Regenerative Medicine by the numbers: a snapshot of how the field is progressing

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Statistics don’t usually make for very exciting blog fodder, but they can be useful in charting progress. Case in point, the recent quarterly report from the Alliance for Regenerative Medicine (ARM), a global advocate and industry group for the field.

In the report ARM takes an in-depth look at cell therapy, gene therapy, tissue engineering and other trends in the regenerative medicine field.

Among the more notable findings are:

  • Companies in the regenerative medicine space collectively raised more than $4.1 billion in the second quarter of this year, up 164 percent over the same period in 2017.
  • Companies focused on cell therapy raised $2.2 billion, up 416 percent over the same period last year.
  • More and more companies in the space are turning to the public markets. So far this year they collectively raised $913.4 million in IPOs (initial public offerings – the very first sale of a company’s stock to the public), up from $254 million during all of last year.
  • Nearly 977 clinical trials testing such therapies are in progress across the globe; more than half of them are trying to treat cancer.

In a news release, Janet Lynch Lambert, ARM’s CEO, was understandably upbeat:

“There has been a tremendous amount of forward momentum during the first half of this year, both clinically and commercially. We’re excited for the continued growth of the regenerative medicine sector, and what it means for patients worldwide.”

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CIRM-funded medical research and development company does $150M deal to improve care for dialysis patients

Fresenius & Humacyte

Nearly half a million Americans with kidney disease are on dialysis, so it’s not surprising the CIRM Board had no hesitation, back in July 2016, in funding a program to make it easier and safer to get that life-saving therapy.

That’s why it’s gratifying to now hear that Humacyte, the company behind this new dialysis device, has just signed a $150 million deal with Fresenius Medical Care, to make their product more widely available.

The CIRM Board gave Humacyte $10 million for a Phase 3 clinical trial to test a bioengineered vein needed by people undergoing hemodialysis, the most common form of dialysis.

Humacyte HAV

The vein – called a human acellular vessel or HAV – is implanted in the arm and used to carry the patient’s blood to and from an artificial kidney that removes waste from the blood. Current synthetic versions of this device have many problems, including clotting, infections and rejection. In tests, Humacyte’s HAV has fewer complications. In addition, over time the patient’s own stem cells start to populate the bioengineered vein, in effect making it part of the patient’s own body.

Fresenius Medical Care is investing $150 million in Humacyte, with a plan to use the device in its dialysis clinics worldwide. As an indication of how highly they value the device, the deal grants Fresenius a 19% ownership stake in the company.

In an interview with FierceBiotech, Jeff Lawson, Humacyte’s Chief Medical Officer, said if all goes well the company plans to file for Food and Drug Administration (FDA) approval in 2019 and hopes it will be widely available in 2020.

In addition to being used for kidney disease the device is also being tested for peripheral artery disease, vascular trauma and other cardiovascular indications. Lawson says testing the device first in kidney disease will provide a solid proving ground for it.

“It’s a very safe place to develop new vascular technologies under clinical study. From a regulatory safety standpoint, this is the first area we could enter safely and work with the FDA to get approval for a complete new technology.”

This is another example of what we call CIRM’s “value proposition”; the fact that we don’t just provide funding, we also provide support on many other levels and that has a whole range of benefits. When our Grants Working Group – the independent panel of experts who review our scientific applications – and the CIRM Board approves a project it’s like giving it the CIRM Good Housekeeping Seal of Approval. That doesn’t just help that particular project, it can help attract further investment in the company behind it, enabling it to expand operations and create jobs and ultimately, we hope, help advance the field as a whole.

Those benefits are substantial. To date we have been able to use our funding to leverage around $2 billion in additional dollars in terms of outside companies investing in companies like Humacyte, or researchers using data from research we funded to get additional funding from agencies like the National Institutes of Health.

So, when a company like Humacyte is the object of such a lucrative agreement it’s not just a compliment to the quality of the work they do, it’s also a reflection of our ability to pick great projects.

CIRM applauds FDA crackdown on stem cell clinics that “peddle unapproved treatments.”

FDA

CIRM is commending the US Food and Drug Administration (FDA) for its action against two stem cell clinics offering unapproved therapies.

