Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
Nearly half of the global population—and 80 percent of patients in therapeutic areas such as immunology—are women. Yet, treatments are frequently developed without tailored insights for female patients, often ignoring critical biological differences such as hormonal impacts, genetic factors, and cellular sex. Historically, women’s health has been narrowly defined through the lens of reproductive organs, while for non-reproductive conditions, women were treated as “small men.” This lack of focus on sex-specific biology has contributed to significant gaps in healthcare.
A recent analysis found that women spend 25 percent more of their lives in poor health compared with men due to the absence of sex-based treatments. Addressing this disparity could not only improve women’s quality of life but also unlock over $1 trillion in annual global GDP by 2040.
Four key factors contribute to the women’s health gap: limited understanding of sex-based biological differences, healthcare systems designed around male physiology, incomplete data that underestimates women’s disease burden, and chronic underfunding of female-focused research. For instance, despite women representing 78 percent of U.S. rheumatoid arthritis patients, only 7 percent of related NIH funding in 2019 targeted female-specific studies.
However, change is happening. Companies have demonstrated how targeted R&D can drive better outcomes for women. These therapies achieved expanded FDA approvals after clinical trials revealed their unique benefits for female patients. Similarly, addressing sex-based treatment gaps in asthma, atrial fibrillation, and tuberculosis could prevent millions of disability-adjusted life years.
By closing the women’s health gap, biopharma companies can drive innovation, improve therapeutic outcomes, and build high-growth markets while addressing long-standing inequities. This untapped opportunity holds the potential to transform global health outcomes for women and create a more equitable future.
Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024
Reporter: Stephen J. Williams, Ph.D.
Endpoints at #JPM24 | Primed to unlock biopharma’s next dealmaking wave
Endpoints at JP Morgan Healthcare Conference
January 8-9 | San Francisco, CA80 Mission St, San Francisco, CA
An oasis has emerged in the biopharma money desert as backers look to replenish capital — still, uncertainty remains on whether it’s a mirage or the much needed dealmaking bump the industry needs. Yet spirits run high as JPM24 marks the triumphant return of inking strategic alliances and peering into the industry crystal ball — while keeping an eye out for some major M&A.
We’re back live from San Francisco for JPM Monday and Tuesday — our calendar of can’t-miss panels and fireside chats will feature prominent biopharma leaders to watch. The Endpoints Hub provides the ultimate coworking space with everything you need — 1:1 and group meeting spots plus guest pass capabilities and more. Join us in-person at the Endpoints Hub or watch online to stay plugged into all the action.
8 JAN
Welcome remarks
8:05 AM – 8:25 AM PST
Pfizer vet Mikael Dolsten has some thoughts on Big Pharma R&D
Endpoints News founding editor John Carroll will sit down with longtime Pfizer CSO Mikael Dolsten to talk about Pfizer’s pipeline, what he’s learned on the job about preclinical research and development and what’s ahead for the pharma giant in drug development and deals.
Mikael Dolsten
Chief Scientific Officer, President, Pfizer Research & Development
Pfizer
Pfizer Mikael Dolsten: Pfizer produced a series of AI generated molecules with new properties. Sees rapid adoption of AI in the area of drug discovery and molecular design.
8:25 AM – 9:05 AM PST
What pharma wants: The industry’s dealmakers look ahead at 2024
The drug industry’s appetite for new assets hasn’t slowed down. Top business development execs will give their outlook on the year, what they’re looking for and how they see the market.
Glenn Hunzinger
Pharmaceutical & Life Sciences Consulting Solutions Leader
PwC US
Rachna Khosla
SVP, Head of Business Development
Amgen
James Sabry
Global Head of Pharma Partnering
Roche
Devang Bhuva
SVP, Corporate Development
Gilead Sciences, Inc.
Endpoints News
Dealmaking panel
Glenn Hunzinger: if you do not have a GLP1 will have a tough time getting a good market price for your company; capital markets are not where they want to be; sees a tough deal making climate like last year. The problem with many biotech companies are they are coming earlier to the venture capital because of greater funding needs and so it is imperative that they articulate the potential of their company in scientific detail
Rachna Khosla: Make sure your investors are not just CAPITAL PARTNERS but use their expertise and involve them in development issues you may have, especially ones that a young firm will face. The problem is most investments assume what the future looks like (for example how antibody drug conjugates, once a field left for dead, has been rejuvenated because of advances in chemistry).
James Sabry: noted that cardiac and metabolic drugs are now at the focus of many investors, especially with the new anti-obesity drugs on market
Devang Bhuva: Most deals we see start as collaborations or partnerships. You want to involve an alliance management team early in the deal making process. This process could take years.
9:05 AM – 9:20 AM PST
The IPO: How Apogee Therapeutics went public in the most challenging market in years
Not many biotechs went public in 2023. And of those that did, not many have had a great time of it. Apogee is the exception and our panel will offer a behind-the-scenes look at their decision to enter the market and what life is like as a young public company.
