JDRF Greater Bay Area Chapter’s Annual Meeting and Research Update Executive Highlights
We recently attended the JDRF Greater Bay Area Chapter’s Annual Meeting and Research Update event at the beautiful Wells Fargo Penthouse in downtown San Francisco. The very well-attended event featured Chapter and Foundation updates from President of the Greater Bay Area Chapter Board and Chairman of the International Board of Directors Mr. Mark Fischer-Colbrie and Executive Director Ms. Nicole Friedland, as well as outstanding rapid-fire presentations on encapsulation from ViaCyte’s Dr. Michael Scott and UCSF’s Drs. Tejal Desai and Shuvo Roy. See below for our top 5 highlights from the event, followed by Q&A from the encapsulation panel (which can be viewed here).
1. Dr. Michael Scott (VP, Device Research and Development, ViaCyte, San Diego, CA) shared that clinical trials of ViaCyte’s PEC-Direct cell replacement therapy product will commence in 1H17. This preclinical compound would be aimed at very high-risk patients; if it progresses, it wouldn’t be likely to reach the market before 2020.
2. Mr. Mark Fischer-Colbrie (President of the Greater Bay Area Chapter Board and Chairman of the International Board of Directors, San Francisco, CA) divulged JDRF’s strategic plan for 202o: The Foundation plans to invest $850 million in research over the next five years. That compares to $588 million between 2011 and 2015.
3. Researcher Dr. Tejal Desai (UC San Francisco, CA) explained her lab’s approach to macroencapsulation (“nanotemplating”) and her view of the most exciting avenues for next-generation encapsulation.
4. UCSF’s Dr. Shuvo Roy is best known for his work developing a bioartificial kidney, and he is currently applying the same principles to the design of a bioartificial pancreas for type 1 diabetes patients.
5. Mr. Chase Urban, a 12-year-old inspirational speaker with type 1 diabetes, won the Chapter’s Volunteer of the Year award.
Top Five Highlights
1. Dr. Michael Scott (VP, Device Research and Development, ViaCyte, San Diego, CA) shared that clinical trials of ViaCyte’s PEC-Direct cell replacement therapy product will commence in 1H17. This preclinical candidate was first introduced at the JDRF Mission Summit in January of this year and is aimed at very high-risk patients. When asked when PEC-Encap/VC-01 and PEC-Direct might be on the market, Dr. Scott shared that the earliest either could be available is around 2020, and that would likely be PEC-Direct “but that’s with your foot on the gas and a turbo-charger.” Given the challenging development and regulatory terrain for a biologic-device combination product, meeting that timeline would require a lot of things going right. He noted that with PEC-Direct the company is planning to seek Breakthrough Therapy Designation, which could accelerate the development. ViaCyte received a $3.9 million grant for pre-clinical development of PEC-Direct from the California Institute for Regenerative Medicine (CIRM) in July. We’re so moved by the JDRF and CIRM’s continued commitment to bringing ViaCyte’s innovative, potentially game-changing technology into the hands of patients.
- PEC-Direct differs from PEC-Encap/VC-01, the company’s more advanced cell replacement therapy, in several ways. PEC-Encap, which is already in an ongoing phase 1/2 clinical trial, encapsulates islets to protect against the adaptive immune system. On the other hand, PEC-Direct differs in that it has a relatively small number of carefully placed ports through which blood vessels can grow and directly contact cells. ViaCyte hopes this approach will promote a robust engraftment, effective differentiation to islet like structures, and rapid dissemination of pancreatic peptides. Furthermore, Dr. Scott estimated that, as with cadaver islet transplants, PEC-Direct could be implanted and effective for many years, potentially longer than full encapsulation approaches like PEC-Encap. The downside is that these ports will also allow host immune cells to enter and attack the grafted cells, so the patient will need to take immunosuppressants, which represents a major negative for most though not all patients. Due to the risk, PEC-Direct is only intended for type 1 patients at high risk for acute complications such as severe hypoglycemic episodes, hypoglycemia unawareness, and/or extreme glycemic variability. PEC-Direct does not represent as great a leap forward as PEC-Encap and we expect it would largely be indicated for a similar population of patients with type 1 diabetes who currently undergo cadaver islet or pancreatic transplantation. However, its use of stem cells would address the current shortage cadaveric islet cells available for transplantation.
