is feasible to calculate a PRS for an embryo. The authors do present several caveats for the use of their procedure for PGT. For example, if a couple has a family history of a disease, they “may unintentionally prioritize” a mutant embryo for PGT-based only on PRS. They also acknowledge that results from research cohorts may not generalize to sibling embryos in IVF, which could limit the clinical utility of their approach. Kumar et al. also acknowledge the “portability” problem, namely PRSs have limited predictive accuracy in people with non-European ancestry(2,3) or of different ages or socioeconomic status.(4,5) They also mention the issue of unequal access to IVF technology in general.(2)
It is also important, However, to stress the limited predictive utility of PRS for common traits, not only diseases. There is increasing use of PRS among social scientists for characteristics such as years of education, which have heritabilities in the 10–15 percent range. Such studies, and potentially this one by Kumar et al., can lead to reduced emphasis on environmental and social associations with diseases or other traits. For omnigenic traits, such as height or body mass index (BMI), that have hundreds or thousands of associated nucleotide polymorphisms, and high heritability, the public might receive the mistaken impression that PGT or other genomic interventions can allow parents to choose their offspring’s phenotype.
For example, a recent study(6) of BMI in 881 subjects from Quebec found that PRS could explain only between 1.2 percent and 7.5 percent of the variance in BMI of these participants. Even when PRSs are statistically significant, their predictive value is too weak to be applied. The use of polygenic risk scores to select embryos, abbreviated ESPS for embryo selection based on polygenic scores, has been criticized before.(7) One of the important points raised by Turley et al.(7) concerns the environmental context of the children of IVG customers, which may be quite different from that of the sample of people from which the PRS was calculated. Because of gene-environment interactions, the predictive power of PRS for any complex trait is limited. As pointed out by Turley et al. (p. 79), “the predictive power of a polygenic score is maximized when the person is from the same environment as the research participants from whom the polygenic scores were derived. But this will never be the case in ESPS.”
PGT and ESPS raise ethical issues beyond IVG that more generally concern designer babies.(7,8) PRSs have been calculated for non-disease related traits such as educational attainment, income, or IQ, and it is conceivable that some prospective parents might regard these as important enough for intervention. There are also traits related to social constructs of race including skin pigmentation or facial features, and parental choice based on these phenotypes could enhance racial prejudices.
References
Kumar, A., K. Im, M. Banjevic, P.C. Ng, T. Tunstall, G. Garcia, L. Galhardo, J. Sun,O.N. Schaedel, B. Levy, D. Hongo, D. Kijacic, M. Kiehl, N.D. Tran, P.C. Klatsky, and M. Rabinowitz. 2022. Whole-genome risk prediction of common diseases in human preimplantation embryos. Nature Medicine28: 514–516. doi: 10.1038/s41591-022-01735-0.
Nature editorial. 2022. The alarming rise of complex genetic testing in human embryo testing. Nature603: 549–550. doi: 10.1038/d41586-022-00787-z.
Rosenberg, N., M. Edge, J. Pritchard, and M. Feldman. 2019. Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences. Evol. Med. Public Health 2019: 26–34. doi: 10.1093/emph/eoy036.
Duncan, L.E., H. Shen, B. Gelaye, J. Meijsen, K.J. Ressler, M.W. Feldman, R.E. Peterson, and B.W. Domingue. 2019. Analysis of polygenic score usage and performance in diverse human populations. Nat. Comm. 10: 3328. doi: 10.1038/s41467-019-11112-0.
De Toro-Martin, J.E., F. Guenard, C. Bouchard, A. Tremblay, L. Perusse, and M.-C. Vohl. 2019. The challenge of stratifying obesity: attempts in the Quebec family study. Front. Genet. 10:994. doi: 10.3389/fgene.2019.00994.
Turley, P., M.N. Meyer, N. Wang, D. Cesarini, E. Hammonds, A.R. Martin, B.M. Neale, H.L. Rehm, L. Wilkins-Haug, D.J. Benjamin, S. Hyman, D. Laibson, and P.M. Visscher. 2021. Problems with using polygenic scores to select embryos. N. Engl. J. Med385(1): 78–86.
Forzano, F., O. Antonova, A. Clarke, G. de Wert, S. Hentze, Y. Jamshidi, Y. Moreau, M. Perola, I. Prokopenko, A. Read, A. Reymond, V. Stefansdottir, C. van El, and M. Genuardi. 2021. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. European Journal of Human Genetics. doi: 10.1038/s41431-021-01000-x.
There has been much opinion, either as commentary in literature, meeting proceedings, or communiques from professional societies warning that this type of “high-impact” genetic information should not be given directly to the consumer as consumers will not fully understand the information presented to them, be unable to make proper risk-based decisions, results could cause panic and inappropriate action such as prophylactic oophorectomy or unwarranted risk-reduction mastectomy, or false reassurance in case of negative result and reduced future cancer screening measures taken by the consumer. However, there have been few studies to investigate these concerns.
The article by Kumar The alarming rise of complex genetic testing in human embryo selection
discusses the common trend of DTC (direct to consumer) and other genetic consutancy groups to offer disease risk assesment based on genetic predispostion genetic information in preimplantation embryos upon in vitro fertilization. Although this editorial discusses some caveats and potential ethical issues the opinion of this reviewer feels a certain number of key issues points have not been addressed (which will be discussed below) including:
the underlying risk of disclosure of all parties involved in decision making based on genetic testing including other family members
complicating ethical issues not addressed through proper guideline establishment and regulation as seen in countries that allow such advances to go without proper review board
a lack of discussion of the health disparities which may result of this type of genetic information or “selection” where groups of people would be shut out of such services due to socioeconomic status
Although the editorial highlights the issue that most genome wide association studies, on which most of the genetic counseling is based upon is from cohorts of European descent (and misses a large cohort which is Asian or African descent), there is little attention given to the issue that most panels of these agreed upon risk associated variants have not been validated in larger GWAS studies or that these panels only focus on the most common variants. An example of this would be BRCA1/2 and assumed future breast cancer risk.
PGS and PGT-A diagnoses have been built on biologically incorrect assumptions and on unvalidated guidelines dating back to 2016. These guidelines, which remain influential to this day, were published without a description of methods, without peer review, with no author identification, and without any references1 . The guidelines changed the binary diagnosis of euploid and aneuploid to normal, mosaic and aneuploid.