On Wednesday, the FDA filed two complaints in federal court seeking a permanent injunction against California Stem Cell Treatment Center Inc. and US Stem Cell Clinic LLC. of Sunrise, Florida. The FDA says the clinics are marketing stem cell products without FDA approval and are not complying with current good manufacturing practice requirements.

“We strongly support the FDA’s strong stance to seek judicial action to stop these  clinics from marketing unproven therapies that pose a threat to the safety of patients” says Maria T. Millan, M.D., CIRM’s President and CEO. “We agree with FDA Commissioner Dr. Scott Gottlieb’s statement that these ‘bad actors leverage the scientific promise of this field to peddle unapproved treatments that put patients’ health at risk.’”

In his statement yesterday, Dr. Gottlieb denounced the clinics saying they are exploiting patients and causing some of them “serious and permanent harm.”

“In the two cases filed today, the clinics and their leadership have continued to disregard the law and more importantly, patient safety. We cannot allow unproven products that exploit the hope of patients and their loved ones. We support sound, scientific research and regulation of cell-based regenerative medicine, and the FDA has advanced a comprehensive policy framework to promote the approval of regenerative medicine products. But at the same time, the FDA will continue to take enforcement actions against clinics that abuse the trust of patients and endanger their health.”

At CIRM, we believe it is critically important for participants in stem cell treatments to be fully informed about the nature of the therapy they are receiving, including whether it is approved by the FDA. Last year we partnered with California State Senator Ed Hernandez to pass Senate Bill No. 512, which required all clinics offering unproven stem cell therapies to post notices warning patients they were getting a therapy that was not approved by the FDA.

The Stem Cell Agency has taken several other actions to protect people seeking legitimate stem cell therapies.

  • All the clinical trials we consider for funding must already have an active Investigational New Drug (IND) status with the FDA and go through a rigorous scientific review by leading experts.
  • All CIRM-funded trials must adhere to strict regulatory standards and safety monitoring.
  • We have created the CIRM Alpha Stem Cell Clinics, a network of six top California medical centers that specialize in delivering patient-centered stem cell clinical trials that meet the highest standards of care and research.
  • CIRM provides access to information on all the clinical trials it supports.

“Through its funding mechanism, active partnership and infrastructure programs, CIRM has shepherded 48 FDA regulated, scientifically sound, rigorously reviewed promising stem cell and regenerative medicine projects into clinical trials,” says Dr. Millan. “Some of these treatment protocols have already started to show preliminary signs of benefit for debilitating and life-threatening disorders. We are committed to doing all we can, in partnership with patients, the research community and with the FDA, to develop transformative treatments for patients with unmet medical needs while adhering to the highest standards to protect the health and safety of patients and the public.”

To help people make informed decisions we have created an infographic and video that detail the information people need to know, and the questions they should ask, before they agree to participate in a clinical trial or get a stem cell therapy.

 

 

CIRM’s Industry Alliance Program: Facilitating Partnerships to Advance Stem Cell Therapies

Some things are better together. Take for instance macaroni and cheese, eggs and bacon, cookies and ice cream. Each of these things are fine on their own, but together, they become something more powerful and delicious.

The right partnerships can bring out the best in things. At CIRM, we fully embrace this concept. That’s why we’re launching the Industry Alliance Program (IAP). It’s a new partnering opportunity to bring the most promising stem cell, gene therapy, and regenerative medicine programs to market where they can help people with unmet medical needs.

CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials.

The CIRM IAP is designed to give pharma, biotech and VC firms direct access to CIRM’s growing stem cell portfolio. These partners work in the stem cell and regenerative medicine field and will be connected to CIRM-funded scientists working on projects relevant to their interests.

In a news release, CIRM’s President and CEO, Dr. Maria T. Millan, explained:

Maria T. Millan

“The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our Agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The first two companies to join the IAP are BlueRock Therapeutics and Vivo Capital. BlueRock is a Cambridge, Massachusetts-based company that is pioneering cell therapies for degenerative diseases while Vivo Capital is a global venture capital firm that invests in life sciences and healthcare companies.

CIRM will continue to selectively recruit new partners to the IAP with the goal of building a collaborative network to support the development and commercialization of CIRM-funded programs.

