Breakthroughs in Pancreatic Cell Replacement: The ViaCyte Interview

I recently had the opportunity to sit down with Manasi Sinha Jaiman, M.D., M.P.H., Vice President of Clinical Development, and Mark Daniels, Senior Director of Clinical Development, of ViaCyte, “a regenerative medicine company focused on delivering novel stem cell-derived cell replacement therapies as a functional cure for all type 1 diabetes and a next-generation treatment for insulin-requiring type 2 diabetes.”

They have amazing things coming down the pike, so I was super excited to speak with them:

Tell our readers about ViaCyte. What’s the company’s mission and story?

Dr. Jaiman: ViaCyte is at the forefront of regenerative medicine approaches to develop a functional cure for type 1 diabetes (T1D). We have cell replacement therapies for pancreatic islet cells contained in a small retrievable pouch implanted under a patient’s skin.

The therapy is designed to enable insulin and glucagon (the counter-regulatory hormone that treats low blood glucose) production with the implanted cells to effectively control blood glucose levels, decrease the risk of hypoglycemia, and mitigate short-term and long-term diabetes-related complications for patients.

What is exciting is that ViaCyte is the first company to advance human stem cell-derived islet cell replacement therapy capable of producing insulin in the clinic, backed by two decades of research and expertise.

We are further augmenting our therapies by optimizing both the delivery device and the cells through collaborations with industry leaders, including W. L. Gore & Associates (the makers of GORE-TEX) and CRISPR Therapeutics.

Our mission is to develop cell replacement therapies offering long-term treatment to decrease the burden of the constant management needed with T1D.

What led you to your work at ViaCyte?

Dr. Jaiman: A significant focus of my medical career has been the integration of technology and medicine to advance treatments that can change the paradigm of diabetes disease management.

My experiences both in research and actively seeing patients with T1D have given me first-hand experience in seeing the daily work required to achieve any form of glycemic control as well as the burden patients and families face from complications from hypoglycemia or DKA.

I have also been able to see the importance of innovative approaches in addressing their needs. When I looked at the ViaCyte technology, I immediately saw great potential in their regenerative medicine approach to lessen the burden of disease and improve quality of life.

Mr. Daniels: Throughout my time in the industry I have been extremely fortunate to be able to work with innovative companies advancing potential, game-changing therapies for difficult-to-treat diseases. I was attracted to ViaCyte because the bar is set high; ViaCyte is looking to develop functional cures for diseases and is not just treating symptoms.

I also believe in the potential of cell replacement therapies and that these will be a meaningful new chapter in the advancement of medical treatments.

In ViaCyte, I have also found a team of extremely gifted and dedicated scientist-coworkers who are all generous with their knowledge and completely aligned in the mission to deliver a functional cure to the type 1 diabetes community.

It is exciting to be the first company to evaluate human stem cell-derived islet cell replacement therapy for its potential to functionally cure type 1 diabetes in the clinic.

Manasi Sinha Jaiman, M.D., M.P.H., Vice President of Clinical Development and Mark Daniels, Senior Director of Clinical Development

Manasi Sinha Jaiman, M.D., M.P.H., Vice President of Clinical Development and Mark Daniels, Senior Director of Clinical Development

What exciting new developments is ViaCyte currently working on?

Dr. Jaiman: Currently, ViaCyte has two clinical cell replacement therapy candidates. First, VC‑02 PEC-Direct is a treatment comprised of pancreatic islet cells in a pouch designed to allow blood vessels to enter the device and directly interact with the implanted cells to produce insulin and glucagon.

This treatment candidate is targeted for those with high-risk type 1 diabetes (hypoglycemia unawareness) able to tolerate immunosuppression.

In contrast, our groundbreaking VC‑01 PEC-Encap device is an advanced treatment comprised of pancreatic islet cells in a pouch that fully encapsulates the cells preventing immune cells from interacting with the implanted cells, which eliminates the requirement for immunosuppressants.

We are collaborating with W. L. Gore & Associates to optimize their innovative membranes which encapsulate the cells in our implanted devices. We expect to share clinical data in the second half of 2021.

Anything new in the pipeline that people with diabetes should be especially excited about?

Dr. Jaiman: One of the challenges with cell replacement therapies is to protect against adverse reactions and rejection of implants by the body’s immune system, which serves as a defense mechanism against foreign bodies.

In collaboration with CRISPR Therapeutics, we are employing gene-editing technology to engineer cells to avoid recognition by the immune system. Our partnership is focused on advancing gene-edited allogeneic stem cell-derived therapies from discovery through commercialization with the goal of developing a potential next-generation functional cure for all insulin-requiring type 1 and type 2 diabetes.