In fact most family risk assesment programs are more effective upon counseling of young women, not at the embryonic stage where genetic risk factors may not be evident or resulting from epigenetic changes or accumulated somatic mutation.
Lack of communication to all related and involved parties
Many times it is women, who having undergone these testings, have problems in communicating these risk findings to their children and family members, resulting in familial strains.
For instance, some women who discover they have the BRCA gene mutation, which puts them at higher risk for breast cancer, choose to tell their children about it before the children are old enough to understand the significance or deal with it, a new study found.
“Parents with the BRCA mutation are discussing their genetic test results with their offspring often many years before the offspring would need to do anything,” said study author Dr. Angela Bradbury, director of the Fox Chase Cancer Center’s Family Risk Assessment Program, in Philadelphia.
According to Bradbury, more than half of parents she surveyed told their children about genetic test results. Some parents reported that their children didn’t seem to understand the significance of the information, and some had initial negative reactions to the news.
“A lot of genetic information is being shared within families and there hasn’t been a lot of guidance from health-care professionals,” Bradbury said. “While this genetic risk may be shared accurately, there is risk of inaccurate sharing.”
In the study, Bradbury’s team interviewed 42 women who had the BRCA mutation. The researchers found that 55 percent of parents discussed the finding and the risk of breast cancer with at least one of their children who was under 25.
Also, most of the women didn’t avail themselves of the services of a doctor or genetic counselor in helping to tell their children, Bradbury’s group found.
The identification of familial risk factors can have very stressful impacts on the affected and their family however an IVF selection might even augment that familial stress. More research is needed on the psychological impact of such testing and a patient’s choice.
2. Lack of health disparity considerations in IVF selection research or guidelines
Another major concern, which has been highlighted in multiple articles on this site, is the growing health disparities between those who can obtain access to quality health care and those who are left out in the void of the medical system, either for economic or sociological reasons. This has been very apparent in the cancer treatment and personalized medicine world (for example the disparities of health care access for cancer treatment in the southern poorer rural parts of the US versus metropolitan areas and the gaping disparities seen between rich and poor countries in Africa). These health disparities have been also apparant in the genetic testing market, and although the DTC market meant to make genetic testing more affordable, interestingly these disparities still exist in this niche market.
3. Lack of proper establishment of Institutional Review Board oversight in countries allowing this technique have been problematic with regard to addressing bioethical concerns
The third concern is, of course, a bioethical concern on the use of advanced genetic technologies in the human and clinical setting. It has come to many people’s attention at the speed at which countries that do not seem to have strong bioethical review boards readily allow this type of research to be carried out without regulatory oversight or consequence. A prime example of this included the shunned Chinese research carried out to produce cloned humans, which was rapidly condemmed in the biomedical world however this research was conducted nonetheless. This lack of attention is addressed in Kumar’s article yet little guidance is given as to best practices to establish review boards overseeing such work and or research.
Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants. We found two coexpressed modules that were associated with transcriptional changes in BD: one enriched for immune and inflammatory genes and the other with genes related to the postsynaptic membrane. Over 50% of BD genome-wide significant loci contained significant expression quantitative trait loci (QTL) (eQTL), and these data converged on several individual genes, including SCN2A and GRIN2A. Thus, these data implicate specific genes and pathways that may contribute to the pathology of BP.
Gene Expression Markers for Bipolar Disorder Pinpointed
The work was led by researchers at Johns Hopkins’ Lieber Institute for Brain Development. The findings, published this week in Nature Neuroscience, represent the first time that researchers have been able to apply large-scale genetic research to brain samples from hundreds of patients with bipolar disorder (BD). They used 511 total samples from 295 unique donors.
“This is the first deep dive into the molecular biology of the brain in people who died with bipolar disorder—studying actual genes, not urine, blood or skin samples,” said Thomas Hyde of the Lieber Institute and a lead author of the paper. “If we can figure out the mechanisms behind BD, if we can figure out what’s wrong in the brain, then we can begin to develop new targeted treatments of what has long been a mysterious condition.”
Bipolar disorder is characterized by extreme mood swings, with episodes of mania alternating with episodes of depression. It usually emerges in people in their 20s and 30s and remains with them for life. This condition affects approximately 2.8% of the adult American population, or about 7 million people. Patients face higher rates of suicide, poorer quality of life, and lower productivity than the general population. Some estimates put the annual cost of the condition in the U.S. alone at $219.1 billion.
While drugs can be useful in treating BD, many patients find they have bothersome side effects, and for some patients, current medications don’t work at all.
In this study, researchers measured levels of messenger RNA in the brain samples. They observed almost eight times more differentially expressed gene features in the sACC versus the amygdala, suggesting that the sACC may play an especially prominent role—both in mood regulation in general and BD specifically.
In patients who died with BD, the researchers found abnormalities in two families of genes: one containing genes related to the synapse and the second related to immune and inflammatory function.
“There finally is a study using modern technology and our current understanding of genetics to uncover how the brain is doing,” Hyde said. “We know that BD tends to run in families, and there is strong evidence that there are inherited genetic abnormalities that put an individual at risk for bipolar disorder. Unlike diseases such as sickle-cell anemia, bipolar disorder does not result from a single genetic abnormality. Rather, most patients have inherited a group of variants spread across a number of genes.”
“Bipolar disorder, also known as manic-depressive disorder, is a highly damaging and paradoxical condition,” said Daniel R. Weinberger, chief executive and director of the Lieber Institute and a co-author of the study. “It can make people very productive so they can lead countries and companies, but it can also hurl them into the meat grinder of dysfunction and depression. Patients with BD may live on two hours of sleep a night, saving the world with their abundance of energy, and then become so self-destructive that they spend their family’s fortune in a week and lose all friends as they spiral downward. Bipolar disorder also has some shared genetic links to other psychiatric disorders, such as schizophrenia, and is implicated in overuse of drugs and alcohol.”
Tweets and Re-Tweets of Tweets by @pharma_BI@AVIVA1950 at 2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021
REAL TIME EVENT COVERAGE as PRESS by invitation from 2021 Virtual World Medical Innovation Forumat #WMIF2021 @MGBInnovation:
for sharing this screen capture of the impressive lineup of #GCT “Disruptive Dozen” panelists at #WMIF2021
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Aviva Lev-Ari
@AVIVA1950
· May 21
@MGBInnovation #WMIF Best Global event on Gene Cell Therapy covered in real time @AVIVA1950 @pharma_BI Disruptive Dozen technologies four are based on Gene Editing, AAV and non viral vector for drug delivery are included
PART 1: ALL THE TWEETS PRODUCED by @AVIVA1950 on May 21, 2021
Bob Carter, MD, PhD Chairman, Department of Neurosurgery, MGH William and Elizabeth Sweet, Professor of Neurosurgery, HMS Neurogeneration REVERSAL or slowing down?
