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Top Industrialization Challenges of Gene Therapy Manufacturing

Guest Authors:

Dr. Mark Szczypka

Global Director, Process Development Services

Pall Corporation

https://www.pall.com/

and

Clive Glover

Director, Cell & Gene Therapy

Pall Corporation

https://www.pall.com/

What Is Gene Therapy? How Does It Save and Improve the Quality of Life?

What Is Gene Therapy?

Gene therapy is a new and exciting technique, defined as the use of genetic material to cure or alleviate disease. It is considered revolutionary, yet still in its infancy, with many new therapies currently undergoing clinical trials. 

Gene therapy has the potential to transform the treatment for diseases, significantly changing how doctors manage and treat patients. 

Two Types of Gene Therapy

There are two main types of gene therapy. 

The first corrects a specific disease causing genetic mutation. These are targeted towards inherited genetic disorders such as hemophilia or Duchenne muscular dystrophy. The second gives new functions to cells allowing them to fight disease.

A good example of these therapies are chimeric antigen receptor T cell (CAR-T) therapies. Both Novartis’ Kymriah and Gilead’s Yescarta are examples of CAR-T therapies, that have demonstrated exceptional cancer remission rates where other forms of treatment have failed.

Cancer is the by far the largest category of disease with 65% of gene therapy clinical trials being investigated, followed by 11.1% for inherited monogenetic disease, 7% for infectious disease, and 6.9% for cardiovascular disease1.

How Does Genetic Material Get Delivered to Host Cell(s)?

Genetic material gets delivered to a host cell via a delivery system known as a vector. Vectors deliver genetic material via one of the two methods. By directly injecting genetic material into the patient (in vivo), and where selected cells collected from the patient, undergo modification outside (ex vivo) before introducing them back into the patient.

The most commonly used type of vector is a virus. While there are other methods of delivering genetic material into a cell, viruses have now been developed that demonstrate a good balance between efficacy and safety. 

 

Commercially Successful Gene Therapies

Developing a commercially successful gene therapy is challenging. It requires balancing several different considerations. Having a clinical effective therapy is essential, but this alone is not sufficient to ensure product success. In addition to this, reimbursement, quality and regulatory considerations, and manufacturing also must be considered. 

To date, a total 11 gene therapies have received marketing approval. However, behind this there is a strong clinical pipeline with >1000 clinical trials underway, and 92 drugs in Phase 32.

Furthermore, there has been significant investment with >$50B being invested in the area in the past 3 years3.

This investment, coupled with the accelerating understanding of disease at the genetic level, holds immense potential. Academic, commercial manufacturers, and industry suppliers are actively seeking new approaches that deliver these therapies as quick as possible to a waiting population.

Author Details:

Clive Glover

Director, Cell & Gene Therapy

Pall Corporation

https://www.pall.com/

Top Industrialization Challenges of Gene Therapy Manufacturing

Manufacturing and scale-up of industrialized processes to manufacture gene therapy products are accompanied by many challenges that must be overcome to succeed in the marketplace. Commercialization of gene therapies for patient use is time consuming and requires substantial financial investment and dedicated resources.

Despite the unique range of challenges associated with gene therapy development, the quest to bring these therapies to market is worthwhile because the therapeutic potential of the treatments is revolutionary and the commercial opportunity is considerable. The process to industrialization is complex, but the benefits of successful development of robust processes are huge. The industry is rapidly expanding and is implementing novel approaches to overcome existing challenges, using innovative methods for medicinal application and developing new drugs to treat rare diseases.

Manufacturing sufficient quantities of high quality product, is an area that requires substantial developmental effort. Challenges surrounding reimbursement for treatment, and the pressures associated with shorter time to approval, both increase burden placed on manufactures to rapidly develop suitable processes that are cost-effective. Cost of goods (COGs) need to be kept below critical threshold levels to drive sufficient profit margins, even though process development timelines are aggressive and short. There are a multitude of critical decisions and considerations to overcome. 

This blog explores some of these fundamental manufacturing challenges in more detail.

Scalable Manufacturing Platform

Technologies used to manufacture gene therapy biologics are advancing at very rapid pace. Not having a platform that is suitable nor scalable is a significant challenge many manufacturers face. It is a necessity throughout clinical development stages to be able to optimize the manufacturing process. However, any change in the manufacturing process that increases product yield or enhances quality is accompanied by the risk of changing the product. It is therefore essential that close attention is paid to tracking variation throughout the development process at every stage.

A substantial amount of early stage development is still being performed using outdated, non-commercially viable platforms and transferring processes to new platforms is required. To achieve manufacturing platform advancement, the product needs to be very well characterized during development so that investigators can generate data sets which demonstrate comparability between products used in clinical studies and those generated with the final manufacturing process.

Cost of Goods

COGs associated with manufacturing any drug product impacts the overall price of the therapy and heavily influences the profit margin realized by gene therapy manufactures. High production cost is a challenge that affects profitability. This is reflected in the high costs associated with newly approved gene therapy drugs such as Yescarta♦, Kymriah♦ and Luxturna♦ which are currently priced in the 100 thousands dollar range per dose. The challenge becomes a critical concern when the product in development cannot be sold at a price high enough to achieve a commercially-viable profit margin.  If acceptable margins cannot be reached, developers may choose to terminate production making the drug unavailable to patients. However, due to the remarkable value and life changing nature of the treatments the entire industry is committed to the pursuit of cost effective methods for manufacturing. There is a significant effort that has been mounted by all players to reach this end.

Currently, the main cost contributor to the overall COGs for gene therapy products is high quality clinical grade plasmid DNA containing the therapeutic gene of interest. This reagent is required for transient transfection of cells and it is imperative that the reagent is of high quality. It is an essential component of the process to assure an acceptable safety profile. Another example of an expensive gene therapy product is Zolgensma♦. This new drug was recently approved for the treatment of spinal muscular atrophy (SMA), which is a rare disease that causes severe muscle weakness for suffers. It affects their ability to breath, speak and move. Most babies born with a common form of SMA die by the time they reach two years of age. Currently there is no cure. Zolgensma represents the only treatment option now available to cure the 10,000 – 25,000 affected individuals in the US. However, the current challenge with this therapy is that it could costs $2.1 million per patient1.

Reimbursement

Market size is an important factor that can limit effective commercial return. If the market size is too small, profitability is limited due to the small number of doses required to treat the patient population. This decreases the profit margin realized by the drug developer and can lower motivation to commercialize the therapy. The most encouraging aspect of the gene therapy revolution is that the first round of gene therapy products has been developed for extremely rare diseases, with small patient populations indicating the commitment to treat previously untreatable diseases. Amazingly, these patients can be cured by a single drug application, however, this inherent property of the therapy can further limit commercial profitability. Patients are often not required to pay for these high-cost medicines themselves, and look to government programs and health care insurance providers to reimburse the manufacturer for treatments. Health insurance reimbursement plans for new products is challenging, particularly so for new category products like gene therapy. It is expected that the process of reimbursement will differ from country to country and it will also be guided by factors like economics, demographic data and politics. If the current cost of manufacturing stands then drugs such as Zolgensma could place a huge financial strain on health systems. In the US for example, it is surmised that treating common diseases such as hemophilia, which affects around 20,000 people in the US alone, could cause a financial crisis1. If we look to the future of modern medicine, commercialization of gene therapies will require not only significant advancement in manufacturing processes to reduce costs but also a practical reimbursement strategy that will allow for drug developers to continue to forge into the new frontiers of medicine.

References:

1. Business Insider. http://www.businessinsider.com/gene-therapy-treats-disease-but-prices-could-strain-us-health-system-2019-2 

♦Kymriah is a trademark of Novartis AG., Luxturna is a trademark of Spark Therapeutics, Inc., Yescarta is a trademark of Kite Pharma, Inc., Zolgensma is a trademark of AveXis Inc.

Author Details:

Dr. Mark Szczypka

Global Director, Process Development Services

Pall Corporation

https://www.pall.com/

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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.

