On December 5, 2017 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported the closing of the global collaboration and license agreement with Incyte Corporation for MGA012, an anti-PD-1 monoclonal antibody (Press release, MacroGenics, DEC 5, 2017, View Source [SID1234522392]). The agreement was announced on October 25, 2017.

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Under the terms of the agreement, MacroGenics will receive an upfront payment of $150 million, while Incyte receives worldwide rights to develop and commercialize MGA012 in all indications. MacroGenics is eligible to receive up to $420 million in potential development and regulatory milestones, and up to $330 million in potential commercial milestones. If MGA012 is approved and commercialized, MacroGenics would be eligible to receive royalties, tiered from 15 percent to 24 percent, on future sales of MGA012 by Incyte.

After a pre-defined transition period, Incyte will lead global development of MGA012. MacroGenics retains the right to develop its own pipeline assets in combination with MGA012, with Incyte commercializing MGA012 and MacroGenics commercializing its asset(s), if any such potential combinations are approved.

In addition, MacroGenics retains the right to manufacture a portion of both companies’ global clinical and commercial supply needs of MGA012. MacroGenics intends to utilize its commercial-scale GMP facility, which is expected to be fully operational in 2018.

On December 5, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing investigational drugs for the treatment of orphan oncology indications, reported new preliminary data in a mouse model of colon cancer indicating that reductions in tumor volume after treatment with CA4P and anti-CTLA-4 combination therapy are associated with an enhanced immune response (Press release, Mateon Therapeutics, DEC 5, 2017, View Source [SID1234522393]). CA4P induces immediate, rapid and extensive tumor cell necrosis which can stimulate the immune system, while antibodies to CTLA-4 stimulate the immune system through a different mechanism, by blocking immunosuppression (which is the same mechanism used by the approved drug marketed under the trade name Yervoy).

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"We are excited about the possibility of using CA4P to improve patient responses to checkpoint inhibitors, which have shown significant but nevertheless limited therapeutic benefits as monotherapy," said William D. Schwieterman, M.D., President and CEO of Mateon Therapeutics. "While the direct clinical benefits of CA4P alone as an anti-cancer agent are limited, these initial data indicate the promise of this agent to stimulate the immune system and enhance the efficacy of checkpoint inhibitors – an exciting and rapidly emerging field of oncology where our unique approach may offer a distinct advantage."

Mateon previously reported data from a CT-26 colon cancer animal model showing that combination treatment with CA4P and anti-CTLA-4 causes large reductions in tumor volume and statistically significant improvements in survival when compared to anti-CTLA-4 alone, CA4P alone, or vehicle control. Similar anti-tumor effects were observed when this combination was studied in an EMT-6 mammary tumor animal model. The CT-26 model was repeated for the studies reported today, again showing large reductions in tumor volume with combination therapy. This repeat study also captured additional data on immune response, with preliminary data showing increases in the median number of tumor-associated white blood cells (WBC’s) (69.2K vs. 39.0K vs. 16.7K for CA4P plus anti-CTLA-4, anti-CTLA-4 alone and vehicle control, respectively), T cells (5.2K vs. 1.6K vs. 1.8K), and effector cytotoxic CD8+ T Cells (2.0K vs. 0.8K vs. 0.5K), indicating a heightened immunologic response to the tumor in the presence of the two-drug combination. Importantly, treatment with both CA4P and anti-CTLA-4 generally maintains an elevated tumor-associated median effector T cell/regulatory T cell ratio, which also indicates a heightened immune response. Work to further characterize the immune response seen with the combination is ongoing.

On December 5, 2017 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (Oncolytics or the Company), a biotech company developing REOLYSIN, also known as pelareorep, an intravenously delivered immuno-oncolytic virus that activates the innate and adaptive immune systems to turn ‘cold’ tumors ‘hot’, reported that the company has received a favorable Final Advice Letter from the European Medicines Agency (EMA) (Press release, Oncolytics Biotech, DEC 5, 2017, View Source [SID1234522394]). The Letter refers to the proposed use of pelareorep in combination with paclitaxel, for the treatment of hormone receptor positive, HER2 receptor negative (HR+/HER2-) metastatic breast cancer patients in a pivotal phase 3 registration study and suggests that a single 400-patient study may be acceptable to form the basis of a Marketing Authorization Application (MAA) in Europe.

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"The EMA’s feedback and Final Advice Letter are very much inline with the feedback and advice we received from the FDA in September and adds to the support we have for our proposed target patient population of HR positive/HER2 negative metastatic breast cancer patients for the registration study," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "Our statistically significant and clinically compelling overall survival data, Fast Track designation and clear guidance from the FDA and EMA allow us to focus on the completion of the adaptive study design that will include approximately four hundred patients with a pre-determined interim analysis at two hundred patients. Furthermore, the EMA provided guidance that if the study achieves its primary endpoint, it may form the basis of a Marketing Authorization Application for commercialization in Europe. The design of the study, feedback from both the FDA and EMA and our recently announced partnership with Adlai Nortye will also drive our ongoing partnering process."

