Matt Porteus

An Open Letter to CIRM for World Sickle Cell Day

/ Kevin McCormack / Leave a comment
Nancy M. Rene

Dear CIRM,

World Sickle Cell Day is this Saturday June 19th. The goal of this day is to increase knowledge of the disease and understanding of the challenges faced.

It is a day that I greet with very mixed feelings.  I’m of course extremely grateful to CIRM for the time and money spent looking for a cure.  The work of doctors, of researchers, the courage of families in the sickle cell community who are taking part in studies, and of course those of you who worked so hard for the original funding for CIRM, I applaud all of you, yet it’s hard to wait for a cure.

While I wait I worry. I worry about my friends who are not getting good care.  They are the ones who can’t find a doctor to treat them, not able to take advantage of the medications that are already approved.  They are the ones who walk into the Emergency Room hoping for knowledgeable treatment while understanding that they may be accused of being a drug seeker,  turned away in excruciating pain. They are the ones who succumb after years of poor care.

With sickle cell disease there is the same level of understanding about medical malpractice that we had of police brutality before George Floyd. We hardly remember Rodney King or Eric Garner. As a country we were aware that something was wrong but we tended to retreat in denial after each terrible headline.

That’s where we are with sickle cell disease.  We may see a heart-wrenching story and watch televised reports with interest, but after all, it’s easier to live in disbelief, to think that medical care is not that bad, rather than understand that people are being dismissed and denied treatment. We call it structural racism without understanding what that term really means.

While I wait I must acknowledge that change is coming.  We have a Sickle Cell Data Collection Project in California that helps us track healthcare for sickle cell disease. This is data that we can use to point to structural weakness and address health disparities.  NASEM, the National Academies of Science Engineering and Medicine, has published a huge report with significant suggestions for improving sickle cell care. Many scientists, researchers and advocates took part in this landmark study, detailing what has gone wrong in health care and how to improve the work. And of course we have CIRM. I am very thankful for the leadership and pioneering work of doctors Donald Kohn, Matthew Porteus, Mark Walters, and Joseph Rosenthal who are using their knowledge and experience in this fight.

When we have successful research on stem cell transplants for sickle cell disease, many of us with sickle cell family members will want to relax, but we can’t forget those who may not be able to get a curative transplant. I hope Dr Niihara at Emmaus, and Dr. Love of Global Blood Therapeutics will continue their important work finding effective treatments. We must continue this fight on all fronts.

World Sickle Cell Day will come again next year.  Let’s see what it brings.

A sickle cell grandmother,

Nancy M. René

CIRM-catalyzed spinout files for IPO to develop therapies for genetic diseases

/ Yimy Villa / 1 Comment

Graphite Bio, a CIRM-catalyzed spinout from Stanford University that launched just 14 months ago has now filed the official SEC paperwork for an initial public offering (IPO). The company was formed by CIRM-funded researchers Matt Porteus, M.D., Ph.D. and Maria Grazia Roncarolo, M.D.

Six years ago, Dr. Porteus and Dr. Roncarolo, in conjunction with Stanford University, received a CIRM grant of approximately $875K to develop a method to use CRISPR gene editing technology to correct the blood stem cells of infants with X-linked severe combined immunodeficiency (X-SCID), a genetic condition that results in a weakened immune system unable to fight the slightest infection.

Recently, Dr. Porteus, in conjunction with Graphite, received a CIRM grant of approximately $4.85M to apply the CRISPR gene editing approach to correct the blood stem cells of patients with sickle cell disease, a condition that causes “sickle” shaped red blood cells. As a result of this shape, the cells clump together and clog up blood vessels, causing intense pain, damaging organs, and increasing the risk of strokes and premature death. The condition disproportionately affects members of the Black and Latin communities.

CIRM funding helped Stanford complete the preclinical development of the sickle cell disease gene therapy and it enabled Graphite to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA), one of the last steps necessary before conducting a human clinical trial of a potential therapy. Towards the end of 2020, Graphite got the green light from the FDA to conduct a trial using the gene therapy in patients with sickle cell disease.

In a San Francisco Business Times report, Graphite CEO Josh Lehrer stated that the company’s goal is to create a platform that can apply a one-time gene therapy for a broad range of genetic diseases.

Progress in the fight against Sickle Cell Disease

/ Kevin McCormack / 1 Comment
Marissa Cors, sickle cell disease patient advocate

Last November Marissa Cors, a patient advocate in the fight against Sickle Cell Disease (SCD), told the Stem Cellar “A stem cell cure will end generations of guilt, suffering, pain and early death. It will give SCD families relief from the financial, emotional and spiritual burden of caring someone living with SCD. It will give all of us an opportunity to have a normal life. Go to school, go to work, live with confidence.” With each passing month it seems we are getting closer to that day.

CIRM is funding four clinical trials targeting SCD and another project we are supporting has just been given the green light by the Food and Drug Administration to start a clinical trial. Clearly progress is being made.

Yesterday we got a chance to see that progress. We held a Zoom event featuring Marissa Cors and other key figures in the fight against SCD, CIRM Science Officer Dr. Ingrid Caras and Evie Junior. Evie is a pioneer in this struggle, having lived with sickle cell all his life but now hoping to live his life free of the disease. He is five months past a treatment that holds out the hope of eradicating the distorted blood cells that cause such devastation to people with the disease.