Michael Henderson
CEO
Apogee Therapeutics
Kyle LaHucik
MODERATOR
Senior Reporter
Endpoints News
Michael Henderson: Not many biotech IPOs deals happened in 2023. Michael feels it is because too many biotechs focused on building platforms, which was a hard sell in 2023. He felt not many biotechs had clear milestones and investors wanted a clear primary validated target. He said many biotech startups are in a funding crunch and most need at least $440M on their balance sheet to get to 2026.
9:50 AM – 10:10 AM PST
Top predictions for biotech in 2024
Catalent CEO Alessandro Maselli will be back at the big JPM healthcare confab to talk with Endpoints News founder John Carroll about their top predictions of what’s coming up for the biotech industry in 2024. The stakes couldn’t be higher as the industry grapples with headwinds and new opportunities in a gale of market forces. Two top observers share their thoughts on the year ahead.
Alessandro Maselli
President & CEO
Catalent
10:15 AM – 10:35 AM PST
Innovation at a crossroads: Keys to unlocking the value of science and technology
The industry has long discussed the promise of technology and the acceleration it provides in scientific advancement and across the industry value chain. However, the promise of its impact has yet to fully be realized. This discussion will outline the keys to unleashing this promise and the implications and actions to be taken by the biopharmaceutical companies across the industry.
Ray Pressburger
North America Life Sciences Industry Lead & Global Life Sciences Strategy Lead
Accenture
SPONSORED BY
10:35 AM – 11:05 AM PST
Activism and Investing: In conversation with Elliott Investment Management’s Marc Steinberg
Elliott has been behind many of 2023’s highest-profile healthcare investments, including multiple activist engagements and taking Syneos Health private. What has made large healthcare companies such interesting investment opportunities for firms like Elliott? What’s Elliott’s investing strategy in healthcare? And what should companies expect when an activist calls?
Marc Steinberg
Senior Portfolio Manager
Elliott Investment Management
Andrew Dunn
MODERATOR
Biopharma Correspondent
Endpoints News
11:05 AM – 11:35 AM PST
Creating ROI from AI
AI is predicted to transform the way drugs are made, from discovery to clinical trials to market. But beyond the initial hype and early adoption, where has AI made meaningful contributions to R&D? How does it help drug developers advance science? Endpoints publisher Arsalan Arif is convening a panel of leading experts to discuss the state of AI in the pharmaceutical landscape and the outlook for 2024. How does AI impact the drug pipeline, from the early steps of discovery to reducing trial failure rate?
Thomas Clozel
Co-Founder & CEO
Owkin
Venkat Sethuraman
SVP, Global Biometrics & Data Sciences
Bristol Myers Squibb
Frank O. Nestle
Global Head of Research & Chief Scientific Officer
Sanofi
Matthias Evers
Chief Business Officer
Evotec
Arsalan Arif
MODERATOR
Founder & Publisher
Endpoints News
SPONSORED BY
11:35 AM – 12:00 PM PST
Biopharma’s dealmaker: Behind the scenes with Centerview Partners co-president Eric Tokat
Almost every major biopharma deal in 2023 had Centerview’s name attached to it. And much of the time, Eric Tokat was the banker making those deals happen. Hear his outlook for 2024, how transactions are getting done and what’s placed his firm at the center of so much action.
E. Eric Tokat
Co-President, Investment Banking
Centerview Partners
CenterView Partners Eric Tokat feels dealmaking will improve in 2024, given the recent flurry of dealmaking at end of last year and right before main JPM Healthcare Conference. He says Centerview wants to help the biotechs they invest in on their strategic path. This may translate into buyers more actively involved (more than startups want) and buyers now are in the drivers seat as far as the timeline of deals and development.
Is the megamerger dead for this year? He says it is very hard to see two major mergers happening but there will be many smaller and mid size biotech deals happening, but these deals will be more speculative in nature.. The focus for large pharma is top line growth. Most of the buyers have an infrastructure and value is more of buying and dropping it in their business so there is now a huge emphasis on due diligence on whether synergies exist or not
12:00 PM – 12:30 PM PST
Founder, legend, leader: In conversation with Nobel laureate Carolyn Bertozzi
Carolyn Bertozzi’s discoveries around bioorthogonal chemistry won the Nobel Prize in Chemistry in 2022 and are at the heart of new therapies being tested in patients. Join us as we discuss what inspires her and where she sees the next big advances.
Carolyn Bertozzi
Prof. of Chemistry, Stanford University and Baker Family Director of Sarafan ChEM-H
Stanford University
Nicole DeFeudis
MODERATOR
Editor
Endpoints News
Bioorthogonal chemistry: class of high yielding chemical reactions that proceed rapidly and selectively in biological environments without side reactions toward endogenous functions. This is also a type of ‘click chemistry’ in biological system where only specifically alter the biomolecule of interest.
