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Boehringer Ingelheim Advances First Pan-KRAS Inhibitor BI 1701963 into Clinical Testing

2019/10/31 8:49:51  文章來源:文傳商訊  作者:文傳商訊
文章簡介: Resultswerepresentedfromthecompany’span-KRASprogramincludingBI1701963,whichisbeinginvestigatedaloneandincombinationwithMEKinhibitioninan

Results were presented from the company’s pan-KRAS program including BI 1701963, which is being investigated alone and in combination with MEK inhibition in an ongoing Phase I clinical study in cancer patients
Around 15% off all cancers can potentially be blocked by this compound, targeting all major oncogenic KRAS mutations
Dual KRAS pathway blockade combining pan-KRAS and MEK inhibition has potential to further enhance efficacy

INGELHEIM, Germany--(BUSINESS WIRE)--Boehringer Ingelheim today presented promising preclinical data from its pan-KRAS program including the novel, oral inhibitor BI 1701963 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, USA1. Based on these results the compound has been advanced to Phase I clinical testing alone and in combination with trametinib in patients with different types of advanced solid tumors with KRAS mutations.

KRAS mutations occur in one in seven of all human metastatic cancers making it the most frequently mutated cancer-causing oncogene, with mutation rates of more than 90 percent in pancreatic cancers, more than 40 percent in colorectal cancers and more than 30 percent in lung adenocarcinomas. It has evaded attempts to develop inhibitors for almost 40 years. Only recently have promising compounds targeting the specific KRAS mutation G12C entered the clinic. There are however many KRAS gene mutations beyond G12C that drive tumor growth and have previously been ‘undrugged,’ such as KRAS-G12D and KRAS-G12V, which make up half of all KRAS driven cancers.

“Our pan-KRAS inhibitor has been designed to target a broad range of oncogenic KRAS variants, including all major G12 and G13 oncoproteins. Effective targeting of the most prevalent KRAS mutant alleles that have so far proved elusive could enable us to develop much needed new therapy regimens for patients with gastrointestinal and lung cancers who have limited treatment options available,” said Norbert Kraut, Ph.D., Head of Global Cancer Research at Boehringer Ingelheim.

“We have a comprehensive KRAS R&D program beyond BI 1701963 and aim to develop therapies for all patients with mutant KRAS driven cancer,” said Clive R. Wood, Ph.D., Corporate Senior Vice President and global head of Discovery Research at Boehringer Ingelheim. “This program is part of our strategy to defeat cancer with optimal combinations of cancer cell-directed and immune cell-directed therapies,” added Wood.

BI 1701963 inhibits KRAS by binding to SOS1, which plays an essential role in activating KRAS through the exchange of RAS-bound GDP for GTP. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type. Preclinical data have shown that the pan-KRAS inhibitor blocks tumor growth for many tested G12 and G13 KRAS gene mutations, the most frequently affected residues of the protein. Further, the compound is selective for cancer cell lines with mutations in the KRAS gene.

In non-clinical studies, the combination of BI 1701963 with a MEK inhibitor demonstrated a strong impact on KRAS signaling and resulted in increased anti-tumor activity based on dual pathway blockade and complementary mechanism of action in keeping KRAS-driven cancers in check. BI 1701963 will be further developed in combination with LNP3794 a MEK inhibitor compound in-licensed from Lupin.

Intended audiences
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

For references and notes to editors, please visit:

http://www.boehringer-ingelheim.com/press-release/first-pan-kras-inhibitor-advances-clinical-testing

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