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Drugs in Developement

BL-8040 - Multiple cancer and hematology indications
AGI-134 - Solid tumors

Indication: Solid tumors
Mode of action: Synthetic αGal immunotherapy
Stage of development: Phase 1/2a
Patent status: AGI-134 composition and methods of its use are covered until 2035 by patents granted or pending worldwide

AGI-134 Overview
AGI-134 is a synthetic αGal immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-αGal (anti-Gal) antibodies to induce a systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on anti-metastatic immune response. αGal is a cell-surface carbohydrate antigen which is not expressed by humans, unlike virtually all other mammals and bacteria. Therefore, humans universally produce and maintain high levels of anti-Gal antibodies, due to exposure to αGal on bacteria in the digestive system.

AGI-134 is injected into the tumor, where it coats the tumor cell membranes, resulting in αGal being exposed on the tumor cell surface. Anti-Gal antibodies bind to the αGal part of AGI-134 to produce an initial immune response that activates complement-dependent and antibody-dependent cellular cytotoxicity (cell death). This cytotoxicity generates immune-tagged cells and cellular debris that trigger an uptake of tumor-associated antigens by antigen-presenting cells (APCs). These APCs induce a follow-on systemic immune response by the activation and clonal expansion of T cells (CD8+) to the patient’s own neo-antigens. This approach not only targets the primary injectable tumor, but has also demonstrated efficacy against existing distant secondary tumors. Furthermore, the mechanism of action suggests the potential of long-term protection against future metastases. 

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 both as monotherapy and in combination with an immune checkpoint inhibitor, in unresectable metastatic solid tumors. The multicenter, open-label study will take place in the United Kingdom and Israel, with possible expansion to the United States and additional countries in Europe in 2019.

The use of intra-tumoral αGal glycolipids to treat solid tumors was invented by Prof. Uri Galili, Ph.D., while at the University of Massachusetts, from which the intellectual property rights were licensed. The intellectual property rights relating to AGI-134 were in-licensed from Kode Biotech Ltd., the inventors of AGI-134.

Pre-Clinical data
AGI-134 has completed numerous pre-clinical studies, demonstrating robust protection against the development of secondary tumors in two models of melanoma.

A single dose of AGI-134 conferred a systemic durable response which resulted in long-term protection against the development of secondary tumors for over 90 days.

AGI-134 was tested in combination with the well-known immune checkpoint inhibitor anti-PD1 antibody. AGI-134 demonstrated to be synergistic in combination with an anti-PD-1, thus offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. A 28-day, repeated-administration GLP toxicology study in monkeys with AGI-134 has also been successfully completed.

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