Biotechnology companies join forces in developing treatment for X-SCID

Jasper Therapeutics, Inc., a biotechnology company focused on blood stem cell therapies, and Graphite Bio, Inc., a biotechnology company focused on gene editing therapies to treat or cure serious diseases, announced a research and clinical collaboration for a treatment for X-SCID.

X-SCID, which stands for X-linked severe combined immunodeficiency, is a genetic disorder that interferes with the normal development of the immune system, leaving infants vulnerable to infections that most people can easily fight off. One treatment for X-SCID involves a blood stem cell transplant, in which the patient’s defective stem cells are wiped out with chemotherapy or radiation to make room for normal blood stem cells to take their place. Unfortunately, the problem with chemotherapy or radiation in young infants is that it can lead to lifelong effects such as neurological impairment, growth delays, infertility, and risk of cancer.

Fortunately, Jasper Therapeutics has developed JSP191, a non-toxic alternative to chemotherapy and radiation. It is an antibody that works by targeting and removing the defective blood forming stem cells. The approach has previously been used in a CIRM-funded clinical trial ($20M award) for X-SCID.

Graphite Bio has developed GPH201, the first-in-human investigational blood stem cell treatment that will be evaluated as a potential cure for patients suffering from X-SCID. GPH201 is generated using precise and efficient gene editing technology, It works by directly replacing a defective gene that causes problems with the immune system. The hope is that GPH201 will ultimately lead to the production of fully functional, healthy immune cells.

The ultimate goal of this collaboration is to use JSP191 as the non-toxic alternative to chemotherapy in patients in order to remove their defective blood stem cells. After that, the gene editing blood stem cell technology developed by Graphite Bio can be introduced to patients in order to treat X-SCID. The two companies have agreed to collaborate on research, and potentially a clinical study, evaluating JSP191 as the non-toxic conditioning agent for GPH201.

In a press release, Josh Lehrer, M.Phil., M.D., chief executive officer at Graphite Bio, expressed excitement about the collaboration between the two companies.

“This collaboration with Jasper demonstrates our shared commitment to pioneering novel therapeutic approaches with the potential to significantly improve the treatment experiences of individuals with devastating conditions who stand to benefit from gene replacement therapies, initially for patients with XSCID. GPH201 harnesses our targeted gene integration platform to precisely target the defective gene that causes XSCID and replace it with a normal copy.”

In the same press release, Bill Lis, executive chairman and CEO of Jasper Therapeutics, also expressed optimism in regards to the two companies teaming up.

“Our collaboration with Graphite Bio is an exciting opportunity to further advance the field of curative gene correction by combining a targeted gene integration platform with our first-in-class targeted CD117 antibody, JSP191, that has already demonstrated preliminary clinical efficacy and safety as a conditioning agent in X-SCID patients and those with blood cancers undergoing allogeneic hematopoietic stem cell transplant.”

Graphite Bio is also developing gene editing technology to help treat sickle cell disease.  It is currently supported by a CIRM  late stage preclinical grant ($4.8M award). Th goal is to complete the final preclinical studies, which will allow Graphite Bio to start clinical studies of the sickle cell disease gene therapy in sickle cell patients in 2021.

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

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

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