Boehringer Ingelheim expands collaboration with Vanderbilt University to tackle some of the most difficult-to-treat cancers

On March 2, 2017 Boehringer Ingelheim reported a new collaboration with Vanderbilt University, Nashville, Tennessee (Press release, Boehringer Ingelheim, MAR 2, 2017, https://www.boehringer-ingelheim.com/press-release/next-generation-cancer-treatment-collaboration [SID1234517972]). The multi-year program complements an already existing collaboration by focusing on the research and development of small molecule compounds targeting the protein SOS (Son Of Sevenless). This molecule activates KRAS, a molecular switch that plays a central role in the onset of some of the deadliest cancers.

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The collaboration combines pioneering research in the laboratory of Stephen W. Fesik, Orrin H. Ingram II professor in cancer research at Vanderbilt University, with the unique expertise and strength of Boehringer Ingelheim in drug discovery and clinical development. The new collaboration adds to an ongoing joint project with Vanderbilt University initiated in 2015 that achieved two major milestones by identifying lead compounds that bind to KRAS with high affinities. These discoveries raise the prospect of developing novel cancer treatment options based on molecules that are able to block this critical cancer driver.

"We are very encouraged by the successful identification of inhibitors of KRAS in our alliance with Professor Fesik and his team at Vanderbilt University and look forward to expanding our collaboration," said Clive R. Wood, Ph.D., senior corporate vice president, discovery research at Boehringer Ingelheim. "With new technologies and the scientific discoveries made by Professor Fesik’s laboratory, we believe the time is now right to step up research efforts to develop novel cancer treatments that work by attacking KRAS and associated signaling pathways."

"Professor Fesik is a pioneer in the discovery of small molecules that bind to and inhibit challenging drug target proteins. His partnership with Boehringer Ingelheim will expedite efforts to discover novel cancer treatments that work on KRAS," said Lawrence J. Marnett, Ph.D., the Mary Geddes Stahlman professor of cancer research, university professor of biochemistry and chemistry and dean of basic sciences for the Vanderbilt University School of Medicine.

Mutations in the genes that encode KRAS are among the most powerful and frequent cancer drivers. They contribute to some of the most aggressive and deadly cancers, including up to 25 percent of lung, 35-45 percent of colorectal and about 90 percent of pancreatic tumors. KRAS has been a particularly difficult protein to target and no effective treatments targeting KRAS have been developed since its discovery in human cancers more than 30 years ago. The development of the first molecules inhibiting KRAS activation promises huge potential for the development of improved cancer therapies, which would offer treating physicians unprecedented options to complement existing treatment regimens.

By researching multiple approaches including direct inhibition of KRAS and indirect inhibition via SOS, Boehringer Ingelheim aims to accelerate the discovery of novel targeted therapies. The new collaboration with Vanderbilt University further strengthens Boehringer Ingelheim’s oncology pipeline, which focuses on tumor cell-directed cancer treatments, new approaches in immune oncology and their combinations. It underscores the companies’ commitment to pioneering emerging fields of research and working closely with its partners to accelerate the development of novel first-in-class, breakthrough medications that fit the needs of patients, caregivers and healthcare professionals.

OncoMed Announces Multiple Abstracts Related to Anti-TIGIT Program Accepted for Presentation at the American Association for Cancer Research Annual Meeting 2017

On March 2, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported that it will present new data related to its clinical and preclinical immuno-oncology and anti-cancer stem cell therapeutic candidates in a total of six presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting to be held April 1-5, 2017 in Washington, DC (Press release, OncoMed, MAR 2, 2017, View Source [SID1234517949]).

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Among the presentations will be three posters detailing preclinical data for OncoMed’s novel anti-TIGIT (OMP-313M32) immuno-oncology therapeutic candidate. These will be the first data that the company has shared publicly for its anti-TIGIT antibody program. New data will also be presented on biomarker research associated with the Phase 1b portion of OncoMed’s tarextumab (anti-Notch2/3, OMP-59R5) clinical trial in small cell lung cancer and OncoMed’s preclinical GITRL-Fc trimer (OMP-336B11) program. In addition, xenograft data will be presented for anti-RSPO3 (OMP-131R10) in combination with taxane chemotherapy in colorectal cancer.