Orthogonal: two chemicals not interacting with each other
Dr. Bertozzi noted she has started a new Antibody-Drug-Conjugate (ADC) company which involves designing with biorthogonal chemistry to make new functional molecules with varying properties
She noted hardly any biologists knew anything about glycobiology when she first started. However now she feels pharma and academia are working very well with each other
Bioorthogonal and Click Chemistry Curated by Prof. Carolyn R. Bertozzi, 2022 winner of the Nobel Prize in Chemistry
The 2022 Nobel Prize in Chemistry has been awarded jointly to ACS Central Science Editor-in-Chief, Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research, for the development of click chemistry and bioorthogonal chemistry.
To celebrate this remarkable achievement, 2022 Nobel Prize winner Professor Carolyn R. Bertozzi has curated this Bioorthogonal and Click Chemistry Virtual Issue, highlighting papers published across ACS journals that have built upon the foundational work in this exciting area of chemistry.
Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Examples from the past decade suggest that a promising strategy for bioorthogonal reaction development begins with an analysis of functional group and reactivity space outside those defined by nature. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. Finally, the reaction must be tested in a variety of environments, escalating from aqueous media to biomolecule solutions to cultured cells and, for the most optimized transformations, to live organisms.
9 JAN
9:40 AM – 10:10 AM PST
Biotech downturn survival school
Our panelists have seen the worst, and made it through to the other side. Join us for downturn survival school as our panelists talk about what sets apart the ones who make it through tough times.
These panalists think it will be specialist capital year to shine while the general capital is still sitting on the sidelines
JJ Kang
CEO
Appia Bio
“2023 was a tough year while 2020 was a boon year to start a company. We will continue to see these cycles; many of these new CEOs have never seen a biotech downturn yet and may not know how to preserve capital for the downturn”.
“Doing a partnership with Kite Pharmaceuticals early in our startp allowed us to get work done without risking a lot of capital, even if it means equity and asset dilution. That makes sense. However even if you are small insist on being an equal partner.”
“There are many investors we talk to who do not want to invest in cell therapy. Too risky now”
Carl Gordon
Managing Partner
OrbiMed Advisors
There are many macroeconomic factors affecting investment and capital today which will carry on through 2024. Not raising money when you do not need money is a bad philosophy. Always bbe raising captial. This is especially true when you have to rely on hedge funds. Parnerships howeve are sometimes the only way for small biotechs to leverage their strengths.
Joshua Boger
Executive Chair
Alkeus Pharmaceuticals, Inc.
Boger: Expect volatility for 2024. This environment feels very different than past downturns.
Even in downturns there is still lots of capital; remember access to human capital is better in a downturn and is easier to access; however it has become harder to get drug approvals
The panelists agree that access to capital and funding will be as tricky in 2024 than 2023. They did
suggest that a new funding avenue, private credit, may be a source of capital. This is discussed below:
When thinking about a private alternative investment asset class, the first thing that springs to mind is private equity. But there’s one more asset class with the word private in its name that has recently gained much attention. We’re talking about private credit.
Indeed, this once little-known investment strategy is now growing rapidly in popularity, offering private investors worldwide an exciting opportunity to diversify their portfolio with, in theory, less risky investments that yield significant returns.
Private credit investments refer to investors lending money to companies who then repay the loan at a given interest rate within the predetermined period.
The private credit market has grown significantly over the past years, rising from $875 million in 2020 to $1.4 trillion at the beginning of 2023.
Please WATCH VIDEO BY GOLDMAN SACHS ON PRIVATE CREDIT
The New Molecule: How breakthrough technologies are actually changing pharma R&D
Join us for a look at how AI, machine learning and generative technologies are actually being applied inside drugmakers’ labs. We’ll explore how new technologies are being used, their implications, how they intersect with regulatory and IP issues and how this fast-changing field is likely to evolve.
Kailash Swarna
Managing Director & Global Life Sciences Clinical Development Lead
Accenture
Artificial Intelligence is making impact in a grand way on biology in three aspects:
Speeding up target validation: now we can get through 300 molecules a day
Predicition like AlphaFold is doing; molecular simulations
Document submission especially with regulatory and IND submissions
Pamela Carroll
COO
Isomorphic Labs formerly of AlphaFold
We were first with Novartis at last year JPM and was one year old but parnering with them in that initial year was very important for sealing the deal.
They are looking now at neurologic diseases like ALS. She wondered whether ALS is actually multiple diseases and we need to stratify patients like we do in oncology trials. Their main competion is the whole tech world like Amazon, Google and other Machine Learning companies so being a tech player in the biotech world means you are not just competing with other biotechs but large tech companies as well.
Jorge Conde
General Partner
Andreessen Horowitz
Need is still great for drug discovery; early adopters show AI tools can be used in big pharma. There are lots of applications of AI in managing care; a lot of back office applications including patient triaging. He does not see big AI mergers with pharma companies – this will be mainly partnerships not M&A deals
Alicyn Campbell
Chief Scientific Officer
Evinova, a Healthtech Subsidiary of the AstraZeneca Group
There is a need to turn AI for real world example. For example AI tools were used in clinical trials to determine patient cohorts with pneumonitis. At Evinova they are determining how AI can hel[p show clinical benefit with respect to efficacy and safety
Joshua Boger at #JPM24 (Brian Benton Photography)
January 12, 2024 09:06 AM ESTUpdated 10:00 AM PeopleStartups
Vertex founder Joshua Boger on surviving downturns, ‘painful’ partnerships, and the importance of culture: #JPM24
While the JP Morgan Healthcare Conference was full of voices of measured optimism, rooting for the market to bounce back in 2024, one longtime biotech leader warned against setting any firm expectations.
