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.

Geron Announces Presentation at American Association for Cancer Research Annual Meeting

On March 2, 2017 Geron Corporation (Nasdaq:GERN) reported an abstract submitted by Janssen Research & Development, LLC describing non-clinical data on imetelstat has been accepted for presentation as a poster at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held in Washington, D.C. from April 1-5, 2017 (Press release, Geron, MAR 2, 2017, View Source;p=RssLanding&cat=news&id=2250980 [SID1234517934]). The abstract is available on the AACR (Free AACR Whitepaper) website at www.aacr.org.

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Abstract Title: Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia (Abstract #1101)

AACR Session Title: Combination Therapy 1
Session Date: Monday, April 3, 2017
Session Time: 8:00 a.m. ET – 12:00 p.m. ET
In accordance with AACR (Free AACR Whitepaper) policies, abstracts submitted to the AACR (Free AACR Whitepaper) Annual Meeting are embargoed from the time of submission. To be eligible for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, information contained in the abstract, as well as additional data and information to be presented at the Annual Meeting, may not be made public before the abstract has been presented in connection with the AACR (Free AACR Whitepaper) Annual Meeting.

Infinity Announces Presentation on IPI-549 at AACR Annual Meeting

On March 2, 2017 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that new Phase 1 data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), will be presented in a clinical trial poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 taking place in Washington, D.C. April 1 – 5 (Press release, Infinity Pharmaceuticals, MAR 2, 2017, View Source;p=RssLanding&cat=news&id=2251054 [SID1234517936]). A Phase 1 clinical study is ongoing to explore the safety and activity of IPI-549 both as a monotherapy and in combination with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors. IPI-549 is believed to be the only PI3K-gamma inhibitor in clinical development.

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Details of the presentation are as follows:
Poster presentation time: Tuesday, April 4, 2017, 8:00 a.m. – 12:00 p.m. ET
Title: IPI-549-01 – A Phase 1/1b, First-in-Human Study of IPI-549, a PI3K-Gamma Inhibitor, as Monotherapy and in Combination with Nivolumab in Patients with Advanced Solid Tumors
Abstract number: CT089
Lead author: Jedd Wolchok, M.D., Ph.D., Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK), as well as Associate Director of the Ludwig Center for Cancer Immunotherapy and Director of the Parker Institute for Cancer Immunotherapy, both at MSK
Location: Convention Center, Halls A-C, Poster Section 33

About the IPI-549 and the Ongoing Phase 1 Study
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical tumor models.1,2 As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in patients with advanced solid tumors.3 The study includes monotherapy and combination dose-escalation phases, in addition to a monotherapy expansion cohort and combination expansion cohorts. Overall, the study is expected to enroll approximately 175 patients.

The expansion cohorts evaluating IPI-549 plus Opdivo will include patients with non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN). There is a great need for additional treatment options for the growing number of patients living with these types of cancers, which account for more than 17 percent of all new cancer cases in the U.S.4,5 Additionally, patients enrolled in the combination expansion cohorts represent a difficult-to-treat population, as they must have demonstrated initial resistance or subsequently develop resistance to a PD-1 or PD-L1 therapy immediately prior to enrolling in the study.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

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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