CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

NIH collaboration aims to develop affordable gene therapies for sickle cell disease and HIV

Sickle cell disease (SCD) and HIV have a major burden on the health of impoverished communities all over the world.

Of the 38 million people living with HIV all over the world, approximately 95% reside within developing countries, with 67% in sub-Saharan Africa, half of whom are living without any treatment.

Fifteen million babies will be born with SCD globally over the next 30 years. Of those births, 75% will occur in sub-Saharan Africa. In this region, SCD is the underlying cause of 1 in 12 newborn deaths and an estimated 50-90% of infants born with SCD in developing countries will die before their 5th birthday.

It is because of this epidemic around the world that the National Institutes of Health (NIH) and The Bill & Melinda Gates Foundation have formed a collaboration, with the bold goal of advancing safe, effective and durable gene-based therapies to clinical trials in the United States and relevant countries in sub-Saharan Africa within the next seven to 10 years. The ultimate goal is to scale and implement these treatments globally in areas hardest hit by these diseases.

Through this collaboration, the NIH plans to invest at least $100 million over the next four years towards gene therapies related to SCD and HIV and in return The Bill and Melinda Gates Foundation will match this investment with an additional $100 million towards the same goal.

Currently, due to their intrinsic complexity and cost of treatment requirements, gene based therapies are generally limited to hospitals in wealthy countries. The collaborative effort between the NIH and the Gates Foundation seeks to change that by investing in the development of curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

In a news release, NIH Director Dr. Francis Collins discusses the potential this agreement holds:

“This unprecedented collaboration focuses from the get-go on access, scalability and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries.”

In the same news release, Dr. Trevor Mundel, President of the Global Health Program at The Bill & Melinda Gates Foundation echoes the same sentiment:

“In recent years, gene-based treatments have been groundbreaking for rare genetic disorders and infectious diseases. While these treatments are exciting, people in low- and middle-income countries do not have access to these breakthroughs. By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene therapy to the world of public health.”

Similarly, CIRM and the National Heart, Lung, and Blood Institute (NHLBI), an institute within the NIH, have entered a landmark agreement on curing SCD. CIRM has already funded one program under this agreement and has another $27 million available to fund other potential therapies.

CIRM & NHLBI Create Landmark Agreement on Curing Sickle Cell Disease

CIRM Board approves first program eligible for co-funding under the agreement

Adrienne Shapiro, co-founder of Axis Advocacy, with her daughter Marissa Cors, who has Sickle Cell Disease.

Sickle Cell disease (SCD) is a painful, life-threatening blood disorder that affects around 100,000 people, mostly African Americans, in the US. Even with optimal medical care, SCD shortens expected lifespan by decades.  It is caused by a single genetic mutation that results in the production of “sickle” shaped red blood cells.  Under a variety of environmental conditions, stress or viral illness, these abnormal red blood cells cause severe anemia and blockage of blood vessels leading to painful crisis episodes, recurrent hospitalization, multi-organ damage and mini-strokes.    

On April 29th the governing Board of the California Institute for Regenerative Medicine (CIRM) approved $4.49 million to Dr. Mark Walters at UCSF Benioff Children’s Hospital in Oakland to pursue a gene therapy cure for this devastating disease. The gene therapy approach uses CRISPR-Cas9 technology to correct the genetic mutation that leads to sickle cell disease. This program will be eligible for co-funding under the landmark agreement between CIRM and the National Heart, Lung and Blood Institute (NHLBI) of the NIH.

This CIRM-NHLBI agreement was finalized this month to co-fund cell and gene therapy programs under the NIH “Cure Sickle Cell” initiative.  The goal is to markedly accelerate the development of cell and gene therapies for SCD. It will deploy CIRM’s resources and expertise that has led to a portfolio of over 50 clinical trials in stem cell and regenerative medicine.     

