On July 18, 2018 Sanofi and REVOLUTION Medicines, Inc. reported an exclusive worldwide partnership to develop and commercialize targeted therapies, based on the biology of the cellular enzyme SHP2, for patients with non-small lung cancer and other types of cancer carrying certain mutations (Press release, Sanofi Genzyme, JUL 18, 2018, View Source [SID1234527769]). This collaboration builds on precision oncology discoveries by REVOLUTION Medicines and preclinical development of RMC-4630, the company’s lead small molecule inhibitor of SHP2, and will apply Sanofi’s expertise in oncology research and drug development.

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In the collaboration, the companies will jointly develop SHP2 inhibitors, which are designed to reduce cell growth signaling that is overactive in cancer. Both parties will contribute to the research and development program, with REVOLUTION Medicines continuing to lead research and early clinical development, and Sanofi leading later development activities for the program. The companies expect to begin first-in-human clinical trials with RMC-4630 in the second half of 2018.

"REVOLUTION Medicines has made great progress in elucidating the role of SHP2 in cancer and advancing RMC-4630 into clinical development," said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer of REVOLUTION Medicines. "The exciting collaboration benefits from the innovation culture and scientific capabilities of our team and the proven oncology research and development capabilities and global commercial resources of Sanofi to continue this momentum and maximize the potential impact for cancer patients."

"This agreement demonstrates our continued commitment to develop new therapies for patients living with cancer," said Joanne Lager, head of oncology development at Sanofi. "We look forward to working with REVOLUTION Medicines to advance investigational therapies that could provide a new way to treat patients with non-small cell lung cancer and other cancers that have specific types of genetic mutations."

REVOLUTION Medicines will receive an upfront fee of $50 million, and Sanofi will cover R&D costs for the joint SHP2 program. Sanofi will receive an exclusive worldwide license for global commercialization of any approved products targeting SHP2, subject to a U.S. co-promote option for REVOLUTION Medicines. The companies will enter into a 50/50 profit and loss share arrangement in the U.S., and REVOLUTION Medicines will receive a tiered royalty reaching mid-double digits on sales in other markets. REVOLUTION Medicines could also receive more than $500 million in development and regulatory milestone payments.

The Role of SHP2 in Cancer

SHP2 (PTPN11), a cellular enzyme in the protein tyrosine phosphatase family, plays an important role in multiple forms of cancer and in regulating the immune system. Recently REVOLUTION Medicines reported discoveries about the regulation by SHP2 of a cell growth signaling pathway, known as the RAS-MAP kinase pathway, that frequently is hyperactive in human cancers. The research revealed that some mutated forms of proteins in the RAS-MAP kinase pathway depend on SHP2 for their oncogenic activity, and that small molecule inhibitors of SHP2 designed by the company can reduce their tumorigenic effects.

On July 18, 2018 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health") reported that it will release its second-quarter 2018 financial results on Tuesday, Aug. 7, 2018 (Press release, Valeant, JUL 18, 2018, View Source [SID1234527770]). Bausch Health will host a conference call and live web cast at 8:00 a.m. EDT to discuss the results and provide a business update. All materials will be made available on the investor relations section of the Bausch Health web site prior to the start of the call.

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Conference Call Details
Date: Tuesday, Aug. 7, 2018
Time: 8:00 a.m. EDT
Webcast: View Source
Participant Event Dial-in: (844) 428-3520 (North America)
(409) 767-8386 (International)
Participant Passcode: 1378128
Replay Dial-in: (855) 859-2056 (North America)
(404) 537-3406 (International)
Replay Passcode:
1378128 (replay available until Oct. 7, 2018)

On July 18, 2018 Vyriad Inc., a clinical-stage, privately held biotechnology company focused on the development of powerful first-in class oncolytic virotherapies, is reported that collaboration agreement with Merck KGaA, Darmstadt, Germany, and Pfizer to expand its ongoing Phase 1 clinical trial program in solid tumors to include a combination study of its lead asset, Voyager-V1, with avelumab*, a human anti-PD-L1 antibody (Press release, Vyriad, JUL 18, 2018, View Source [SID1234527771]). For more information on this novel immuno-oncology combination study, please see clinicaltrials.gov.

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"We are delighted to be working with Merck KGaA, Darmstadt Germany, and Pfizer on this innovative combination treatment approach," said Stephen Russell, M.D., Ph.D., CEO of Vyriad. "Voyager-V1 is being administered to inflame the tumors, and avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models."

