On October 6, 2017 Eli Lilly and Company (NYSE: LLY) reported that interim results from the double-blind, placebo-controlled Phase 3 MONARCH 3 study evaluating VerzenioTM (abemaciclib), a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with a nonsteroidal aromatase inhibitor (NSAI) (anastrozole or letrozole) were published online in the Journal of Clinical Oncology (JCO) (Press release, Eli Lilly, OCT 6, 2017, View Source [SID1234520807]). These data, presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in September, demonstrated that abemaciclib plus an NSAI resulted in a statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to an NSAI alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

“The significant results seen in MONARCH 3 confirm the clinical value of combining abemaciclib with an aromatase inhibitor in patients with endocrine-sensitive advanced breast cancer, and we look forward to seeing the final PFS data in the coming months,” said lead author Matthew P. Goetz, M.D., professor of oncology and pharmacology at Mayo Clinic and co-lead investigator of the MONARCH 3 study. “These data further demonstrate that abemaciclib is an effective treatment in the CDK4 & 6 class. This class represents a new standard of care in the treatment of advanced breast cancer.”

MONARCH 3 met a rigorous threshold for demonstrating efficacy at the time of pre-planned interim analysis with a 46 percent reduction in the risk of progression or death in patients receiving initial therapy for metastatic disease. The median PFS for abemaciclib in combination with an NSAI was not reached (i.e., the disease had not progressed significantly), compared to 14.7 months in the placebo arm (HR: 0.54; 95% CI: 0.41-0.72; P=0.000021). These results are supported by an improvement in response rate, with a 59.2 percent ORR in patients with measurable disease, including five patients (1.5%) achieving a complete response. Median duration of response (DoR) was not reached in the abemaciclib-plus-NSAI arm. Final PFS results are expected at the end of the year and will be presented at a scientific congress in the first half of 2018.

“At Lilly, we remain deeply committed to delivering standard-of-care changing medicines that improve the lives of many cancer patients,” said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. “We now have evidence from two randomized trials showing that the addition of Verzenio to an endocrine therapy provides clinical benefit to women with metastatic breast cancer and we look forward to further advancing our MONARCH clinical program.”

In MONARCH 3, abemaciclib in combination with an NSAI was generally well tolerated. The most frequent adverse events (AEs) of any grade in the abemaciclib-plus-NSAI arm were diarrhea, neutropenia, fatigue, infections, and nausea. Of these, the reported Grade 3/4 AEs in the abemaciclib-plus-NSAI arm versus the placebo-plus-NSAI arm were diarrhea (Grade 3: 9.5% vs 1.2%; no Grade 4 observed), neutropenia (Grade 3: 19.6% vs 0.6%; Grade 4: 1.5% vs 0.6%), fatigue (Grade 3: 1.8% vs 0%; no Grade 4 observed), infections (Grade 3: 4.0% vs 2.5%; Grade 4: 0.9% vs 0.6%), and nausea (Grade 3: 0.9% vs 1.2%; no Grade 4 observed).

Severity and frequency of diarrhea generally decreased following 28 days (one month), and was managed with over-the-counter antidiarrheal medication and dose adjustment. The majority (76.3%) of patients in the abemaciclib-plus-NSAI arm with an AE of diarrhea did not require treatment modification (dose interruption, reduction, or discontinuation), and 2.3 percent of patients discontinued treatment with abemaciclib due to diarrhea.

The MONARCH 3 study also included exploratory subgroup analyses that underscored consistency of results (when compared to the overall intention-to-treat [ITT] results) in patients with certain challenging disease characteristics. Further studies are needed to explore these findings.

MONARCH 3 was designed to evaluate the efficacy and safety of abemaciclib in combination with NSAIs as initial endocrine-based therapy for postmenopausal women with advanced (locoregionally recurrent or metastatic) breast cancer who have had no prior systemic treatment for advanced disease. If neoadjuvant/adjuvant endocrine therapy was administered, a disease-free interval of more than 12 months since completion of endocrine therapy was required. A total of 493 patients were randomized 2:1 to receive 150 mg of abemaciclib or placebo orally twice a day, without interruption, given in combination with either 1 mg of anastrozole or 2.5 mg of letrozole once daily until disease progression or unacceptable toxicity. The primary endpoint of the study was PFS, with key secondary endpoints of ORR, DoR, overall survival and safety.

