On April 18, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that preclinical data from its TTI-622 (SIRPa-IgG4 Fc) immune checkpoint inhibitor program were presented at the 109th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Trillium Therapeutics, APR 18, 2018, View Source [SID1234525500]).
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TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. It consists of the CD47-binding domain of human SIRPa linked to an IgG4 Fc region and is being developed primarily for combination therapy.
The data presented at AACR (Free AACR Whitepaper) demonstrate that TTI-622 induces the phagocytosis of a broad panel of tumor cells derived from patients with both hematological and solid tumors. As a monotherapy, TTI-622 treatment resulted in decreased tumor growth and improved survival in a B cell lymphoma xenograft model, and enhanced the efficacy of cetuximab (anti-EGFR) and daratumumab (anti-CD38) antibodies in solid and hematological xenograft models, respectively. Unlike CD47-blocking antibodies, TTI-622 bound minimally to human erythrocytes and did not induce hemagglutination in vitro.
"The preclinical data presented at AACR (Free AACR Whitepaper) reinforce our confidence in this target and provide a solid foundation for initiating a clinical program with TTI-622," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. This second SIRPaFc decoy receptor complements TTI-621, and allows us to evaluate the effects of CD47 blockade using different levels of Fc receptor engagement. Importantly, we believe the minimal binding of TTI-622 to human red blood cells distinguishes this agent from other IgG4-based CD47 targeted therapies."
A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. 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 PD-1 inhibitor or a proteasome inhibitor-containing regimen.