On January 6, 2018 Context Therapeutics, a biopharma company dedicated to developing new medicines for patients with hormone responsive cancers, reported that it has acquired worldwide rights to Apristor (Onapristone XR) (Press release, Context Therapeutics, JAN 16, 2018, View Source [SID1234523265]). Onapristone has been extensively studied and has established efficacy in two Phase 2 metastatic breast cancer clinical trials. In these trials, meaningful clinical benefit and response rates were seen in 120 metastatic breast cancer patients, 101 of whom were actively progressing on Tamoxifen before Onapristone treatment initiation. Onapristone has been studied in over 200 patients, and it was well tolerated with no drug-related serious adverse events.

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Martin Lehr, CEO of Context stated: "We are excited to advance the development of Apristor and to potentially provide a mechanistically novel option for patients diagnosed with metastatic breast cancer. Unfortunately, the median life expectancy of a woman diagnosed with metastatic breast cancer is approximately three years. In the United States alone 40,000 women die each year as a result. These women deserve better, and we are committed to improving their treatment and removing the fear that comes along with this diagnosis."

Apristor blocks the binding of progesterone, a carcinogen, to the progesterone receptor (PR). Up to 70% of metastatic breast cancers express PR and are said to be PR+. If approved, Apristor would provide physicians with a novel product that could be used in combination with standard of care agents targeting the estrogen receptor or as a monotherapy.

Context made a one-time payment to Arno Therapeutics in exchange for the worldwide rights to Apristor. Apristor is a new chemical entity and is protected by a robust patent estate that should provide exclusivity through at least 2034.

Scott Applebaum, President of Context stated: "Context has taken a big leap forward and is now a clinical-stage company. This transformation is consistent with our mission of discovering, developing, and commercializing treatments for hormone-responsive cancers. We are building a world-class global clinical trial organization to bring Apristor to market as fast as possible. In addition, we have an Apristor fast-follower program for progesterone receptor-mediated diseases and continue to advance our preclinical Sigma1 program."

On January 16, 2018 Oncoceutics Inc. and Frontida BioPharm, Inc. reported that the two companies have entered into a product development and commercialization agreement to further develop and scale-up the finished product manufacturing process for ONC201, Oncoceutics’ lead molecule (Press release, Oncoceutics, JAN 16, 2018, https://oncoceutics.com/oncoceutics-frontida-biopharm-announce-product-development-commercialization-partnership/ [SID1234558375]). ONC201 is an antagonist of the G-protein coupled receptor (GPCR) dopamine receptor D2 (DRD2) and is the first molecule designed to target this receptor specifically for oncology. The drug is currently in Phase II clinical trials for select advanced cancers, including multiple trials in high-grade gliomas, where patients treated with the compound have shown complete regressions of tumor lesions.

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As a part of this agreement Frontida will manufacture ONC201 drug product in their GMP certified facilities for clinical trials and future commercial purpose. Frontida has also made an equity investment in Oncoceutics.

"Our partnership with Oncoceutics gives Frontida an important and strategic opportunity to contribute our development and manufacturing expertise toward the commercialization of a promising oncology therapy," said Ron Connolly, Chief Operations Officer of Frontida. "Oncoceutics’ lead molecule ONC201 has yielded compelling clinical outcomes, and our team is excited to have the opportunity to contribute to its advancement to commercialization."

"We are pleased to enter into this agreement with Frontida that provides Oncoceutics with the scale of ONC201 drug product manufacturing necessary for future commercialization," said Martin Stogniew Ph.D., Chief Development Officer of Oncoceutics. "The fact that Frontida has become a manufacturer and investor makes them a partner in Oncoceutics development programs, not simply a service provider."

On January 16, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported the upcoming presentation of updated safety results and clinical activity from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of encorafenib, a BRAF inhibitor, binimetinib, a MEK inhibitor and cetuximab, an anti-EGFR antibody, in patients with BRAF-mutant colorectal cancer (CRC) (Press release, Array BioPharma, JAN 16, 2018, View Source;p=RssLanding&cat=news&id=2326690 [SID1234523136]). These data will be presented at the 2018 Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, California.

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BEACON CRC SAFETY LEAD-IN

Title:

Abstract #627: BEACON CRC Study Safety Lead-in (SLI) in Patients With BRAFV600E Metastatic Colorectal Cancer (mCRC): Efficacy and Tumor Markers

Presenter:

Eric Van Cutsem, M.D., University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium

Date:

Saturday, January 20

Times:

7:00 am – 7:55 am PT and 12:30 pm – 2:00 pm PT

Updated data on the safety and tolerability profile of the triplet combination and measures of efficacy, including mPFS, ORR, duration of response, as well as tumor marker data, will be available as part of the presentation on January 20. The presentation will be available as a PDF from the Publications section of the Array website starting January 20.

Array’s BEACON CRC Phase 3 trial safety lead-in abstract published on January 16 contains previously presented safety and clinical activity data, as well as new data on changes in tumor markers.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS trial.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications (NDAs) to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition, the European Medicines Agency (EMA) is reviewing the Marketing Authorization Applications for encorafenib and binimetininb.

Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. The BEACON CRC trial is being conducted with support from Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

On January 16, 2018 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research and development in cancer epigenetics, reported it has initiated a Phase 1b/2 clinical trial to evaluate CPI-1205, a small-molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2), combined with checkpoint inhibitor ipilimumab (marketed as YERVOY by Bristol-Myers Squibb) and potentially other cancer immunotherapies (Press release, Constellation Pharmaceuticals, JAN 16, 2018, View Source [SID1234523138]). The study, named ORIOn-E, is based on translational insights which identified combination approaches using epigenetics-mediated mechanisms aimed at Overcoming Resistance to Immune Oncology therapies by inhibiting EZH2.

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"This is the second combination study we’ve initiated evaluating the potential for CPI-1205 to overcome resistance mechanisms to existing cancer therapies," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "Our preclinical results with CPI-1205 demonstrate that epigenetic targets can be utilized by cancers to suppress the immune system and render immunotherapy treatment options less effective. We aim to build on this insight with CPI-1205 in clinical trials and with other epigenetic therapies that we discover and develop in this important area of research."

CPI-1205 is a potent, highly selective, first-generation small-molecule inhibitor of an enzyme called EZH2. In pre-clinical studies, CPI-1205 has shown potential to re-wire T regulatory and T effector cells within tumors to enhance tumor rejection alone and synergistically in combination with immune checkpoint inhibition.

"Since they were first made available in the U.S., checkpoint inhibitor therapies like ipilimumab have provided considerable benefit for patients with many different cancers. However, many patients do not respond to therapy or relapse after initial response," said Adrian Senderowicz, M.D., senior vice president and chief medical officer of Constellation Pharmaceuticals. "CPI-1205 plays a critical role in inhibiting the suppressive function of regulatory T cells and consequently may address resistance mechanisms that limit the benefit of immune checkpoint inhibitors in patients."

The Phase 1b portion is a dose escalation study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and the assessment of potential predictive biomarkers in patients across solid tumors when treated with CPI-1205 in combination with ipilimumab. The Phase 2 portion will be conducted in melanoma patients, among other cancers.

About CPI-1205
CPI-1205 is a therapeutic candidate from Constellation Pharmaceuticals’ EZH2 portfolio and is an inhibitor of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several pro-cancer pathways that contribute to drug resistance.

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