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
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
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
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
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
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
Nabiha Saklayen, PhD CEO and Co-Founder, Cellino scale production of autologous cells foundry using semiconductor process in building cassettes by optic physicists
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
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
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
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
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
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
The # of US patients with Parkinson’s Disease is expected to double over next 30 years. Penelope Hallett PhD, Co-Director of the Neuroregeneration Research Inst
Marcela Maus, MD PhD, are working to expand the reach of this transformative technology. #WMIF2021
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Mass General Brigham Innovation
@MGBInnovation
· 3h
Disruptive Dozen: 12 Technologies that Will Reinvent GCT #9. Building the Next Wave of CAR-T-cell Therapies #WMIF2021 #GCT #GeneAndCellTherapy #CellTherapy #CarT #DisruptiveDozen
and global colleagues at #WMIF2021. On Thursday, May 20, my colleagues and I will discuss the advantages of RNA-targeted medicines and how they might shape the future of medicine for patients.
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Mass General Brigham Innovation
@MGBInnovation
· May 10
Are you part of the @MassGenBrigham network and interested in #GeneAndCellTherapy? Join us at the World Medical Innovation Forum on 5/19-5/21. Register today! https://worldmedicalinnovation.org/register/ #WMIF2021
Incredible opportunity to get up to speed with the most innovative technologies in medicine ! Gene and cell therapy are revolutionizing healthcare ! #WMIF2021#MedTwitter
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Mass General Brigham Innovation
@MGBInnovation
· May 11
#WMIF2021 is an opportunity for innovators from around the globe to meet, explore, challenge, and reflect on the issues influencing the adoption of novel technologies in #healthcare. Register now to join the conversation: https://worldmedicalinnovation.org/register/
Currently, the only cure for some common blood disorders is a bone marrow transplant, which can be risky. Now, gene therapies are also in the works, including a CRISPR-based #genetherapy being tested in clinical trials with encouraging early results. #WMIF2021
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Mass General Brigham Innovation
@MGBInnovation
· 3h
Disruptive Dozen: 12 Technologies that Will Reinvent GCT #2. A Genetic Fix for Two Common Blood Disorders #WMIF2021 #GCT #GeneAndCellTherapy #BloodDisorders #DisruptiveDozen
Researchers have pinpointed key genes involved in cholesterol and lipid metabolism that represent promising targets for new cholesterol-lowering treatments. #WMIF2021
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Mass General Brigham Innovation
@MGBInnovation
· 3h
Disruptive Dozen: 12 Technologies that Will Reinvent GCT #1. A New Generation of Cholesterol-Loweing Therapies #WMIF2021 #GCT #GeneAndCellTherapy #DisruptiveDozen
I really enjoyed this remarkable panel #WMIF2021. Thank you Meredith Fisher for moderating and thank you David, Bob and Kush for openly sharing your big picture view
Variability, delays, manufacturing as an afterthought make #GCT challenging from an investment POV — need to rethink the ecosystem and drive efficiency, invest in tech innovation says Bob Nelson ARCH Venture Partners
We need to change the scale and scope of how #GCT is advancing from discovery to development — systematization critical. Can’t have thousands of one-off therapies say early-stage investors. Major mis-match between where things are now and what could be.
Today I moderated a panel on Gene and Cell Therapy Delivery, Perfecting the Technology. We highlighted non-viral delivery technologies as key enablers of gene therapy and editing. Learn more: https://lnkd.in/d-Xqzqh#WMIF2021
Congratulations to the 2021 Innovation Discovery Grants winners: @lynchielydia, Peter Sage, @GrishchukL, Benjamin Kleinstiver, Petr Baranov, announced at the #WMIF2021. It’s exciting to see the range of breakthrough research in #geneticdisease at @MassGenBrigham…
for sharing this screen capture of the impressive lineup of #GCT “Disruptive Dozen” panelists at #WMIF2021
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Aviva Lev-Ari
@AVIVA1950
· May 21
@MGBInnovation #WMIF Best Global event on Gene Cell Therapy covered in real time @AVIVA1950 @pharma_BI Disruptive Dozen technologies four are based on Gene Editing, AAV and non viral vector for drug delivery are included
PART 1: ALL THE TWEETS PRODUCED by @AVIVA1950 on May 20, 2021
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
Jeannie Lee, MD, PhD Molecular Biologist, MGH Prof Genetics, HMS 200 disease X chromosome unlock for neurological genetic diseases: Rett Syndrome, autism spectrum disorders female model vs male mice model restore own protein
Suneet Varma Global President of Rare Disease, Pfizer review of protocols and CGT for Hemophilia Pfizer: You can’t buy Time With MIT Pfizer is developing a model for Hemophilia CGT treatment
Gallia Levy, MD, PhD CMO, Spark Therapeutics Hemophilia CGT is the highest potential for Global access logistics in underdev countries working with NGOs practicality of the Tx Roche reached 120 Counties great to be part of the Roche
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
Suneet Varma Global President of Rare Disease, Pfizer Gene therapy at Pfizer small, large molecule and CGT – spectrum of choice allowing Hemophilia patients to marry 1/3 internal 1/3 partnership 1/3 acquisitions review of protocols
Ron Renaud CEO, Translate Bio What strain of Flu vaccine will come back in the future when people do not use masks. AAV vectors small transcript size fit reach cytoplasm more development coming
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
Lindsey Baden, MD Director, Clinical Research, Division of Infectious Diseases, BWH Associate Professor, HMS In vivo delivery process regulatory for new opportunities for same platform new indication using multi valence vaccines
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
Ron Renaud CEO, Translate Bio 1.6 Billion doses produced rare disease monogenic correct mRNA like CF multiple mutation infection disease and oncology applications
Melissa Moore CSO, Moderna mRNA vaccine 98% efficacy for Pfizer and Moderna more then 10 years 2015 mRNA was ready (ZIKA, RSV), as the proteine is identify manufacturing temp less of downside in the future ability to store at Ref
Richard Wang, PhD CEO, Fosun Kite Biotechnology Co. Ltd Possibilities to be creative and capitalize the new technologies for new drug Support of the ecosystem by funding new companies Autologous in patients differences cost challenge
Tian Xu, PhD Vice President, Westlake University ICH Chinese FDA -r regulation similar to the US Difference is the population recruitment, in China patients are active participants Dev of transposome non-viral methods, price
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
We’re excited to attend this week’s #WMIF2021 to talk all things cell and genetic therapies. Join our Chief of VCGT Bastiano Sanna tomorrow at 9:50am EDT for a discussion on the promise of cell therapies for type 1 diabetes. Register now! https://bit.ly/3otngYd
John Fish, Board Chair, Brigham Health, Chairman & CEO, Suffolk on the Novartis Main Stage to introduce the “Collaboration is Key: GCT R&D of the Future” fireside chat with Jay Bradner, MD, President, NIBR
Thomas VanCott, PhD, Chief Technology & Strategy Officer, Catalent Cell & Gene Therapy, says that time, improvements and scaling up in manufacturing will lead to allogeneic cell therapies. He recognizes that upfront costs are high, but will decrease in the long term #WMIF2021
Today Lisa Michaels, Editas CMO, will participate in the panel “Gene Editing – Achieving Therapeutic Mainstream” at the World Medical Innovation Forum #WMIF2021 in Boston. For those attending, be sure to tune in!
