Tustin, California based biotech firm Peregrine Pharmaceuticals, Inc. has announced preclinical data that further validates the company’s immune-stimulatory mechanism proprietary to its novel phosphatidylserine (PS)-targeting immuno-oncology platform.

The company noted that results of new research indicate that when a PS-targeting antibody that is similar to its Bavituximab product is administered together with an anti-PD-1 antibody, statistically significant suppression of tumor growth was observed, as well as a substantial increase in the production of T-cells into the microenvironment of the tumor, in comparison to anti-PD-1 antibody treatment used alone when tested as part of an immune competent animal model for breast cancer. This new data is to be presented by Peregrine Pharmaceuticals’ Vice President, Pre-Clinical Development, Jeff Hutchins, Ph.D. in a presentation entitled, “Phosphatidylserine (PS) Targeting Antibodies Enhances Activity of Immune Checkpoint Inhibitors by Repolarizing Immunosuppressive Immune Cells Populating the Tumor Microenvironment,” at ImVacS, the 9th Annual Immunotherapies and Vaccine Summit hosted by Cambridge Healthtech Institute, which is set to be held from August 11-14, 2014 in Boston, Massachusetts. The company’s lead product Bavituximab is also being tested in the second-line non-small cell lung cancer (NSCLC) indication in the SUNRISE pivotal Phase III clinical trial.

Peregrine describes PS as “a phospholipid normally residing in the inner leaflet of the plasma membrane that becomes exposed on cells of the tumor microenvironment, promoting an immunosuppressive microenvironment (MDSCs, immature dendritic cells, M2 macrophages, anti-inflammatory cytokines). Peregrine’s lead PS-targeting candidate Bavituximab in combination with chemotherapy has demonstrated promising signs of anti-tumor activity and survival trends in patients with non-small cell lung cancer (NSCLC) and advanced breast cancer. Bavituximab, a PS-targeting antibody, repolarizes this microenvironment, enhancing innate and adaptive anti-tumor immunity. In the presentation, Dr. Hutchins will demonstrate that PS targeting antibodies enhance anti-tumor activity of multiple forms of standard therapy, including anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies without the side-effects of systemic immune activation.”

“These statistically significant results are an important extension of earlier data obtained combining our PS-targeting antibodies with other immune checkpoint inhibitors in different tumor types and our clinical experience in treating breast cancer patients,” Dr. Hutchins notes in a press release. “These data further validate that blocking the immunosuppressive effects of PS facilitate an increase in tumor-fighting T-cells, and that the combination with PD-1 then allows for a more effective anti-tumor T-cell response. We believe these studies, along with our previously released Phase II breast cancer results, warrant an expanded clinical investigation in breast cancer that would build on our ongoing immunotherapy combination clinical trial in advanced melanoma.”

In his presentation, Dr. Hutchins’ overview outlines the company’s unique PS-targeting platform, which includes preclinical data that is being produced from the Peregrine’s immuno-oncology R&D program. The presentation specifically includes new data for the ch1N11 antibody that targets PS, revealing that test animals treated with it, when combined with anti-PD-1 in an EMT-6 mouse breast tumor model, was shown to markedly delay the group receiving treatment median tumor growth in comparison to the use of anti-PD-1 alone.

Specifically, when breast cancer patients were given ch1N11/anti-PD-1 therapies once a week, the growth of tumors was inhibited by 78.7% (p= 0.0048 on day 23) compared to anti-PD-1 used in mono therapy. Additionally, 50% of tumors that were treated with combination therapy were found to either regress or not progress when compared to 0% when using anti-PD-1 alone. Adding to this, the combo treatment administered once weekly achieved a 78% and 81% increase in intratumoral CD4+ and CD8+ T cells. These are two important indicators that reveal that immune cells that fight cancer are indeed present in a tumor’s local environment, when compared to the use of a single agent such as anti-PD-1.

“With these combination results, we are clearly seeing both a significant delay in tumor growth as a group and a decrease in the number of animals with tumor progression,” says Bruce Freimark, Ph.D., director of pre-clinical research in oncology. “We believe these data present encouraging observations to support the expanded clinical use of tumor immunotherapy combinations using PS-targeting antibodies.

Peregrine’s release notes that recent research demonstrates that tumors actually evade detection due in part to PS expression of a significantly immunosuppressive molecule that is exploited by the presence of tumors. The result of Peregrine’s immuno-oncology R&D program has led to the development of Bavituximab, which is recognized by the company as “a first-in-class investigational PS-targeting monoclonal antibody that targets and binds to PS and blocks the immunosuppressive effects of PS while activating tumor fighting immune cells, thus enabling the immune system ability to recognize and fight cancer. Data from a recent published study show that PS-targeting antibodies mediate multiple immunostimulatory changes in the tumor environment, including a reduction of tumor-promoting immune cells and an increase in tumor fighting macrophages, dendritic cells and T-cells.”

Bavituximab’s immune-stimulatory mechanism-of-action data is the subject of a manuscript published in the October 2013 issue of the American Association for Cancer Research (AACR) peer-reviewed journal, Cancer Immunology Research. entitled, “Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation.” In addition to breast cancer, Bavituximab, which was given fast-track status by the FDA inJanuary of 2014, is also being tested as a treatment for non-small cell lung cancer, rectal cancer, liver cancer, and advanced melanoma.

Bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the “SUNRISE trial”) along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications.

In a Phase 2 clinical trial, in patients who mirror the entry criteria for the SUNRISE trial, the 3mg/kg bavituximab plus docetaxel arm resulted in a median overall survival of 11.7 months compared to 7.3 months in the control arm with the 3 mg/kg bavituximab plus docetaxel combination arm being well-tolerated with no significant differences in adverse events between the trial arms.

For more information on Bavituximab clinical trials,visit:
http://www.peregrineinc.com/clinical-trials/bavituximab-trials.html

For a video explaining how Bavituximab works, see:
http://www.sunrisetrial.com/

Sources:

Peregrine Pharmaceuticals, Inc.
ClinicalTrials.gov
ImVacS, the Cambridge Healthtech Institute’s 9th Annual Immunotherapies and Vaccine Summit

Image Credits:
Peregrine Pharmaceuticals, Inc.