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LEXINGTON, Mass.—Immuno-oncology company Agenus Inc. has announced the establishment of a collaboration and license agreement with Merck, known outside the United States and Canada as MSD, through a subsidiary, under which the companies will seek to discover and develop therapeutic antibodies to immune checkpoints as novel treatments for cancer. Agenus will discover and optimize fully human antibodies against two Merck checkpoint targets utilizing the 4-Antibody Retrocyte Display platform, while Merck will be responsible for handling the clinical development and commercialization of the discovered in the collaboration.
 
Per the terms of the agreement, Agenus stands to receive approximately $100 million in potential milestone payments if all clinical, regulatory and commercial goals are met for the two candidates from Merck. Beyond that, Agenus is also eligible for royalty payments on worldwide sales of any products that result from the agreement.
 
“This collaboration with Agenus complements our active immuno-oncology discovery programs,” Dr. Eric Rubin, vice president of clinical oncology for Merck Research Laboratories, said in a press release. “We look forward to working to advance these programs with the potential to address the unmet medical needs of people with cancer.”
 
Immune checkpoints exist in the body to moderate immune activity and prevent excessive immune response. As Agenus notes on its website, the immune checkpoints are “processes usually involving specific receptors on T-lymphocytes and their ligands on antigen presenting cells that play a role in detecting and ‘presenting’ non-self antigens. Some of these checkpoints stimulate immune responses and some inhibit immune responses, regulating the immense power of the immune system and preventing uncontrolled tissue destruction.” The issue, however, is that cancer cells are also able to take advantage of these checkpoints in order to protect themselves against the immune system.
 
Agenus currently has six checkpoint antibodies in its pipeline, all of which are still in the preclinical phase of development. The company expects to submit Investigational New Drug filings for all of them in either 2015 or 2016. Among the product candidates are a GITR agonist, an OX-40 agonist and antagonists of cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death receptor-1 (PD-1), TIM-3 and LAG-3. Agenus is pursuing these candidates under a strategic collaboration with Ludwig Cancer Research. Antibodies that bind to PD-1 and CTLA-4 are designed to help immune cells defeat the checkpoint defenses of cancer cells. GITR and OX40, other checkpoint proteins, are receptors located on T cells that stimulate immune function.
 
“We are delighted to be working with Merck, who is a leader in the rapidly developing immuno-oncology space,” Dr. Bob Stein, chief scientific officer of Agenus, commented in a statement. “We believe our Retrocyte Display technology has significant advantages for creation of high quality antibody development candidates. This collaboration broadens our efforts in immuno-oncology beyond our previously disclosed checkpoint programs with a world-class research and development partner.”
 
The 4-Antibody Retrocyte Display technology platform is one of the assets Agenus secured with its acquisition of private biopharmaceutical company 4-Antibody AG in February of this year. The platform enables the discovery and optimization of fully human antibodies against a range of molecular targets.

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