Neil Littman, CIRM’s Director of Business Development, concluded:

Neil Littman

“The IAP is essentially a built-in concierge service for the stem cell space. Our unique vantage-point both inside and outside of California – spanning discovery, translation, and clinical trials – allows us to effectively match CIRM-funded programs with the strategic objectives of our IAP partners.  We’re excited to work with partners such as BlueRock and Vivo who have a demonstrated commitment to advance stem cell-based therapies to the market.”

For more information about CIRM’s new IAP program, visit our website.

If you’re into stem cell manufacturing, this is the conference for you!

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Manufacturing stem cells: Photo courtesy of Pluristem

Fulfilling CIRM’s mission doesn’t just mean accelerating promising stem cell treatments to patients. It also involves accelerating the whole field of regenerative medicine, which involves not just research, but developing candidate treatments, manufacturing cell therapies, and testing these therapies in clinical trials.

Manufacturing and the pre-clinical safety evaluation of cell therapies are topics that don’t always receive a lot of attention, but they are essential and crucial steps in bringing cell therapies to market. Manufacturing cells that meet the strict standards for use in human trials is often a bottleneck where different methods of making pluripotent stem cells (PSCs) are used and standardization is not readily possible.

Abla-8Abla Creasey, Vice President of Therapeutics and Strategic Infrastructure at CIRM, notes:

“The field of stem cell research and regenerative medicine has matured to the point where there are over 900 clinical trials worldwide. It is critical to develop a system of effective regulation of how these stem cell treatments are developed and manufactured so patients can benefit from future treatments.”

To address this challenge, CIRM has teamed up the International Alliance for Biological Standardization to host the 4th Cell Therapy Conference on Manufacturing and Testing of Pluripotent Stem Cells on June 5-6th in Los Angeles, California.

WHAT

The aim of this conference is twofold. Speakers will discuss how product development programs can be moved forward in a way that will meet regulatory requirements, so treatments can be approved.

The conference will also focus on key unresolved issues that need to be addressed for the manufacturing and safety testing of pluripotent stem cell-based therapies and then make recommendations to inform the future national and international policies. The overall aim is to provide participants with a road map so new treatments can achieve the highest regulatory standards and be made available to patients around the world.

The agenda of the conference will cover four main topics:

  1. Learning from the current pluripotent space and the development of international standards
  2. Bioanalytics and comparability of therapeutic stem cells
  3. Tumorigenicity testing for therapeutic safety
  4. Pluripotent stem cell manufacturing, storage, and shipment Issues

Using this “big tent” approach, speakers will exchange knowledge, experience and expertise to develop consensus recommendations around stem cell manufacturing and testing.  New data in this area will be introduced at the conference for the first time, such as a multi-center study to identify and optimize manufacturing-compatible methods for cell therapy safety.

WHO

The conference will bring together leading experts from industry, academia, health services and therapeutic regulatory bodies around the world, including the US Food and Drug Administration, European Medicines Agency, Japan Pharmaceuticals and Medical Devices Agency, and World Health Organization.

CIRM and IABS encourage individuals and organizations actively pursuing the development of stem cell therapies to attend.

WHY

robert deansIf you’re interested, but not quite sold on this conference, take the word of these experts:
Robert Deans, Chief Technology Officer at BlueRock Therapeutics:

“I believe standardization will be an increasingly crucial element in securing commercial success for regenerative cell therapies.  This applies to all facets of development, from cell characterization and patent protection through safety testing of final product.  Most important is the adherence of players in this sector to harmonized standards and creation of a scientifically credible market to the capital community.”

martin-pera-profileProfessor Martin Pera of the Jackson Laboratory, who directs the International  Stem Cell Initiative Genetics and Epigenetics Study Group:

“Participants at this meeting will survey and discuss the state of the art in the development of definitive assays for assessing the safety of pluripotent stem cell based therapies, a critical issue for the future of the field.  Anyone active in cell therapy should attend this meeting to contribute to a dialogue that will impact on research directions and ultimately help to define best practice in this sector.”

When and Where

The conference will be held in Los Angeles Airport Marriott on June 5-6th, 2018. Registration is now open on the IABS website and you can take advantage of discounted early bird registration before April 24th.

Recap of the 2018 Alliance for Regenerative Medicine Cell and Gene Therapy State of the Industry

What happened in the Cell and Gene Therapy sector in 2017, and what should we be looking out for in 2018? Over 500 executives, investors, scientists and patient advocates gathered together yesterday to find out at the Alliance for Regenerative Medicine (ARM) State of the Industry Briefing in San Francisco, California.

