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 SIRPa. SIRPa 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 SIRPa 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 SIRPa, which may allow it to address a broader patient population than other SIRPa-directed therapies. ADU-1805 has also been optimized to bind preferentially to SIRPa vs. other SIRP family members, which may enhance its ability to stimulate immune cells.

SIRPa 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. SIRPa 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.

SIRPa 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, SIRPa 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. Financial Considerations: Under the terms of the agreement, Exelixis will make an upfront payment to Sairopa of $40 million and an additional $70 million in near-term milestones for an option to obtain an exclusive, worldwide license to develop and commercialize ADU-1805 and other anti-SIRPa antibodies, and for certain expenses to be incurred by Sairopa in conducting prespecified phase 1 clinical studies of ADU-1805 during the option period. Sairopa is eligible to receive additional success-based development milestone payments during the option period.

Following the completion of the prespecified clinical studies, Exelixis has the right to exercise its option for an option exercise fee of $225 million. If Exelixis exercises the option, Sairopa is eligible to receive additional payments upon achievement of specified clinical, commercial and net sales milestones, as well as tiered royalties on net sales worldwide.