Agenus

Agenus is a Lexington, Massachusetts-based biotechnology company focused on immunotherapy including immuno-oncology, a field that uses the power of the immune system to control or cure cancer. The company is developing checkpoint modulators (CPMs), patient-specific anti-cancer vaccines, and adjuvants that can be used with a range of vaccines. CPM development is a particularly fast-moving field, since early products have produced unprecedented clinical benefits for patients.^[1] In light of the advances made, Science magazine hailed cancer immunotherapy as its 2013 Breakthrough of the Year.^[2]

History

Agenus (formerly Antigenics Inc.) was founded in 1994 by Garo H. Armen and Pramod K. Srivastava. The company has pioneered immunotherapies, including heat shock protein-based cancer vaccines, a program that has developed into its Prophage Series of personalized anti-cancer vaccines. Antigenics became a public company in February 2000 on the NASDAQ exchange with the ticker symbol AGEN. In 2000 Agenus acquired Aquila Biopharmaceuticals and a year later it acquired Aronex Pharmaceuticals. In February 2014 the company acquired a European firm, 4-Antibody, along with their portfolio of checkpoint modulators (CPMs) and a platform (Retrocyte Display® technology) to rapidly and efficiently discover new antibodies.

CEO Garo Armen

In October 2013, Agenus CEO Garo Armen issued a press release revealing that after an 18 month follow up on the RTS,S Malaria vaccine using QS21-Stimulon® is working well enough to support a regulatory filing in 2014. This is the first proof of the efficacy of Agenus's patented "QS-21 Stimulon" adjuvant ^[3]

In April 2014, Agenus inked a deal with Merck potentially worth $100 million. Under the terms of that deal, Agenus is using its proprietary Retrocyte Display technology to discover antibodies against a pair of undisclosed checkpoint targets for the treatment of cancer. Agenus has advanced two of its own CPM candidates into early drug development and the company is planning to advance several more antibodies in clinical trials.

Today, Agenus is focused on developing a range of immuno-oncology products, including the Prophage vaccines, multiple checkpoint modulators (also known as checkpoint inhibitors or checkpoint antibodies) and its QS21-Stimulon adjuvant. The company’s personalized, heat shock protein-based vaccines are in Phase 2 studies. The QS-21 Stimulon adjuvant platform is partnered with GlaxoSmithKline and Janssen. Several of those collaborations involve Phase 3 trials. Altogether, the company and its partners are sponsoring approximately 20 clinical trials of Agenus products.

Key Partners and Deals

Merck: April 2014, Agenus announced a deal worth potentially $100 million with Merck. The deal involves the discovery and development of therapeutic antibodies to two undisclosed Merck checkpoint targets, both thought to be relevant for cancer treatment. Agenus will use its proprietary Retrocyte Display® platform to discover and optimize antibodies against the targets.

4-Antibody: February 2014, Agenus acquired European biotechnology firm 4-Antibody, along with its Retrocyte Display technology and a portfolio of checkpoint modulator antibody candidates .

Ludwig Cancer Research: 4-Antibody had been working on the checkpoint targets for several years in collaboration with Ludwig Cancer Research, one of the world’s most renowned institutions for research into cancer and the immune system. The leader of the Ludwig collaborative laboratory at Memorial Sloan Kettering Cancer Center, Jedd Wolchok, is recognized as one of immuno-oncology’s leading pioneers.

GlaxoSmithKline (GSK): March 2012, GSK paid Agenus $9 million to include additional rights to the two firms’ agreement around Agenus’ QS-21 Stimulon® adjuvant. The deal amended license and manufacturing terms. It also included royalty payments to Agenus for an undisclosed indication upon commercialization of a vaccine.

Product Descriptions

Checkpoint Modulators (CPMs) interfere with cancers’ ability to “hijack” natural immune defense systems. To protect the body against disease, but without attacking healthy cells, the immune system uses multiple “checkpoint” systems. Some checkpoints stimulate immune responses while others inhibit them. Cancer cells can evolve means to evade checkpoints, and CPMs can reverse that effect, helping the immune system better fight the cancer.

Agenus currently has programs targeting the checkpoint modulators GITR, OX40, CTLA-4, LAG-3, TIM-3 and PD-1. The company is expanding that portfolio by using its proprietary Retrocyte Display® discovery system to generate fully human therapeutic antibody drug candidates. The platform is a high-throughput approach incorporating IgG format human antibody libraries expressed in mammalian B-lineage cells.

The Prophage Series of patient-specific cancer vaccine candidates can also enhance the immune system’s response to tumors. Because each cancer is unique, the vaccine is derived from the patient’s own tumor sample. To process these samples, Agenus has established a multi-product Good Manufacturing Practices (GMP) facility, which has already helped process over 1,000 tumor samples from across the globe.

The company's QS-21 Stimulon® adjuvant platform strengthens and broadens immune responses to antigens on cancers or foreign invaders’ surfaces. Agenus has multiple partnerships around this product to study its effects with vaccines for diseases including Alzheimer’s, melanoma, and malaria. In October 2013, GlaxoSmithKline and Agenus announced positive data from an 18-month follow-up of GSK’s RTS,S malaria vaccine with QS21-Stimulon. GSK stated that the treatment was working well enough to support a regulatory filing. RTS,S is the most advanced vaccine for malaria in development.

References

Articles

• Wall Street Journal article on company and FDA