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Making a difference in Transplant:
- Rigel is focusing its organ transplant rejection program on Janus Tyrosine Kinase 3 (JAK3) inhibition. JAK3 is critical to immune system activation and is an attractive target because its expression is limited to key cells in the immune system.
- Approximately 90,000 organ transplants occur worldwide per year and 25% of those are in the U.S. First year survival rates are ~90% for the major organs, but chronic rejection rates are high (~50% at 5-10 years).
- Current global pharmaceutical sales in the transplant market are approximately $4B.
- JAK3 expression is generally limited to T & B cells, natural killer (NK) cells, mast cells, and macrophages. It also plays a critical role in lymphocyte development and function. Rigel’s R348 is a selective, potent inhibitor of JAK3.
- Rigel is considering additional indications for its JAK3 inhibitor, such as GvHD.
Highlights:
- Initiated a Phase 1 clinical trial in January 2008.
- In preclinical studies, R348 is well tolerated in animal studies and has good efficacy in the heterotopic heart allograft model.
Next Steps:
- We expect to initiate a POC study in '08 in Psoriasis.
Latest News:
Disease background and current therapeutic approaches
Transplant rejection is when a transplant recipient's immune system attacks the transplanted organ or tissue. This is caused by identification of foreign antigens on the allograft resulting in destruction of the foreign tissue. Although drugs to treat acute rejection have made significant progress chronic rejection and drug related toxicities remain a major unmet need.
Transplant recipients are currently given immunosuppressants as therapy both before, during and after treatment. Many current therapies suffer from dose limiting toxicities.
Current Therapeutic Focus:
*Reduce calcineurins (eg. cyclosporine) and steroid use
*Better balance between toxicity and immune suppression
Current Patient Needs:
*Reduce toxicities
*Prevention of chronic rejection and vascular disease |
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R788 - RA
