On November 10, 2017 Alexo Therapeutics, a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint mechanism exploited by cancer cells to evade the immune system, reported data from Alexo’s first-in-human Phase 1 study of its lead candidate, ALX148, at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held in National Harbor, Maryland (Press release, Alexo Therapeutics, NOV 10, 2017, View Source [SID1234522016]). Preliminary results from the single agent portion of the trial (NCT03013218) showed that ALX148 is generally well tolerated in patients with advanced malignancy, with no dose-dependent impact on normal blood cells.
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"ALX148 is generally well tolerated and its clinical safety profile is consistent with that seen in our preclinical studies," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of Alexo. "Given the unique design of this high affinity CD47 blocker, we were able to achieve anticipated safety and pharmacokinetics, and complete CD47 target occupancy across the dosing interval. Having demonstrated single agent safety, we are encouraged to explore ALX148 in combination as a potential treatment option for cancer patients."
As of October 2017, ALX148 was intravenously administered as a single agent over a dose range of 0.3 mg/kg to 30 mg/kg in 17 patients with advanced malignancy. There was one treatment-related serious adverse event (neutropenia plus infection; 3.0 mg/kg) with no additional treatment-related events of neutropenia or infection of any grade reported. Most treatment-related adverse events were Grade 1 or 2 and occurred across eight patients, as sole events. Evaluation of the highest protocol defined dose level (30 mg/kg) is ongoing. Upon completion of the single agent portion, the second half of the trial will evaluate ALX148 in combination with checkpoint inhibitors and targeted anti-cancer antibodies.
About ALX148
ALX148 is a fusion protein that comprises an engineered high affinity CD47 binding domain of SIRPα linked to an inactive Fc region of human immunoglobulin. ALX148 potently and selectively binds CD47, blocking its interaction with SIRPα, thereby inhibiting a key immune checkpoint mechanism exploited by cancer cells. In preclinical studies, ALX148 enhances checkpoint inhibition by activating dendritic cells and reducing suppression by tumor-associated macrophages, and enhances targeted anti-cancer antibodies by maximizing phagocytosis to selectively eliminate tumor cells. ALX148 has demonstrated significant inhibition of tumor growth in these combinations with no adverse effect on CD47-expressing normal blood cells in preclinical models.