"We are encouraged by the potential of Voyager-V1, which has demonstrated early clinical activity in patients with solid tumors," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which operates in the U.S. and Canada as EMD Serono. "We look forward to investigating how combining Voyager-V1 with avelumab may advance patient care."

"A primary focus of our clinical development program for avelumab is to evaluate the role and potential of immunotherapy combination regimens, in an effort to support patients with challenging cancers," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We look forward to working with Vyriad to explore this novel combination for patients with solid tumors."

Avelumab has received accelerated approval** by the U.S. Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of various solid tumors and has not been demonstrated to be safe and effective for this indication. There is no guarantee that avelumab will be approved for specific solid tumors by any health authority worldwide.

About Voyager-V1

Voyager-V1 (VSV-IFNβ-NIS) is derived from Vesicular Stomatitis Virus (VSV), a bullet-shaped, negative-sense RNA virus with low human seroprevalence, specifically engineered to replicate selectively in and kill human cancer cells. Voyager-V1 encodes human IFNβ to boost antitumoral immune responses and increase tumor specificity, plus the thyroidal sodium iodide symporter NIS to allow imaging of virus spread. Three first-in-human Phase 1 clinical studies of Voyager-V1 are exploring intravenous and intratumoral routes of administration.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials and nearly 8,300 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Indications in the U.S.**

The U.S. Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the U.S. FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, U.S.

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, U.S., enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

On July 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has entered into a license agreement with F. Hoffmann-La Roche, Ltd. for the ROS1/TRK inhibitor entrectinib (Development Code: RG6268), which is under development for tumors that harbor ROS1 or NTRK fusions (Press release, Chugai, JUL 17, 2018, View Source [SID1234529698]).

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Under the terms of agreement, Chugai obtains exclusive rights for the development and marketing of entrectinib in Japan, and will make upfront and milestone payments to Roche.

Entrectinib is an orally bioavailable CNS-active tyrosine kinase inhibitor that potently and selectively inhibits the ROS1 (c-ros oncogene 1) and TRK (tropomyosin receptor kinase) family. Entrectinib targets ROS1 fusion gene positive non-small cell lung cancer and NTRK fusion gene positive solid tumors. Currently, Roche is conducting a global phase II clinical study (The STARTRK-2 study). Entrectinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in May 2017 and PRIME (PRIority MEdicines) Designation by the European Medicines Agency (EMA) in October 2017 for the treatment of NTRK fusion positive solid tumors. In Japan, entrectinib also received the Sakigake Designation by the Ministry of Health, Labour and Welfare in March 2018.

To date, Chugai has made contributions to healthcare through the launches of innovative anti-cancer agents. With the addition of the ROS1/TRK inhibitor entrectinib to our product portfolio, Chugai’s strength as a leading pharmaceutical company in the area of oncology will be enriched, enabling Chugai to make greater contributions to the advancement of cancer treatment.

Chugai is committed to continuing its efforts to meet unmet medical needs by effectively utilizing the research and development resources of Roche to find innovative new drugs.

About ROS1 fusion gene positive non-small cell lung cancer
ROS1 fusion gene is an abnormal gene that can be formed by fusing the ROS1 gene and other genes (CD74, etc.) as a result of chromosomal translocation for some reason. The ROS1 fusion kinase made from ROS1 fusion gene is thought to promote cancer cell proliferation. ROS1 fusion gene is found in about one to two percent of non-small cell lung cancer, among which it is more expressed in adenocarcinoma.

About NTRK fusion gene positive cancer
NTRK fusion gene is an abnormal gene that can be formed by fusing the NTRK genes (NTRK1, NTRK2, NTRK3 encode TRKA, TRKB, TRKC protein, respectively) and other genes (ETV6, LMNA, TPM3, etc.) as a result of chromosomal translocation. The TRK fusion kinase made from NTRK fusion gene is thought to promote cancer cell proliferation. There is very rare expression of NTRK fusion but in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor (GIST), infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas.

About Sakigake Designation
Sakigake aims at shortening pre-market review period for innovative medical products that satisfy certain criteria by designating such products during the early stages of development, and providing prioritized consultation services and substantial pre-application consultation. By taking advantage of the benefits offered by Sakigake, the target review period for the designated products will be reduced to as short as 6 months.

On July 17, 2018 Advaxis presented the corporate presentation (Presentation, Advaxis, JUL 17, 2018, View Source [SID1234527762]).

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