Instead of predicting when the downturn may end, Vertex Pharmaceuticals founder Joshua Boger said he advises biotech leaders to expect — and plan for — volatility. Speaking Tuesday on an Endpoints News panel alongside OrbiMed’s Carl Gordon and Appia Bio CEO JJ Kang, Boger shared lessons learned on surviving downturns, striking pharma deals, and the importance of keeping a company’s culture based on his two decades of founding and leading Vertex as CEO from 1989 to 2009. The 72-year-old is now serving as executive chairman of Alkeus Pharmaceuticals, a startup developing a rare disease drug.
“I never experienced a straight line up,” Boger said. “Everything had its cycles, and it was how you respond to the cycle, not by predicting when the end is going to be, but just by responding to the present situation.”
At Boger’s first appearance at the JP Morgan conference in 1991, he said the conference’s theme was the end of biotech financing. Just a few months later, Regeneron successfully went public, rapidly changing the outlook for the whole field.
“We had no idea we were ever going to take public money,” he said. “When Regeneron did their IPO, we went, ‘Whoa, there’s something happening here,’ and we pivoted quickly.”
Vertex went public later that year. Throughout his 20-year tenure, Boger said no pharma company ever made an acquisition offer for Vertex, which now commands a market value of $110 billion and recently won the first FDA approval for a CRISPR gene editing therapy.
“We had an uber corporate policy to always make ourselves more expensive than anyone would stomach,” Boger said.
However, Vertex did strike a range of partnerships with Big Pharmas, which Boger described as a painful but necessary part of running a biotech startup.
“It’s impossible for a partnership not to slow you down,” he said. “You can and should try as hard as you can not to do that, but just count on it. They’ll slow you down.”
Boger said startups should insist on being equal partners in pharma deals, at least making sure they have a seat at a partner’s development meetings.
“Realize they’re going to be painful, it’s going to be horrible, and you need to do it,” Boger said.
While Vertex suffered through layoffs, stock price plunges, and trial failures, Boger credited a focus on culture as key to its long-term success.
“It’s the most important ingredient for a successful company,” he said. “Technology is acquirable. Culture is not acquirable. There are 10 companies that will fail because of culture for every one that succeeds, and the successful companies in retrospect will almost always have special cultural aspects that kept them through those downtimes.”
JPM24 opens with ADCs the hottest ticket in San Francisco
The overall deal flow in biopharma tapered off in 2023 but the big companies sure know what they want (what they really, really want), according to a new report from J.P. Morgan.
And that’s antibody-drug conjugates, which drove a fourth-quarter spike in licensing deal proceeds and provided a glimmer of hope to an industry battered by outside forces and grim financing prospects.
J.P. Morgan’s annual 2023 Biopharma Licensing and Venture Report arrived on the eve of the firm’s famous conference, which is set to welcome thousands of attendees in San Francisco today—East Coast weather permitting.
2023 was tough, but clinical biotechs still had a lot of opportunities to wheel and deal, according to J.P. Morgan. While licensing deals, venture investments, M&A and IPOs were down overall in the fourth quarter, deal values stayed fairly high thanks to a flurry of late-stage tie ups.
Follow the Fierce team’s coverage of the 2024 J.P. Morgan Healthcare Conference here.
Biopharma licensing partnerships accounted for $63 billion in total value during the fourth quarter from 108 deals. Just one deal—Merck’s ADC partnership with Daiichi Sankyo—accounted for $22 billion of that. Another huge one was another ADC bet, with Bristol Myers Squibb signing on to work with SystImmune for a total value of $8.4 billion. If you exclude the Merck deal, the total value of these partnerships is still higher than the previous quarter, which ended with $32.1 billion.
The total number of licensing deals compares to 149 in the same quarter a year earlier, 195 for Q4 2021 and 223 for Q4 2022.
As for venture investments, the year closed out with $17 billion total across 250 rounds, thanks to $3.5 billion earned through 79 rounds in the last quarter. Aiolos Bio snagged the title of largest venture round of the quarter with $245 million, which also proved to be the largest series A, too.
There was just one IPO in all of the fourth quarter—Cargo Therapeutics making the plunge for $300 million—and 13 overall for the year. It’s a far cry from the heyday of 2021 and experts are still unsure what 2024 will hold. J.P. Morgan reported $2.5 billion raised from 12 completed biopharma IPOs for the year on Nasdaq and NYSE. Nine out of the 12 companies had clinical programs when they took the leap to the public markets. As of December 13, five of the companies were trading above their IPO price.
