Novartis Snaps Up KRAS Inhibitor R&D
Difficult-To-Target Oncogenic Proteins Yield To Drug Discovery
Executive Summary
Novartis has taken an option on novel inhibitors of the KRAS cell signaling pathway while it funds the drug discovery research at the Cancer Research UK’s Beatson Institute.
Novartis AG is the latest big pharma company to collaborate on the development of novel inhibitors of KRAS, cellular signaling proteins which when mutated have been widely linked to the development of cancer but previously found difficult to design drugs against.
In a multi-year agreement, Novartis will advance novel KRAS inhibitors discovered by researchers at Cancer Research UK’s Beatson Institute in Glasgow, Scotland, and has an option exclusively to license promising compounds identified during the collaboration.
Mutations in the RAS gene family, including KRAS, HRAS and NRAS, are thought to be involved in a third of all human cancers, including in 95% of pancreatic cancers and 45% of colorectal cancers. Affected cells multiply uncontrollably and ignore cell death signals, and drug discoverers have until recently been unable to develop therapies which target the oncogenes and their proteins. The Beatson Institute researchers have designed small molecules which directly disrupt KRAS activity.
Other companies active in the area include most notably Amgen Inc., which has a KRAS inhibitor, AMG 510, in early clinical studies in lung and colorectal cancer patients.
Boehringer Ingelheim International GmbH has several investigational KRAS inhibitors, which it says it wants to evaluate in combination with Lupin Ltd.’s MEK inhibitor, LNP3794. (Also see "Boehringer Ingelheim Snaps Up Lupin's MEK Inhibitor For Difficult-To-Treat Cancers" - Scrip, 4 Sep, 2019.)
And other companies with KRAS-targeting candidates in early clinical studies, according to the drug development database Biomedtracker, include Mirati Therapeutics Inc. (MRTX849), Jacobio Pharmaceuticals Co. Ltd. (JAB-3312), WellSpring Pharmaceutical Corp. (JNJ74699157), and Moderna Inc. (mRNA-5671). Cambridge, MA-based Elicio Therapeutics is developing a vaccine candidate, ELI-002, which targets KRAS mutations. (Also see "Finance Watch: 3Q Biopharma Venture Capital Financings Fell From 2Q Spike" - Scrip, 10 Oct, 2019.)
Upfront Payment
The Switzerland-based multinational will fund the research and will make an upfront payment to the CRT Pioneer Fund, which previously funded some of the research; the research included a collaboration with the US National Cancer Institute to develop tests to analyze RAS inhibitors.
The CRT Pioneer Fund could also receive milestone payments during development of the inhibitors, and single-digit royalties on successfully marketed products.
The CRT Pioneer Fund, which is managed by Sixth Element Capital, was set up in 2012 by the charity, Cancer Research UK’s, commercial arm, Cancer Research Technology, along with the European Investment Fund (EIF) and other funding bodies to bridge the funding gap in the UK between cancer drug discovery and early clinical development.
Over the past several years, the Fund has supported several promising anticancer projects to the point at which pharmaceutical companies have licensed them or, alternatively, participated in setting up a start-up biotech with other investors to further advance the project.
In 2019 such moves have included Stemline Therapeutics Inc. licensing worldwide rights to the selective RET inhibitor, SL-1001, discovered at the CRC UK’s Manchester Institute, announced in March 2019, and Sierra Oncology Inc.’s (formerly ProNAi Therapeutics) licensing of the checkpoint kinase 1 inhibitor, PNT737/SRA737, in September 2016. (Also see "Finance Watch: Gene Therapy, Targeted Oncology Driving IPOs Despite Biopharma Stock Shakiness" - Scrip, 2 Jul, 2019.)