, views GCT as the ultimate precision medicine. AI, machine learning, and data science comprise one of the big disruptive forces that will address misdiagnosis, smooth out workflow, reduce cost and enhance recovery. #WMIF2021
CSO Laura Sepp-Lorenzino, PhD, in our “GCT Delivery | Perfecting the Technology” panel this afternoon! #WMIF2021
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Intellia Therapeutics
@intelliatweets
· 6h
Today, Intellia CSO, @LauraSeppLore will be participating in the World Medical Innovation Forum’s panel on Gene and Cell Therapy Delivery, Perfecting the Technology. #WMIF2021 @MGBInnovation. Click here to learn more: https://worldmedicalinnovation.org
is back with us this afternoon sharing a First Look at “Versatile Polymer-Based Nanocarriers for Targeted Therapy and Immunomodulation.” #WMIF2021#GCT#geneandcelltherapy
VP of Clinical Development, Manasi Jaiman, during the “Diabetes | Grand Challenge” panel today. #WMIF2021
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ViaCyte
@ViaCyte
· 8h
Join us at #WMIF2021 today! Our own Manasi Jaiman, VP, Clinical Development, will participate in the Diabetes: Grand Challenge panel to discuss regenerative medicine approaches for T1D utilizing stem-cell derived islet cell replacement therapy.
, discusses how GCT is in the embryonic phase. Bayer is ready to treat its first Parkinson’s patient, and is exploring therapeutic technologies to treat diseases with single gene defects #WMIF2021
Today Lisa Michaels, Editas CMO, will participate in the panel “Gene Editing – Achieving Therapeutic Mainstream” at the World Medical Innovation Forum #WMIF2021 in Boston. For those attending, be sure to tune in! @MassGenBrigham https://bit.ly/3hx1XTV #geneediting #biotechnology
to discuss the current state of CAR-T and its future prospects. These conversations are important for the development of potential #CART therapies. #WMIF2021
‘s #WMIF2021 — Thanks to the MGB team for facilitating a great discussion!
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Mass General Brigham Innovation
@MGBInnovation
· 7h
Overview of our #mRNA Vaccines panel today, highlighting improved manufacturing capabilities & potential for #personalizedmedicine. Thank you to Lindsey Baden @bwh_id & panelists Kate Bingham, SV Health Investors, Melissa Moore @moderna_tx and Ron Renaud @TranslateBio #WMIF2021
investigators are ready to give you an early preview of their #GCT research in the First Look sessions at #WMIF2021. Exciting opportunities to dramatically change how disease is treated!
Our “Rare and Ultra Rare Diseases | GCT Breaks Through” panelists on the role of family organizations & patient advocacy groups in moving us forward on the regulatory side – “It’s absolutely essential” #WMIF2021
Congratulations! Lydia Lynch PhD, Brigham and Women’s Hospital receives an Innovation Discovery Grant for “Generating Superior ‘Killers’ for Adoptive Cell Therapy in Cancer” at #WMIF2021.
Looking forward to the Diabetes Grand Challenge and how #GCT could help millions of people. Read about what facing this disease and how cell therapies could lessen the burden from Manasi Jaiman, MD, VP, Clinical Development
Today is Day 2 of the World Medical Innovation Forum. Which panel you are most excited to see today? Reply and let us know! #WMIF2021 https://worldmedicalinnovation.org/agenda/
Cell and gene therapies hold promising potential for rare disease, blood cancers, and viral diseases. Register for #WMIF21 to hear about our work to pioneer cutting-edge science across our pipeline to advance breakthroughs that change patients’ lives: https://on.pfizer.com/3f3CGzj
Congratulations! Peter Sage PhD, Brigham and Women’s Hospital receives an Innovation Discovery Grant for “Novel Strategies to Enhance Tfr Treatment of Autoimmunity” at #WMIF2021
Congratulations! Yulia Grishchuk PhD, Massachusetts General Hospital, receives an Innovation Discovery Grant for “AAV-Based Gene Replacement Therapy Improves Targeting and Clinical Outcomes in a Childhood CNS Disorder” at #WMIF2021
Congratulations! Jinjun Shi, PhD, Brigham and Women’s Hospital, receives an Innovation Discovery Grant for “Long-Lasting mRNA Therapy for Genetic Disorders” at #WMIF2021
Final thoughts from “Benign Blood Disorders” panelists on academic/industry collaboration — the pace of #innovation is incredibly exciting, and I think it will be even faster together. #WMIF2021
Congratulations! Benjamin Kleinstiver PhD, Massachusetts General Hospital, receives an Innovation Discovery Grant for “Towards a Permanent Genetic Cure for Spinal Muscular Atrophy” at #WMIF2021
FDA’s Peter Marks, at #WMIF2021, notes # of INDs for gene therapies was flat in 2020 vs. 2019. But the fact IND submissions didn’t decline, he said, is a sign of how strong the gene therapy field is, given pandemic’s disruption.