Oncolytics’ proposed target population for its phase 3 study of pelareorep is patients with HR+/HER2- mBC, which represents approximately 73 percent of metastatic breast cancer cases that have limited treatment options that offer survival benefit. Details of the pivotal phase 3 registration study will be made available following evaluation and completion of discussions with clinical advisors and potentially partners.

About Metastatic Breast Cancer
Metastatic breast cancer, also known as advanced or Stage 4 breast cancer, has spread to other parts of the body. Most commonly the lungs, liver, bones or brain. The disease affects over 154,000 women in the United States and according to the American Cancer Society, has a five-year survival rate of just 22 percent. Significantly lower than stage 3, with a five-year relative survival rate of 72 percent and stage 2, with a five-year survival rate over 90 percent.

About REOLYSIN/Pelareorep
REOLYSIN, also known as pelareorep, is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers.

On December 5, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that updated clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, will be presented at the 2017 San Antonio Breast Cancer Symposium, December 5-9, 2017 in San Antonio, Texas (Press release, Calithera Biosciences, DEC 5, 2017, View Source [SID1234535249]). The data demonstrate the clinical activity and tolerability of CB-839 in combination with paclitaxel, and highlight the unique mechanism of action of CB-839 in patients with advanced/metastatic triple negative breast cancer (TNBC). Based on these data, Calithera has opened a Phase 2 trial exploring the treatment combination in both first line and late line metastatic TNBC patients.

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"Effective treatment for triple negative breast cancer in the advanced and metastatic population remains a significant unmet need. In our Phase 1 study, we were pleased to have observed responses in patients who were heavily pretreated and the Phase 2 study will help us further understand the role of CB-839 in inhibiting glutaminase to help control the progression of cancer in advanced metastatic TNBC patients," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

In a poster presentation representing an update from data presented at SABCS 2016, Dr. Kevin Kalinsky from Columbia University Medical Center will present, "Phase I study of CB-839, a first-in-class inhibitor of glutaminase, in combination with paclitaxel in patients with advanced triple negative breast cancer," (Abstract PD3-13). Eligible patients must have locally advanced/metastatic TNBC, with no restrictions on prior exposure to taxanes, or the number of prior therapies. As of October 23, 2017, 49 triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four; 44 were evaluable for response. Patients were heavily pretreated, having received a median of 3 prior therapies for advanced metastatic disease. A majority of patients had received prior taxane therapy in either the neo-adjuvant (37%) or metastatic setting (51%). Among all evaluable patients treated with CB-839 doses of at least 600 mg bid (n=37), there were 8 partial responses (22%) and disease control (response or stable disease) in 22 patients (59%). Among African Americans, there was a 36% response rate in patients who had received previous taxanes in the metastatic setting; all responders were refractory to prior taxanes. Exploratory biomarker analysis shows a trend for the strongest clinical benefit occurring in patients with LAR and/or desmoplastic stromal gene expression signatures1.

The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been primarily low grade and reversible. Consistent with the previous report, there was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient. The most frequent adverse event ≥ Grade 3 was neutropenia (27%). A low rate of ≥ Grade 3 peripheral neuropathy (4.2%) was observed despite 88% of the patients having prior taxane exposure. 1Lehmann et al., J Clin Invest 2011; Chen et al, Cancer Inform 2012; Jovanovic et al BMC Cancer 2017; Saleh et al, Cancer Research 2017

About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents

On December 5, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY): reported that following close consultation and agreement on study modifications with the U.S. Food and Drug Administration (FDA), the partial clinical holds placed on the Phase Ib and Phase Ib/II studies evaluating TECENTRIQ in combination with an immunomodulatory medicine (IMiD) in relapsed/refractory multiple myeloma and relapsed/refractory follicular lymphoma have been lifted (Press release, Hoffmann-La Roche, DEC 5, 2017, View Source [SID1234522368]). The studies will continue in accordance with the protocol amendments agreed upon by the FDA.

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The studies had been placed on partial clinical hold as part of an FDA evaluation of all ongoing blood cancer trials, investigating PD-1/PD-L1 inhibitors in combination with an IMiD to determine if there was a class-wide (PD-1/PD-L1 inhibitor) concern in multiple myeloma/blood cancers, or a specific concern with certain combinations with IMiDs. The FDA evaluation was prompted by interim data from clinical trials evaluating pembrolizumab in combination with either lenalidomide or pomalidomide in multiple myeloma.