Exelixis, Inc. and Sairopa B.V. announced that the companies have entered into an exclusive clinical development and option agreement for ADU-1805, a potentially best-in-class monoclonal antibody that targets SIRPα. SIRPα expressed on myeloid cells interacts with CD47 present on the surface of cancer cells and blocks the ability of macrophages to clear tumor cells via phagocytosis and inhibits tumor antigen presentation to T-cells. Blocking SIRPα has the potential to improve the immune system’s ability to attack tumors by addressing a significant immune-suppressive component of the tumor microenvironment. ADU-1805 is active against all human alleles of SIRPα, which may allow it to address a broader patient population than other SIRPα-directed therapies. ADU-1805 has also been optimized to bind preferentially to SIRPα vs. other SIRP family members, which may enhance its ability to stimulate immune cells.
“ADU-1805 is a promising antibody that has been carefully optimized to maximize the potential benefit of blocking the SIRPα – CD47 checkpoint, while minimizing potential toxicities and allowing for treatment of the broadest population of appropriate patients. We believe that ADU-1805 represents a differentiated and potentially best-in-class approach to this pathway,” said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer, Exelixis. “With an Investigational New Drug filing anticipated in the first quarter of 2023, this agreement provides an exciting opportunity to expand our clinical pipeline. There is a strong scientific rationale for blockade of this pathway in multiple solid tumor types and for combining ADU-1805 with XL092, our novel tyrosine kinase inhibitor, and with approved immune checkpoint inhibitors, further expanding the potential clinical and commercial value of ADU-1805.”
“Sairopa was founded to develop a portfolio of therapeutic antibodies that modulate immune system activity to provide benefit to cancer patients. The preclinical data we have generated to date for ADU-1805 are compelling and suggest that this novel antibody has best-in-class potential, both as a single agent and in combination with other novel therapies or immune checkpoint inhibitors,” said Dharminder Chahal, Managing Director, Sairopa. Commenting on the news, Gurvinder Chahal, Sairopa’s Chief Business Officer, added: “With a track record of success in advancing and commercializing novel therapies in diverse oncology indications, Exelixis was our partner of choice for realizing the broad potential of ADU-1805 and achieving our shared mission to improve outcomes for patients living with cancer.”
SIRPα is expressed on the surface of macrophages and other myeloid cells, which are a significant component of the tumor microenvironment and are believed to contribute to an immune-suppressive environment. SIRPα interacts with CD47 expressed on the surface of cancer cells to inhibit antibody-dependent cellular phagocytosis (ADCP), the process by which the immune system clears tumor cells that have therapeutic antibodies bound to them from the body. Inhibition of ADCP can limit the efficacy of antibody-based therapies. SIRPα blockade also enhances tumor antigen uptake induced by tumor cytotoxic approaches such as radiotherapy or chemotherapy and enhances antigen presentation, which when combined with other immune checkpoint inhibitors is believed to enhance the anti-tumor immune response. Several CD47-targeted therapies are in development and have shown clinical efficacy both as single agents and in combination with opsonizing antibodies. However, the broad expression of CD47 in healthy tissues and CD47 inactivation of T-cells has resulted in significant toxicities, including anemia and thrombocytopenia. In contrast, SIRPα has a more limited pattern of expression that excludes red blood cells and platelets and has the potential for an improved safety profile compared with anti-CD47 therapies.