ARM Chairman, Robert Preti, and ARM CEO, Janet Lynch Lambert, kicked off the session by discussing how 2017 marked an inflection point for the sector. They underscored the approval of three cell/gene therapies (see slide below) by the U.S. Food and Drug Administration (FDA), a “bright and robust” future pipeline that should yield over 40 approved therapies in the next five years, and an improving regulatory environment that’s accelerating approvals of regenerative medicine therapies. This year alone, the FDA has granted 12 Regenerative Medicine Advanced Therapy (RMAT) designations through the 21st Century Cures Act (see slide below for companies/products that received RMAT in 2017).

In 2017, a total of four cell/gene therapies were approved and the US FDA awarded 12 RMAT designations. This slide is from the 2018 ARM Cell and Gene Therapy State of the Industry Briefing presentation.

Next up was a snapshot of the clinical landscape highlighting a total of 946 ongoing clinical trials at the end of 2017, and their breakdown by disease (see chart below). Oncology (cancer) is the clear winner comprising over 50% of the trials while Cardiovascular (heart) took second with 8.6% and diseases of the central nervous system (brain and spinal cord) took third with 6.5%.

Lambert also gave a brief overview of finances in 2017 and listed some impressive numbers. $7.5 Billion in capital was raised in 2017 compared to $4.2 Billion in 2016. She also mentioned major acquisitions, mergers, partnerships and public financings that paved the way for this year’s successes in cell and gene therapy.

Lambert concluded that while there was significant progress with product approvals, growing public awareness of successes in the sector, regulatory advances and financial maturity, there is a need for further commercial support and a focus on policy making, industrialization and manufacturing.

The Industry Update was followed by two panel sessions.

The first panel focused on cell-based cancer immunotherapies and featured company leaders from Juno Therapeutics, Mustang Bio, Adaptimmune, Novartis, and Fate Therapeutics.

In the cancer field, companies are aggressively pursuing the development of cell-based immunotherapies including Chimeric Antigen Receptor T (CAR-T) cells, modified T-cells and Natural Killer (NK) cells, to name a few. These therapies all involve engineering or modifying human immune cells to identify and target cancer cells that resist first-line cancer treatments like radiation or chemotherapy.

The panelists spoke of a future that involved the development of combination therapies that partner cell-based immunotherapies with other drugs and treatments to better target specific types of cancer. They also spent a significant portion of the panel discussing the issues of manufacturing and reimbursement. On manufacturing, the panel argued that a centralized cell manufacturing approach will be needed to deliver safe products to patients. On reimbursement, they addressed the difficulty of finding a balance between pricing life-saving therapies and navigating reimbursements from insurance companies.

The second panel focused on the state of gene therapy and the outlook for 2018. This panel featured company and academic leaders from CRISPR Therapeutics, Sangamo Therapeutics, BioMarin Pharmaceutical, Adverum Biotechnologies, and the Gladstone Institutes.

ARM Gene Therapy Panel: Martha Rook (MilliporeSigma), Deepak Srivastava (Gladstone Institutes), Amber Salzman (Adverum Biotechnologies), Bill Lundberg (CRISPR Therapeutics), Geoff Nichol (BioMarin Pharmaceutical), Sandy Macrae (Sangamo Therapeutics)

The panel spoke about the difference between gene editing (fixing an existing gene within a cell) and gene therapy (adding a new gene into a cell) technologies and how the delivery of these therapies into tissues and cells is the biggest challenge in the area right now.

Sandy Macrae, President and CEO of Sangamo Therapeutics, made an interesting point when he said that for gene therapy to be successful, companies need to plan two to three years in advance for a phase III trial (the final stage before a product is approved) because manufacturing gene therapies takes a long time. He said the key for success is about having medicines that are ready to launch, not just reporting good results.

Overall, ARM’s State of the Industry provided an exciting overview of the progress made in the Cell and Gene Therapy Sector in 2017 and shared outlooks for 2018 and beyond.

You can access the Live Webcast of ARM’s State of the Industry Briefing including both panel sessions on the ARM website. Be sure to check out our blog featuring our 2018 Stem Cell Conference Guide for more ARM events and other relevant stem cell research meetings in the coming year.