- On the competitive landscape: Sernova is currently developing Cell Pouch, a thin, implantable device that provides a vascularized environment for beta cells and the company hopes to eventually develop microencapsulation technologies to locally protect cells within the device. We’re curious if ViaCyte’s PEC-Direct may be an early foray into the development of a similar microencapsulation device for a broader type 1 diabetes indication. ViaCyte holds an advantage in this approach in that it already holds an unlimited cell source (PEC-01 cells) for its replacement therapies, while Sernova is still currently using donor islets in its device and is investigating several unlimited cell source options. Moreover, ViaCyte is the first group to conduct clinical trials on a cell therapy protected from the immune system by macroencapsulation, thus the knowledge they are gaining is likely providing them with valuable insights for future improvements.
2. Mr. Mark Fischer-Colbrie (President of the Greater Bay Area Chapter Board and Chairman of the International Board of Directors, San Francisco, CA) shared JDRF’s strategic plan for 202o: The Foundation plans to invest $850 million in research over the next five years, compared to $588 million from 2011-2015. It will increase its core fundraising and leverage partnerships to provide ~$600 million by 2020, but currently still faces a funding gap of ~$250 million. The breakdown of where the money is expected to go is as follows: $200 million to beta cell replacement, $195 million to prevention, $175 million to restoration, $170 million to artificial pancreas, $50 million to glucose-responsive insulin, and $60 million to “other.” We’re curious if the funding breakdown reflects the JDRF’s thoughts on the short-term feasibility of each approach. We expect glucose-responsive insulin could be a complete game-changer and will require much more than $50 million to substantially move the field forward, but the current research on this front is very early-stage and should be easier to supplement by Big Pharma (theoretically). That said, Merck very recently completed its phase 1 trial of its glucose-responsive insulin candidate MK-2640 according to ClinialTrials.gov and we’re excited to see where this field will be by 2020. Clearly there is a lot of interest and anticipation for a glucose-responsive insulin, as evidenced by the buzz at the JDRF/Helmsley Charitable Trust Glucose Responsive Insulin Workshop last April.
3. Researcher Dr. Tejal Desai (UC San Francisco, CA) explained her lab’s approach to macroencapsulation (“nanotemplating”) and the most exciting avenues for next-generation encapsulation. Her lab created the “nanotemplating” technique to nano-engineer flexible, semi-permeable membranes where implantable beta cells can exist, protected from the host immune response (her earlier work showed the beta cells produce less insulin on a stiff environment relative to an elastic one). “Nanotemplating” allows for control over the size and concentration of pores on the membrane: A thin polycaprolactone (PCL) membrane is spun over ZnO rods that stick up and poke holes in the membrane. Next, the rods are dissolved, leaving behind a film with nano-size pores that can exclude antibodies from accessing the encapsulated islets. Dr. Desai sees many directions to take this preliminary technology: (i) The size, length, and density of pores can be engineered to include and exclude molecules of different size – this can be translated to any device, not only macroencapsulation of beta cells; (ii) surface topography and chemistry can be tailored, potentially reducing fibrosis; (iii) an immune-tolerant microenvironment with drug- and cytokine-releasing capsules can be created; and (iv) Pre-vascularized non-immunogenic islets, perhaps from the patient’s own stem cells, can be created. This would eliminate the delay between implantation and vascularization (which occurs between 7-14 days in rodent models), and therefore promote earlier function. Dr. Desai’s research is still early-stage, but and we are eager to see where her ideas take her. We’re especially interested in how this “nanotemplating” approach compares to current macroencapsulation approaches such as ViaCyte’s and to microencapsulation approaches such as Sernova’s.