You can listen to his story, and hear about the other progress being made. Here’s a recording of the Zoom event.

You can also join Marissa every week on her live event on Facebook, Sickle Cell Experience Live.

CIRM-Funded Project Targeting Sickle Cell Disease Gets Green Light for Clinical Trial

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Dr. Matthew Porteus

The US Food and Drug Administration (FDA) has granted Investigational New Drug (IND) permission enabling Graphite Bio to test the investigational, potentially revolutionary gene editing therapy GPH101 developed under the supervision of Matthew Porteus, MD, PhD, in a clinical trial for people with sickle cell disease (SCD).

The California Institute for Regenerative Medicine (CIRM) has been supporting this project with a $5.2 million grant, enabling Dr. Porteus and his team at the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University to conduct the preclinical manufacturing and safety studies required by the FDA.

“We congratulate the Graphite Bio team for obtaining the IND, a critical step in bringing the GPH101 gene therapy forward for Sickle Cell Disease,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM is committed to the national Cure Sickle Cell initiative and are delighted that this technology, the product of CIRM funded research conducted by Dr. Porteus at Stanford, is progressing to the next stage of development”

Sickle cell disease is caused by a genetic mutation that turns normally smooth, round red blood cells into rigid, sickle shaped cells. Those cells clump together, clogging up blood vessels, causing intense pain, damaging organs and increasing the risk of strokes and premature death. There are treatments that help control the damage, but the only cure is a bone marrow stem cell transplant, which can only happen if the patient has a stem cell donor (usually a close relative) who has matching bone marrow.  

The investigational therapy GPH101 harnesses the power of CRISPR and natural DNA repair mechanisms to cut out the single mutation in the sickle globin gene and paste in the correct “code.” Correction of this mutation would reverse the defect and result in healthy non-sickling red blood cells.  

CEDAR, a Phase 1/2, multi-center, open-label clinical study is designed to evaluate the safety, preliminary efficacy and pharmacodynamics of GPH101 in adult and adolescent patients with severe SCD.

For patient advocate Nancy Rene, the news is personal: “It’s always exciting to hear about the progress being made in sickle cell research.  If successful it will mean that my grandson, and especially other young adults, can look forward to a life free of pain and organ damage.  They can actually begin to plan their lives, thinking about careers and families. I want to thank Dr. Porteus and all of the scientists who are working so hard for people with sickle cell disease. This is wonderful news.”

CIRM has funded four clinical trials for Sickle Cell Disease using different approaches and has a unique partnership with the National Heart, Lung and Blood Institutes under the NIH “Cure Sickle Cell” initiative.

Graphite Bio launches and will prepare for clinical trial based on CIRM-funded research

/ Yimy Villa / Leave a comment
Josh Lehrer, M.D., CEO of Graphite Bio

This week saw the launch of the 45th startup company enabled by CIRM funding of translational research at California academic institutions. Graphite Bio officially launched with the help of $45M in funding led by bay area venture firms Versant Ventures and Samsara BioCapital to spinout a novel CRISPR gene editing platform from Stanford University to treat severe diseases. Graphite Bio’s lead candidate is for sickle cell disease and it harnesses CRISPR gene correction technology to correct the single DNA mutation in sickle cell disease and to restore normal hemoglobin expression in the red blood cells of sickle cell patients (Learn more about CRISPR from a previous blog post linked here).

Matt Porteus, M.D., Ph.D (left) and Maria Grazia Roncarolo, M.D. (right)
Graphite Bio scientific founders

Matt Porteus, M.D., Ph.D and Maria Grazia Roncarolo, M.D., both from Stanford University, are the company’s scientific founders. Dr. Porteus, Dr. Roncarolo, and the Stanford team are currently supported by a CIRM  late stage preclinical grant  to complete the final preclinical studies and to file an Investigational New Drug application with the FDA, which will enable Graphite Bio to commence clinical studies of the CRISPR sickle cell disease gene therapy candidate in sickle cell patients in 2021.

Josh Lehrer, M.D., was appointed CEO of Graphite Bio and elaborated on the company’s gene editing approach in a news release.

“Our flexible, site-specific approach is extremely powerful and could be used to definitively correct the underlying causes of many severe genetic diseases, and also is applicable to broader disease areas. With backing from Versant and Samsara, we look forward to progressing our novel medicines into the clinic for patients with high unmet needs.”

In a press release, Dr. Porteus take a retrospective look on his preclinical research and its progress towards a clinical trial.

“It is gratifying to see our work on new gene editing approaches being translated into novel therapies. I’m very excited to be working with Versant again on a start-up and I look forward to collaborating with Samsara and the Graphite Bio team to bring a new generation of genetic treatments to patients.”

CIRM’s funding of late stage preclinical projects such this one is critical to its funding model, which de-risks the discovery, translational development and clinical proof of concept of innovative stem cell-based treatments until they can attract industry partnerships. You can learn more about CIRM-enabled spinout companies and CIRM’s broader effort to facilitate industry partnering for its portfolio projects on CIRM’s Industry Alliance Program website.

You can contact CIRM’s Director of Business Development at the email below to learn more about the Industry Alliance Program.

Shyam Patel, Ph.D.
Director, Business Development
Email: spatel@cirm.ca.gov