AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body’s pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient’s own tumor neo-antigens.
Mode of action
Synthetic alpha-Gal immunotherapy
Stage of development
Clinical studies initiation in 2018
AGI-134 has been evaluated in numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained through the acquisition of Agalimmune Ltd.
In August 2018, we initiated a Phase 1/2a clinical study for AGI-134 that is primarily designed to evaluate the safety and tolerability of AGI-134 given monotherapy in unresectable metastatic solid tumors. The multi-center, open label study is being carried out in the UK, Spain, Israel and the US. Results from the first part of the study showed that AGI-134 was safe and well tolerated, with no serious drug-related adverse events or dose-limiting toxicities reported. Initial proof of mechanism results from the second part of the study, commenced in September 2019, are expected in the first half of 2022.
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