How CIRM funding creates additional financial support for stem cell research in California

CIRM’s 2017 Annual Report will be going live online very soon. In anticipation of that we are highlighting some of the key elements from the report here on the Stem Cellar.

Two businessman shaking hands

Partnerships that help advance stem cell research

CIRM funds stem cell research.  We all know that.  What you may not know is that CIRM funds also help bring in additional funding and investments to these projects, and as a result, to the state of California.  CIRM’s investment can also be seen as helping validate the credibility of a particular project, taking some of the risk out of investing in it.

We call this second wave of support “Leveraged Funding”. Since we were created in 2004 we have brought in $1.5 billion in Leveraged Funds.

We break that down into three main categories:

  1. Co-Funding– This is funding that was specifically committed to help co-fund a CIRM project. For example, if we fund a for-profit company to do a Phase 1 clinical trial we expect them to co-fund 30% of the cost of the trial. If it’s a Phase 3 clinical trial the co-funding amount rises to 50%.  To date we have received $911 million in co-funding.
  2. Partnership Funding– Partnership Funding – This is non-CIRM funding committed by partners, not already captured by Co-Funding. For example, our Board’s decision to invest in a project can sometimes be seen as a kind of “Good Housekeeping Seal of Approval” because it shows this project has been reviewed by experts and recommended for funding.  Our funding allows investigators to do the early work and get data that helps attract funding from outside investors. These funds can be committed or spent at the same time as CIRM funds or to further the project after the CIRM award expires. Since 2004, we have helped generate $528 million in partnership funding.
  3. Additional Leverage– This is everything not covered by the first two categories but is mainly non-CIRM funding reported in the “Outcomes Survey”, which the lead investigator on the project completes at the end of the award. This lets us know about any non-CIRM funding they received as a result of their CIRM project (such as money from the National Institutes of Health or other agency grants). More than $395 million in additional leverage funding has been raised because of CIRM.

In 2017, we saw eight projects that we support attract additional support, almost $390 million, from outside investors.

  Disease Area  Industry Partner 2017 Funding
1. Adenosine deaminase-deficient Severe Combined Immunodeficiency Orchard Therapeutics $110,000,000
2. X-Linked Chronic Granulomatous Disease Orchard Therapeutics Not disclosed
3. Acute Myeloid Leukemia Forty Seven, Inc. $75,000,000
4. Pediatrics Genetic Disorder AVROBIO, Inc. Not disclosed
5. HIV/AIDS CSL Behring $91,000,000
6. Chronic Lymphocytic Leukemia Oncternal, Inc. $18,400,000
7. Brain Cancer Mustang Bio, Inc. $94,500,000
8. Age-related Macular Degeneration Santen Pharmaceutical Not disclosed
  Total   $388,900,000

Our goal is to do all we can to support the best science and move it out of the lab and into clinical trials in people. Obviously, providing funding is a key step, but it’s far from the only step. For us, it’s really just the first step.

On Wednesday, we’ll profile one of the CIRM-funded researchers whose work is attracting support from outside investors, work that is taking a whole new approach to fighting a deadly brain cancer.

CIRM Board invests in three new stem cell clinical trials targeting arthritis, cancer and deadly infections

knee

Arthritis of the knee

Every day at CIRM we get calls from people looking for a stem cell therapy to help them fight a life-threatening or life-altering disease or condition. One of the most common calls is about osteoarthritis, a painful condition where the cartilage that helps cushion our joints is worn away, leaving bone to rub on bone. People call asking if we have something, anything, that might be able to help them. Now we do.

At yesterday’s CIRM Board meeting the Independent Citizens’ Oversight Committee or ICOC (the formal title of the Board) awarded almost $8.5 million to the California Institute for Biomedical Research (CALIBR) to test a drug that appears to help the body regenerate cartilage. In preclinical tests the drug, KA34, stimulated mesenchymal stem cells to turn into chondrocytes, the kind of cell found in healthy cartilage. It’s hoped these new cells will replace those killed off by osteoarthritis and repair the damage.

This is a Phase 1 clinical trial where the goal is primarily to make sure this approach is safe in patients. If the treatment also shows hints it’s working – and of course we hope it will – that’s a bonus which will need to be confirmed in later stage, and larger, clinical trials.