Melissa Moore/Moderna- one advantage of mRNA is ability to do multivalent vaccines she said. She said they are already testing multivalent covid vaccines in clinical trials & testing flu vaccines. #wmif2021
Kate Bingham/SV Health & former head of UK Vaccine Taskforce: they haven’t seen escape variants in UK yet she said. mRNA is quickest platform to address escape variants probably. Needle delivery w/ supply cold chain has been the challenge. Deploying 3 vaccines in UK #WMIF2021
, notes that the science behind gene cell therapies is converging with technological development. How therapies are brought to market is still the question, as there is no roadmap when reimagining medicine #WMIF2021
Melissa Moore/Moderna: clear advantage of mRNA vaccine is how quickly we can manufacture the vaccines. Downsides- need 2store at low temperatures & limited shelflife 4storage in refrigerator. I know that both companies [Moderna, Pfizer/BioNTech] r working 2change this #wmif2021
We’re committed to addressing the unmet needs of people living with rare genetic diseases. Our SVP, External Innovation and Strategic Alliances, Leah Bloom, discusses the promise #genetherapy holds for communities impacted by rare diseases during #WMIF2021.
Speed of vaccination is critical to prevent escape variants says Kate Bingham, SV Health Investors, UK, at #WMIF2021, exploring what’s next for the technology w panel led by Lindsey Baden MD,
for sharing this screen capture of the impressive lineup of #GCT “Disruptive Dozen” panelists at #WMIF2021
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Aviva Lev-Ari
@AVIVA1950
· May 21
@MGBInnovation #WMIF Best Global event on Gene Cell Therapy covered in real time @AVIVA1950 @pharma_BI Disruptive Dozen technologies four are based on Gene Editing, AAV and non viral vector for drug delivery are included
PART 1: ALL THE TWEETS PRODUCED by @AVIVA1950 on May 19, 2021
Thomas VanCott, PhD Global Head of Product Dev, Gene & Cell Therapy, Catalent 2/3 autologous 1/3 allogeneic CAR-T high doses scale up is not done today logistics issues centralized vs decentralized allogeneic are health donors
Ropa Pike, Director, Enterprise Science & Partnerships, Thermo FIsher Scientific Centralized biopharma industry is moving to decentralized models site specific license
Rahul Singhvi, ScD CEO and Co-Founder, National Resilience, Inc. Investment company in platforms to be shared by start ups in CGT. Production cost of allogeneic: cost of quality 30% reagents 30% cell 30% Test is very expensive
Oladapo Yeku, MD, PhD Clinical Assistant in Medicine, MGH Outstanding moderator and most gifted panel on solid tumor success window of opportunities studies
Knut Niss, PhD CTO, Mustang Bio tumor hot start in 12 month clinical trial solid tumors Combination therapy will be an experimental treatment long journey checkpoint inhibitors to be used in combination maintenance
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
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
Jay Short, PhD Chairman, CEO, Cofounder, BioAlta, Inc. Tumor type is not enough for R&D therapeutics other organs are involved in periphery difficult to penetrate solid tumors biologics activated in the tumor only, positive changes
Stefan Hendriks Global Head, Cell & Gene, Novartis Confirmation the effectiveness of CAR-T therapies, 1 year response to 5 years 26 months Patient not responding a lot to learn Patient after 8 months of chemo can be helped by CAR-T
Jeffrey Infante, MD , Oncology, Janssen R&D 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
Nino Chiocca, MD, PhD Neurosurgeon-in-Chief BWH, HMS Oncolytic therapy DID NOT WORK Pancreatic Cancer and Glioblastoma Intra-tumoral heterogeniety hinders success Oncolytic VIRUSES – “coldness” GADD-34 20,000 GBM 40,000 pancreatic
Loic Vincent, PhD Head of Oncology Drug Discovery Unit, Takeda Classification of Patients by prospective response type id UNKNOWN yet, population of patients require stratification
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 IV
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?
David Reese, MD Executive Vice President, R&D , Amgen Inter lesion injection of agent vs systemic therapeutics cold tumors immune resistant render them immune susptible Oncolytic virus is a Mono therapy addressing the unknown
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 suseptible Oncolytic virus is a Mono therapy
Robert Coffin, PhD Chief R&D 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
Ann Silk, MD Physician, Dana Farber-Brigham and Women’s Cancer Center, HMS Which person gets oncolytics virus if patient has immune supression due to other indications Safety of oncolytic virus greater than Systemic treatment
Marianne De Backer/Bayer on post M&A & company culture: They acquired AskBio & thought about how to preserve their freedom so they could continue to operate. Bayer decided to keep them independent & so they can operate at arm’s length. #wmif2021
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 @pharma_BI@AVIVA1950
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?
