Doubling down on KRAS

Boehringer Ingelheim and Vanderbilt University expand collaboration to tackle difficult-to-treat cancers

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INGELHEIM, Germany—In an effort to expand its long-term partnerships with academic leaders in the oncology field and further boost its KRAS research and development efforts, Boehringer Ingelheim (BI) earlier this spring announced a new collaboration with U.S. academic institution Vanderbilt University in Nashville, Tenn. The multiyear program complements an existing collaboration between the pharma and the university 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 is considered to play a key role in the onset of many of the deadlier cancers.
BI had established the original Vanderbilt collaboration in 2015 with the cancer drug discovery laboratory of Dr. Stephen W. Fesik, the Orrin H. Ingram II Chair in Cancer Research and a professor of biochemistry, pharmacology and chemistry. The aim of that collaboration was to pursue the research and development of small-molecule inhibitors of oncogenic Ras for the treatment of cancer.
That work achieved two major milestones by identifying lead compounds that bind to KRAS with high affinities, which could lead to developing novel cancer therapeutics based on molecules that are able to block this critical cancer driver.
“With new technologies and the scientific discoveries made by Prof. 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,” said Dr. Clive R. Wood, senior corporate vice president of discovery research at BI.
“Prof. 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,” added Dr. Lawrence J. Marnett, the Mary Geddes Stahlman professor of cancer research and dean of basic sciences for the Vanderbilt University School of Medicine.
Mutations in the genes that encode KRAS contribute to some of the most aggressive and deadly cancers, including up to 25 percent of lung, 35 to 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 company notes.
The new collaboration with Vanderbilt University further strengthens Boehringer Ingelheim’s oncology pipeline. Lung cancer—which of course is one of the cancers closely associated with KRAS—is an area in particular where BI, already one of the world's 20 leading pharmas, seeks to become an industry leader. “Boehringer Ingelheim has successfully launched two products for NSCLC, which have been widely adopted and established as valuable additions to current clinical practice,” the company notes. “Continuous insights and learnings from research and development are key parts of innovation and our way forward to advance clinical practice in lung cancer and other cancer types.”
And speaking of the lung, other recent news out of BI reveals that the first patient recently was enrolled in the PF-ILD (progressive fibrosing interstital lung disease) trial. This study investigates the efficacy and safety of nintedanib in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis (IPF).
More than 200 conditions can affect the tissue and space around the air sacs of the lungs, or the interstitium, and these conditions are called interstitial lung diseases (ILDs.) Based on clinical observations, there are groups of patients with ILD who—independent from the classification of the ILD—exhibit a progressive fibrosing behavior. The proposed terminology for describing this group of patients is PF-ILD. In these patients, the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activities, as well as early mortality despite treatment.
“This trial enrolls patients who have lung fibrosis of at least 10 percent by chest imaging that is getting worse by symptoms, physiology or imaging despite treatment,” said Kevin Flaherty, coordinating principal investigator of the PF-ILD trial. “This trial is an innovative way to study a potential treatment for patients with progressive fibrosing lung diseases and is an important step in exploring the way fibrosis of the lung is treated and whether nintedanib could be an effective therapy.”

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