On October 06, 2017 Molecular Templates, Inc., (Nasdaq:MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported that Eric E. Poma, Ph.D., Chief Executive and Chief Scientific Officer, will provide a corporate overview at the 2017 BIO Investor Forum, being held October 17-18 in San Francisco, California (Press release, Molecular Templates, OCT 6, 2017, View Source [SID1234520805]).
BIO Investor Forum
Date: Tuesday, October 17
Time: 10:30am Pacific Time
Location: Westin St. Francis, San Francisco, Elizabethan C Ballroom
Webcast: http://www.veracast.com/webcasts/bio/investorforum2017/25111335172.cfm

On October 6, 2017 Kitov Pharmaceuticals Holdings Ltd. (NASDAQ: KTOV, TASE: KTOV), (“Kitov” or “the Company”) an innovative biopharmaceutical company, reported the acquisition of an additional 27% stake in TyrNovo Ltd., a privately- held developer of novel small molecules in the oncology therapeutic field, from unaffiliated minority shareholders (Press release, Kitov Pharmaceuticals , OCT 6, 2017, View Source [SID1234520804]). As announced on January 13, 2017, Kitov had acquired a controlling interest, which is now approximately 65% of TyrNovo. After the closing of this transaction, Kitov will hold approximately 92% of TyrNovo’s issued and outstanding ordinary shares.

Following negotiations with a group of unaffiliated minority shareholders who collectively hold approximately 27%, of TyrNovo, the Company has entered into an agreement to acquire their shares based on an agreed upon TyrNovo valuation of $7 million. In exchange for these TyrNovo shares, Kitov will issue 13,169,689 new shares (equivalent to 658,484 American Depositary Shares or ADSs) of Kitov, at an agreed upon price, in excess of prevailing market prices, of $2.50 per ADS.

“Since early 2017, NT219 demonstrated impressive efficacy results including in combination with Keytruda, where it converted non-responding tumors to responders and blocked tumor progression in an immuno-oncology preclinical model. We are pleased to have negotiated the opportunity for Kitov to increase its stake in TyrNovo. We are committed to the development of NT219, which we believe is a highly attractive asset for Kitov’s shareholders in the growing field of oncology” stated Mr. Isaac Israel, Chief Executive Officer. “We believe that expanding our ownership in TyrNovo provides a significant opportunity for further growth of Kitov and added value to our shareholders.”

“Based on the pre-clinical results generated to date, we are receiving solid preliminary interest from potential strategic partners for NT219, which presents a novel, first-in-class mechanism of action in the oncology field.”

About NT219

NT219 is a small molecule that presents a new concept in cancer therapy by promoting the degradation and the phosphorylation of two oncology-related checkpoints, Insulin Receptor Substrates (IRS) 1 and signal transducer and activator of transcription 3 (STAT3), respectively. While targeted anti-cancer drugs inhibit the “ON” signal, NT219 activates the “OFF” switch, extensively blocking major oncogenic pathways. In pre-clinical trials, NT219, in combination with several approved cancer drugs, displayed potent anti-tumor effects and increased survival in various cancers by preventing the tumors from developing -drug resistance and reversing resistance after it has been acquired. In combination with various approved oncology drugs, NT219 demonstrated potent anti-tumor effects and increased survival in various cancer models including sarcoma, melanoma, pancreatic, lung, ovarian, head & neck, prostate and colon cancers, through the prevention of acquired resistance and regression of resistant tumors.

On October 6, 2017 Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151, President and CEO: Nobuo Hanai, “Kyowa Hakko Kirin”) reported the discontinuation for developing ARQ 197 (generic name: tivantinib) (Press release, Kyowa Hakko Kirin, OCT 6, 2017, View Source [SID1234520801]).

ARQ 197 is an oral agent whose molecular target is c-Met, which was discovered by ArQule, Inc. (NASDAQ: ARQL, “ArQule”). Kyowa Hakko Kirin signed a license agreement with ArQule for the exclusive rights to the development and sales of tivantinib in Japan and some parts of Asia (China, Korea, and Taiwan) on April 27th, 2007.

Under the license agreement, Kyowa Hakko Kirin developed ARQ 197 for indications of gastric cancer, non-small-cell lung cancer and hepatocellular carcinoma in its territory. However, positive results were not acquired in any studies. Concerning the situation, Kyowa Hakko Kirin discontinued ARQ 197 development project.

“We are disappointed in these results, as we had hoped ARQ197 might offer a new option for the thousands of cancer patients,” said Mitsuo Satoh, Ph.D., Head of Research and Development Division of Kyowa Hakko Kirin. “We would like to express our sincere thanks for the patients in our studies, as well as to the investigators, for their contributions to our development. We are continuously committed to tackling the unmet medical needs in cancer.”

The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

About c-Met
c-Met is receptor tyrosine kinase. When abnormally activated, the c-Met receptor tyrosine kinase plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.