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 At the American Society of Hematology (ASH) (Free ASH Whitepaper)’s 59th Annual Meeting and Exposition in Atlanta, Georgia, researcher Gustavo Milone, MD, and his team reported that will present a study that investigates the post-marketing trends of Novex, a biosimilar rituximab that has been approved in Argentina for the same indications as the reference product (MabThera, Rituxan) (Press release, mAbxience, DEC 5, 2017, View Source [SID1234594760]).1 Since Novex’s commercial launch, the first national pharmacovigilance plan for a biosimilar monoclonal antibody has been implemented, and data from this post-marketing surveillance show that, in terms of tolerability, this biosimilar has a similar safety profile to that of the reference product.

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In order to determine deviations from expected frequencies of adverse events (AEs), a prospective treatment registry for the biosimilar was implemented from the start of its commercialization on November 26, 2014. Data in the study are reported until June 30, 2017. Physicians, 180 in total, tracked age, gender, indication, dose, dose frequency, and date of treatment initiation and finalization for each patient receiving the biosimilar.

The study comprised the records of 525 patients who had at least 1 follow-up. The majority of patients were female (52%), the mean age was 63.3 years (range, 10-90), and most patients received the biosimilar rituximab for hematological disease (91.2% of cases). The treatment duration ranged from 154 to 309 days, with the number of treatment cycles varying from 1 to 12. Individual Case Safety Reports (ICSRs) were collected from 24 patients with 29 AEs.

The most frequently reported AEs were:

Acute infusion-related reaction (14)
Arrhythmia (3)
Pneumonia (2)
Stroke (2)
The researchers noted that 41 treatments with rituximab were initiated before the launch of the product; assuming treatment began with MabThera, these 41 treatments imply switching to the biosimilar from the reference.

Researchers investigating data from the post-marketing surveillance found a similar incidence of AEs after the use of rituximab biosimilar when compared to the published data of the reference product. Thus, in terms of tolerability, the biosimilar has a similar safety profile compared with its reference.

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 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.