Debby Baron, Worldwide Business Development, Pfizer Scalability and manufacturing regulatory conversations, clinical programs safety in parallel to planning getting drug to patients
Marianne De Backer, PhD Head of Strategy, BD & Licensing, Bayer Absolute Leadership: Gene editing, gene therapy, via acquisition and alliances Operating model of the acquired company discussed acquired continue independence
Sean Nolan Board Chairman, Encoded Therapeutics & Affinia Executive Chairman Jaguar Gene Therapy Istari Oncology As acquiree multiple M&A acquirer looks at integration and cultures companies Traditional integration vs acquisition
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
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
Manny Simons, PhD CEO, Akouos 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
Mathew Pletcher, PhD SVP, Head of Gene Therapy Research and Technical Operations, Astellas Continue to explore large animal guinea pig not the mice, not primates (ethical issues) for understanding immunogenicity and immune response
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
Rick Modi CEO, Affinia Therapeutics Speed R&D Speed better gene construct get to clinic with better design vs ASAP Data sharing clinical experience patients selection, vector selection, mitigation, patient type specific
Dave Lennon, PhD President, Novartis Gene Therapies big pharma therapeutics not one drug across Tx areas: cell, gene iodine therapy collective learning infrastructure development Acquisitions growth # applications for scaling
Rick Modi CEO, Affinia Therapeutics Copy, paste EDIT from product A to B novel vectors variant of vector coder optimization choice of indication is critical exploration on larger populations Speed to R&D to better gene construct get
Louise Rodino-Klapac, PhD EVP, Chief Scientific Officer, Sarepta Therapeutics AV based platform 15 years in development 1 disease indication vs more than one indication stereotype, analytics as hurdle 1st was 10 years 2nd was 3 years
Katherine High, MD President, Therapeutics, AskBio Three drugs approved in Europe in the CGT Regulatory Infrastructure CGT drug approval – as new class of therapeutics Participants investigators, regulators, patients i.e., MDM
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 50% more staff
Peter Marks, MD, PhD Director, Center for Biologics Evaluation and Research, FDA Recover Work load for the pandemic Gene Therapies IND application remained flat Rare diseases urgency remains Guidance T-Cell therapy vs Regulation
Peter Marks, MD, PhD Director, Center for Biologics Evaluation and Research, FDA June 2020 belief that vaccine challenge manufacture scaling up FDA did not predicted the efficacy of mRNA vaccine vs other approaches expected to work
Jim Holland CEO, http://Backcountry.com Parkinson patient Constraints by regulatory on participation in clinical trial wish to take Information dissemination is critical
Patricia Musolino, MD, PhD Co-Director Pediatric Stroke and Cerebrovascular Program What is the Power of One – the impact that a patient can have on their own destiny connecting with other participants in same trial can be beneficial
Barbara Lavery Chief Program Officer, ACGT Foundation Patient has the knowledge of the symptoms and recording all input needed for diagnosis by multiple clinicians Early application for CGT
Jack Hogan Patient, MEE Constraints by regulatory on participation in #clinicaltrials advance stage is approved participation Patients to determine the level of #risk they wish to take
Barbara Lavery Chief Program Officer, ACGT Foundation Advocacy agency beginning of work Global Genes educational content and out reach to access the information
Dave Lennon, PhD President, Novartis Gene Therapies Modality one time intervention, long duration of impart, reimbursement, ecosystem FDA works by indications and risks involved, Standards manufacturing payments over time payers
Dave Lennon, PhD President, Novartis Gene Therapies Promise of CGT realized, what part? #FDA role and interaction in CGT #Manufacturing aspects which is critical
Julian Harris, MD Partner, Deerfield Hope that CGT emerging, how therapies work, #neuro, #muscular, #ocular, #genetic diseases of #liver and of #heart revolution for the industry 900 #IND application 25 approvals #Economic driver
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
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 #delivery
The field of #genetherapy is growing. New therapies will come to market for rare and chronic diseases, and new therapies will drive scientific innovation and economic growth. #WMIF2021 (2/6)
In our First Look sessions clinicians/researchers from Harvard-affiliated hospitals highlight the potential of their research & new technologies. Next we’ll hear from Khalid Shah PhD, Vice Chair of Research
Tomorrow is Day 1 of #WMIF2021! Hear from the world-renowned CEOs, investors, clinicians and scientists bringing game-changing discoveries and insights to #GCT. Register to attend today: https://worldmedicalinnovation.org/register/
‘s World Medical Innovation Forum this week, discussing the future of #genetherapy. Here are our five predictions for where the industry is headed. #WMIF2021 (1/6)
explains at #WMIF2021 why the first FDA-approved gene therapy for inherited disease was for an inherited retinal degeneration, and what lessons have been learned from the success of that treatment.
Together with @BayerPharma, we are pleased to be part of #WMIF2021, organized by @MassGenBrigham. This year’s event focuses on the transformative potential of #cellandgene therapy (#GCT).
“We are more committed to our mission than ever before – laser-focused on realizing the transformative potential of #genetherapy for patients.” – Dave Lennon, President, during #WMIF2021
Patricia Musolino, MD PhD, Co-Director Pediatric Stroke and Cerebrovascular Program at MGH, discusses her work developing #genetherapy treatments for cerebral genetic vasculopathies #GCT #geneandcelltherapy #WMIF2021
chair Dr. Joan Miller moderates a panel on AAV gene therapy featuring director of Inherited Retinal Disorders Service and Ocular Genomics Institute, Dr. Eric Pierce.
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Our “AAV Success Studies | Retinal Dystrophy | Spinal Muscular Atrophy” panelists have taken the stage. #WMIF2021 @MassEyeAndEar @REGENXBIO @spark_tx @NovartisGene
We are proud sponsors of the Virtual World Medical Innovation Forum (#WMIF2021). This year’s program will focus on the impact of gene and cell therapy as a way to potentially advance quality patient care, reduce cost and improve outcomes. Learn more:
Jonathan Kraft introducing #wmif2021 session with Pfizer CSO & president of R&D Mikael Dolsten and MGH oncologist & chair of MGH Cancer Center Daniel Haber.
president Dave Lennon & Deerfield partner Julian Harris having a “fireside chat.” Dave/Novartis: sees gene therapy as driver for economy generating need for highly skilled workers Incl manufacturing
Kite Pharma CEO (Gilead subsidiary) Christi Shaw said there are 120 biopharma companies working on CAR-T cell therapy & they are continuing to look for new partnerships. She also mentioned logistical challenges currently getting to Israel & helping patients there. #WMIF2021
FDA’s Dir of Center for Biologics Evaluation & Research Peter Marks interviewed by Vicki Sato- chairwoman of Vir Biotechnology, ex Vertex president & ex Biogen VP Research. Around June ’20, started 2c progress in covid vaccines w/ enough candidates moving forward #WMIF2021 1/n
“Once you work on cell and gene therapy, its really hard to go back and work on anything else” says moderator Marcela Maus, MD PhD in our “CAR-T | Lessons Learned | What’s Next” panel #WMIF2021#GCT#geneandcelltherapy
Ex Merck president R&D Roger Perlmutter is now Eikon Therapeutics CEO & is on #WMIF2021 oncolytic virus in cancer panel w/Amgen EVP R&D David Reese, ex BioVex CTO (T-VEC inventor
, join our leaders for panels and presentations discussing what’s next for #genetherapy and the key trends shaping the industry as it evolves. #WMIF2021https://bit.ly/3eYYls4
Dolsten/Pfizer discussed covid vaccines and real world evidence study in Israel. Was sole provider of vaccines in Israel. 95%-98% efficacy replicated in real world. Well above 90% efficacy in asymptomatic disease. #wmif2021
ICYMI: An illustration depicting the “AAV Delivery” panel discussion about advances in the area of #AAVGeneTherapy delivery. Thank you to the panelists from
Casey Maguire PhD, Associate Professor of Neurology, at the podium to present his work developing improved #genetherapy vectors. #WMIF2021 “First Look: Enhanced Gene Delivery and Immunoevasion of AAV Vectors without Capsid Modification”
Casey Maguire PhD, Associate Professor of Neurology, at the podium to present his work developing improved #genetherapy vectors. #WMIF2021 “First Look: Enhanced Gene Delivery and Immunoevasion of AAV Vectors without Capsid Modification”
Mikael Dolsten, MD PhD, CSO & President, Worldwide Research, Development and Medical @pfizer takes the stage for a Fireside Chat, moderated by @MGHCancerCenter Daniel Haber, MD, PhD. “Pfizer’s Future in Cell and Gene Therapy” #WMIF2021
Dave Lennon/Novartis: manufacturing has been a roadblock for many cell & gene therapy companies. Expects to see more investments earlier. Engineering advances will unlock scale & address bigger & bigger patient populations. Oppty to ID patients early #WMIF2021
Marianne De Backer/Bayer on post M&A & company culture: They acquired AskBio & thought about how to preserve their freedom so they could continue to operate. Bayer decided to keep them independent & so they can operate at arm’s length. #wmif2021
Ken Custer/Eli Lilly-said they’re relatively new in cell & gene therapy. They invested in 1 of Sean Nolan’s (ex AveXis CEO) new companies,Jaguar Gene Therapy. Lilly’s legacy in neuroscience is noted & bought Prevail last yr. Clinical trial w/ Parkinson’s w/GBA1 mutation #wmif2021