From a purely selfish perspective, it will be nice for us to be able to tell callers that we do have a clinical trial underway and are hopeful it could lead to an effective treatment. Right now the only alternatives for many patients are powerful opioids and pain killers, surgery, or turning to clinics that offer unproven stem cell therapies.

Targeting immune system cancer

The CIRM Board also awarded Poseida Therapeutics $19.8 million to target multiple myeloma, using the patient’s own genetically re-engineered stem cells. Multiple myeloma is caused when plasma cells, which are a type of white blood cell found in the bone marrow and are a key part of our immune system, turn cancerous and grow out of control.

As Dr. Maria Millan, CIRM’s President & CEO, said in a news release:

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells.  Less than half of patients with multiple myeloma live beyond 5 years. Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

In a news release from Poseida, CEO Dr. Eric Ostertag, said the therapy – called P-BCMA-101 – holds a lot of promise:

“P-BCMA-101 is elegantly designed with several key characteristics, including an exceptionally high concentration of stem cell memory T cells which has the potential to significantly improve durability of response to treatment.”

Deadly infections

The third clinical trial funded by the Board yesterday also uses T cells. Researchers at Children’s Hospital of Los Angeles were awarded $4.8 million for a Phase 1 clinical trial targeting potentially deadly infections in people who have a weakened immune system.

Viruses such as cytomegalovirus, Epstein-Barr, and adenovirus are commonly found in all of us, but our bodies are usually able to easily fight them off. However, patients with weakened immune systems resulting from chemotherapy, bone marrow or cord blood transplant often lack that ability to combat these viruses and it can prove fatal.

The researchers are taking T cells from healthy donors that have been genetically matched to the patient’s immune system and engineered to fight these viruses. The cells are then transplanted into the patient and will hopefully help boost their immune system’s ability to fight the virus and provide long-term protection.

Whenever you can tell someone who calls you, desperately looking for help, that you have something that might be able to help them, you can hear the relief on the other end of the line. Of course, we explain that these are only early-stage clinical trials and that we don’t know if they’ll work. But for someone who up until that point felt they had no options and, often, no hope, it’s welcome and encouraging news that progress is being made.

 

 

ViaCyte treats first patients in PEC-Direct stem cell trial for type 1 diabetes

Today, ViaCyte shared an update on its latest clinical trial for type 1 diabetes (T1D). The company is based in San Diego and is developing two stem cell-based products that attempt to replace the pancreatic beta islet cells that are attacked by the immune system of patients with T1D.

Their first product, called VC-01 or PEC-Encap, is an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood. Because the cells are encapsulated in a protective semi-permeable membrane, hormones and nutrients can pass in and out of the device, but the implanted cells are guarded against the patient’s immune system. VC-01 is currently being tested in a Phase 1 clinical trial that is funded CIRM.

ViaCyte now has a second product called VC-02, or PEC-Direct, that also transplants pancreatic progenitors but in a device that allows a patient’s blood vessels to make direct contact with the implanted cells. This “direct vascularization” approach is being tested in patients that are at high risk for severe complications associated with T1D including hypoglycemia unawareness – a condition where patients fail to recognize when their blood glucose level drops to dangerously low levels because the typical symptoms of hypoglycemia fail to appear.

ViaCyte’s PEC-Direct device allows a patient’s blood vessels to integrate and make contact with the transplanted beta cells.

In May, ViaCyte announced that the US Food and Drug Administration (FDA) approved their Investigational New Drug (IND) application for PEC-Direct, which gave the company the green light to proceed with a Phase 1 safety trial to test the treatment in patients. ViaCyte’s pre-IND work on PEC-Direct was supported in part by a late stage preclinical grant from CIRM.

Today, the ViaCyte announced in a press release that it has treated its first patients with PEC-Direct in a Phase 1/2 trial at the University of Alberta Hospital in Edmonton, Alberta and at the UCSD Alpha Stem Cell Clinic in San Diego, California.

“The first cohort of type 1 diabetes patients is receiving multiple small-format cell-filled devices called sentinels in order to evaluate safety and implant viability.  These sentinel units will be removed at specific time points and examined histologically to provide early insight into the progression of engraftment and maturation into pancreatic islet cells including insulin-producing beta cells.”