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

#WMIF21

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

will be in attendance producing the e-Proceedings

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

@pharma_BI

@AVIVA1950

LPBI’s Eighteen Books in Medicine

https://lnkd.in/ekWGNqA

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

Topics for May 19 -21 include:

Impact on Patient Care – Therapeutic and Potentially Curative GCT Developments

GCT Delivery, Manufacturing – What’s Next

GCT Platform Development

Oncolytic Viruses – Cancer applications, start-ups

Regenerative Medicine/Stem Cells

Future of CAR-T

M&A Shaping GCT’s Future

Market Priorities

Venture Investing in GCT

China’s GCT Juggernaut

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

Click here for the current WMIF agenda  

 

Plus:

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

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

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

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

AGENDA

8:00 AM – 8:10 AM

Opening Remarks

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

Introducer:
Scott Sperling
  • Co-President, Thomas H. Lee Partners
  • Chairman of the Board of Directors, PHS
Presenter:
Anne Klibanski, MD
  • CEO, Mass General Brigham
8:10 AM – 8:30 AM

The Grand Challenge of Widespread GCT Patient Benefits

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

Moderator:
Susan Hockfield, PhD
  • President Emerita and Professor of Neuroscience, MIT
Speakers:
Nino Chiocca, MD, PhD
  • Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
  • Harvey W. Cushing Professor of Neurosurgery, HMS
Susan Slaugenhaupt, PhD
  • Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
  • Professor, Neurology, HMS
Ravi Thadhani, MD
  • CAO, Mass General Brigham
  • Professor, Medicine and Faculty Dean, HMS
Luk Vandenberghe, PhD
  • Grousbeck Family Chair, Gene Therapy, MEE
  • Associate Professor, Ophthalmology, HMS
8:35 AM – 8:50 AM

FIRESIDE

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

Moderator:
Julian Harris, MD
  • Partner, Deerfield
Speaker:
Dave Lennon, PhD
  • President, Novartis Gene Therapies
  • Q&A

    8:55 AM – 9:10 AM
8:55 AM – 9:20 AM

The Patient and GCT

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

Moderator:
Patricia Musolino, MD, PhD
  • Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
  • Assistant Professor of Neurology, HMS
Speakers:
Jack Hogan
  • Patient, MEE
Jeanette Hogan
  • Parent of Patient, MEE
Jim Holland
  • CEO, Backcountry.com
Barbara Lavery
  • Chief Program Officer, ACGT Foundation
Dan Tesler
  • Clinical Trial Patient, BWH/DFCC
Sarah Beth Thomas, RN
  • Professional Development Manager, BWH
  • Q&A

    9:25 AM – 9:40 AM
9:25 AM – 9:45 AM

FIRESIDE

GCT Regulatory Framework | Why Different?

Moderator:
Vicki Sato, PhD
  • Chairman of the Board, Vir Biotechnology
Speaker:
Peter Marks, MD, PhD
  • Director, Center for Biologics Evaluation and Research, FDA
  • Q&A

    9:50 AM – 10:05 AM
9:50 AM – 10:15 AM

Building a GCT Platform for Mainstream Success

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

  • How are GCT approaches set around defining and building a platform?
  • Is AAV the leading modality and what are the remaining challenges?
  • What are the alternatives?
  • Is it just a matter of matching modalities to the right indications?
Moderator:
Jean-François Formela, MD
  • Partner, Atlas Venture
Speakers:
Katherine High, MD
  • President, Therapeutics, AskBio
Dave Lennon, PhD
  • President, Novartis Gene Therapies
Rick Modi
  • CEO, Affinia Therapeutics
Louise Rodino-Klapac, PhD
  • EVP, Chief Scientific Officer, Sarepta Therapeutics
  • Q&A

    10:20 AM – 10:35 AM
10:20 AM – 10:45 AM

AAV Success Studies | Retinal Dystrophy | Spinal Muscular Atrophy

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

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

  • Is AAV gene therapy restricted to genetically defined disorders, or will it be able to address common diseases in the near term?
  • Lessons learned from these first-in-class approvals.
  • Challenges to broaden this modality to similar indications.
  • Reflections on safety signals in the clinical studies?
Moderator:
Joan Miller, MD
  • Chief, Ophthalmology, MEE
  • Cogan Professor & Chair of Ophthalmology, HMS
Speakers:
Ken Mills
  • CEO, RegenXBio
Eric Pierce, MD, PhD
  • Director, Ocular Genomics Institute, MEE
  • Professor of Ophthalmology, HMS
Ron Philip
  • Chief Operating Officer, Spark Therapeutics
Meredith Schultz, MD
  • Executive Medical Director, Lead TME, Novartis Gene Therapies
  • Q&A

    10:50 AM – 11:05 AM
10:45 AM – 10:55 AM
10:55 AM – 11:05 AM

FIRST LOOK

Control of AAV pharmacology by Rational Capsid Design

Luk Vandenberghe, PhD
  • Grousbeck Family Chair, Gene Therapy, MEE
  • Associate Professor, Ophthalmology, HMS
  • Q&A

    11:05 AM – 11:25 AM
11:05 AM – 11:15 AM

FIRST LOOK

Enhanced gene delivery and immunoevasion of AAV vectors without capsid modification

Casey Maguire, PhD
  • Associate Professor of Neurology, MGH & HMS
  • Q&A

    11:15 AM – 11:35 AM
11:20 AM – 11:45 AM

HOT TOPICS

AAV Delivery

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

Moderators:
Xandra Breakefield, PhD
  • Geneticist, MGH, MGH
  • Professor, Neurology, HMS
Florian Eichler, MD
  • Director, Center for Rare Neurological Diseases, MGH
  • Associate Professor, Neurology, HMS
Speakers:
Jennifer Farmer
  • CEO, Friedreich’s Ataxia Research Alliance
Mathew Pletcher, PhD
  • SVP, Head of Gene Therapy Research and Technical Operations, Astellas
Manny Simons, PhD
  • CEO, Akouos
Andre Turenne
  • CEO, Voyager Therapeutics
  • Q&A

    11:50 AM – 12:05 PM
11:50 AM – 12:15 PM

M&A | Shaping GCT Innovation

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

Moderator:
Adam Koppel, MD, PhD
  • Managing Director, Bain Capital Life Sciences
Speakers:
Kenneth Custer, PhD
  • Vice President, Business Development and Lilly New Ventures, Eli Lilly and Company
Marianne De Backer, PhD
  • Head of Strategy, Business Development & Licensing, and Member of the Executive Committee, Bayer
Sean Nolan
  • Board Chairman, Encoded Therapeutics & Affinia
  • Executive Chairman, Jaguar Gene Therapy & Istari Oncology
  • Q&A

    12:20 PM – 12:35 PM
12:15 PM – 12:25 PM

FIRST LOOK
12:25 PM – 12:35 PM

FIRST LOOK

Gene Therapy for Neurologic Diseases

Patricia Musolino, MD, PhD
  • Co-Director Pediatric Stroke and Cerebrovascular Program, MGH
  • Assistant Professor of Neurology, HMS
  • Q&A

    12:35 PM – 12:55 PM
12:35 PM – 1:15 PM
1:15 PM – 1:40 PM

Oncolytic Viruses in Cancer | Curing Melanoma and Beyond

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

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

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

Moderator:
Nino Chiocca, MD, PhD
  • Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
  • Harvey W. Cushing Professor of Neurosurgery, HMS
Speakers:
Robert Coffin, PhD
  • Chief Research & Development Officer, Replimune
Roger Perlmutter, MD, PhD
  • Chairman, Merck & Co.
David Reese, MD
  • Executive Vice President, Research and Development, Amgen
Ann Silk, MD
  • Physician, Dana Farber-Brigham and Women’s Cancer Center
  • Assistant Professor of Medicine, HMS
  • Q&A

    1:45 PM – 2:00 PM
1:45 PM – 2:10 PM

Market Interest in Oncolytic Viruses | Calibrating

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

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

  • Will these need to be combined with other agents to realize their full efficacy and how will that impact the market?
  • Why are these companies pursuing OVs while several others are taking a pass?
Moderators:
Martine Lamfers, PhD
  • Visiting Scientist, BWH
Robert Martuza, MD
  • Consultant in Neurosurgery, MGH
  • William and Elizabeth Sweet Distinguished Professor of Neurosurgery, HMS
Speakers:
Anlong Li, MD, PhD
  • Clinical Director, Oncology Clinical Development, Merck Research Laboratories
Peter Liebowitz, MD, PhD
  • Global Therapeutic Area Head, Oncology, Janssen Research & Development
Loic Vincent, PhD
  • Head of Oncology Drug Discovery Unit, Takeda
  • Q&A

    2:15 PM – 2:30 PM
2:10 PM – 2:20 PM

FIRST LOOK

Oncolytic viruses: turning pathogens into anticancer agents

Nino Chiocca, MD, PhD
  • Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH
  • Harvey W. Cushing Professor of Neurosurgery, HMS
  • Q&A

    2:25 PM – 2:40 PM
2:20 PM – 2:45 PM

Entrepreneurial Growth | Oncolytic Virus

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

  •  How are small companies equipped to address the challenges of developing OV therapies better than large pharma or biotech?
  • Will the success of COVID vaccines based on Adenovirus help the regulatory environment for small companies developing OV products in Europe and the USA?
  • Is there a place for non-viral delivery and other immunotherapy companies to engage in the OV space?  Would they bring any real advantages?
Moderator:
Reid Huber, PhD
  • Partner, Third Rock Ventures
Speakers:
Caroline Breitbach, PhD
  • VP, R&D Programs and Strategy, Turnstone Biologics
Brett Ewald, PhD
  • SVP, Development & Corporate Strategy, DNAtrix
Paul Hallenbeck, PhD
  • President and Chief Scientific Officer, Seneca Therapeutics
Stephen Russell, MD, PhD
  • CEO, Vyriad
  • Q&A

    2:50 PM – 3:05 PM
2:45 PM – 3:00 PM
3:00 PM – 3:25 PM

CAR-T | Lessons Learned | What’s Next

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

  • Is CAR-T still an industry priority – i.e. are new investments being made by large companies? Are new companies being financed? What are the trends?
  • What have we learned from first-generation products, what can we expect from CAR-T going forward in novel targets, combinations, armored CAR’s and allogeneic treatment adoption?
  • Early trials showed remarkable overall survival and progression-free survival. What has been observed regarding how enduring these responses are?
  • Most of the approvals to date have targeted CD19, and most recently BCMA. What are the most common forms of relapses that have been observed?
  • Is there a consensus about what comes after these CD19 and BCMA trials as to additional targets in liquid tumors? How have dual-targeted approaches fared?
Moderator:
Marcela Maus, MD, PhD
  • Director, Cellular Immunotherapy Program, Cancer Center, MGH
  • Associate Professor, Medicine, HMS
Speakers:
Jakob Dupont, MD
Kristen Hege, MD
  • Senior Vice President, Early Clinical Development, Hematology/Oncology & Cell Therapy, BMS
Stefan Hendriks
  • Gobal Head, Cell & Gene, Novartis
Christi Shaw
  • CEO, Kite
  • Q&A

    3:30 PM – 3:45 PM
3:30 PM – 3:55 PM

HOT TOPICS

CAR-T | Solid Tumors Success | When?

