SUMMARY OF INVENTION

MSK investigators in collaboration with the Tri-Institutional Therapeutics Discovery Institute have developed a high affinity and highly specific SIRPα-targeting monoclonal antibody “F05”. This antibody exhibits enhanced binding to SIRPα while minimizing binding to SIRPβ and SIRPγ compared to existing SIRPα antibodies.

Additionally, F05 modulates critical immune therapeutic pathways in vitro and is effective in animal models of hematopoietic and solid tumors in conjunction with monoclonal antibodies.

CHALLENGE WE’RE ADDRESSING

T cell immune checkpoint blockade therapies have shown remarkable success across many cancers; however, many patients and tumor types do not respond to therapy. SIRPα, also known as the “do not eat me” signal, is a protein found on the surface of phagocytic cells such as monocytes.

Recent clinical advancements involve agents that disrupt the interaction between CD47 and SIRPα, enhancing macrophage-driven tumor cell engulfment when combined with monoclonal antibody therapy. Yet CD47-targeted agents can lead to off-target toxicities due to CD47’s presence on all human cells, including red blood cells and platelets. A significant antigen sink is also created, which decreases antibody efficacy. In distinct contrast, SIRPα is expressed only on myelomonocytic cells, offering a potential avenue for reducing off-target toxicities and avoiding the antigen sink.

VALUE PROPOSITION

• MSK’s SIRPα antibody, F05, has demonstrated efficacy both in vitro and in animal models of solid tumors and hematopoietic cancers.
• Lower toxicity and far lower doses are possible when targeting SIRPα rather than CD47, due to the highly restricted expression of SIRPα on phagocytic cells only.
• F05 exhibits higher affinity and specificity in targeting SIRPα compared to other antibodies available or in published researched

MARKET OPPORTUNITY

The CD47-SIRPα checkpoint interaction is an emerging target for cancer therapy, with an expanding market size, yet in contrast to MSK’s approach, most companies are developing antibodies targeting CD47 instead of SIRPα.

As an indication of potential market size for this new technology, increased expression of CD47 has been found to be correlated with poor prognosis in oral squamous cell carcinoma, nasopharyngeal carcinoma, triple-negative breast cancers, ovarian carcinoma, and non-small cell lung cancer.

PATENT INFORMATION

Provisional application (63/586,301) filed in Sep 2023.

PUBLICATIONS

Kurtz et al. (2023) A human antibody specific for SIRPα reprograms macrophages and promotes antibody mediated anti-cancer activity, submitted

LEAD INVESTIGATOR

David Scheinberg, PhD, MD, Vincent Astor Chair; and Chairman, Center for Experimental Therapeutics; Deputy Director for Therapeutic Discovery, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center

CONTACT INFORMATION

James Delorme, PhD

Senior Licensing Manager
E-mail: [email protected]