, was the first in the U.S. to be approved for FDA gene therapy surgery. In 2018 he underwent therapy to treat retinitis pigmentosa by having a synthetic gene inserted into his retina. With improved eyesight he can now play sports #WMIF2021
The acquisition market in #GCT: looking for breakthroughs for patients, technologies for intractable diseases, manufacturing expertise, pioneering companies with deep experience — all for “the modality of the future”. M&A panel at #WMIF2021
Christi Shaw/Kite Pharma: Only 4 out of 10 patients eligible for CAR-T are being referred for CAR-T cell therapy by oncologists. The other 6 out of 10, referred to palliative care only. Consistency of manufacturing is also very important. #wmif2021 1/n
Marianne De Backer/Bayer on post M&A & company culture: They acquired AskBio & thought about how to preserve their freedom so they could continue to operate. Bayer decided to keep them independent & so they can operate at arm’s length. #wmif2021
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
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
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
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
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
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 CGTDan Tesler
Clinical Trial Patient, BWH/DFCC
Experimental Drug clinical trial patient participation in clinical trial is very important to advance the state of scienceSarah Beth Thomas, RN
Professional Development Manager, BWH
Outcome is unknown, hope for good, support with resources all advocacy groups,
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
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
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
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?
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
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 vectorsRon 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
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,
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
Ataxia requires therapy targeting multiple organ with one therapy, brain, spinal cord, heart several IND, clinical trials in 2022Mathew 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
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
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
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
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
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
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?
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?
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
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?
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.
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
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?
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
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 delayPin 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 biologicalRichard 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 challengeTian 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
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?
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
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
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
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
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?
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
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
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.
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
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?
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
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
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:
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
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
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?
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?
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?
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
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
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
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
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
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
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
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
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
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.
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
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
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?
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
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
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:
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
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
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?
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?
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?
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
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
Strategies, success what changes are needed in the drug discovery process Speakers:
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
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
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
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
Ear inside the scall compartments and receptors responsible for hearing highly differentiated tall ask to identify cell for anticipated differentiation
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
Saturation reached or more investment is coming in CGT
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
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
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
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:
Bob Carter, MD, PhD Chairman, Department of Neurosurgery, MGH William and Elizabeth Sweet, Professor of Neurosurgery, HMS Neurogeneration REVERSAL or slowing down?
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
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
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
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
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
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
Nabiha Saklayen, PhD CEO and Co-Founder, Cellino scale production of autologous cells foundry using semiconductor process in building cassettes by optic physicists
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
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
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
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
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
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
Cancer has been characterized as a heterogeneous disease consisting of many different subtypes. The early diagnosis and prognosis of a cancer type have become a necessity in cancer research, as it can facilitate the subsequent clinical management of patients. The importance of classifying cancer patients into high or low-risk groups has led many research teams, from the biomedical and the bioinformatics field, to study the application of machine learning (ML) and Artificial Intelligence (AI) methods. Therefore, these techniques have been utilized as an aim to model the progression and treatment of cancerous conditions by predicting new algorithms.
In the majority of human cancers, heritable loss of gene function through cell division may be mediated as often by epigenetic as by genetic abnormalities. Epigenetic modification occurs through a process of interrelated changes in CpG island methylation and histone modifications. Candidate gene approaches of cell cycle, growth regulatory and apoptotic genes have shown epigenetic modification associated with loss of cognate proteins in sporadic pituitary tumors.
On 11th November 2020, researchers from the University of California, Irvine, has established the understanding of epigenetic mechanisms in tumorigenesis and publicized a previously undetected repertoire of cancer driver genes. The study was published in “Science Advances”
Researchers were able to identify novel tumor suppressor genes (TSGs) and oncogenes (OGs), particularly those with rare mutations by using a new prediction algorithm, called DORGE (Discovery of Oncogenes and tumor suppressor genes using Genetic and Epigenetic features) by integrating the most comprehensive collection of genetic and epigenetic data.
The senior author Wei Li, Ph.D., the Grace B. Bell chair and professor of bioinformatics in the Department of Biological Chemistry at the UCI School of Medicine said
Existing bioinformatics algorithms do not sufficiently leverage epigenetic features to predict cancer driver genes, even though epigenetic alterations are known to be associated with cancer driver genes.
The Study
This study demonstrated how cancer driver genes, predicted by DORGE, included both known cancer driver genes and novel driver genes not reported in current literature. In addition, researchers found that the novel dual-functional genes, which DORGE predicted as both TSGs and OGs, are highly enriched at hubs in protein-protein interaction (PPI) and drug/compound-gene networks.
Prof. Li explained that the DORGE algorithm, successfully leveraged public data to discover the genetic and epigenetic alterations that play significant roles in cancer driver gene dysregulation and could be instrumental in improving cancer prevention, diagnosis and treatment efforts in the future.
