On January 21, 2016 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company developing checkpoint modulator antibodies and cancer vaccines, reported that the U.S. Food and Drug Administration (FDA) cleared the company’s investigational new drug (IND) application for AGEN1884, an immune checkpoint modulator (CPM) antibody that binds to cytotoxic T-lymphocyte antigen-4 (CTLA-4) (Press release, Agenus, JAN 21, 2016, View Source [SID:1234508833]). Clearance was also received for a second CPM antibody partnered with Incyte (NASDAQ: INCY) for INCAGN1876, which targets glucocorticoid-induced TNFR-related protein (GITR). Clinical trials for both candidates are expected to begin in the first half of 2016.

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"We are pleased with the prospects of both CTLA-4 and GITR moving rapidly into and through the clinic, and in our efforts to bring profoundly effective medicines to cancer patients," said Garo Armen, PhD, Chairman and CEO of Agenus. "We are also diligently advancing several other product candidates into the clinic and are aiming to begin a number of clinical trials in 2016."

These two compounds were developed utilizing Agenus’ state-of-the-art monoclonal antibody platform capabilities and leverage the company’s world-class expertise in immuno-oncology and related drug discovery and development. The antibodies were discovered during an earlier collaboration with Ludwig Cancer Research. Recepta, a Brazilian biotech company, was also involved in the collaboration that led to the discovery of AGEN1884, which is partnered with Recepta for certain South American rights. INCAGN1876 is now being co-developed with Incyte.

"CTLA-4 is emerging as an important foundational target for immuno-oncology combination regimens, showing terrific promise when used with other CPMs and cancer vaccines. Our CTLA-4 antagonist antibody, AGEN1884, is a natural potential fit with our expanding vaccine portfolio. This includes Prophage, slated to enter a randomized placebo-controlled study in newly diagnosed GBM in the second half of 2016, and AutoSynVax, which we also plan to take into the clinic in the second half of 2016," said Robert B. Stein, MD, PhD, Agenus’ President, Research & Development. "I would like to acknowledge the research and development teams at Agenus, and Incyte for GITR, for their tireless efforts to achieve our goal of filing these INDs by the end of 2015."

About Checkpoint Modulators

Promising 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), have generated considerable excitement in the field of cancer immunotherapy. These molecules serve as checks employed by the body to prevent a runaway immune response, which can be debilitating, and even deadly. Unfortunately, these necessary mechanisms of control can hinder the anti-cancer immune response. They can be harnessed by cancer cells as a defense against immune attack. Agenus is developing a broad pipeline of antibodies that bind to key checkpoint proteins and activate or block their activities for use in cancer therapy.

On January 21, 2016 Asterias Biotherapeutics, Inc. (NYSE MKT: AST), reported that it has completed the transfer of its manufacturing processes to produce AST-VAC2 to Cancer Research UK (Press release, BioTime, JAN 21, 2016, View Source [SID:1234508832]).

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AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase permits enhanced stimulation of immune responses to the protein. The AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells.

To accelerate clinical development of AST-VAC2, Asterias has an ongoing partnership with Cancer Research UK and Cancer Research Technology, the charity’s development and commercialization arm, to execute the first clinical trial of AST-VAC2. As part of this partnership, Cancer Research UK will perform cGMP manufacture of AST-VAC2 at their Biotherapeutics Development Unit. In preparation for cGMP production, Asterias developed the production process for AST-VAC2 to support the transfer and further scale-up in Cancer Research UK’s manufacturing facility for the Phase 1/2 clinical study. To that end, Asterias has completed transfer of the AST-VAC2 manufacturing process information to Cancer Research UK. Cancer Research UK is now verifying and scaling up the production of AST-VAC2 in their facility in preparation for pilot and full cGMP campaigns. Upon successful completion of AST-VAC2 production campaigns, Cancer Research UK’s Centre for Drug Development ("CDD") will submit a Clinical Trial Authorisation application to the UK regulatory authorities for a Phase 1/2 clinical trial in non-small cell lung cancer, which will be sponsored, managed and funded by CDD. The clinical trial will examine the safety, immunogenicity and activity of AST-VAC2 and position the immunotherapy to be tested for numerous clinical indications.

"Transfer of the manufacturing process for AST-VAC2 marks an important milestone in our partnership with Cancer Research UK and is a critical step towards initiating the first clinical trial of AST-VAC2," said Pedro Lichtinger, Chief Executive Officer of Asterias. "The program with Cancer Research UK will assess the safety and activity of AST-VAC2 and serve as a foundation for further clinical development in lung and other cancers."

"The design of AST-VAC2 affords three unique properties to this dendritic cell immunotherapy," stated Jane S. Lebkowski, Ph.D., President of R&D and Chief Scientific Officer of Asterias. "Being produced from pluripotent stem cells, AST-VAC2 can be manufactured at batch-scale and be available on-demand for patient use. Second, the telomerase protein in AST-VAC2 is specifically engineered to target the two major pathways stimulating T cell immune responses, inducing more robust and durable cellular immune responses to telomerase. Lastly, the non-patient specific, allogeneic, nature of AST-VAC2 could potentially provide signals to further amplify immune responses."

"Based on its mode of action, AST-VAC2 is likely to be synergistic with immune checkpoint inhibitors and other adoptive immunotherapies that are being used for treatment now," stated Katy Spink Ph.D., Chief Operating Officer of Asterias. "The combination of the immunostimulatory activity of AST-VAC2 with the drugs that downregulate inhibitors of immune responses could provide a very powerful tool for the treatment of multiple cancers."

Dr. Nigel Blackburn, Cancer Research UK’s director of drug development, said: "This drug could potentially treat most tumour types as it targets the telomerase protein – which is faulty in 95 per cent of all cancers. The treatment’s design means it could also boost the effects of other immunotherapies and be used in combination.

"Lung cancer is the biggest cancer killer so we desperately need to find new treatments for the disease. And we’re pleased to be working with Asterias Biotherapeutics to develop this new treatment and to test it in clinical trials for non-small cell lung cancer for the first time."