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

  •  How would industry and investor strategy for CAR-T and solid tumors be characterized? Has it changed in the last couple of years?
  •  Does the lack of tumor antigen specificity in solid tumors mean that lessons from liquid tumor CAR-T constructs will not translate well and we have to start over?
  •  Whether due to antigen heterogeneity, a hostile tumor micro-environment, or other factors are some specific solid tumors more attractive opportunities than others for CAR-T therapy development?
  •  Given the many challenges that CAR-T faces in solid tumors, does the use of combination therapies from the start, for example, to mitigate TME effects, offer a more compelling opportunity.
Moderator:
Oladapo Yeku, MD, PhD
  • Clinical Assistant in Medicine, MGH
Speakers:
Jennifer Brogdon
  • Executive Director, Head of Cell Therapy Research, Exploratory Immuno-Oncology, NIBR
Knut Niss, PhD
  • CTO, Mustang Bio
Barbra Sasu, PhD
  • CSO, Allogene
Jay Short, PhD
  • Chairman, CEO, Cofounder, BioAlta, Inc.
  • Q&A

    4:00 PM – 4:15 PM
4:00 PM – 4:25 PM

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

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

  • Help us all understand the different manufacturing challenges for cell therapies. What are the trade-offs among storage cost, batch size, line changes in terms of production cost and what is the current state of scaling naïve and stem cell therapy treatment vs engineered cell therapies?
  • For cell and gene therapy what is the cost of Quality Assurance/Quality Control vs. production and how do you think this will trend over time based on your perspective on learning curves today?
  • Will point of care production become a reality? How will that change product development strategy for pharma and venture investors? What would be the regulatory implications for such products?
  • How close are allogeneic CAR-T cell therapies? If successful what are the market implications of allogenic CAR-T? What are the cost implications and rewards for developing allogeneic cell therapy treatments?
Moderator:
David Hallal
  • CEO, ElevateBio
Speakers:
Dannielle Appelhans
  • SVP TechOps and Chief Technical Officer, Novartis Gene Therapies
Thomas Page, PhD
  • VP, Engineering and Asset Development, FUJIFILM Diosynth Biotechnologies
Rahul Singhvi, ScD
  • CEO and Co-Founder, National Resilience, Inc.
Thomas VanCott, PhD
  • Global Head of Product Development, Gene & Cell Therapy, Catalent
  • Q&A

    4:30 PM – 4:45 PM
4:30 PM – 4:40 PM

FIRST LOOK

CAR-T

Marcela Maus, MD, PhD
  • Director, Cellular Immunotherapy Program, Cancer Center, MGH
  • Assistant Professor, Medicine, HMS
  • Q&A

    4:40 PM – 5:00 PM
4:40 PM – 4:50 PM

FIRST LOOK

Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy

Khalid Shah, PhD
  • Vice Chair, Neurogurgery Research, BWH
  • Director, Center for Stem Cell Therapeutics and Imaging, HMS
  • Q&A

    4:50 PM – 5:10 PM
4:50 PM – 5:00 PM

FIRST LOOK

Other Cell Therapies for Cancer

David Scadden, MD
  • Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
  • Jordan Professor of Medicine, HMS
  • Q&A

    5:00 PM – 5:20 PM
5:00 PM – 5:20 PM

FIRESIDE

Fireside with Mikael Dolsten, MD, PhD

Introducer:
Jonathan Kraft
Moderator:
Daniel Haber, MD, PhD
  • Chair, Cancer Center, MGH
  • Isselbacher Professor of Oncology, HMS
Mikael Dolsten, MD, PhD
  • Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer
  • Q&A

    5:25 PM – 5:40 AM
5:20 PM – 5:30 PM
8:00 AM – 8:25 AM

GCT | The China Juggernaut

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

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

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

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

Moderator:
Min Wu, PhD
  • Managing Director, Fosun Health Fund
Speakers:
Alvin Luk, PhD
  • CEO, Neuropath Therapeutics
Pin Wang, PhD
  • CSO, Jiangsu Simcere Pharmaceutical Co., Ltd.
Richard Wang, PhD
  • CEO, Fosun Kite Biotechnology Co., Ltd
Tian Xu, PhD
  • Vice President, Westlake University
Shunfei Yan, PhD
  • Investment Manager, InnoStar Capital
  • Q&A

    8:30 AM – 8:45 AM
8:30 AM – 8:55 AM

Impact of mRNA Vaccines | Global Success Lessons

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

  • How will the COVID success impact the rest of the industry both in therapeutic and prophylactic vaccines and broader mRNA lessons?
  • How will the COVID success impact the rest of the industry both on therapeutic and prophylactic vaccines and broader mRNA lessons?
  • Beyond from speed of development, what aspects make mRNA so well suited as a vaccine platform?
  • Will cost-of-goods be reduced as the industry matures?
  • How does mRNA technology seek to compete with AAV and other gene therapy approaches?
Moderator:
Lindsey Baden, MD
  • Director, Clinical Research, Division of Infectious Diseases, BWH
  • Associate Professor, HMS
Speakers:
Melissa Moore
  • Chief Scientific Officer, Moderna
Ron Renaud
  • CEO, Translate Bio
  • Q&A

    9:00 AM – 9:15 AM
9:00 AM – 9:25 AM

HOT TOPICS

Benign Blood Disorders

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

Moderator:
Nancy Berliner, MD
  • Chief, Division of Hematology, BWH
  • H. Franklin Bunn Professor of Medicine, HMS
Speakers:
Theresa Heggie
  • CEO, Freeline Therapeutics
Gallia Levy, MD, PhD
  • Chief Medical Officer, Spark Therapeutics
Amir Nashat, PhD
  • Managing Partner, Polaris Ventures
Suneet Varma
  • Global President of Rare Disease, Pfizer
  • Q&A

    9:30 AM – 9:45 AM
9:25 AM – 9:35 AM

FIRST LOOK

Treating Rett Syndrome through X-reactivation

Jeannie Lee, MD, PhD
  • Molecular Biologist, MGH
  • Professor of Genetics, HMS
  • Q&A

    9:35 AM – 9:55 AM
9:35 AM – 9:45 AM

FIRST LOOK

Rare but mighty: scaling up success in single gene disorders

Florian Eichler, MD
  • Director, Center for Rare Neurological Diseases, MGH
  • Associate Professor, Neurology, HMS
  • Q&A

    9:45 AM – 10:05 AM
9:50 AM – 10:15 AM

HOT TOPICS

Diabetes | Grand Challenge

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

  •  Islet transplantation for type 1 diabetes has been attempted for decades. Problems like loss of transplanted islet cells due to autoimmunity and graft site factors have been difficult to address. Is there anything different on the horizon for gene and cell therapies to help this be successful?
  • How is the durability of response for gene or cell therapies for diabetes being addressed? For example, what would the profile of an acceptable (vs. optimal) cell therapy look like?
Moderator:
Marie McDonnell, MD
  • Chief, Diabetes Section and Director, Diabetes Program, BWH
  • Lecturer on Medicine, HMS
Speakers:
Tom Bollenbach, PhD
  • Chief Technology Officer, Advanced Regenerative Manufacturing Institute
Manasi Jaiman, MD
  • Vice President, Clinical Development, ViaCyte
  • Pediatric Endocrinologist,
Bastiano Sanna, PhD
  • EVP, Chief of Cell & Gene Therapies and VCGT Site Head, Vertex Pharmaceuticals
Rogerio Vivaldi, MD
  • CEO, Sigilon Therapeutics
  • Q&A

    10:20 AM – 10:35 AM
10:20 AM – 10:40 AM

FIRESIDE

Building A Unified GCT Strategy

Introducer:
John Fish
  • CEO, Suffolk
  • Chairman of Board Trustees, Brigham Health
Moderator:
Meg Tirrell
  • Senior Health and Science Reporter, CNBC
Speaker:
Jay Bradner, MD
  • President, NIBR
  • Q&A

    10:45 AM – 11:00 AM
10:40 AM – 10:50 AM
10:50 AM – 11:00 AM

FIRST LOOK

Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy

Christine Seidman, MD
  • Director, Cardiovascular Genetics Center, BWH
  • Smith Professor of Medicine & Genetics, HMS
  • Q&A

    11:00 AM – 11:20 AM
11:00 AM – 11:10 AM

FIRST LOOK

Unlocking the secret lives of proteins in health and disease

Anna Greka, MD, PhD
  • Medicine, BWH
  • Associate Professor, Medicine, HMS
  • Q&A

