SIRPαFc

Our lead program, SIRPαFc, targets CD47, a molecule that is expressed at high levels by many different types of cancer cells. CD47 binds to SIRPα on macrophages and delivers a “do not eat” signal that inhibits the ability of macrophages to phagocytose (engulf and destroy) malignant cells. The inhibitory CD47 signal is an important mechanism by which malignant cells escape immune-mediated attack, and high levels of CD47 are correlated with poor patient prognosis in a number of cancers.

SIRPαFc is a fusion protein consisting of a portion of the SIRPα receptor linked to an immunoglobulin Fc region. This antibody-like molecule binds to CD47 on the tumor cells with high affinity and functions as a decoy receptor, preventing malignant cells from delivering the suppressive “do not eat” signal. SIRPαFc enables macrophages to kill tumor cells in vitro (while sparing normal cells) and induces potent anti-tumor effects in vivo.

Quick Facts

SIRPαFc targets CD47, a molecule highly expressed in many types of cancer cells

CD47 delivers a "do not eat" signal to macrophages

SIRPαFc is a fusion protein that prevents cancer cells from delivering a "do not eat" signal

A Phase 1 clinical trial (NCT02663518) evaluating SIRPaFc (TTI-621) is ongoing in advanced hematologic malignancies, and a second Phase 1 trial is underway in solid tumors (NCT02890368). TTI-622 is an IgG4 SIRPaFc protein, which is primarily being developed for combination therapy. An IND filing is targeted for 2H/17.

Two unique SIRPαFc agents in development for monotherapy and combination studies

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