The news release also revealed plans for enrollment of a larger cohort of patients by the end of 2017.

“A second cohort of up to 40 patients is expected to begin enrolling later this year to evaluate both safety and efficacy.  The primary efficacy measurement in the trial will be the clinically relevant production of insulin, as measured by the insulin biomarker C-peptide, in a patient population that has little to no ability to produce endogenous insulin at the time of enrollment.  Other important endpoints will be evaluated including injectable insulin usage and the incidence of hypoglycemic events.  ViaCyte’s goal is to demonstrate early evidence of efficacy in the first half of 2018 and definitive efficacy 6 to 12 months later.”

President and CEO of ViaCyte, Dr. Paul Laikind, is hopeful that PEC-Direct will give patients with high-risk T1D a better treatment option than what is currently available.

ViaCyte’s President & CEO, Paul Laikind

“There are limited treatment options for patients with high-risk type 1 diabetes to manage life-threatening hypoglycemic episodes. We believe that the PEC-Direct product candidate has the potential to transform the lives of these patients and we are excited to move closer to that goal with the initiation of clinical evaluation announced today.  This also represents a step towards a broader application of the technology.  We remain fully committed to developing a functional cure for all patients with insulin-requiring diabetes.  To that end, we are hard at work on next-generation approaches as well, and expect the work with PEC-Direct to further advance our knowledge and drive progress.”


Related links:

Stem Cell Stories that Caught our Eye: CRISPRing Human Embryos, brain stem cells slow aging & BrainStorm ALS trial joins CIRM Alpha Clinics

Here are the stem cell stories that caught our eye this week. Enjoy!

Scientists claim first CRISPR editing of human embryos in the US.

Here’s the big story this week. Scientists from Portland, Oregon claim they genetically modified human embryos using the CRISPR/Cas9 gene editing technology. While their results have yet to be published in a peer review journal (though the team say they are going to be published in a prominent journal next month), if they prove true, the study will be the first successful attempt to modify human embryos in the US.

A representation of an embryo being fertilized. Scientists can inject CRISPR during fertilization to correct genetic disorders. (Getty Images).

Steve Connor from MIT Technology Review broke the story earlier this week noting that the only reports of human embryo modification were published by Chinese scientists. The China studies revealed troubling findings. CRISPR caused “off-target” effects, a situation where the CRISPR machinery randomly introduces genetic errors in a cell’s DNA, in the embryos. It also caused mosaicism, a condition where the desired DNA sequences aren’t genetically corrected in all the cells of an embryo producing an individual with cells that have different genomes. Putting aside the ethical conundrum of modifying human embryos, these studies suggested that current gene editing technologies weren’t accurate enough to safely modify human embryos.

But a new chapter in human embryo modification is beginning. Shoukhrat Mitalipov (who is a member of CIRM’s Grants Working Group, the panel of scientific experts that reviews our funding applications) and his team from the Oregon Health and Science University said that they have developed a method to successfully modify donated human embryos that avoids the problems experienced by the Chinese scientists. The team found that introducing CRISPR at the same time an embryo was being fertilized led to successful correction of disease-causing mutations while avoiding mosaicism and “off-target” effects. They grew these embryos for a few days to confirm that the genetic modifications had worked before destroying them.

The MIT piece quoted a scientist who knows of Mitalipov’s work,

“It is proof of principle that it can work. They significantly reduced mosaicism. I don’t think it’s the start of clinical trials yet, but it does take it further than anyone has before.”

Does this discovery, if it’s true, open the door further for the creation of designer babies? For discussions about the future scientific and ethical implications of this research, I recommend reading Paul Knoepfler’s blog, this piece by Megan Molteni in Wired Magazine and Jessica Berg’s article in The Conversation.

Brain stem cells slow aging in mice

The quest for eternal youth might be one step closer thanks to a new study published this week in the journal Nature. Scientists from the Albert Einstein College of Medicine in New York discovered that stem cells found in an area of the brain called the hypothalamus can slow the aging process in mice.

The hypothalamus is located smack in the center of your brain near the brain stem. It’s responsible for essential metabolic functions such as making and secreting hormones, managing body temperature and controlling feelings of hunger and thirst. Because the body’s metabolic functions decline with age, scientists have suspected that the hypothalamus plays a role in aging.