    11:10 AM – 11:30 AM
11:10 AM – 11:35 AM

Rare and Ultra Rare Diseases | GCT Breaks Through

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

  • What is driving the interest in rare diseases?
  • What are the biggest barriers to making breakthroughs ‘routine and affordable?’
  • What is the role of retrospective and prospective natural history studies in rare disease?  When does the expected value of retrospective disease history studies justify the cost?
  • Related to the first question, what is the FDA expecting as far as controls in clinical trials for rare diseases?  How does this impact the collection of natural history data?
Moderator:
Susan Slaugenhaupt, PhD
  • Scientific Director and Elizabeth G. Riley and Daniel E. Smith Jr., Endowed Chair, Mass General Research Institute
  • Professor, Neurology, HMS
Speakers:
Leah Bloom, PhD
  • SVP, External Innovation and Strategic Alliances, Novartis Gene Therapies
Bobby Gaspar, MD, PhD
  • CEO, Orchard Therapeutics
Emil Kakkis, MD, PhD
  • CEO, Ultragenyx
Stuart Peltz, PhD
  • CEO, PTC Therapeutics
  • Q&A

    11:40 AM – 11:55 AM
11:40 AM – 12:00 PM

FIRESIDE

Partnering Across the GCT Spectrum

Moderator:
Erin Harris
  • Chief Editor, Cell & Gene
Speaker:
Marc Casper
  • CEO, ThermoFisher
  • Q&A

    12:05 PM – 12:20 PM
12:05 PM – 12:30 PM

CEO Panel | Anticipating Disruption | Planning for Widespread GCT

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

Moderator:
Meg Tirrell
  • Senior Health and Science Reporter, CNBC
Speakers:
Lisa Dechamps
  • SVP & Chief Business Officer, Novartis Gene Therapies
Kieran Murphy
  • CEO, GE Healthcare
Christian Rommel, PhD
  • Head, Pharmaceuticals Research & Development, Bayer AG
  • Q&A

    12:35 PM – 12:50 PM
12:35 PM – 12:55 PM

FIRESIDE

Building a GCT Portfolio

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

Moderator:
Ansbert Gadicke, MD
  • Co-Founder, Managing Director, MPM Capital
Speaker:
Wolfram Carius, PhD
  • EVP, Pharmaceuticals, Head of Cell & Gene Therapy, Bayer AG
  • Q&A

    1:00 PM – 1:15 PM
12:55 PM – 1:35 PM
1:40 PM – 2:05 PM

GCT Delivery | Perfecting the Technology

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

Moderator:
Natalie Artzi, PhD
  • Assistant Professor, BWH
Speakers:
Geoff McDonough, MD
  • CEO, Generation Bio
Sonya Montgomery
  • CMO, Evox Therapeutics
Laura Sepp-Lorenzino, PhD
  • Chief Scientific Officer, Executive Vice President, Intellia Therapeutics
Doug Williams, PhD
  • CEO, Codiak BioSciences
  • Q&A

    2:10 PM – 2:25 PM
2:10 PM – 2:20 PM

FIRST LOOK

Enhancing vesicles for therapeutic delivery of bioproducts

Xandra Breakefield, PhD
  • Geneticist, MGH, MGH
  • Professor, Neurology, HMS
  • Q&A

    2:20 PM – 2:35 PM
2:20 PM – 2:30 PM

FIRST LOOK
2:55 PM – 3:20 PM

HOT TOPICS

Gene Editing | Achieving Therapeutic Mainstream

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

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

  • Successes in gene editing – lessons learned from late-stage assets (sickle cell, ophthalmology)
  • When to use what editing tool – pros and cons of traditional gene-editing v. base editing.  Is prime editing the future? Specific use cases for epigenetic editing.
  • When we reach widespread clinical use – role of off-target editing – is the risk real?  How will we mitigate? How practical is patient-specific off-target evaluation?
Moderator:
J. Keith Joung, MD, PhD
  • Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
  • Professor of Pathology, HMS
Speakers:
John Evans
  • CEO, Beam Therapeutics
Lisa Michaels
  • EVP & CMO, Editas Medicine
  • Q&A

    3:25 PM – 3:50 PM
3:25 PM – 3:50 PM

HOT TOPICS

Common Blood Disorders | Gene Therapy

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

  • What are the pros and cons of various strategies for treatment? There are AAV-based editing, non-viral delivery even oligonucleotide recruitment of endogenous editing/repair mechanisms. Which approaches are most appropriate for which disease?
  • How can companies increase the speed of recruitment for clinical trials when other treatments are available? What is the best approach to educate patients on a novel therapeutic?
  • How do we best address ethnic and socio-economic diversity to be more representative of the target patient population?
  • How long do we have to follow up with the patients from the scientific, patient’s community, and payer points of view? What are the current FDA and EMA guidelines for long-term follow-up?
  • Where are we with regards to surrogate endpoints and their application to clinically meaningful endpoints?
  • What are the emerging ethical dilemmas in pediatric gene therapy research? Are there challenges with informed consent and pediatric assent for trial participation?
  • Are there differences in reimbursement policies for these different blood disorders? Clearly durability of response is a big factor. Are there other considerations?
Moderator:
David Scadden, MD
  • Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH
  • Jordan Professor of Medicine, HMS
Speakers:
Samarth Kukarni, PhD
Nick Leschly
  • Chief Bluebird, Bluebird Bio
Mike McCune, MD, PhD
  • Head, HIV Frontiers, Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation
  • Q&A

    3:55 PM – 4:15 PM
3:50 PM – 4:00 PM

FIRST LOOK

Gene Editing

J. Keith Joung, MD, PhD
  • Robert B. Colvin, M.D. Endowed Chair in Pathology & Pathologist, MGH
  • Professor of Pathology, HMS
  • Q&A

    4:00 PM – 4:20 PM
4:20 PM – 4:45 PM

HOT TOPICS

Gene Expression | Modulating with Oligonucleotide-Based Therapies

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

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

  • Will oligonucleotides improve as a class that will make them even more effective?   Are further advancements in backbone chemistry anticipated, for example.
  • Will oligonucleotide based therapies blaze trails for follow-on gene therapy products?
  • Are small molecules a threat to oligonucleotide-based therapies?
  • Beyond exon skipping and knock-down mechanisms, what other roles will oligonucleotide-based therapies take mechanistically — can genes be activating oligonucleotides?  Is there a place for multiple mechanism oligonucleotide medicines?
  • Are there any advantages of RNAi-based oligonucleotides over ASOs, and if so for what use?
Moderator:
Jeannie Lee, MD, PhD
  • Molecular Biologist, MGH
  • Professor of Genetics, HMS
Speakers:
Bob Brown, PhD
  • CSO, EVP of R&D, Dicerna
Brett Monia, PhD
  • CEO, Ionis
Alfred Sandrock, MD, PhD
  • EVP, R&D and CMO, Biogen
  • Q&A

    4:50 PM – 5:05 PM
4:45 PM – 4:55 PM

FIRST LOOK

RNA therapy for brain cancer

Pierpaolo Peruzzi, MD, PhD
  • Nuerosurgery, BWH
  • Assistant Professor of Neurosurgery, HMS
  • Q&A

    4:55 PM – 5:15 PM
8:30 AM – 8:55 AM

Venture Investing | Shaping GCT Translation

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

Moderator:
Meredith Fisher, PhD
  • Partner, Mass General Brigham Innovation Fund
Speakers:
David Berry, MD, PhD
  • CEO, Valo Health
  • General Partner, Flagship Pioneering
Robert Nelsen
  • Managing Director, Co-founder, ARCH Venture Partners
Kush Parmar, MD, PhD
  • Managing Partner, 5AM Ventures
  • Q&A

    9:00 AM – 9:15 AM
9:00 AM – 9:25 AM

Regenerative Medicine | Stem Cells

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

  • Stem cell sourcing
  • Therapeutic indication growth
  • Genetic and other modification in cell production
  • Cell production to final product optimization and challenges
  • How to optimize the final product
Moderator:
Ole Isacson, MD, PhD
  • Director, Neuroregeneration Research Institute, McLean
  • Professor, Neurology and Neuroscience, HMS
Speakers:
Kapil Bharti, PhD
  • Senior Investigator, Ocular and Stem Cell Translational Research Section, NIH
Joe Burns, PhD
  • VP, Head of Biology, Decibel Therapeutics
Erin Kimbrel, PhD
  • Executive Director, Regenerative Medicine, Astellas
Nabiha Saklayen, PhD
  • CEO and Co-Founder, Cellino
  • Q&A

    9:30 AM – 9:45 AM
9:25 AM – 9:35 AM

FIRST LOOK

Stem Cells

Bob Carter, MD, PhD
  • Chairman, Department of Neurosurgery, MGH
  • William and Elizabeth Sweet, Professor of Neurosurgery, HMS
  • Q&A

    9:35 AM – 9:55 AM
9:35 AM – 10:00 AM

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

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

Moderator:
Roger Kitterman
  • VP, Venture, Mass General Brigham
Speakers:
Ellen Hukkelhoven, PhD
  • Managing Director, Perceptive Advisors
Peter Kolchinsky, PhD
  • Founder and Managing Partner, RA Capital Management
Deep Nishar
  • Senior Managing Partner, SoftBank Investment Advisors
Oleg Nodelman
  • Founder & Managing Partner, EcoR1 Capital
  • Q&A

