Ludwig, Agenus move forward with oncology antibodies

Compounds consist of a CTLA-4 antagonist and two GITR agonists

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NEW YORK & LEXINGTON, Mass.—The Ludwig Institute for Cancer Research and Agenus Inc. have announced their selection of three monoclonal antibody checkpoint modulators (CPMs) that Agenus will advance into preclinical development. The two product candidates are part of Agenus recent acquisition of 4-Antibody AG, which, in collaboration with Ludwig Cancer Research, developed the compounds.
Working together, the three organizations plan to advance the portfolio of CPMs as single agents and in combinations, which may include combinations with the company’s anti-cancer vaccine and other agents.
“The collaboration with 4-Antibody allowed us to rapidly advance antibodies into development,” Jonathan Skipper, executive director of Technology Development at Ludwig Cancer Research, said in a press release. “We are now planning clinical studies to evaluate novel combinations of these antibodies. Ludwig has been at the forefront of translational research in immuno-oncology for several decades. Our ongoing relationship with Agenus is a good example of our broader strategy to advance cancer therapy.”
Immune checkpoints exist to modulate immune system activity, such as preventing overactive immune responses, but they can also be hijacked by cancer cells in order to defend tumors against attack. The three compounds being advanced consist of two GITR agonists and a CTLA-4 antagonist, which target cell-surface checkpoint proteins that control immune responses. Antibodies that bind to PD-1 and CTLA-4 and antagonize their activity have been found to override the control mechanism, enabling the immune cells to surmount the cancer cells’ defenses. Ludwig Cancer Research, Agenus and 4-Antibody AG also have programs underway for the discovery and development of other immune checkpoint modulator antibodies, including OX40 agonists and LAG-3, TIM-3 and PD-1 antagonists.
“GITR, a checkpoint protein on T-lymphocytes, plays an important role in amplifying specific cellular immune responses, including those against tumors. We are encouraged to have identified high-quality agonist antibodies for this very competitive target, something that has proven difficult for many other companies,” Robert B. Stein, M.D., Ph.D., chief scientific officer of Agenus, commented in a statement. “Furthermore, it is rational to combine CPMs such as CTLA-4 and PD-1 antagonists with anti-cancer vaccines, and we are collaborating on an on-going Phase 2 trial exploring Prophage and Yervoy (CTLA-4 antagonist) in patients with metastatic melanoma. Intelligently designed translational studies may improve the odds of success for our CPMs and accelerate their clinical development.”
“The Retrocyte Display1 technology developed by 4-Antibody over the last decade has allowed us to create attractive CPM antibodies directed against key checkpoint targets,” said Robert Burns, Ph.D., CEO of 4-Antibody AG. “By combining our know-how with Agenus’ immunotherapy development expertise, we expect to propel these candidates through preclinical and clinical development.”
SOURCE: Ludwig Institute for Cancer Research press release

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