Mr. Daniels: With our preclinical candidate, VCTX210 PEC-QT, pancreatic islet cells would be in the same pouch as PEC-Direct, allowing the implanted cells to interact directly with blood vessels, an approach intended to enable robust and consistent engraftment.

Yet by designing the cells to be immune-evasive through CRISPR Therapeutics’ gene editing we would expect to eliminate the need for immunosuppressants as are required with PEC-Direct. We look forward to sharing more about this unique program in the future.

Photo credit: ViaCyte

Where do you envision ViaCyte and people’s lives affected by diabetes in five years? Ten years?

Mr. Daniels: This year marks the 100th anniversary of the development of therapeutic insulin to regulate blood glucose, yet dependency on tedious insulin injections are still a common course of treatment for many living with type 1 diabetes.

Within the next five years, we envision delivering significant progress in later clinical-stage studies with increased time in range, reduction in hypoglycemic events, and reduction in (or elimination of) the need for insulin injections in patients following our cell replacement treatments as we move toward making these therapies more widely available.

Dr. Jaiman: Within five years, we expect to be moving through the final phases of our regulatory process for our human stem cell-derived islet cell replacement therapy enabling availability more broadly for patients with type 1 diabetes.

It is our hope that within a decade, cell replacement therapy will offer longer-term treatment, easing the burden of constantly monitoring blood glucose. A functional cure will no longer be a dream, rather, a reality.

Is the ever-elusive cure on the horizon? A functional cure?

Dr. Jaiman: Yes, we believe a functional cure is on the horizon!

ViaCyte is focused on advancing cell replacement therapies toward a functional cure with a combination of implanted cells and device engineering.

This cell replacement therapy could represent insulin production protected from the immune system in a way that totally mitigates the underlying disease. Our technology is designed to safely implant the missing cells that make insulin and glucagon – that’s the breakthrough that gets us to the functional cure.

How can people with diabetes get involved or learn more?

Mr. Daniels: As ViaCyte is advancing novel treatments for type 1 diabetes, our team has been very fortunate to collaborate with multiple incredible research and advocacy organizations, including the Juvenile Diabetes Research Foundation (JDRF), Beyond Type 1, and California Institute for Regenerative Medicine (CIRM).

These organizations are focused on education and support for finding a cure for diabetes with resources for both patients and researchers on their websites. A great resource is the website www.clinicaltrials.gov – by typing “ViaCyte” into the search window, you can find more details regarding our ongoing clinical trials.

This includes details about the entry criteria to participate as well as the geographical locations of the sites (to find the one closest to you) and contact details necessary to reach out and connect with the study site team to learn more about what is involved in the study participation.

Photo credit: ViaCyte

Anything else you’d like to share?

Dr. Jaiman: Insulin treatment has largely transformed type 1 diabetes from a fatal illness to a chronic one, yet it is not a cure. At ViaCyte we recognize the long journey in the evolution of diabetes management, and we are keen to deliver a solution that offers real hope for a functional cure for type 1 diabetes.

Every single member of our team is passionate and dedicated to this endeavor. Managing diabetes can be difficult at any time, however, this past year has highlighted the need for accelerating therapeutic advancements to help reduce COVID-associated morbidity and mortality in the vulnerable population with diabetes.

With the pandemic still ever-present, we believe our mission of realizing a functional cure is even more critical for patients as they navigate living with a chronic disease during this very trying time. Our leadership team is wholly focused on improving patient care with an eye to the future.

Mr. Daniels: I am very appreciative of the Diabetes Daily team for providing this forum to connect to their community. The stories of family member’s and loved one’s experiences (including those of some of our own coworkers) with T1D resonate clearly within us and fuel our motivation behind the work we do.

It is only through the support of the T1D community and especially the valued study participants that we are able to advance this important research.

We are proud to be part of the biotech and biopharma community advancing some of the world’s most promising medical devices and therapeutic treatments. We look forward to sharing more details regarding the value of these treatments in the clinic.

Source: diabetesdaily.com

Connecting Type 1 Diabetes Researchers: The Sugar Science

This content originally appeared on Beyond Type 1. Republished with permission.

By Monica Westley

As a scientist and a parent of a child with type 1 diabetes, I was compelled to fully understand the etiology of the disease. I created a group called “The Sugar Mamas” to connect parents to live, interactive interviews with researchers. I reached out to scientists and scheduled regular “Lunch and Learns.” After each Skype call, parents went away feeling hopeful and inspired. It was a powerful connection for parents to understand how hard scientists were working on this disease. Last fall, I shared my process and helped Beyond Type 1 implement the connection of their community to researchers as well. I am a true believer in the adage, “the more information, the better!”