“CIRM currently has 23 clinical stage programs in cell and gene therapy.  Given the advancements in these approaches for a variety of unmet medical needs, we are excited about the prospect of leveraging this to NIH-NHLBI’s Cure Sickle Cell Initiative,” says Maria T. Millan, M.D., the President and CEO of CIRM. “We are pleased the NHLBI sees value in CIRM’s acceleration and funding program and look forward to the partnership to accelerate cures for sickle cell disease.”

“There is a real need for a new approach to treating SCD and making life easier for people with SCD and their families,” says Adrienne Shapiro, the mother of a daughter with SCD and the co-founder of Axis Advocacy, a sickle cell advocacy and education organization. “Finding a cure for Sickle Cell would mean that people like my daughter would no longer have to live their life in short spurts, constantly having their hopes and dreams derailed by ER visits and hospital stays.  It would mean they get a chance to live a long life, a healthy life, a normal life.”

CIRM is currently funding two other clinical trials for SCD using different approaches.  One of these trials is being conducted at City of Hope and the other trial is being conducted at UCLA.

CIRM & NIH: a dynamic duo to advance stem cell therapies

NIH

National Institutes of Health

There’s nothing more flattering than to get an invitation, out of the blue, from someone you respect, and be told that they are interested in learning about the way you work, to see if it can help them improve the way they work.

That’s what happened to CIRM recently. I will let Randy Mills, who was our President & CEO at the time, pick up the story:

“Several weeks ago I got a call from the head of the National Heart. Lung and Blood Institute (NHLBI) asking would we be willing to come out to the National Institutes of Health (NIH) and talk about what we have been doing, the changes we have made and the impact they are having.”

Apparently people at the NIH had been reading our Strategic Plan and our Annual Report and had been hearing good things about us from many different individuals and organizations. We also heard that they had been motivated to engage more fully with the regenerative medicine community following the passage of the 21st Century Cures Act.

We were expecting a sit down chat with them but we got a lot more than that. They blocked out one and a half days for us so that we had the time to engage in some in-depth, thoughtful conversations about how to advance the field.

collins-portrait_1

Dr. Francis Collins, NIH Director

The meeting was kicked off by both Francis Collins, the NIH Director, and Gary Gibbons, the NHLBI Director. Then the CIRM team – Dr. Mills, Dr. Maria Millan, Gabe Thompson and James Harrison – gave a series of presentations providing an overview of how CIRM operates, including our vision and strategic priorities, our current portfolio, the lessons learned so far, our plans for the future and the challenges we face.

The audience included the various heads and representatives from the various NIH Institutes who posed a series of questions for us to answer, such as:

  • What criteria do we use to determine if a project is ready for a clinical trial?
  • How do we measure success?
  • How have our strategies and priorities changed under CIRM 2.0?
  • How well are those strategies working?

The conversation went so well that the one day of planned meetings were expanded to two. Maria Millan, now our interim President & CEO, gave an enthusiastic summary of the talks

“The meetings were extremely productive!  After meeting with Dr. Collins’ group and the broader institute, we had additional sit down meetings.   The NIH representatives reported that they received such enthusiastic responses from Institute heads that they extended the meeting into a second day. We met with with the National Institutes of Dental and Craniofacial Research, Heart, Lung and Blood, Eye Institute, Institute on Aging, Biomedical Imaging and Bioengineering, Diabetes, and Digestive and Kidney Diseases, and the National Center for Advancing Translational Sciences.  We covered strategic and operational considerations for funding the best science in the stem cell and regenerative medicine space.  We explored potential avenues to join forces and leverage the assets and programs of both organizations, to accelerate the development of regenerative medicine and stem cell treatments.”

This was just a first meeting but it laid the groundwork for what we hope will be a truly productive partnership. In fact, shortly after returning from Washington, D.C., CIRM was immediately invited to follow-up NIH workgroups and meetings.

As this budding partnership progresses we’ll let you know how it’s working out.