Another new algorithmic prediction for the identification of cancer genes by Machine Learning has been carried out by a team of researchers at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin and the Institute of Computational Biology of Helmholtz Zentrum München combining a wide variety of data analyzed it with “Artificial Intelligence” and identified numerous cancer genes. They termed the algorithm as EMOGI (Explainable Multi-Omics Graph Integration). EMOGI can predict which genes cause cancer, even if their DNA sequence is not changed. This opens up new perspectives for targeted cancer therapy in personalized medicine and the development of biomarkers. The research was published in Nature Machine Intelligence on 12th April 2021.
In cancer, cells get out of control. They proliferate and push their way into tissues, destroying organs and thereby impairing essential vital functions. This unrestricted growth is usually induced by an accumulation of DNA changes in cancer genes—i.e. mutations in these genes that govern the development of the cell. But some cancers have only very few mutated genes, which means that other causes lead to the disease in these cases.
The aim of the study has been represented in 4 main headings
Additional targets for personalized medicine
Better results by combination
In search of hints for further studies
Suitable for other types of diseases as well
The team was headed by Annalisa Marsico. The team used the algorithm to identify 165 previously unknown cancer genes. The sequences of these genes are not necessarily altered-apparently, already a dysregulation of these genes can lead to cancer. All of the newly identified genes interact closely with well-known cancer genes and be essential for the survival of tumor cells in cell culture experiments. The EMOGI can also explain the relationships in the cell’s machinery that make a gene a cancer gene. The software integrates tens of thousands of data sets generated from patient samples. These contain information about DNA methylations, the activity of individual genes and the interactions of proteins within cellular pathways in addition to sequence data with mutations. In these data, a deep-learning algorithm detects the patterns and molecular principles that lead to the development of cancer.
Marsico says
Ideally, we obtain a complete picture of all cancer genes at some point, which can have a different impact on cancer progression for different patients
Unlike traditional cancer treatments such as chemotherapy, personalized treatments are tailored to the exact type of tumor. “The goal is to choose the best treatment for each patient, the most effective treatment with the fewest side effects. In addition, molecular properties can be used to identify cancers that are already in the early stages.
Roman Schulte-Sasse, a doctoral student on Marsico’s team and the first author of the publication says
To date, most studies have focused on pathogenic changes in sequence, or cell blueprints, at the same time, it has recently become clear that epigenetic perturbation or dysregulation gene activity can also lead to cancer.
This is the reason, researchers merged sequence data that reflects blueprint failures with information that represents events in cells. Initially, scientists confirmed that mutations, or proliferation of genomic segments, were the leading cause of cancer. Then, in the second step, they identified gene candidates that are not very directly related to the genes that cause cancer.
Clues for future directions
The researcher’s new program adds a considerable number of new entries to the list of suspected cancer genes, which has grown to between 700 and 1,000 in recent years. It was only through a combination of bioinformatics analysis and the newest Artificial Intelligence (AI) methods that the researchers were able to track down the hidden genes.
Schulte-Sasse says “The interactions of proteins and genes can be mapped as a mathematical network, known as a graph.” He explained by giving an example of a railroad network; each station corresponds to a protein or gene, and each interaction among them is the train connection. With the help of deep learning—the very algorithms that have helped artificial intelligence make a breakthrough in recent years – the researchers were able to discover even those train connections that had previously gone unnoticed. Schulte-Sasse had the computer analyze tens of thousands of different network maps from 16 different cancer types, each containing between 12,000 and 19,000 data points.
Many more interesting details are hidden in the data. Patterns that are dependent on particular cancer and tissue were seen. The researchers were also observed this as evidence that tumors are triggered by different molecular mechanisms in different organs.
Marsico explains
The EMOGI program is not limited to cancer, the researchers emphasize. In theory, it can be used to integrate diverse sets of biological data and find patterns there. It could be useful to apply our algorithm for similarly complex diseases for which multifaceted data are collected and where genes play an important role. An example might be complex metabolic diseases such as diabetes.
Main Source
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Evolution of the Human Cell Genome Biology Field of Gene Expression, Gene Regulation, Gene Regulatory Networks and Application of Machine Learning Algorithms in Large-Scale Biological Data Analysis
Scientists have recognized human genes that fight against the SARS-CoV-2 viral infection. The information about genes and their function can help to control infection and aids the understanding of crucial factors that causes severe infection. These novel genes are related to interferons, the frontline fighter in our body’s defense system and provide options for therapeutic strategies.
Sumit K. Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys reported in the article that they focused on better understanding of the cellular response and downstream mechanism in cells to SARS-CoV-2, including the factors which causes strong or weak response to viral infection. He is the lead author of the study and explained that in this study they have gained new insights into how the human cells are exploited by invading virus and are still working towards finding any weak point of virus to develop new antivirals against SARS-CoV-2.
With the surge of pandemic, researchers and scientists found that in severe cases of COVID-19, the response of interferons to SARS-CoV-2 viral infection is low. This information led Chanda and other collaborators to search for interferon-stimulated genes (ISGs), are genes in human which are triggered by interferons and play important role in confining COVID-19 infection by controlling their viral replication in host.
The investigators have developed laboratory experiments to identify ISGs based on the previous knowledge gathered by the outbreak of SARS-CoV-1 from 2002-2004 which was similar to COVID-19 pandemic caused by SARS-CoV-2 virus.
The article reports that Chanda mentioned “we found that 65 ISGs controlled SAR-CoV-2 infection, including some that inhibited the virus’ ability to enter cells, some that suppressed manufacture of the RNA that is the virus’s lifeblood, and a cluster of genes that inhibited assembly of the virus.” They also found an interesting fact about ISGs that some of these genes revealed control over unrelated viruses, such as HIV, West Nile and seasonal flu.
Laura Martin-Sancho, Ph.D., a senior postdoctoral associate in the Chanda lab and first author of the study reported in the article that they identified 8 different ISGs that blocked the replication of both SARS-CoV-1 and CoV-2 in the subcellular compartments responsible for packaging of proteins, which provide option to exploit these vulnerable sites to restrict infection. They are further investigating whether the genetic variability within the ISGs is associated with COVID-19 severity.
The next step for researchers will be investigating and observing the biology of variants of SARS-CoV-2 that are evolving and affecting vaccine efficacy. Martin-Sancho mentioned that their lab has already started gathering all the possible variants for further investigation.
“It’s vitally important that we don’t take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic,” reported in the article by Chanda.
“We’ve come so far so fast because of investment in fundamental research at Sanford Burnham Prebys and elsewhere, and our continued efforts will be especially important when, not if, another viral outbreak occurs,” concluded Chanda.
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