    10:05 AM – 10:20 AM
10:00 AM – 10:10 AM

FIRST LOOK
10:10 AM – 10:35 AM

HOT TOPICS

Neurodegenerative Clinical Outcomes | Achieving GCT Success

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

  •  What are the commonalities driving GCT success in neurodegenerative disease and non-neurologic disease, what are the key differences?
  • Overcoming treatment administration challenges
  • GCT impact on degenerative stage of disease
  • How difficult will it be to titrate the size of the cell therapy effect in different neurological disorders and for different patients?
  • Demonstrating clinical value to patients and payers
  • Revised clinical trial models to address issues and concerns specific to GCT
Moderator:
Bob Carter, MD, PhD
  • Chairman, Department of Neurosurgery, MGH
  • William and Elizabeth Sweet, Professor of Neurosurgery, HMS
Speakers:
Erwan Bezard, PhD
  • INSERM Research Director, Institute of Neurodegenerative Diseases
Nikola Kojic, PhD
  • CEO and Co-Founder, Oryon Cell Therapies
Geoff MacKay
  • President & CEO, AVROBIO
Viviane Tabar, MD
  • Founding Investigator, BlueRock Therapeutics
  • Chair of Neurosurgery, Memorial Sloan Kettering
  • Q&A

    10:40 AM – 10:55 AM
10:35 AM – 11:35 AM

Disruptive Dozen: 12 Technologies that Will Reinvent GCT

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

11:35 AM – 11:45 AM

Concluding Remarks

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

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

In-vitro fertilisation (IVF) is now regarded as a huge clinical success which has benefitted an estimated 16 million parents, at the time the development not only sparked moral outrage but led to political and legislative constraints. Patients undergoing IVF may be presented with numerous assisted reproductive treatments purportedly increasing the chances of pregnancy. Such commercialised “IVF add-ons” often come at high costs without clinical evidence of validity. Additionally, long-term studies of children born through IVF have historically been scarce and inconsistent in their data collection. This has meant that potential genetic predispositions, such as increased body fat composition and blood pressure, as well as congenital abnormalities long associated with IVF births, lack proof of causality.

 

With Preimplantation genetic testing mutated embryos are automatically discarded, whereas CRISPR could correct mutations to increase the number of viable embryos for implantation. Moreover, in instances where all embryos in a given cycle are destined to develop with severe or lethal mutations, CRISPR could bring success for otherwise doomed IVF treatments. Genetic screening programs offered to couples in hot-spot areas of carrier frequency of monogenic disorders have had huge success in alleviating regional disease burdens. Carried out since the 1970s these programs have altered the course of natural evolution, but few would dispute their benefits in preventing heritable disease transmission.

 

Mutations are as inevitable as death and taxes. Whilst age is considered one of the largest factors in de-novo mutation generation, it appears that these are inherited primarily from the paternal line. Thus, the paternal age of conception predominantly determines the mutation frequency inherited by children. Whereas advanced maternal age is not associated with mutagenic allele frequency but chromosomal abnormalities. The risk of aneuploidy rises steadily in mothers over the age of 26. Although embryos are screened for aneuploidy prior to implantation, with so many other factors simultaneously being screened the probability of having enough embryos remaining to allow for 50% rate of blastocyte development in-vitro are often fairly low.

 

Despite IVF being used routinely for over 40 years now, it’s not abundantly clear if, or how often, IVF may introduce genomic alternations or off-target affects in embryos. Likewise, scientists and clinicians are often unable to scrutinise changes produced through natural cellular processes including recombination and aging. So, it may be OK to do controlled experiments on using CRISPR to try and prevent multi-generational suffering. But, there has to be a long term investigation on the side effects of germline genome editing. Science has advanced a lot but still there are lot of things that are yet to be described or discovered by science. Trying to reduce human suffering should not give rise to new bigger sufferings and care must be taken not to create a Frankenstein.

 

References:

 

http://www.frontlinegenomics.com/news/29321/opinion-piece-morally-is-germline-genome-editing-all-that-different-to-ivf/

 

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From Technicall.y Philly.com

Reporter: Stephen J. Williams, PhD

Spark Therapeutics’ $4.8B deal confirmed as biggest-ever VC-backed exit in Philly

Quick update on this week’s news: The University City life sciences company’s acquisition by Swiss pharma giant Roche is the biggest acquisition ever of a VC-backed company within city limits, per PitchBook and PACT.

The eye-popping $4.8 billion sticker price on Spark Therapeutics’acquisition deal with Roche announced on Monday is shaping up to be the largest exit ever within city limits for a venture-backed company, according to data from financial data provider PitchBook and the Philadelphia Alliance for Capital and Technologies (PACT).

“Filtering down to just Philadelphia proper does reveal that Spark Therapeutics, once the deal closes, will be the biggest exit ever for Philly-based venture-backed exits,” the company said in an email, citing data from an upcoming report.

According to the Seattle-based company’s data, the current holder of the largest Philly-proper exit title goes to Avid Radiopharmaceuticals, which in 2010 announced its acquisition by Lilly in a deal valued at up to $800 million.

Founded in 2013, Spark is a publicly traded spinout of Children’s Hospital of Philadelphia (CHOP), which invested $33 million in the company. The Philadelphia Inquirer reports that CHOP stands to reap a total return of $430 million for its minority stake in Spark Therapeutics.

As part of the acquisition deal, the company will remain based out of 3711 Market St., and continue to do business as a standalone Roche company.

“This transaction demonstrates the enormous value that global biotech companies like Roche see in gene therapy, a field in which Philadelphia is the unquestioned leader,” said Saul Behar, senior VP of  advancement and strategic initiatives at the University City Science Center, the West Philly research park where Spark began and grew its operations. “[This] further validates Greater Philadelphia’s status as a biotech hub with a very bright future.”

Spark CEO Jeff Marrazzo said the deep pool of resources from Roche, the company plans to “accelerate the development of more gene therapies for more patients for more diseases and further expedite our vision of a world where no life is limited by genetic disease.”

Other articles on Gene Therapy and Retinal Disease on this Open Access Online Journal include:

Women Leaders in Cell and Gene Therapy

AGTC (AGTC) , An adenoviral gene therapy startup, expands in Florida with help from $1 billion deal with Biogen

Artificial Vision: Cornell and Stanford Researchers crack Retinal Code

D-Eye: a smartphone-based retinal imaging system

 

 

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The Puzzle of Stem Cells and Cancer Stem Cells: The MIT Stem Cell Initiative

Reporter: Irina Robu, PhD

The MIT Stem Cell Initiative is looking to research fundamental biological questions about normal adult stem cells and their malignant counterparts, cancer stem cells. The MIT Stem Cell Initiative is applying new technologies and approaches in pursuit of this goal. In particular, the MIT Stem Cell Initiative has focused on the breast and colon, as these tissues are quite different from each other, yet each constitutes a major portion of cancer occurrence. The program purposes are to

(a) identify the stem cells and cancer stem cells in various tissues and tumor types,

(b) control how these cells change during aging or with disease progression and

(c) determine the similarities and differences between

  • normal cells, and
  • cancer stem cells,

with the goal of finding weaknesses in cancer stem cells that can be feasible and exact targets for treatment.

In due course, the ability to identify, purify, and establish several populations of stem cells and cancer stem cells could aid researchers to understand the biology of these cells, and learn how to exploit them more efficiently in regenerative medicine applications and target them in cancer.

Normal adult stem cells are undifferentiated cells within a tissue that divide to produce two daughter cells and divide periodically to replenish or repair the tissue. One of the two daughter cells remain in the stem cell state and the other adopts a partially differentiated state, then goes on to divide and differentiate further to harvest multiple cell types that form that tissue. The division process is through a precise process to ensure that tissues are restricted to the appropriate size and cell content.

Cancer stem cells perform the same division but, rather than differentiating, the additional cells produced by the second daughter cell amass to form the bulk of the tumor.

  • Cancer stem cells can regrow the tumor, and
  • are frequently resistant to chemotherapy.

This exclusive ability of normal and cancer stem cells to both self-renew and form a tissue or tumor is referred to by researchers as “stemness,” and has important implications for biomedical applications.

As a result, cancer stem cells are thought to be responsible for

  • tumor recurrence after remission, and also for the
  • formation of metastases, which account for the majority of cancer-associated deaths.

Accordingly, an anti-cancer stem cell therapy that can target and kill cancer stem cells is one of the holy grail of cancer treatment as means to suppress both tumor recurrence and metastatic disease. One of the important tasks to studying normal and cancer stem cells, and to ultimately harnessing that knowledge is developing the ability to identify, purify, and propagate these cells. Accordingly, the main goal in stem cell and cancer stem cell research is discovering ways to distinguish them, preferably by identifying unique surface markers that can be used to cleanse stem cell and cancer stem cell populations and enable their study.

New technologies are permitting the researchers to make significant headway in these investigations, progress that was not possible just a few years ago. Explicitly, they are using

  • a mixture of specially cultured cells,
  • highly controllable mouse models of cancer, and s
  • ingle-cell RNA sequencing and
  • computational analysis techniques that are extremely matched to extracting an excessive deal of information from the moderately small number of stem cells.