4. UCSF’s Dr. Shuvo Roy is best known for his work developing a bioartificial kidney, but he is currently applying the same principles to the design of a bioartificial pancreas for type 1 diabetes patients. The concept shares some characteristics with a hemodialyzer: Blood is actively pumped through a capsule constructed from semi-permeable silicon nanopore membranes, which houses islets. The membranes isolate the islets from the immune system, while allowing hormones and nutrients in and out. The active pumping of blood ensures a rapid cellular response and that resultant insulin is quickly driven back into the bloodstream. The other feature that sets Dr. Roy’s system apart is that the ultrafiltration capsule is not implanted subcutaneously, but stitched together with blood vessels, similar to a bypass graft in patients who undergo cardiac bypass surgeries. Initial feasibility trials in pigs were very successful, as the device allowed blood flow without coagulation and no immunosuppressants were required. Further in vitro studies show that the islets survive and are functional (release C-peptide) for extended durations. Similar to Dr. Desai’s project, Dr. Roy’s is still in the very preliminary stages, but we love to see so many groups striving to develop viable cell replacement therapies.
5. Mr. Chase Urban, a 12-year-old inspirational speaker with type 1 diabetes, won the Chapter’s Volunteer of the Year award. As Ms. Nicole Friedland (Executive Director, JDRF Bay Area Chapter, CA) listed the past year’s fundraising events, the common denominator was Mr. Urban’s name in the “Speaker” category. He has spoken to and inspired over 2,000 people (!), and raised well over $70,000 for the JDRF in three walks over the course of the year. Mr. Fischer-Colbrie said believes that Mr. Urban will probably be President of the US one day – we should be so lucky (and what a way to put diabetes front and center on the national political stage)! Way to go Chase!
Panel Discussion
Q: How close are you to using your respective devices in humans?
Dr. Scott: Viacyte is in clinics at UCSD and Edmonton currently.
Dr. Desai: Ways away. Our next phases are in larger animals, pigs. After that, we would like to follow path of ViaCyte. They’ve paved the way for combination cell therapy products.
Q: I’m an older type 1. Fortunately, I’ve had no complications. Since I’ve been diagnosed, 30 years ago, my endocrinologist has been saying that there will be a cure in 5 years. Will this happen in the next 5, 10, 20 years?
Dr. Scott: Depends what the data tells us. Based on what you have to do to get a Biologics License Application (BLA) from the FDA, the earliest that a cure could happen, if everything goes as well as we could hope for, is 2021 or 2022. Five to six years. That could be for PEC-Direct or PEC-Encap. But that’s with your foot on the gas and a turbo-charger. There’s a reason regulatory is so cautious. We get a lot of support from the FDA, but they have a mandate to protect patients. For teams that are preclinical, they must first demonstrate basic safety and tolerability, then dose-finding, and finally stage a pivotal trial, which is for safety and efficacy. So they build.
Dr. Desai: To accelerate progress, we’re thinking about partnering with cell therapy companies.
Q: Is there some possibility that vascularization of the device could create a pathway for the T cells?
Dr. Scott: You’re asking if the membrane can change over time. Biostability. Is the material stable over time, or will the membrane be affected by the body? We’re actively seeking to answer that question.
Dr. Desai: There’s a fine balance between appropriate and too much vascularization. The body initiates vascularization in times of stress and disease. We need to make sure that the type of vascularization we’re seeing is stable and patent (allowing blood flow without coagulation), and not initiating a chronic inflammatory cascade.
Q: Would that ViaCyte timeline be just for people with extreme risk of complications? When would it be available for the general population?
Scott: PEC-Direct is for patients with special risk. Those types of devices get special treatment, with 18-24 months cut off of regulatory process. I can tell you that we are pursuing both arms. I can’t tell you which will win the race, but both are a possibility for the time frame given.
Q: How long will the device last before it needs to be replaced?
Dr. Scott: It’d be different for the two approaches I described. If fully encapsulated, cells have to survive on their own with no support or matrix. The body has macrophages that clean up debris and rejuvenate – you don’t have that function if the host cells are blockaded. That will necessarily limit the duration of benefit. Full encapsulation (Pec-Encap) will not make it as long as PEC-Direct, which could last many years. We’re hoping PEC-Encap will last up to two years.
Dr. Desai: We use a biodegradable material that lasts two to three years. It stays stable for a time we design, then all of a sudden erodes away. If we have pores a certain size, they stay that way until the designated time. We would then implant another, or we’d have two devices that overlap.
-- by Brian Levine, Helen Gao, and Kelly Close