As for M&A, December saw a rush of Big Pharmas snapping up companies around Christmas. J.P. Morgan tallied the fourth quarter at $37.6 billion and $128.8 billion across 112 total acquisitions for all of 2023.
AbbVie was the top buyer of the quarter with the two largest acquisitions thanks to the $10 billion outlay for ImmunoGen and $8.7 billion buy of Cerevel Therapeutics.
All of this adds up to 270 total deals in the fourth quarter total, which is lower than the third quarter which exceeded 300.
J.P. Morgan sees some big potential for smaller biopharmas looking for licensing partners, as Big Pharmas have been handing out larger upfront payments for the deals they really want.
Cancer was once again the most in-demand therapeutic areas, reaching a new height of $86.1 billion in 2023. Followed by $21.1 billion for neurological disorders.
For More Articles on Real Time Conference Coverage in this Open Access Scientific Journal see:
Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use
In this curation we wish to present two breaking through goals:
Goal 1:
Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer
Goal 2:
Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.
According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.
These eight subcellular pathologies can’t be measured at present time.
In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.
Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases
Glycation
Oxidative Stress
Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
Membrane instability
Inflammation in the gut [mucin layer and tight junctions]
Epigenetics/Methylation
Autophagy [AMPKbeta1 improvement in health span]
Diseases that are not Diseases: no drugs for them, only diet modification will help
Image source
Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease
These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:
Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL
In the Bioelecronics domain we are inspired by the work of the following three research sources:
Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia
THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC
PENDING
THE VOICE of Stephen J. Williams, PhD
Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes
25% of US children have fatty liver
Type II diabetes can be manifested from fatty live with 151 million people worldwide affected moving up to 568 million in 7 years
A common myth is diabetes due to overweight condition driving the metabolic disease
There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
Thirty percent of ‘obese’ people just have high subcutaneous fat. the visceral fat is more problematic
there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects. Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
At any BMI some patients are insulin sensitive while some resistant
Visceral fat accumulation may be more due to chronic stress condition
Fructose can decrease liver mitochondrial function
A methionine and choline deficient diet can lead to rapid NASH development
The Vibrant Philly Biotech Scene: Proteovant Therapeutics Using Artificial Intelligence and Machine Learning to Develop PROTACs
Reporter:Stephen J. Williams, Ph.D.
It has been a while since I have added to this series but there have been a plethora of exciting biotech startups in the Philadelphia area, and many new startups combining technology, biotech, and machine learning. One such exciting biotech is Proteovant Therapeutics, which is combining the new PROTAC (Proteolysis-Targeting Chimera) technology with their in house ability to utilize machine learning and artificial intelligence to design these types of compounds to multiple intracellular targets.
PROTACs (which actually is under a trademark name of Arvinus Operations, but is also refered to as Protein Degraders. These PROTACs take advantage of the cell protein homeostatic mechanism of ubiquitin-mediated protein degradation, which is a very specific targeted process which regulates protein levels of various transcription factors, protooncogenes, and receptors. In essence this regulated proteolyic process is needed for normal cellular function, and alterations in this process may lead to oncogenesis, or a proteotoxic crisis leading to mitophagy, autophagy and cellular death. The key to this technology is using chemical linkers to associate an E3 ligase with a protein target of interest. E3 ligases are the rate limiting step in marking the proteins bound for degradation by the proteosome with ubiquitin chains.
A review of this process as well as PROTACs can be found elsewhere in articles (and future articles) on this Open Access Journal.
Protevant have made two important collaborations:
Oncopia Therapeutics: came out of University of Michigan Innovation Hub and lab of Shaomeng Wang, who developed a library of BET and MDM2 based protein degraders. In 2020 was aquired by Riovant Sciences.
Riovant Sciences: uses computer aided design of protein degraders
Proteovant Company Description:
Proteovant is a newly launched development-stage biotech company focusing on discovery and development of disease-modifying therapies by harnessing natural protein homeostasis processes. We have recently acquired numerous assets at discovery and development stages from Oncopia, a protein degradation company. Our lead program is on track to enter IND in 2021. Proteovant is building a strong drug discovery engine by combining deep drugging expertise with innovative platforms including Roivant’s AI capabilities to accelerate discovery and development of protein degraders to address unmet needs across all therapeutic areas. The company has recently secured $200M funding from SK Holdings in addition to investment from Roivant Sciences. Our current therapeutic focus includes but is not limited to oncology, immunology and neurology. We remain agnostic to therapeutic area and will expand therapeutic focus based on opportunity. Proteovant is expanding its discovery and development teams and has multiple positions in biology, chemistry, biochemistry, DMPK, bioinformatics and CMC at many levels. Our R&D organization is located close to major pharmaceutical companies in Eastern Pennsylvania with a second site close to biotech companies in Boston area.
The ubiquitin proteasome system (UPS) is responsible for maintaining protein homeostasis. Targeted protein degradation by the UPS is a cellular process that involves marking proteins and guiding them to the proteasome for destruction. We leverage this physiological cellular machinery to target and destroy disease-causing proteins.