SOURCE

http://news.mit.edu/2018/mit-initiative-delves-into-stem-cell-biology-1015

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NHLBI decision to halt Heart Stem-Cell Study (CONCERT-HF trial) due to concerns about Anversa’s Animal Studies, not due to any Data generated by the Clinical trial itself, no compromised patient safety by trial

Reporter: Aviva Lev-Ari, PhD, RN

Doubts about Anversa’s work arose in the early 2000s after other researchers failed to replicate his findings and questioned whether cardiac stem cells existed2,3,4.

Paper of Former HMS Prof. Withdrawn, Clinical Trial Paused after Harvard Requests Retractions

https://www.thecrimson.com/article/2018/10/31/medical-school-paper-retracted/

NHLBI NEWS

Statement

Statement on NHLBI decision to pause the CONCERT-HF trial

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is pausing the CONCERT-HF trialexternal link, which involves patients with chronic heart failure. Recent calls for the retraction of journal articles in related fields of cell therapy research have raised concerns about the scientific foundations of this trial.  While none of the articles in question derive from the CONCERT-HF trial itself, the NHLBI convened CONCERT-HF’s Data and Safety Monitoring Board (DSMB) out of an abundance of caution to ensure the study continues to meet the highest standards for participant safety and scientific integrity. Informed by the DSMB recommendations of October 25, 2018, the NHLBI is pausing the trial. While the DSMB did not have any participant safety concerns, this pause enables the DSMB to complete its review.

The safety of all clinical trial participants is paramount to NHLBI. NHLBI will honor its commitment to CONCERT-HF participants and continue the follow-up protocol during this pause for all participants who have already been treated in the study. Participants are being notified of the status of the trial and how to request additional information.

The CONCERT-HF trial seeks to determine whether c-kit+ cells, either alone or in combination with mesenchymal stem cells derived from the bone marrow, are safe and benefit patients with chronic heart failure, who have very limited treatment options. Despite significant medical and surgical advances, patients with heart failure continue to experience a low quality of life and about half of them will die within five years of receiving a diagnosis.

The scientific basis of CONCERT-HF is supported by a body of evidence in several preclinical models in a number of studies in a variety of laboratories and was reviewed by a Protocol Review Committee (PRC) independent of the trial. The cell therapies that CONCERT-HF is testing are under an investigational new drug (IND) designation which is overseen by the U.S. Food and Drug Administration (FDA). The cells are produced by an accredited laboratory independent of the clinical sites. In addition, as part of standard oversight of clinical trials, the DSMB routinely reviews and monitors CONCERT-HF to ensure participant safety and that the study continues to ask compelling scientific questions with implications for patient care.

The DSMB’s review will be conducted as expeditiously as possible and will inform NHLBI’s future actions that will ensure the highest standards of participant safety and scientific integrity.

SOURCE

https://www.nhlbi.nih.gov/news/2018/statement-nhlbi-decision-pause-concert-hf-trial

References

  1. Quaini, F. et al. N. Engl. J. Med. 346, 5–15 (2002).
  1. Murry, C. E. et al. Nature 428, 664–668 (2004).
  1. Balsam, L. B. Nature 428, 668–673 (2004).
  1. Nygren, J. M. et al. Nature Med. 10, 494–501 (2004).

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Stem Cells Used as Delivery Truck for Brain Cancer Drugs

Reporter: Irina Robu, PhD

Medulloblastoma, common brain cancer in children has been very difficult to treat therapeutically with traditional interventions which relies on surgical techniques to remove the bulk of the cancerous tissue. The researchers seen the need for novel treatments of medulloblastomas that have recurred, as well as for treatments that are less toxic overall. For this reason, data from University of North Carolina (UNC) Lineberger Comprehensive Cancer Center and  Eshelman School of Pharmacy published a study in PLOS named “Intra-cavity stem cell therapy inhibits tumor progression in a novel murine model of medulloblastoma surgical resection”, validates how cancer-hunting stem cells can track down and deliver a drug to terminate medulloblastoma cells hiding after surgery.

The technology in the research is an extension of a discovery that won researchers a Nobel Prize in 2012 and showed they could transform skin cells into stem cells. The research team started by reprogramming skin cells into stem cells and genetically engineered them to manufacture a substance that becomes toxic to other cells when exposed to another drug. Inserting the drug carries the stem cells into the brain of laboratory models after surgery decreased the size of tumors by 15 times and extended median survival in mice by 133%.

In this study, the scientists indicated they could shrink tumors in murine models of medulloblastoma, hence extending the rodents life. The approach holds promise for reducing side effects and helping more children with medulloblastoma. Amazingly the researchers also developed a laboratory model of medulloblastoma that allowed them to simulate the way standard care is currently delivered—surgery followed by drug therapy. Using this model, they discovered that after surgically removing a tumor, the cancer cells that remained grew faster.

According to the study investigator, Shawn Hingtgen, PhD, the cells are like a FedEx truck that will deliver cytotoxic agents directly into the tumor to a particular location. In earlier studies, Dr. Hingtgen and his colleagues showed that they could flip skin cells into stem cells that hunt and transport cancer-killing drugs to glioblastoma, the deadliest malignant brain tumor in adults.

Medulloblastoma is cancer that happens mostly in kids between ages of three and eight, and while current therapy has changed survival pretty dramatically, it can still be pretty toxic. The ability to use a patient’s own cells to target the tumor directly would be “the holy grail” of therapy, the investigators trust it could hold capacity for other rare, and sometimes fatal, brain cancer types that occur in children as well.

Source

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198596

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Collaboration that corrected a major problem in Hip Replacement Surgery

Reporter:Irina Robu, PhD

British orthopedic surgeon, John Charnley performed an operation that almost miraculously restored pain-free movement and active lives to patients whose hip-joint damage had made even the simple act of walking across the room difficult.

However, with the advance in materials Charnley removed the damaged joint and replaced it with one made of Teflon. He cut off the top of the thigh bone and inserted the end of a rod like metal implant into its center, cementing it in place. The round head of the implant fits perfectly into the Teflon hip socket. The procedure seemed to work, but within some year complications arose. The routine movement of the balls in the sockets made the Teflon wear quickly, loosening the implants. Charnley was required to operate on nearly 300 patients after they developed an infection around the implant.
Charnley filled that need with a more-resistant material called high-density polyethylene, which he began using in a new version of the artificial hip joint in 1962. In 1974, a noted orthopedic surgeon at Massachusetts General Hospital had a patient who had replaced surgery but his X-ray showed that a large portion of his thigh bone had been eaten away. Even after further tests, it was confirmed that the patient was cancer free. Harris saw three similar cases that year and many more over the years and it was defined as a new disease, periprosthetic osteolysis.

The condition led not just to implant failures, hip fractures, femur fractures, and complex reoperations to install new implants. It would take decades to devise a solution, in the form of a new material , highly crosslinked polyethylene invented in the labs of Harris and his Massachusetts Institute of Technology collaborator, Edward Merrill. A few years after Harris described the condition, in 1976, another separate research effort drawn its cause to tiny particles of the cement that secured the metal thigh implant inside the femur. Those particles caused a massive immune reaction that in turn triggered osteoclasts, the only cell in the body capable of destroying bone.

The discovery led to the condition being called “cement disease,” warning the development in the early 1980s of porous-metal implants that allowed the bone to grow into the implant and hold it in place in the thigh bone. Further research displayed that particles were still there, but of the polyethylene that made up the hip socket. Nevertheless, the polyethylene was far more durable than Teflon, the even motion of the ball in the socket caused wear, producing particles that set off the same destructive immune reaction.

By that discovery, researchers finally understood what was happening in the body. With so many hip replacement surgeries ongoing around the world, what was needed was a material more durable as polyethylene. Harris had asked patients to donate implants for study after they died, and he worked with lab members to examine them under a scanning electron microscope. The long, skinny molecules of high-density polyethylene, which normally curl had become aligned in the direction of the back-and-forth motion of the joint.

Harris worked with Merrill who mentioned that he can created polyethylene into a new form: highly crosslinked polyethylene. Meanwhile in 1998, the first artificial hips using highly crosslinked polyethylene were put in patients and it shows a huge progress.

