On November 24, 2014 Transposagen Biopharmaceuticals reported that they have entered into a research collaboration and worldwide license agreement with Janssen Biotech, Inc. (Janssen) to develop allogeneic Chimeric Antigen Receptor T-cells (CAR-T) (Press release Transposagen, NOV 24, 2014, View Source [SID:1234501015]). To date, CAR-T therapies have shown promise in early human clinical trials for the treatment of blood cancers and allogeneic CAR-Ts have the potential for use as off-the-shelf cancer treatments without the need of matching donor with recipient.

Transposagen will be using its proprietary genome editing technologies, including the piggyBacTM Footprint-FreeTM Gene Editing System, to create the allogeneic CAR-T therapies. Under the agreement, Janssen has exclusive rights to any allogeneic CAR-T therapy that is jointly developed by Transposagen and Janssen. In addition, Janssen has received a non-exclusive research license to utilize Transposagen’s proprietary gene editing technologies for gene and cell therapy solutions for treating diseases with significant unmet medical need. Transposagen will retain the rights to develop autologous CAR-T therapies and CAR-T therapies using Natural Killer (NK) cells or NK-like cells.

Janssen will pay Transposagen up to $292 million per CAR-T therapeutic, which includes an up-front fee and potential development, regulatory, and commercial milestone payments. Transposagen will also receive tiered royalties on net sales of any allogeneic CAR-T products that are commercialized by Janssen.

Transposagen will enter into a 3-year research collaboration with Janssen whereby both companies will work together on preclinical research. Janssen will be responsible for manufacturing and commercialization of allogeneic CAR-T therapies.

“The research collaboration with Janssen will pair Transposagen’s cutting-edge gene editing and gene delivery technology and expertise with Janssen industry-leading technologies in the antibody and antibody alternative areas to create what may be the ideal CAR-T therapy,” said Eric Ostertag, President and CEO of Transposagen.

On November 24, 2014 Bristol-Myers Squibb and Five Prime Therapeutics reported that they have entered into an exclusive clinical collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of combining Opdivo (nivolumab), Bristol-Myers Squibb’s investigational PD-1 (programmed death-1) immune checkpoint inhibitor, with FPA008, Five Prime’s monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R) (Press release Bristol-Myers Squibb, NOV 24, 2014, View Source [SID:1234501008]). The Phase 1a/1b study will evaluate the combination of Opdivo and FPA008 as a potential treatment option for patients with non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer and malignant glioma. Bristol-Myers Squibb has proposed the name Opdivo, which, if approved by health authorities, will serve as the trademark for nivolumab.

Opdivo and FPA008 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system to fight cancer. Opdivo is approved in Japan for the treatment of patients with unresectable melanoma, and is being developed in multiple tumor types in more than 50 clinical trials. FPA008, in development as a potential treatment for rheumatoid arthritis (RA) and solid tumors, has initiated dosing for a Phase 1 clinical trial in RA. Preclinical data suggest that combining antibodies targeting PD-1 and CSF1R may lead to an enhanced anti-tumor immune response compared to either approach alone in treating cancer.

“This collaboration supports our strategy to expand the clinical development of Opdivo, including novel combination regimens and across numerous tumor types,” said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. “We are excited to build upon our existing relationship with Five Prime Therapeutics in immuno-oncology, and explore the full potential of Opdivo and FPA008 in multiple tumor types.”

“We are pleased to establish a second collaboration with Bristol-Myers Squibb in the area of immuno-oncology,” said Lewis T. “Rusty” Williams, M.D., Ph.D., president and chief executive officer of Five Prime. “Their vision aligns with our commitment to advancing promising immune-modulating targets, alone or in combination, to create next-generation immunotherapies for cancer patients. We look forward to initiating this study and expanding the development of FPA008 as a potential immunotherapy for these six types of cancer.”

Under the terms of this agreement, Bristol-Myers Squibb will make a one-time payment of $30 million to Five Prime and will be responsible for study costs. Five Prime will conduct the clinical trial, which is expected to begin in 2015. The agreement provides for exclusivity with respect to the development, with a collaborative partner, of combination regimens of anti-PD-1/PDL1 antagonists together with an anti-CSF1R antagonist. Bristol-Myers Squibb will have a time-limited right of first refusal subject to certain conditions if Five Prime wishes to seek a partner for FPA008.

On November 24, 2014 Amgen reported the termination of all Amgen-sponsored clinical studies of rilotumumab in advanced gastric cancer, including the Phase 3 RILOMET-1 and RILOMET-2 studies (Press release Amgen, NOV 24, 2014, View Source [SID:1234501006]). Amgen’s decision is based on a planned safety review by the RILOMET-1 independent data monitoring committee that found an increase in the number of deaths in the rilotumumab and chemotherapy treatment arm when compared to the chemotherapy treatment only arm. Protocol-defined futility criteria would likely have been met at the planned interim analysis, scheduled for March 2015. Detailed results of RILOMET-1 will be submitted for presentation and publication.

“While we are disappointed with these results, we will work with lead investigators to further analyze the data in order to help inform future research and therapies in this area,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “There is a high unmet need for new treatments to address advanced gastric cancer, one of the leading causes of cancer death worldwide.”

Amgen is in communication with investigators in rilotumumab studies to coordinate study termination and provide guidance for study subject follow-up.