Unlike traditional small molecule inhibitors, our approach is not limited by the classic “active site” requirements. For example, we can target transcription factors and scaffold proteins that lack a catalytic pocket. These classes of proteins, historically, have been very difficult to drug. Further, we selectively degrade target proteins, rather than isozymes or paralogous proteins with high homology. Because of the catalytic nature of the interactions, it is possible to achieve efficacy at lower doses with prolonged duration while decreasing dose-limiting toxicities.
Biological targets once deemed “undruggable” are now within reach.
Roivant develops transformative medicines faster by building technologies and developing talent in creative ways, leveraging the Roivant platform to launch “Vants” – nimble and focused biopharmaceutical and health technology companies. These Vants include Proteovant but also Dermovant, ImmunoVant,as well as others.
Roivant’s drug discovery capabilities include the leading computational physics-based platform for in silico drug design and optimization as well as machine learning-based models for protein degradation.
The integration of our computational and experimental engines enables the rapid design of molecules with high precision and fidelity to address challenging targets for diseases with high unmet need.
Our current modalities include small molecules, heterobifunctionals and molecular glues.
Roivant Unveils Targeted Protein Degradation Platform
– First therapeutic candidate on track to enter clinical studies in 2021
– Computationally-designed degraders for six targets currently in preclinical development
– Acquisition of Oncopia Therapeutics and research collaboration with lab of Dr. Shaomeng Wang at the University of Michigan to add diverse pipeline of current and future compounds
– Clinical-stage degraders will provide foundation for multiple new Vants in distinct disease areas
– Platform supported by $200 million strategic investment from SK Holdings
Other articles in this Vibrant Philly Biotech Scene on this Online Open Access Journal include:
A laboratory for the use of AI for drug development has been launched in collaboration with Pfizer, Teva, AstraZeneca, Mark and Amazon
Reporter: Aviva Lev-Ari, PhD, RN
AION Labs unites pharma, technology and funds companies including IBF to invest in startups to integrate developments in cloud computing and artificial intelligence to improve drug development capabilities. An alliance of four leading pharmaceutical companies – AION Labs , the first innovation lab of its kind in the world and a pioneer in the process of adopting cloud technologies, artificial intelligence and computer science to solve the R&D challenges of the pharma industry, today announces its launch. AstraZeneca , Mark , Pfizer and Teva – and two leading companies in the field of high-tech and biotech investments, respectively – AWS ( Amazon Web Services Inc ) and the Israeli investment fund IBF ( Israel Biotech Fund ) – which joined together to establish groundbreaking ventures Through artificial intelligence and computer science to change the way new therapies are discovered and developed. “We are excited to launch the new innovation lab in favor of discoveries of drugs and medical devices using groundbreaking computational tools,” said Matti Gil, CEO of AION Labs. We are prepared and ready to make a difference in the process of therapeutic discoveries and their development. With a strong pool of talent from Israel and the world, cloud technology and artificial intelligence at the heart of our activities and a significant commitment by the State of Israel, we are ready to contribute to the health and well-being of the human race and promote industry in Israel. I thank the partners for the trust, and it is an honor for me to lead such a significant initiative. ” In addition, AION Labs has announced a strategic partnership with X BioMed , an independent biomedical research institute operating in Heidelberg, Germany. BioMed X has a proven track record in advancing research innovations in the field of biomedicine at the interface between academic research and the pharmaceutical industry. BioMed X’s innovation model, based on global mass sourcing and incubators to cultivate the most brilliant talent and ideas, will serve as the R & D engine to drive AION Labs’ enterprise model.
Greylock Partners has raised $500 million to invest exclusively in seed-stage startups. The announcement comes a year after the firm raised $1 billion for its 16th flagship fund to invest in early- and growth-stage tech startups.
Guo and general partner Saam Motamedi said in an interview the fund is part of an expansion of a $1.1 billion fund, which we reported last year, to $1.6 billion, The Information reported. The funding is among the industry’s largest devoted to seed investments, which often represent a startup’s first outside capital.
The pool of funds will give the 56-year-old venture capital firm the ability to write large checks at “lean-in valuations” and emphasize its commitment to early-stage investing, said general partner Sarah Guo. In a thread post on Twitter, Greylock said, “We at @GreylockVC are excited to announce we’ve raised $500M dedicated to seed investing. This is the industry’s largest pool of venture capital dedicated to backing founders at day one.”