SOURCE

Harvard surgeon publishes ‘Vanishing Bone: Conquering a Stealth Disease Caused by Total Hip Replacements’

 

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Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders at https://www.amazon.com/dp/B078313281 – electronic Table of Contents 

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

Available on Kindle Store @ Amazon.com since 12/9/2017

List of Contributors & Contributors’ Biographies

Volume Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Preface, all Introductions, all Summaries and Epilogue

Part One:

1.4, 1.5, 1.6, 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.2.1, 2.2.2, 2.2.3, 2.3, 2.4, 2.4.1, 2.4.2, 2.5, 2.6.1, 2.6.2, 2.6.3, 2.6.4, 2.7, 2.8, 2.9, 2.10, 3.1, 3.2, 3.3, 3.4, 4.1, 4.2, 4.3

Part Two:

5.2, 5.3, 5.6, 6.1.2, 6.1.4, 6.2.1, 6.2.2, 6.3.2, 6.3.4, 6.3.5, 6.3.6, 6.3.8, 6.3.10, 6.4.1, 6.4.2, 6.5.1.2, 6.5.1.3, 6.5.2.2, 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 8.9.1, 8.9.3, 8.9.4, 8.9.5, 8.9.6, 8.10.1, 8.10.2, 8.10.3, 8.10.4, 9.2, 9.3, 9.5, 9.6, 9.7, 9.8, 9.9, 9.10, 9.11, 9.12, 9.13, 9.14, 9.15, 9.16, 10.2, 10.5, 10.6, 10.7, 10.8, 10.10, 10.11, 11.1, 11.2, 11.3, 11.5, 11.6, 11.7, 12.1, 12.2, 12.3, 12.4, 12.5, 12.7, 12.8, 12.9, 12.10, 12.11, 12.12, 13.1, 13.2, 13.3, 13.6, 13.12, 13.13, 14.1, 14.2

Guest Authors:

Pnina Abir-Am, PhD Part Two: 6.1.1

Stephen J Williams, PhDPart Two: 6.2.6, 6.5.2.2, 10.4, 10.9, 13.4

Aviva Lev-Ari, PhD, RN:

Part One:

1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2.2.1, 2.3

Part Two:

5.1, 5.4, 5.5, 5.7, 5.8, 5.9, 5.10, 5.11, 6.1.3, 6.2.3, 6.2.4, 6.2.5, 6.3.1, 6.3.3, 6.3.7, 6.3.9, 6.4.3, 6.5.1.1, 6.5.2.1, 6.5.2.2, 6.5.3.1, 6.5.4, 6.5.5, 6,5,6, 8.9.2, 8.10.2, 9.1, 9.4, 10.1, 10.3, 11.4, 12.6, 13.5, 13.7, 13.8, 13.9, 13.10, 13.11

Adam Sonnenberg, BSC, MSc(c)Part Two: 13.9

 

electronic Table of Contents

PART ONE:

Physician as Authors, Writers in Medicine and Educator in Public Health

 

Chapter 1: Physicians as Authors

Introduction

1.1  The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy – Best writers Among the WRITERS

1.2 Atul Gawande: Physician and Writer

1.3 Editorial & Publication of Articles in e-Books by  Leaders in Pharmaceutical Business Intelligence:  Contributions of Larry H Bernstein, MD, FCAP

1.4 Abraham Verghese, MD, Physician and Notable Author

1.5 Eric Topol, M.D.

1.6 Gregory House, MD

1.7 Peter Mueller, MD  Professor of Radiology @MGH & HMS – 2015 Synergy’s Honorary Award Recipient

Summary

Chapter 2: Professional Recognition

Introduction

2.1 Proceedings

2.1.1 Research Presentations

2.1.2 Proceedings of the NYAS

2.1.3 Cold Spring Harbor Conference Meetings

2.1.4 Young Scientist Seminars

2.2 Meet Great Minds

2.2.1 Meet the Laureates

2.2.2 Richard Feynman, Genius and Laureate

2.2.3 Fractals and Heat Energy

2.3 MacArthur Foundation Awards

2.4 Women’s Contributions went beyond Rosie the Riveter

2.4.1 Secret Maoist Chinese Operation Conquered Malaria

2.4.2 Antiparasite Drug Developers Win Nobel

2.5 Impact Factors and Achievement

2.6   RAPsodisiac Medicine

2.6.1 Outstanding-achievements-in-radiology-or-radiotherapy

2.6.2 Outstanding-achievement-in-anesthesiology

2.6.3 Outstanding-achievement-in-pathology

2.6.4 Topics in Pathology – Special Issues from Medscape Pathology

2.7 How to win the Nobel Prize

2.8 Conversations about Medicine

2.9 Current Advances in Medical Technology

2.10 Atul Butte, MD, PhD

Summary

Chapter 3:  Medical and Allied Health Sciences Education

Introduction

3.1 National Outstanding Medical Student Award Winners

3.2 Outstanding Awards in Medical Education

3.3 Promoting Excellence in Physicians and Nurses

3.4 Excellence in mentoring

Summary

Chapter 4: Science Teaching in Math and Technology (STEM)

Introduction

4.1 Science Teaching in Math and Technology

4.2 Television as a Medium for Science Education

4.2.1 Science Discovery TV

4.3 From Turing to Watson

Summary

PART TWO:

Medical Scientific Discoveries Interviews with Scientific Leaders

Chapter 5: Cardiovascular System

Introduction

5.1 Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

5.2 Mitochondrial Dysfunction and Cardiac Disorders

5.3 Notable Contributions to Regenerative Cardiology

5.4 For Accomplishments in Cardiology and Cardiovascular Diseases: The Arrigo Recordati International Prize for Scientific Research

5.5 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

5.6 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

5.7 CVD Prevention and Evaluation of Cardiovascular Imaging Modalities: Coronary Calcium Score by CT Scan Screening to justify or not the Use of Statin

5.8 2013 as A Year of Revolutionizing Medicine and Top 11 Cardiology Stories

5.9 Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013

5.10 Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

5.11 Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Summary

Chapter 6: Genomics

Introduction
6.1 Genetics before the Human Genome Project

6.1.1 Why did Pauling Lose the “Race” to James Watson and Francis Crick? How Crick Describes his Discovery in a Letter to his Son

6.1.2 John Randall’s MRC Research Unit and Rosalind Franklin’s role at Kings College

6.1.3 Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin

6.1.4 The Initiation and Growth of Molecular Biology and Genomics, Part I

6.2 The Human Genome Project: Articles of Note  @ pharmaceuticalintelligence.com by multiple authors

6.2.1 CRACKING THE CODE OF HUMAN LIFE: The Birth of BioInformatics & Computational Genomics

6.2.2 What comes after finishing the Euchromatic Sequence of the Human Genome?

6.2.3 Human Genome Project – 10th Anniversary: Interview with Kevin Davies, PhD – The $1000 Genome

6.2.4 University of California Santa Cruz’s Genomics Institute will create a Map of Human Genetic Variations

6.2.5 Exceptional Genomes: The Process to find them

6.2.6 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

6.3 The Impact of Genome Sequencing on Biology and Medicine

6.3.1 Genomics in Medicine – Establishing a Patient-Centric View of Genomic Data

6.3.2 Modification of genes by homologous recombination – Mario Capecchi, Martin Evans, Oliver Smithies

6.3.3 AAAS February 14-18, 2013, Boston: Symposia – The Science of Uncertainty in Genomic Medicine

6.3.4 The Metabolic View of Epigenetic Expression

6.3.5  Pharmacogenomics

6.3.6 Neonatal Pathophysiology

6.3.7 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

6.3.8 3D mapping of genome in combine FISH and RNAi

6.3.9 Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence

6.3.10 DNA mutagenesis and DNA repair

6.4 Scientific Leadership Recognition for Contributions to Genomics

6.4.1 Interview with Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak (44 minutes)

6.4.2 DNA Repair Pioneers Win Nobel – Tomas Lindahl, Paul Modrich, and Aziz Sancar 2015 Nobel Prize in Chemistry for the mechanisms of DNA repair

6.4.3  Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

6.5 Contemporary Field Leaders in Genomics

6.5.1 ROBERT LANGER

6.5.1.1 2014 Breakthrough Prizes Awarded in Fundamental Physics and Life Sciences for a Total of $21 Million – MIT’s Robert Langer gets $3 Million

6.5.1.2 National Medal of Science – 2006 Robert S. Langer

6.5.1.3  Confluence of Chemistry, Physics, and Biology

6.5.2 JENNIFER DOUDNA

6.5.2.1 Jennifer Doudna, cosmology teams named 2015 Breakthrough Prize winners

6.5.2.2 UPDATED – Medical Interpretation of the Genomics Frontier – CRISPR – Cas9: Gene Editing Technology for New Therapeutics

6.5.3 ERIC LANDER

6.5.3.1  2012 Harvey Prize in April 30: at the Technion-Israel Institute of Technology to Eric S. Lander @MIT & Eli Yablonovitch @UC, Berkeley

6.5.4 2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

6.5.5 Recognitions for Contributions in Genomics by Dan David Prize Awards

6.5.6   65 Nobel Laureates meet 650 young scientists covering the fields of physiology and medicine, physics, and chemistry, 28 June – 3 July, 2015, Lindau & Mainau Island, Germany

Summary

Chapter 7: The RNAs

Introduction

7.1 RNA polymerase – molecular basis for DNA transcription – Roger Kornberg, MD

7.2  One gene, one protein – Charles Yanofsky

7.3 Turning genetic information into working proteins – James E. Darnell Jr.

7.4 Small but mighty RNAs – Victor Ambros, David Baulcombe, and Gary Ruvkun, Phillip A. Sharp

7.5 Stress-response gene networks – Nina V. Fedoroff

Summary

Chapter 8: Proteomics, Protein-folding, and Cell Regulation
Introduction.