The following abstracts have been selected for presentation by OncoMed scientists:

Sunday, April 2, 2017 1:00 PM — 5:00 PM
Title: Pharmacodynamic biomarkers for anti-TIGIT treatment and prevalence of TIGIT expression in multiple solid tumor types
Presenting author: Fiore Cattaruzza, Pharm. D., Ph.D., Senior Scientist II, Translational Medicine
Abstract Number: 599
Session: T-cell Immunity to Cancer: New Progress
Location: Poster section 26; Poster board 3

Monday, April 3, 2017 8:00 AM – Noon
Title: Antibody against TIGIT (T-cell immunoreceptor with Ig and ITIM domains) induces anti-tumor immune response and generates long-term immune memory
Presenting author: Angie Inkyung Park, Ph.D., Senior Director Immunotherapy
Abstract Number: 2003
Session: Tumor Microenvironment
Location: Poster section 44; Poster board 18

Title: Circulating Tumor Cells (CTCs) in patients with extensive-stage small cell lung cancer and their association with clinical outcome
Abstract number: 1727
Presenting author: Chun Zhang, Ph.D., Director, Translational Medicine
Session: Liquid Biopsies 1: Circulating Tumor Cells
Location: Poster section 30; Poster board 17

Title: R-SPONDIN3 antagonism sensitizes colorectal cancer to taxane treatment
Abstract Number: 1911
Presenting author: Marcus Fischer, Scientist
Session: Normal and Neoplastic Stem Cells
Location: Poster section 41; Poster board 12

Monday, April 3, 2017 1:00 PM — 5:00 PM
Title: Anti-TIGIT induces T cell mediated anti-tumor immune response and combines with immune checkpoint inhibitors to enhance strong and long term anti-tumor immunity
Abstract number: 2612
Presenting author: Minu Srivastava, Ph.D., Senior Scientist II
Session: Checkpoints 2: Small Molecule Inhibitors (Note: anti-TIGIT is a monoclonal antibody)
Location: Poster section 25; Poster board 1

Wednesday, April 5, 2017 8:00 AM – Noon
Title: Prevalence of GITR expression and pharmacodynamic (PD) biomarkers in syngeneic tumor models treated by a GITR agonist (GITRL-Fc)
Abstract number: 5621
Presenting author: Min Wang, Ph.D., Director, Translational Medicine
Session: Immune Checkpoints and Immunosurveillance
Location: Poster section 25; Poster board 23

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Regulus has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Regulus, MAR 2, 2017, View Source [SID1234517975]).

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FDA Accepts New Drug Application and Grants Priority Review for Enasidenib in Relapsed or Refractory AML with an IDH2 Mutation

On March 1, 2017 Celgene Corporation (CELG) and Agios Pharmaceuticals (AGIO) reported that the U.S. Food and Drug Administration (FDA) has accepted Celgene’s New Drug Application (NDA) for enasidenib (AG-221/CC-90007) for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation (Press release, Agios Pharmaceuticals, MAR 1, 2017, View Source;p=RssLanding&cat=news&id=2250587 [SID1234517906]). The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of Aug. 30, 2017. Celgene completed the NDA submission in late December 2016.

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"We accelerated this application – submitting the NDA just three years after the first patient was treated in the enasidenib pivotal investigational trial – because we believe that there is a significant unmet need for people with relapsed or refractory AML," said Michael Pehl, president, Hematology/Oncology for Celgene. "The acceptance of the enasidenib NDA is a significant milestone in what we hope will be a new era of molecularly targeted therapies for patients with this devastating disease."

Enasidenib is a first-in-class, oral, targeted inhibitor of mutant IDH2. The NDA submission is based on results from AG221-C-001, a single-arm phase I/II study of enasidenib in patients with advanced hematologic malignancies with an IDH2 mutation. Early data from the relapsed or refractory AML patients in this study were presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"Having received NDA acceptance and priority review for enasidenib, we look forward to working with our partner Celgene and the FDA to advance a first-in-class therapy for relapsed or refractory AML with an IDH2 mutation," said David Schenkein, M.D., chief executive officer at Agios. "We hope that the continued adoption of molecular profiling and availability of new targeted therapies such as enasidenib will have a significant impact on patients living with AML."

Additionally, Abbott has submitted a Premarket Approval (PMA) application for the FDA approval of an IDH2 assay on the Abbott m2000 RealTime System, a polymerase chain reaction (PCR) molecular diagnostics instrument. IDH2 mutations occur in about 8 to 19 percent of AML patients. Recent publications have highlighted the advances in the understanding of the genetics underlying AML and the need for routine mutational analysis at diagnosis and relapse.

Celgene is also evaluating enasidenib compared with conventional therapy in older patients with an IDH2 mutation and relapsed or refractory AML in the ongoing phase III IDHENTIFY trial (NCT02577406).

Enasidenib is an investigational drug that has not been approved for any use in any country.

About Acute Myelogenous Leukemia (AML)

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. Less than 10 percent of U.S. AML patients are eligible for bone marrow transplant and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH2 mutations are present in about 8 to 19 percent of AML cases.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Merrimack has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Merrimack, MAR 1, 2017, View Source [SID1234517916]).

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