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
Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries
1.1 Outline of Medical Discoveries between 1880 and 1980
1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century
1.3 The Classification of Microbiota
1.4 Selected Contributions to Chemistry from 1880 to 1980
1.5 The Evolution of Clinical Chemistry in the 20th Century
1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics
Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes
2.1 The life and work of Allan Wilson
2.2 The evolution of myoglobin and hemoglobin
2.3 More complexity in proteins evolution
2.4 Life on earth is traced to oxygen binding
2.5 The colors of life function
2.6 The colors of respiration and electron transport
2.7 Highlights of a green evolution
Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response
3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression
Chapter 4. Problems of the Circulation, Altitude, and Immunity
4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury
4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics
Chapter 5. Problems of Diets and Lifestyle Changes
5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements
Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics
6.1 Natural Products Chemistry
6.2 The Challenge of Antimicrobial Resistance
6.3 Viruses, Vaccines and immunotherapy
6.4 Genomics and Metabolomics Advances in Cancer
6.5 Proteomics – Protein Interaction
6.6 Pharmacogenomics
6.7 Biomarker Guided Therapy
6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present
6.09 The Union of Biomarkers and Drug Development
6.10 Proteomics and Biomarker Discovery
6.11 Epigenomics and Companion Diagnostics
Chapter 7
Integration of Physiology, Genomics and Pharmacotherapy
7.1 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
7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD
7.3 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs
7.4 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging
1.2 State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine (TM)
1.3 Risk of Bias in Translational Science
1.4Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers
Chapter 2: Causes and the Etiology of Cardiovascular Diseases: Translational Approaches for Cardiothoracic Medicine
2.1 Genomics
2.1.1 Genomics-Based Classification
2.1.2 Targeting Untargetable Proto-Oncogenes
2.1.3 Searchable Genome for Drug Development
2.1.4 Zebrafish Study Tool
2.1.5 International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome.
2.2 Proteomics
2.2.1 The Role of Tight Junction Proteins in Water and Electrolyte Transport
2.2.2 Selective Ion Conduction
2.2.3 Translational Research on the Mechanism of Water and Electrolyte Movements into the Cell
2.2.4 Inhibition of the Cardiomyocyte-Specific Kinase TNNI3K Oxidative Stress
2.2.5 Oxidized Calcium Calmodulin Kinase and Atrial Fibrillation
2.2.6 S-Nitrosylation in Cardiac Ischemia and Acute Coronary Syndrome
2.2.7 Acetylation and Deacetylation
2.2.8 Nitric Oxide Synthase Inhibitors (NOS-I)
2.3 Cardiac and Vascular Signaling
2.3.1 The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets
2.3.2 Leptin Signaling in Mediating the Cardiac Hypertrophy associated with Obesity
2.3.3 Triggering of Plaque Disruption and Arterial Thrombosis
2.3.4 Sensors and Signaling in Oxidative Stress
2.3.5 Resistance to Receptor of Tyrosine Kinase
2.3.6 S-nitrosylation signaling in cell biology.
2.4 Platelet Endothelial Interaction
2.4.1 Platelets in Translational Research 1
2.4.2 Platelets in Translational Research 2: Discovery of Potential Anti-platelet Targets
2.4.3 The Final Considerations of the Role of Platelets and Platelet Endothelial Reactions in Atherosclerosis and Novel Treatments
2.4.4 Endothelial Function and Cardiovascular Disease Larry H Bernstein, MD, FCAP
2.5 Post-translational modifications (PTMs)
2.5.1 Post-Translational Modifications
2.5.2. Analysis of S-nitrosylated Proteins
2.5.3 Mechanisms of Disease: Signal Transduction: Akt Phosphorylates HK-II at Thr-473 and Increases Mitochondrial HK-II Association to Protect Cardiomyocytes
2.5.4 Acetylation and Deacetylation of non-Histone Proteins
2.5.5 Study Finds Low Methylation Regions Prone to Structural Mutation
2.6 Epigenetics and lncRNAs
2.6.1 The Magic of the Pandora’s Box : Epigenetics and Stemness with Long non-coding RNAs (lincRNA)
2.6.2 The SILENCE of the Lambs” Introducing The Power of Uncoded RNA
2.6.3 Long Noncoding RNA Network regulates PTEN Transcription
2.6.4 How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis.
2.6.5 Transposon-mediated Gene Therapy improves Pulmonary Hemodynamics and attenuates Right Ventricular Hypertrophy: eNOS gene therapy reduces Pulmonary vascular remodeling and Arterial wall hyperplasia
2.6.6 Junk DNA codes for valuable miRNAs: non-coding DNA controls Diabetes
2.6.7 Targeted Nucleases
2.6.8 Late Onset of Alzheimer’s Disease and One-carbon Metabolism Dr. Sudipta Saha
2.6.9 Amyloidosis with Cardiomyopathy
2.6.10 Long non-coding RNAs: Molecular Regulators of Cell Fate
2.7 Metabolomics
2.7.1 Expanding the Genetic Alphabet and Linking the Genome to the Metabolome
2.7.2 How Methionine Imbalance with Sulfur-Insufficiency Leads to Hyperhomocysteinemia
2.7.3 A Second Look at the Transthyretin Nutrition Inflammatory Conundrum
2.7.4 Transthyretin and Lean Body Mass in Stable and Stressed State
2.7.5 Hyperhomocysteinemia interaction with Protein C and Increased Thrombotic Risk
2.7.6 Telling NO to Cardiac Risk
2.8 Mitochondria and Oxidative Stress
2.8.1 Reversal of Cardiac Mitochondrial Dysfunction
2.8.2 Calcium Signaling, Cardiac Mitochondria and Metabolic Syndrome
2.8.3. Mitochondrial Dysfunction and Cardiac Disorders
2.8.4 Mitochondrial Metabolism and Cardiac Function
2.8.5 Mitochondria and Cardiovascular Disease: A Tribute to Richard Bing
2.8.6 MIT Scientists on Proteomics: All the Proteins in the Mitochondrial Matrix Identified
2.8.7 Mitochondrial Dynamics and Cardiovascular Diseases
2.8.8 Mitochondrial Damage and Repair under Oxidative Stress
2.8.9 Nitric Oxide has a Ubiquitous Role in the Regulation of Glycolysis -with a Concomitant Influence on Mitochondrial Function
2.8.10 Mitochondrial Mechanisms of Disease in Diabetes Mellitus
2.8.11 Mitochondria Dysfunction and Cardiovascular Disease – Mitochondria: More than just the “Powerhouse of the Cell”
Chapter 3: Risks and Biomarkers for Diagnosis and Prognosis in Translational Cardiothoracic Medicine
