Day Two of the World Medical Innovation Forum took a deeper dive into the potential of GCT therapeutics to treat different diseases—from ultra-rare genetic disorders to highly prevalent chronic diseases such as diabetes.
Discussions touched on different strategies for modifying genes and delivering therapies, as well as opportunities for using lessons learned from last year’s rapid mobilization of the biotech community to respond to the pandemic to increase the speed of GCT development, approval and distribution.
GCT in China: The Next Juggernaut?
The day began with a panel discussion on the potential of GCT therapies coming out of China. The country recently revamped its regulatory system to implement a fast track approval process, has a large patient population, and a growing network of hospitals qualified to conduct high scale clinical trials.
Unlike other areas of drug development where the country had a late start, China is on pace with Western countries when it comes to GCT, said Pin Wang, PhD, CSO of Jiangsu Simcere Pharmaceutical.
“The clinical potential of GCTs is so great that everyone wants to commit to developing innovative therapies,” added Richard Wang, PhD, VP & CTO for Fosun Pharma. “There is a lot of investment going to support this ecosystem. Almost every week we see new companies getting funded by VCs and other investment institutions.”
What’s Next for mRNA?
With the overwhelming success of mRNA-based vaccines for COVID-19, is there a potential to use the technology to advance other therapies as well?
Panelists discussed several future uses, from multivalent vaccines (vaccines equipped with multiple antigens) to protect against SARS-CoV-2 variants to improving the efficacy of the annual flu vaccine by including antigens from multiple influenza strains.
The same platform could also be adapted to deliver gene therapies and personalized cancer vaccines, participants said.
“Messenger RNA is the message, and we just have to decide what message we want to deliver to the cell,” said moderator Lindsey Baden, MD, of Brigham and Women’s Hospital. “The promise of this technology could not be more front and center for all of us.”
GCTs for Chronic Conditions, Rare Diseases and Other Disorders
Could diabetes be the first widespread chronic disease to be treated with GCT? Tackling a disease as prevalent and complex as diabetes will require a massive scale up in production and new strategies to protect transplanted islet cells from the body’s immune system, panelists said.
When it comes to developing new gene therapy treatments for rare diseases, it will be important to convince regulators to accept changes in biomarkers as proof of treatment efficacy in cases where natural disease histories will take too long or be too expensive to use as a control arm, panelists said.
“Rare diseases are highly variable, and biomarkers will tell you what is really going on with the treatment,” said Emil Kakkis, MD, PhD, CEO of Ultragenyx. “We need to stop looking at biomarkers as a compromise.”
Working with rare disease patients is essential when lobbying regulators for approval, added Bobby Gaspar, MD, PhD, CEO of Orchard Therapeutics. “You can only say so much with graphs and data. When families speak about what they’ve been through with their child and the suffering they’ve experienced, I think regulators need to hear that and what a difference a treatment can make.”
Innovation Discovery Grants (IDG) Awarded
Thursday afternoon highlights also included the awarding of six Innovation Discovery Grants (IDG) to Mass General Brigham investigators working on gene and cell therapy (GCT) advancements.
Each award winner will receive $100,000 toward ongoing development and future commercialization, based on the potential to improve health outcomes, meet articulated milestones, and attract follow-on investment as assessed by independent industry experts.
In a new aspect of the IDG awards this year, drug development experts from Bayer will provide mentoring to the awardees, covering scientific, technological, strategic and commercial aspects of innovation from proof of concept to market. Please join us in congratulating the awardees:
Generating Superior ‘Killers’ for Adoptive Cell Therapy in Cancer
Lydia Lynch, PhD, Brigham and Women’s Hospital
- There is an unmet need for developing cell therapy that will work in solid tumors, which account for the majority of the 1.7 million cancer diagnoses every year. New cell therapies may offer the ability to reach and penetrate these tumors. The project aims to use ‘innate T cells’ for adoptive cell therapy for solid tumors, capitalizing on their innate homing abilities, use of donor blood products instead of patient blood, and their metabolic fitness to survive in the tumor.
Novel Strategies to Enhance Tfr Treatment of Autoimmunity
Peter Sage, PhD, Brigham and Women’s Hospital
- It’s estimated that 50 million people are living with autoimmune diseases in the U.S. alone, creating a large need for therapeutic strategies to limit a host of potentially debilitating, and in some cases, life threatening diseases. The project centers on cell therapy that deploys Follicular Regulatory T (Tfr) cells as a much more specific and potent way to limit B cell mediated autoimmunity in diseases such as multiple sclerosis, as well as for chronic rejection after kidney transplantation. It uses an in vivo CRISPR screen to identify new pathways that can form the basis for novel therapeutics.
Long-Lasting mRNA Therapy for Genetic Disorders
Jinjun Shi, PhD, Brigham and Women’s Hospital
- The use of synthetic mRNA nanotherapeutics has attracted significant attention given the recent FDA emergency-use authorization of mRNA COVID-19 vaccines. This IDG grant supports research that aims to develop a clinically translatable lipid nanoparticle (LNP) platform technology enabling long-lasting mRNA therapy for genetic disorders. Goals are to achieve a prolonged duration of mRNA-mediated protein expression in mice for at least 30 days after a single injection; and validate the efficacy and safety of the new mRNA LNPs for a particular severe genetic bleeding disorder, hemophilia A. This long-lasting mRNA LNP technology could be readily expanded to other genetic diseases that require restoration of normal protein functions, and to other biomedical applications such as cancer and metabolic diseases.
AAV-Based Gene Replacement Therapy Improves Targeting and Clinical Outcomes in a Childhood CNS Disorder
Yulia Grishchuk, PhD, Massachusetts General Hospital
- Mucolipidosis IV (MLIV) is a highly debilitating central nervous system disorder resulting in resulting in motor and cognitive deficits and vision loss among children. There is currently no therapy for this disease. The project is developing and testing adeno-associated virus (AAV) gene replacement therapy with improved biodistribution and tissue targeting to address complex pathology involving CNS dysfunction and vision loss. The research may also pave the way for expanding use of this vector for other diseases.
Towards a Permanent Genetic Cure for Spinal Muscular Atrophy, Benjamin Kleinstiver, PhD
Massachusetts General Hospital, Center for Genomic Medicine
- Spinal Muscular Atrophy (SMA) is one of the leading causes of infantile death worldwide. While there are promising, FDA-approved therapies, these have potential limitations such as the need for repeated dosing or incomplete efficacy. The goal of this project is to develop a permanent genetic cure for SMA using novel genome editing technologies that target and permanently correct the disease-causing mutations of the SMN genes. This approach could establish a new paradigm for treating SMA, and, more broadly, other neurogenetic diseases.
Differentiation of Retinal Neurons for Cell Replacement in Glaucoma
Petr Baranov, MD, PhD, Massachusetts Eye and Ear
- An estimated three million people are affected by glaucoma in the U.S., and increasing lifespans exacerbate the disease’s socio-economic and quality of life impact. The human retina lacks the ability to regenerate, and glaucoma has historically led to irreversible vision loss. Currently no cell or other therapies are available to compensate for the lost function or to regenerate or replace retinal ganglion cells (RCGs). The long-term goal of the project is to develop cell replacement therapy for glaucoma with the potential to restore lost vision.
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