An Optimistic Outlook for Jasper in 2023

By Ronald Martell , President and Chief Executive Officer of Jasper Therapeutics

With the new year came several exciting announcements, driving our optimism about the opportunities ahead for our lead c-Kit targeting antibody, briquilimab, in chronic diseases and stem cell transplant for rare diseases. This holds a personal connection for me. A few years ago, I lost my father to a blood cancer called myelodysplastic syndromes (MDS), a disease that can be cured by a hematopoietic stem cell transplant. Unfortunately, this wasn’t an option at the time because his doctor was concerned about potential toxicities from the procedure and my father’s age. When I joined Jasper last year, it became part of my personal mission that our company do everything possible to make stem cell and gene therapies more accessible for patients and their families.

At Jasper, we are developing briquilimab, a monoclonal antibody that targets a receptor called c-Kit (CD117) involved in a key signaling pathway in stem cells and mast cells. It’s being developed for use as a conditioning agent to help reduce the toxicity of existing conditioning approaches for cell and gene therapies – the limiting factor that prevented my father from receiving a transplant – and as a standalone therapy for diseases driven by mast cells and stem cells. Conditioning is a preparative step for stem cell transplants that is used to open up space in the bone marrow for new, healthy stem cells to engraft.

To date, briquilimab’s potential has been validated in five of five transplant patient populations that we have studied: severe combined immunodeficiency (SCID), acute myeloid leukemia (AML), MDS, Fanconi anemia and sickle cell disease (SCD). In addition, it has been shown that targeting c-Kit signaling pathways has therapeutic potential in chronic diseases such as lower-risk MDS and chronic spontaneous urticaria. Given this broad potential, we recently raised $103.5 million in new capital from leading biotech investors to support the development of briquilimab across these diseases. In 2023, our goal is to show as soon as possible how briquilimab’s differentiated mechanism and therapeutic profile have the potential to overcome challenges encountered by other therapies in development for certain chronic and rare diseases.

New briquilimab program for people with chronic spontaneous urticaria

In a recent announcement, we shared that Jasper will be starting a clinical study of briquilimab as a standalone therapy in chronic urticaria, commonly referred to as hives, which is an allergic reaction that occurs when the body’s immune system attacks its own tissues, causing inflammation of the skin. In many diseases, including urticaria, it is thought that unregulated mast cell activation may cause this unwanted inflammation. Briquilimab is designed to directly block c-Kit signaling, and work by Jasper and others has shown that this approach will deplete mast cells and could provide therapeutic benefit.

A safe and effective treatment option for chronic spontaneous urticaria is urgently needed. Currently, first line therapy includes antihistamines; however, the disease is uncontrolled in as many as half the patients that take these medications. The only other approved agent, which does not deplete mast cells, is only prescribed to a fraction of the patients and leaves many with uncontrolled disease. Development of briquilimab in chronic spontaneous urticaria could expand briquilimab’s profile beyond transplant to become a chronic, potentially disease modifying, treatment for patients.

Promising data for briquilimab in people with sickle cell disease and beta thalassemia?

Briquilimab is also showing great potential as a conditioning agent to help prepare people to receive cell and gene therapies. For decades, the only curative treatment for SCD has been a donor stem cell transplant and more recently, gene therapies that modify stem cells before transplant; however, one of the greatest barriers limiting patient access to these treatments is the toxic chemotherapy required to open up space in the bone marrow for new stem cells to engraft.

We recently announced the first data from an investigator-initiated Phase 1/2 clinical trial of briquilimab in patients with SCD and beta thalassemia; the study is exploring the addition of briquilimab as a way to achieve a higher percentage of donor chimerism without increased toxicity from chemotherapy-based conditioning. The Phase 1/2 clinical study is led by Dr. John F. Tisdale, Director of the Cellular and Molecular Therapeutics Laboratory, National Heart, Lung, and BIood Institute (NHLBI). All three patients showed complete takeover of their bone marrow by the donor cells as measured by myeloid chimerism, which is the main efficacy endpoint of the study. And in the first participant where we had five months of follow up, we saw a significant increase in hemoglobin to reach normal levels. ?

Supportive data of briquilimab in people living with Fanconi anemia

Fanconi anemia is a rare but serious blood disorder that prevents bone marrow from making sufficient new red blood cells or causes it to make abnormal blood cells. It can lead to serious complications, including bone marrow failure and severe aplastic anemia. Patients affected by Fanconi anemia can be treated with stem cell transplant but have increased sensitivity to conventional conditioning regimens and radiation due to genetic defects in their DNA repair. Briquilimab offers a targeted conditioning strategy that eliminates the need for radiation or highly toxic agents like busulfan.

Initial data from an investigator-initiated study suggest that a conditioning regimen that includes briquilimab has the potential to achieve successful donor transplant. A Phase 1/2 clinical trial utilizing briquilimab to treat Fanconi anemia patients in bone marrow failure requiring allogeneic transplant with non-sibling donors showed 100% complete donor chimerism was achieved through six months for the first patient and at one month for the second patient. Neutrophil engraftment was reached on day 11 for both patients, and platelet engraftment was achieved on days 9 and 14. Briquilimab was cleared by day 9 after dosing and no treatment-related adverse events or toxicities were observed.

An exciting year ahead

With compelling data across several disease areas to date, coupled with our FDA Fast Track Designation in the treatment of patients with SCID, our recently announced orphan drug designation in Europe, and most recent new financing, the near- and long-term future looks bright for briquilimab and Jasper. We are grateful to patients, clinical investigators, our team and external partners for helping us advance this program.

We will present positive data at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (February 15-19, 2023; Orlando, FL) to further reinforce the broad opportunity for briquilimab in AML/MDS stem cell transplant, the type of transplant that my father was unable to receive. The progress we make in each program is supportive and positive for the others, including the longer-term opportunity in AML/MDS, for which we will continue to work with the FDA and potential partners to be ready for a pivotal Phase 3 study in the future. Ultimately, we want to ensure that people like my father, who are in need of a stem cell transplant / gene therapy or face other chronic diseases, have the ability to access the curative potential of our therapies.?

For more information, please visit us at www.jaspertherapeutics.com.