TTI-622

TTI-622 is Trillium’s second SIRPαFc fusion protein. TTI-622 consists of the same extracellular CD47-binding domain of human SIRPα as TTI-621 but has an IgG4 Fc region instead of an IgG1 Fc (see Figure below).

TTI-622

The IgG4 Fc region of TTI-622 interacts more modestly with Fc receptors than IgG1, and thus TTI-622 is predicted to deliver a more modest "eat" signal to macrophages. These two decoy receptors thus allow us to equivalently block the inhibitory CD47 signal while tuning the amount of Fc "eat" signal that macrophages receive. Importantly, TTI-622 also does not bind appreciably to human red blood cells, and thus could potentially achieve best-in-class status among IgG4-based CD47 blocking agents.

TTI-622 induces phagocytosis of a broad panel of tumor cells derived from patients with both hematological and solid tumors.

TTI-622 binds minimally to human erythrocytes and does not induce hemagglutination.

TTI-622 treatment resulted in decreased tumor growth and improved survival in a B cell lymphoma in a DLBCL xenograft tumor model, and enhanced the efficacy of cetuximab (anti-EGFR) and daratumumab (anti-CD38) antibodies in solid and hematological xenograft models, respectively.

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 (NCT03530683) has been initiated in patients with advanced relapsed or refractory lymphoma or multiple myeloma. In the phase 1a dose-escalation study, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b study, patients will be treated with TTI-622 in combination with rituximab, a proteasome inhibitor-containing regimen, or a PD-1 inhibitor.

More details regarding this clinical study can be found in the CLINICAL TRIALS section.

 

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