8.1 The Life and Work of Allan Wilson

8.2 Proteomics

8.3 More Complexity in Protein Evolution

8.4 Proteins: An evolutionary record of diversity and adaptation

8.5 Heroes in Basic Medical Research – Leroy Hood

8.6 Ubiquitin researchers win Nobel – Ciechanover, Hershko, and Rose awarded for discovery of ubiquitin-mediated proteolysis

8.7 Buffering of genetic modules involved in tricarboxylic acid cycle metabolism provides homeostatic regulation

8.8 Dynamic Protein Profiling

8.9 Protein folding

8.9.1 Protein misfolding and prions – Susan L. Lindquist, Stanley B. Prusiner

8.9.2 A Curated Census of Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy

8.9.3 Voluntary and Involuntary S-Insufficiency

8.9.4 Transthyretin and Lean Body Mass in Stable and Stressed State

8.9.5 The matter of stunting in the Ganges Plains

8.9.6 Proteins, Imaging and Therapeutics

8.10 Protein Folding and Vesicle Cargo

8.10.1 Heat Shock Proteins (HSP) and Molecular Chaperones

8.10.2 Collagen-binding Molecular Chaperone HSP47: Role in Intestinal Fibrosis – colonic epithelial cells and sub epithelial myofibroblasts

8.10.3 Biology, Physiology and Pathophysiology of Heat Shock Proteins

8.10.4 The Role of Exosomes in Metabolic Regulation 


Summary

Chapter 9:  Neuroscience

Introduction

9.1 Nobel Prize in Physiology or Medicine 2013 for Cell Transport: James E. Rothman of Yale University; Randy W. Schekman of the University of California, Berkeley; and Dr. Thomas C. Südhof of Stanford University

9.2 Proteins that control neurotransmitter release – Richard H. Scheller

9.3 Heroes in Basic Medical Research – Robert J. Lefkowitz

9.4 MIND AND MEMORY: BIOLOGICAL AND DIGITAL – 2014 Dan David Prize Symposium

9.5 A new way of moving – Michael Sheetz, James Spudich, Ronald Vale

9.6 Role the basal ganglia

9.7 The Neurogenetics of Language – Patricia Kuhl – 2015 George A. Miller Award

9.8 The structure of our visual system

9.9 Outstanding Achievement in Schizophrenia Research

9.10 George A. Miller, a Pioneer in Cognitive Psychology, Is Dead at 92

9.11 – To understand what happens in the brain to cause mental illness

9.12 Brain and Cognition

9.13 – To reduce symptoms of mental illness and retrain the brain

9.14 Behavior

9.15 Notable Papers in Neurosciences

9.16 Pyrroloquinoline quinone (PQQ) – an unproved supplement

Summary

Chapter 10: Microbiology & Immunology

Introduction

10.1 Reference Genes in the Human Gut Microbiome: The BGI Catalogue

10.2 Malnutrition in India, high newborn death rate and stunting of children age under five years

10.3 In His Own Words: Leonard Herzenberg, The Immunologist Who Revolutionized Research, Dies at 81

10.4 Heroes in Medical Research: Dr. Robert Ting, Ph.D. and Retrovirus in AIDS and Cancer

10.5 Tang Prize for 2014: Immunity and Cancer

10.6 Halstedian model of cancer progression

10.7 The History of Hematology and Related Sciences

10.8 Pathology Emergence in the 21st Century

10.9 Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin

10.10  T cell-mediated immune responses & signaling pathways activated by TLRs – Bruce A. Beutler, Jules A. Hoffmann, Ralph M. Steinman

10.11 Roeder – the coactivator OCA-B, the first cell-specific coactivator, discovered by Roeder in 1992, is unique to immune system B cells

Summary

Chapter 11: Endocrine Hormones

Introduction

11.1 Obesity – 2010 Douglas L. ColemanJeffrey M. Friedman

11.2 Lonely Receptors: RXR – Jensen, Chambon, and Evans – Nuclear receptors provoke RNA production in response to steroid hormones

11.3 The Fred Conrad Koch Lifetime Achievement Award—the Society’s highest honor—recognizes the lifetime achievements and exceptional contributions of an individual to the field of endocrinology

11.4 Gerald D Aurbach Award for Outstanding Translational Research

11.5 Roy O. Greep Award for Outstanding Research in Endocrinology – Martin M. Matzuk

11.6 American Physiology Society Awards

11.7 Solomon Berson and Rosalyn Yalow

Summary

Chapter 12. Stem Cells

Introduction

12.1 Mature cells can be reprogrammed to become pluripotent – John Gurdon and Shinya Yamanaka

12.2 Observing the spleen colonies in mice and proving the existence of stem cells – Till and McCulloch

12.3 McEwen Award for Innovation: Irving Weissman, M.D., Stanford School of Medicine, and Hans Clevers, M.D., Ph.D., Hubrecht Institute

12.4 Developmental biology

12.5  CRISPR/Cas-mediated genome engineering – Rudolf Jaenisch

12.6 Ribozymes and RNA Machines –  Work of Jennifer A. Doudna

12.7 Ralph Brinster, ‘Father of Transgenesis’

12.8 Targeted gene modification

12.9 Stem Cells and Cancer

12.10 ALPSP Awards

12.11 Eppendorf Award for Young European Investigators

12.12 Breaking news about genomic engineering, T2DM and cancer treatments

Summary
Chapter 13: 3D Printing and Medical Application

Introduction

13.1 3D Printing

13.2 What is 3D printing?

13.3 The Scientist Who Is Making 3D Printing More Human

13.4 Join These Medical 3D Printing Groups on Twitter and LinkedIn for great up to date news

13.5 Neri Oxman and her Mediated Matter group @MIT Media Lab have developed a technique for 3D-printing Molten Glass

13.6 The ‘chemputer’ that could print out any drug

13.7 3-D-Bioprinting in use to Create Cardiac Living Tissue: Print your Heart out

13.8 LPBI’s Perspective on Medical and Life Sciences Applications – 3D Printing: BioInks, BioMaterials-BioPolymer

13.9 Medical MEMS, Sensors and 3D Printing: Frontier in Process Control of BioMaterials

13.10 NIH and FDA on 3D Printing in Medical Applications: Views for On-demand Drug Printing, in-Situ direct Tissue Repair and Printed Organs for Live Implants

13.11 ‘Pop-up’ fabrication technique trumps 3D printing

13.12 Augmentation of the ONTOLOGY of the 3D Printing Research

13.13 Superresolution Microscopy

Summary

Chapter 14: Synthetic Medicinal Chemistry

Introduction

14.1 Insights in Biological and Synthetic Medicinal Chemistry

14.2 Breakthrough work in cancer

Summary to Part Two

Volume Summary and Conclusions

EPILOGUE

 

 

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LIVE Key Note Presentations @Biotech Week Boston, October 5, 2016 3:25PM

Boston Convention and Exhibition Center

 

#BiotechWeekBoston

 avivalev-ari@alum.berkeley.edu

@pharma_BI

@AVIVA1950

ANNOUNCEMENT

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

pharma_bi-background0238

will cover in REAL TIME

Biotech Week Boston, October 5, 2016 @ Boston Convention and Exhibition Center

 

In Attendance, streaming LIVE using Social Media

Aviva Lev-Ari, PhD, RN

Editor-in-Chief

http://pharmaceuticalintelligence.com

 

Key Sessions

Arnold I. Caplan, Ph.D.

Adult Mesenchymal Stem Cells: The New Medicine

Case Western Reserve University

  • HSC – hematopoietic Stem Cells
  • MSC – mesengenic in vitro not in Tissue Engineering – can be derived from multiple tissue sources
  1. all MSC are Pericytes cells on capillaries and microvessels – CD34 CD146
  2. during injury – pericyte – differentiates – sentinal fro damage and innate tissue regenerations, sense environment
  3. MSC = Medicinal Signaling Cell – the injury specific – 655 Clinical Trials – KIDNEY AND OTHER ORGAN TRANSPLANTATION
  4. hCAP-18/LL37 is secreted by hMSCs
  5. LL37 is in Maternal milk and prevent infection in neonatals
  6. Lipoaspirate
  7. immunomodulatory and Trophic activity
  8. Universal Stem Cell Niche pMSC, Niche
  9. MSCs in cancer metastasis: BRCA, prostate and Melanoma (binding protein) – pericyte pull
  10. http://www.ctte

David DiGiusto, Ph.D.

Building a Sustainable Academic Engine for Feeding De-Risked Assets into the Biopharma Pipeline

Stanford Health Care / Stanford School of Medicine, Cell and Gene Medicine

  1. viral vector
  2. bacterial culture
  3. standard tissue
  • Risks of developing Academic Cell Therapy Products
  • Center for Definitive and Curative Medicine – Regenerative Medicine
  1. translational Staging Score: min 6 points
  2. Scientific Review and Prioritization: 0-9 points
  • Lentiviral vector mediated FOXP3 converts T effector cells into T regulatory cells – CD4 LV-FOXP3
  • CD34 CD90+ blood stem cells: ADM of alpha CD117mAB 0 transplant HSC
  • Cancer Immunotherapy: CD19/CD@@: Leukemia
  • cell transduction
  • Vector Production
  • Plasmid Production
  • Skin DEBnb- low keratinocyte stem cells – neoantigen
  • COmbining CRISPR/Cas9 and rAAV6 mediates High Targeting Efficiencies into peripheral blood CD34+ +HSPCs
  1. Cutting: mRNA and RNP
  2. recombination – AAV only, mRNA : Total population vs Sorted GFP(high)  – get 95% due to Gene correction
  3. Genome editing:
  • starting DNA
  • Edited DNA
  • Edited Protein

4. Closed systems, scalable technology, reagents and automation, clean reagents

5. Invest in the Delivery Channel: Basic Research, Product development, clinical research

6. Transplantation Blood and marrow

7. Cell pharmacy

8. Translational Research : Funding Mix Commercialization, licensing and commercial

9. Infrastructure utilized by every stage of development is different

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