On February 24, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported new pharmacology data from its ongoing Phase 1 a/b trial of TTI-621, a SIRPaFc fusion protein targeting CD47 in patients with advanced hematologic malignancies (Filing, 6-K, Trillium Therapeutics, FEB 24, 2017, View Source [SID1234517990]). The presentation took place at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in Orlando, Florida.
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The company presented the following new information from the trial:
Receptor occupancy increases with multiple infusions of TTI-621, conferring robust CD47 blockade on circulating leukemic cells: Compared to the initial infusion, the extent and duration of CD47 occupancy on peripheral leukocytes was elevated following the sixth dose. Importantly, emerging data suggests increased receptor occupancy on circulating leukemic blast cells. The level of target engagement achieved is associated with strong phagocytosis activity of tumor cells in vitro.
Increases in cytokines associated with macrophage activation suggest rapid engagement of the innate immune system: Post-infusion elevations were observed in MIP-1a, MIP-1b and other cytokines associated with macrophage activation, supporting the proposed role of TTI-621 as an innate immune checkpoint inhibitor.
Transient thrombocytopenia due to target mediated clearance is attenuated subsequent to the first infusion of TTI-621: Additional data has clarified that the transient thrombocytopenia observed following TTI-621 exposure is often diminished after multiple infusions. This suggests that there may be an opportunity to increase TTI-621 exposure in patients after the initial dose.
Weekly infusions lead to a longer half-life and accumulation of circulating drug, overcoming the platelet antigen sink: After six infusions the terminal half-life of TTI-621 increased to 3.7 days with an attendant rise in circulating drug trough levels, which is consistent with the half-lives of many marketed Fc fusion proteins. Drug accumulation was accompanied by stable pre-dose platelet counts, suggesting that multiple infusions of TTI-621 overcome the platelet antigen sink.
"This recently expanded data set markedly advances our understanding of TTI-621’s pharmacological properties, and exemplifies the emerging nature of this exciting development program," said Dr. Niclas Stiernholm, Trillium’s Chief Executive Officer. "These latest results suggest that we overcome the antigen sink and achieve meaningful TTI-621 exposure while maintaining acceptable platelet counts. We are excited to continue the exploration of this unique checkpoint inhibitor in patients with multiple types of blood cancers, as well as in patients with solid tumors."
The ASCO (Free ASCO Whitepaper)-SITC poster presentation on TTI-621 can be found on the company’s website at www.trilliumthera