TUSTIN, Calif.—AstraZeneca and Peregrine Pharmaceuticals, Inc., a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine’s investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase 1/1b trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
Peregrine and AstraZeneca will collaborate on a non-exclusive basis, to evaluate the combination of bavituximab and durvalumab with chemotherapy as a potential treatment in various solid tumors. The Phase 1 part of the trial is expected to establish a recommended dose regimen for the combination and the Phase 1b part of the trial will assess the safety and efficacy of the investigational combination. Under the terms of the agreement, the initial trial will be conducted by Peregrine.
This comes as the latest indication of significant interest in Peregrine’s bavituximab as a potential key component in immuno-oncology combinations. The company is already planning to initiate a Phase 2 trial in combination with Opdivo in NSCLC by year-end and also has recently announced a deal with Memorial Sloan Kettering Cancer Center for additional research into combination regimens. The drug’s unique ability to inhibit phosphatidylserine (PS), a “global immune checkpoint,” outfits it with synergistic potential for a broad range of cancer treatments, the company stated in a release.
Robert Iannone, head of immuno-oncology, Global Medicines Development, at AstraZeneca said, “We believe that combination therapy in immuno-oncology has the potential to be a novel and highly effective approach to treating cancer. Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers.”
Bavituximab and durvalumab are investigational immunotherapies with different mechanisms of action that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment. The treatment increases activated T cells in tumors and fights cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate. MEDI4736 is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T cells to continue attacking the tumor.
"Data generated to date have shown significant potential for combining bavituximab with agents targeting the PD-1/PDL-1 pathway and we’re excited to further explore this approach in studies with AstraZeneca’s durvalumab," said Steven W. King, president and chief executive officer of Peregrine. “AstraZeneca is a recognized leader in the immuno-oncology field and this collaboration will play a key role as we continue to fully explore the potential of bavituximab in combination immunotherapies for a variety of clinical applications.”
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumor's immune-evading tactics. MEDI4736 is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase 3 development for the treatment of second-line non-small cell lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc., which provides development and biomanufacturing services for both Peregrine and third-party customers.
Oncology is a therapeutic area in which AstraZeneca has a deep-rooted heritage. It will be potentially transformational for the company’s future, becoming the sixth growth platform. The company’s vision is to help patients by redefining the cancer treatment paradigm and one day eliminate cancer as a cause of death. By 2020, Astrazeneca plans to bring six new cancer medicines to patients, focused on four main disease areas—ovarian, lung, breast and hematological cancers. These are being targeted through four key platforms—immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.