In February 2014 Agenus (AGEN) acquired 4-Antibody and with it its breakthrough Retrocyte Display technology. Two months later, Agenus signed a collaboration and license agreement with Merck, for the discovery and development of therapeutic antibodies to immune checkpoints for the treatment of cancer through the newly acquired Retrocyte Display technology.
This quick agreement underlines the value of the Retrocyte Display technology. This technology is high throughput cellular antibody expression platform that allows expression and screening of full-length immunoglobulin antibody libraries in mammalian B-lineage cells. It enables the identification of antigen-specific fully human monoclonal antibodies.
The technology has been described in published articles. It can be used for:
- Direct screening combinations of antibody heavy and light chain libraries for antigen-specific binders
- Converting a non-human antibody with desired properties into a fully human antibody with near-identical characteristics – all in favor of discovering fully human antibodies de novo.
- Screening complex heavy and light chain libraries against target antigens.
- Creating high quality antibody development candidates.
The entire tasks can be performed in weeks.
The Agreement With Merck: Under the terms of the agreement, Agenus will discover and optimize fully human antibodies against two undisclosed Merck checkpoint targets, using the 4-Antibody Retrocyte Display® platform. Merck will be responsible for clinical development and commercialization of candidates generated under the collaboration.
The Beef: Agenus is eligible to receive approximately $100 million in potential payments associated with the completion of certain clinical, regulatory and commercial milestones for the two candidates from Merck. In addition, Agenus is eligible to receive royalty payments on worldwide product sales.
Agenus stated that the collaboration broadens its efforts in immuno-oncology beyond its previously disclosed checkpoint programs with a world-class research and development partner.
The 4-Antibody company’s assets included:
- The Retrocyte Display technology platform,
- Multiple preclinical checkpoint modulator programs in development including GITR and OX40 agonists and antagonists of TIM-3, LAG-3, PD-1 and CTLA-4.
These programs are being pursued through a strategic collaboration with Ludwig Cancer Research.
A New Agenus
Following the acquisition of 4-Antibody, Agenus has become the owner the Retrocyte Display technology that attracted Merck into signing the licensing and collaborating agreement with Agenus and new immune checkpoint molecule agonists and antagonists antibodies.
Clinical data from studies employing monoclonal antibodies that bind to checkpoint molecules, such as cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), point to the fact that these therapeutic antibodies are game changer in the field of immuno-oncology.
Checkpoints are natural body shields that aim at preventing immune responses against the normal body cells and tissues as in the case of autoimmune diseases that can be debilitating or deadly.
Unfortunately, cancer cells can use the same checkpoint mechanisms as a defense against immune attack. Antibodies that bind to PD-1 and CTLA-4 are designed to help immune cells overcome the checkpoint defenses in case of cancer.
Other checkpoint proteins, such as GITR and OX40, which are currently targeted by Agenus antibodies, are receptors found on T cells that stimulate immune function. Agenus and Ludwig Cancer Research are driving the programs to discover and develop fully human monoclonal antibodies that bind to key checkpoint proteins and activate or block their activities for use in cancer.
Agenus’ expertise is in therapeutic and preventive vaccines. The vaccines aim at boosting the immune system towards treating intractable diseases, especially cancer. Agenus QS-21 Stimulon adjuvant is a key component in 20 clinical development programs including Agenus’ HerpV program and its programs in preventive and therapeutic vaccines with GlaxoSmithKline (GSK), and with Johnson & Johnson (J&J).
The vaccine candidates containing QS-21 Stimulon target infectious diseases, cancer, and central nervous system disorders.
Prohost Word: Agenus involvement in modulating immune checkpoints a huge plus for the company’s product pipeline, including the firm’s therapeutic vaccines. Combining Agenus therapeutic cancer vaccines with the novel monoclonal antibodies against immune checkpoints will eliminate cancer resistance to the immunological reaction.
Having in hand the Retrocyte Display technology is a luxury. It turns Agenus into a designer and developer of full-length monoclonal antibodies targeting antigens for immunotherapy of intractable diseases and cancer.
Agenus will be in a position to develop these monoclonal antibodies for other firms too for upfront payments, licensing payments, milestone payments and royalties on products’ sales.
The first customer, Merck, has already signed.
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