The mouse hypothalamus. (NIH, Wikimedia).

In the current study, the team found that stem cells in the hypothalamus gradually disappear as mice age. They were curious whether the disappearance of these stem cells could jump start the aging process. When they removed these stem cells, the mice showed more advanced mental and physical signs of aging compared to untreated mice.

They also conducted the opposite experiment where they transplanted hypothalamic stem cells taken from baby mice (the idea being that these stem cells would exhibit more “youthful” qualities) into the brains of middle-aged mice and saw improvements in mental and physical functions and a 10% increase in lifespan.

So what is it about these specific stem cells that slows down aging? Do they replenish the aging brain with new healthy cells or do they secrete factors that keep the brain healthy? Interestingly, the scientists found that these stem cells secreted vesicles that contained microRNAs, which are molecules that regulate gene expression by turning genes on or off.

They injected these microRNAs into the brains of middle-aged mice and found that they reversed symptoms of aging including cognitive decline and muscle degeneration. Furthermore, when they removed hypothalamic stem cells from middle-aged mice and treated them with the microRNAs, they saw the same anti-aging effects.

In an interview with Nature News, senior author on the study, Dongsheng Cai, commented that hypothalamic stem cells could have multiple ways of regulating aging and that microRNAs are just one of their tools. For this research to translate into an anti-aging therapy, “Cai suspects that anti-ageing therapies targeting the hypothalamus would need to be administered in middle age, before a person’s muscles and metabolism have degenerated beyond a point that could be reversed.”

This study and its “Fountain of Youth” implications has received ample attention from the media. You can read more coverage from The Scientist, GenBio, and the original Albert Einstein press release.

BrainStorm ALS trial joins the CIRM Alpha Clinics

Last month, the CIRM Board approved $15.9 million in funding for BrainStorm Cell Therapeutic’s Phase 3 trial that’s testing a stem cell therapy to treat patients with a devastating neurodegenerative disease called amyotrophic lateral sclerosis or ALS (also known as Lou Gehrig’s disease).

The stem cell therapy, called NurOwn®, is made of mesenchymal stem cells extracted from a patient’s bone marrow. The stem cells are genetically modified to secrete neurotrophic factors that keep neurons in the brain healthy and prevent their destruction by diseases like ALS.

BrainStorm has tested NurOwn in early stage clinical trials in Israel and in a Phase 2 study in the US. These trials revealed that the treatment was “safe and well tolerated” and that “NurOwn also achieved multiple secondary efficacy endpoints, showing clear evidence of a clinically meaningful benefit.  Notably, response rates were higher for NurOwn-treated subjects compared to placebo at all time points in the study out to 24 weeks.”

This week, BrainStorm announced that it will launch its Phase 3 CIRM-funded trial at the UC Irvine (UCI) CIRM Alpha Stem Cell Clinic. The Alpha Clinics are a network of top medical centers in California that specialize in delivering high quality stem cell clinical trials to patients. UCI is one of four medical centers including UCLA, City of Hope, and UCSD, that make up three Alpha Clinics currently supporting 38 stem cell trials in the state.

Along with UCI, BrainStorm’s Phase 3 trial will also be conducted at two other sites in the US: Mass General Hospital in Boston and California Pacific Medical Center in San Francisco. Chaim Lebovits, President and CEO, commented,

“We are privileged to have UCI and Dr. Namita Goyal join our pivotal Phase 3 study of NurOwn. Adding UCI as an enrolling center with Dr. Goyal as Principal Investigator will make the treatment more accessible to patients in California, and we welcome the opportunity to work with this prestigious institution.”

Before the Phase 3 trial can launch at UCI, it needs to be approved by our federal regulatory agency, the Food and Drug Administration (FDA), and an Institutional Review Board (IRB), which is an independent ethics committee that reviews biomedical research on human subjects. Both these steps are required to ensure that a therapy is safe to test in patients.

With promising data from their Phase 1 and 2 trials, BrainStorm’s Phase 3 trial will likely get the green light to move forward. Dr. Goyal, who will lead the trial at the UCI Alpha Clinic, concluded:

“NurOwn is a very promising treatment with compelling Phase 2 data in patients with ALS; we look forward to further advancing it in clinical development and confirming the therapeutic benefit with Brainstorm.”