Creating The Sugar Science

Through countless interviews with researchers in the type 1 diabetes (T1D) field, I began to understand recurring pain points in the scientific community that was hindering more rapid progress. With the data in hand and a personal call to action, I began to build a digital platform in March 2020. We currently are a devoted and dedicated team of 23 talented volunteers, the majority with a close connection to T1D. Together we created The Sugar Science (TSS) to serve the wishes of scientists and catalyze a cure.

Our platform has already received endorsements from top researchers in the T1D world, including Dr. Douglas Melton (Harvard) and Dr. Alice Long (Benaroya), who act as our advisors. The Diabetes Research Connection (DRC), as well as Unanimous A.I., have partnered with us. Gaining validity, we were semi-finalists for the Women Who Tech grant, and we won a Google grant.

TSS revitalizes scientific communication in the same way that our social communications have transformed by digital tools over the last decade. Social networking and AI tools on the TSS platform are poised to bring together a field that has been silo-ed for decades, not due to the considerable effort of scientists, but due to the multi-factorial nature of the disease.

Providing Tools

Online meeting

Image source: Beyond Type 1

The Sugar Science provides tools that scientists working in T1D have requested. Current tools include The Collaborator, Thought Experiment, and KG.

The Collaborator is “speed dating” for ideas. Scientists post just three slides with short descriptions of their idea. The community gives feedback as to whether this is a “good idea,” and other scientists can connect to collaborate. A “match” can submit a fast-tracked grant to the DRC for funding.

Thought Experiments (TE) is a tool where scientists can post controversial (or not) ideas and the community can weigh in. Scientists whose answers gain “likes” from the community will gain a reputation. These scientists will be invited to participate in a SWARM AI event, tackling the toughest questions in type 1 diabetes along with experts in the field.

KG is the Knowledge Graph. We are building a knowledge graph to reflect all historical papers against a backdrop of negative data. This will give scientists studying T1D a new perspective on work that has already been done in the field as well as show places where work needs to be done.

Moving Forward

Overall, we remain true to our mission: to help T1D scientists connect, collaborate, and fund their best ideas. TSS features podcasts and interviews with scientists. We are scheduling “off the record” private brainstorms. We want to elevate young scientists interested in T1D and support them. In this spirit, we are hosting a PITCH COMP for post-docs and graduate students who study T1D on September 25, 2020. It will be a chance to shine for labs looking to connect, and the best pitches will be awarded funding. This event is particularly meaningful with the COVID-19 pressures that the scientific community is experiencing.

Please feel free to support our mission. The general public can donate (we are a tax-deductible foundation) on our website, via our socials or using Amazon Smile. All donors will receive our monthly digital newsletter.

As a parting comment, I would say for myself and my team, for us it is all about a cure. We know first-hand what this disease is like, what it does to those who have it and their families. As an all-volunteer organization, no one is paid. And yet, we are getting things done, moving forward. Our team at The Sugar Science is all about the end game: a cure.

Source: diabetesdaily.com

“Inverse Vaccine” to Treat Type 1 Diabetes Passes Phase I Clinical Trial

In people with type 1 diabetes (T1D), the immune system destroys the insulin-producing cells in the pancreas, leading to high blood glucose levels, which are deadly if left untreated. All people with type 1 diabetes rely on insulin injections or infusions to regulate their blood glucose levels. Individual insulin requirements are affected by many factors and tailoring the dosing regimen around the clock requires a lot of mental effort, with many patients finding it difficult to consistently achieve their target ranges.

The search for better clinical approaches for type 1 diabetes is ongoing, with many labs around the world focusing on better treatments and the ever-elusive “diabetes cure”. Most recently, researchers at the City of Hope described the first-ever human phase I clinical trial of a “inverse vaccine” to treat type 1 diabetes patients.

We previously reported on this novel potential treatment approach when it was still in its pre-clinical stages at the ADA Scientific Sessions last June. Now, we have reconnected with the lead researcher, Dr. Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes at City of Hope and director of The Wanek Family Project for Type 1 Diabetes, to learn about the outcomes of the first-ever human trial.

What Is an “Inverse Vaccine”?

When we think of a vaccine in a traditional sense, we are usually referring to the stimulation of the immune system to develop an immunity and prevent illness from a particular microbe. An “inverse vaccine”, on the other hand, is designed to stop a specific immune response (e.g., the unwanted autoimmune response that destroys beta cells in patients with type 1 diabetes).

How Does the Treatment Work?