3.1 Biomarkers. Diagnosis and Management: Biomarkers. Present and Future.
3.2 Landscape of Cardiac Biomarkers for Improved Clinical Utilization
3.3 Achieving Automation in Serology: A New Frontier in Best
3.4 Accurate Identification and Treatment of Emergent Cardiac Events
3.5 Prognostic Marker Importance of Troponin I in Acute Decompensated Heart Failure (ADHF)
3.6 High-Sensitivity Cardiac Troponin Assays Preparing the United States for High-Sensitivity Cardiac Troponin Assays
3.7 Voices from the Cleveland Clinic On Circulating apoA1: A Biomarker for a Proatherogenic Process in the Artery Wall
3.8 Triggering of Plaque Disruption and Arterial Thrombosis
3.9 Relationship between Adiposity and High Fructose Intake Revealed
3.10 The Cardio-Renal Syndrome (CRS) in Heart Failure (HF)
3.11 Aneuploidy and Carcinogenesis
3.12 “Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US
Chapter 4: Therapeutic Aspects in Translational Cardiothoracic Medicine
4.1 Molecular and Cellular Cardiology
4.1.1 αllbβ3 Antagonists As An Example of Translational Medicine Therapeutics
4.1.2 Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function post MI
4.1.3 Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
4.1.4 CELLWAVE Randomized Clinical Trial: Modest improvement in LVEF at 4 months “Shock wavefacilitated intracoronary administration of BMCs” vs “Shock wave treatment alone”
4.1.5 Prostacyclin and Nitric Oxide: Adventures in vascular biology – a tale of two mediators
4.1.7 Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH
4.2 Interventional Cardiology and Cardiac Surgery – Mechanical Circulatory Support and Vascular Repair
4.2.1 Mechanical Circulatory Support System, LVAD, RVAD, Biventricular as a Bridge to Heart Transplantation or as “Destination Therapy”: Options for Patients in Advanced Heart Failure
4.2.2 Heart Transplantation: NHLBI’s Ten Year Strategic Research Plan to Achieving Evidence-based Outcomes
4.2.3 Improved Results for Treatment of Persistent type 2 Endoleak after Endovascular Aneurysm Repair: Onyx Glue Embolization
4.2.4 Carotid Endarterectomy (CEA) vs. Carotid Artery Stenting (CAS): Comparison of CMMS high-risk criteria on the Outcomes after Surgery: Analysis of the Society for Vascular Surgery (SVS) Vascular Registry Data
4.2.5 Effect of Hospital Characteristics on Outcomes of Endovascular Repair of Descending Aortic Aneurysms in US Medicare Population
4.2.6 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
4.2.7 Preventive Medicine Philosophy: Excercise vs. Drug, IF More of the First THEN Less of the Second
4.2.8 Cardio-oncology and Onco-Cardiology Programs: Treatments for Cancer Patients with a History of Cardiovascular Disease
Summary to Part One
Part Two:
Cardiovascular Diseases and Regenerative Medicine
Introduction to Part Two
Chapter 1: Stem Cells in Cardiovascular Diseases
1.1 Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)
1.2 Notable Contributions to Regenerative Cardiology by Richard T. Lee (Lee’s Lab, Part I)
1.3 Contributions to Cardiomyocyte Interactions and Signaling (Lee’s Lab, Part II)
3.4 Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel
3.5 Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs
3.6 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD
Chapter 4: Research Proposals for Endogenous Augmentation of circulating Endothelial Progenitor Cells (cEPCs)
4.1 Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes
4.2 Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?
4.3 Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation
4.4 Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography
4.5 Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral
4.6 Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs
4.7 Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs
4.8 Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production
4.9 Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair
4.10 Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk
4.12 Heart Vasculature – Regeneration and Protection of Coronary Artery Endothelium and Smooth Muscle: A Concept-based Pharmacological Therapy of a Combination Three Drug Regimen including THYMOSIN
Nursing School Doesn’t Have to be so DAMN Hard! CPP=MAP-ICP Normal range should be greater than 70 mmHg How to calculate, regulate, and manage CPP or cerebra…
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