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Maverick is Pioneering the Next Generation of Redirected T Cell Therapeutics in Immuno-oncology

Immuno-oncology is one of the most exciting areas of drug discovery and development today. By leveraging recent breakthroughs in our understanding of immune cell function and regulation, immuno-oncology approaches hope to harness the patients’ immune system to eliminate their tumors, and potentially cure cancer. Much of this research is focused on cytotoxic T cells, a powerful killer of cancer cells when properly activated.

The principle of engaging cytotoxic T cells for redirected lysis of cancer cells using bispecific antibodies was first described in 1985. But it was not until 2014 that this approach was shown to be clinically and commercially viable with the approval of blinatumomab (Blincyto®) for treatment of adult patients with relapsed or refractory acute B-lymphoblastic leukemia. While blinatumomab validated the therapeutic principle of engaging T cells for cancer therapy, Maverick has dedicated its internal efforts towards developing a next generation of proprietary T cell-engaging therapeutics. In particular, Maverick is seeking to engineer recombinant antibody-based therapeutics that are designed to target tumor cells and engage cytotoxic T cells but only in a highly localized fashion to minimize toxicity.

Maverick’s Approach is Designed to Overcome the Limitations of Conventional Bispecific Formats

Conventional bispecific antibodies are highly dependent on target antigens that are predominantly or exclusively expressed by cancer cells. If these antigens are also expressed by normal tissues, the therapeutic window of bispecific T cell-engaging antibodies may become very narrow and lead to on-target toxicities before clinically relevant drug levels are reached. Maverick uses tumor microenvironment-dependent activation modules in its therapeutic candidates with the goal to activate them inside tumors, while avoiding their activation outside the tumor. After activation and clearance from the tumor environment, Maverick’s compounds are designed to be swiftly eliminated from the body. This design strategy will enable targeting more broadly expressed tumor antigens on solid tumors, which when targeted with conventional bispecific formats have led to toxicities in normal tissues and organs.

T Lymphocytes Attack Cancer Cell

T lymphocytes attacking a cancer cell

Maverick’s COBRA™ Platform

The Maverick proprietary platform is termed COnditional Bispecific Redirected Activation (COBRA™) and individual therapeutics agents are COBRAs. COBRAs are administered to patients as long-lived precursor molecules that get targeted to tumor tissues. Once activated by the tumor microenvironment, they unfold their T cell-engaging potential in a unique fashion that requires binding to target cells. This strategy is designed to broaden the therapeutic index of Maverick’s T cell-engaging platform at several levels and will allow Maverick to take advantage of tumor-associated antigens that are not accessible (due to therapeutic index limitations) to more conventional bispecific antibodies.

The COBRA technology is also suited for dual targeting of cancer cells. This means that activation of COBRA molecules will not only be dependent on the unique microenvironment of tumor tissue but also on the simultaneous expression of two different target antigens on the same cancer cell. If one such antigen is expressed on cells of normal tissue in the absence of the second antigen, COBRA molecules fail to accumulate in normal tissues and remain inactive. This unique mechanism of action has the potential to further enhance the safety margin of this highly potent class of molecules.

Maverick Therapeutics COBRA Triangle Diagram

The COBRA™ Platform

For additional background on T cell-engaging antibodies, please read:

May C, Sapra P and Gerber HP. Advances in Bispecific Biotherapeutics for the Treatment of Cancer. Biochem Pharm. 2012, 84(9):1105-12

Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013, 17(3):385-92

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