This treatment aims to retrain the patient’s immune system to self-tolerate the insulin-producing beta cells in the pancreas. First, specific immune cells (called dendritic cells, DCs) are collected from the patient’s blood and are specifically treated, in particular, with pro-insulin peptide and vitamin D. When the stimulated cells are injected back into the patients, in a series of “vaccinations”, they can elicit a specific subset of the patient’s T cells (regulatory T cells, or Tregs), which should, in turn, act to regulate the unwanted autoimmune response seen in type 1 diabetes.

Dr. Roep explained more:

“We want to negotiate with the immune system rather than bombard it into submission, because the latter may affect your chances of fighting off cancer and infections, including coronavirus.”

First Clinical Trial Results Show Promise

The novel vaccine was recently tested to assess safety and tolerability in nine patients with type 1 diabetes of long duration (at baseline, only three patients had detectable C-peptide levels, indicating some degree of insulin production). The results of the study were just published last week.

The treatment “passed the test” with respect to serious adverse events. The researchers describe that,

“Most importantly, there were no signs of systemic immune suppression, no induction of allergy to insulin, no interference with insulin therapy, and no accelerated loss in beta-cell function in patients with the remaining C-peptide. In conclusion, generation and intradermal administration of [the treatment] appears feasible and safe.”

Clinicians monitored various other health parameters throughout the trial, including glycemic management, which remained stable for all participants. Notably, Dr. Roep stated that,

“With regard to the unexpected clinical benefits: while we told the participating patients that it was a safety and feasibility trial, they have all-time low HbA1c years after our therapy (long after the trial ended) and on average, 13 years after their diagnosis. This is bizarre, and could point to beta-cell regeneration (perhaps once you stop the immune attack) or possibly waking up hibernating beta cells that came out of hiding after the immune system got back in check. Speculation, of course, but tantalizing observation nonetheless, in the preferred direction.”

Why were patients with long-standing diabetes selected for this initial investigation? Dr. Roep explained:

“There are two reasons why we involved patients with long-term disease.

First, to build-in extra safety precautions in this first in-human trial, we selected patients with long-term disease whose condition is less likely to worsen. After all, we injected a vaccine built on their pancreatic islets, so in theory, this could aggravate islet autoimmunity.

The other reason is a frustration that I share with my stakeholders, the diabetes patients: all efforts to intervene in the disease are biased toward a short period after diagnosis. We just learned that most patients keep beta cells for most of their lives, so it is worth protecting those beta cells and serving patients with longstanding T1D at the same time. Our novel strategy is also perfectly suited to do so: perhaps it is even smarter to negotiate with the immune system once the medical emergency is over and remaining beta cells (and the immune system) get some rest. All other strategies so far bombarded the immune system into submission; this big hammer is probably better justified early on.”

You can read even more about the study, including the patient selection process and the specific treatment protocol here.

What’s Next?

Based on the success of the phase I trial that evaluated the safety and tolerability, the research group expect to conduct more human testing:

“Our results warrant subsequent clinical testing in patients with a shorter diagnosis of type 1 diabetes and with preserved C-peptide production, to assess whether this novel immune intervention strategy is able to delay or halt progressive loss of beta-cell function. Further testing would tell whether [the treatment] protects beta cells from autoimmune destruction and can act as curative therapy for type 1 diabetes.”

Dr.  Roep and colleagues are optimistic about the future:

“Our research brings us one step closer to finding a vaccine against type 1 diabetes, an ambitious quest at City of Hope, and the hope of many patients with this disease.”

Of course, there is a long road ahead before we can know for sure whether this type of therapy will be truly effective. Moreover, the way that type 1 diabetes develops differs between patients, and it is likely that immunotherapies will have to be tailored to different patient subsets, as we previously discussed with Dr. Roep.

Nevertheless, such a tailored approach constitutes a previously unexplored form of treatment for type 1 diabetes patients, which could lead to effective therapies, and perhaps even a cure. We will continue to follow this research and provide updates as more research is conducted.

Read the official press release about this clinical trial from the City of Hope here.

Source: diabetesdaily.com

Diabetes Research Institute and Foundation: Committed to Curing Diabetes

Learn about the mission and diabetes advocacy efforts of the Diabetes Research Institute and Foundation. Check out this summary to learn more about who they are, what they do, and more.
Source: diabetesdaily.com

Is a Functional Cure for Type 1 Diabetes on the Horizon?

Have you heard about the ongoing research on cell-based therapies for type 1 diabetes? Dr. Paul Laikind is the President and CEO of ViaCyte, a company that aims to develop “a product that can free patients with type 1 and type 2 diabetes from long-term insulin dependence.” Hear more about the novel research and the recent […]
Source: diabetesdaily.com

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