The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.
Hookipa Pharma Inc.’s nearly $1 billion collaboration with Roche Holding AG dissolved along with 30% of the company’s staff. The New York-based company said Roche ended the October 2022 deal involving the HB-700 program in treating KRAS mutated cancers but did not say why the agreement fell apart. Leerink Partners analyst Andrew Berens wrote Jan. 29 that the firm spoke to management, which indicated the program was progressing according to plan and that Roche's decision was based more on its own internal pipeline strategy, lessening its focus on oncology after high profile failures vs. the program having issues in development.
As gene therapies gain unprecedented traction into 2024, preclinical-stage South Korean biotech Genecraft Inc. said it raised ₩10 billion (US$7.48 million) in a series A financing to further R&D for its therapy against lung cancer.
As gene therapies gain unprecedented traction into 2024, preclinical-stage South Korean biotech Genecraft Inc. said it raised ₩10 billion (US$7.48 million) in a series A financing to further R&D for its therapy against lung cancer.
In an article published on Dec. 18, 2023, in Nature, researchers from the Centre for Genomic Regulation in Barcelona (Spain) and Wellcome Sanger Institute in Hinxton (U.K.) reported achieving a milestone regarding KRAS targeting in cancer. The team quantified the impact of >26,000 KRAS variants and how these mutations affected protein folding and its interaction with the six main effectors – RAF1, PIK3CG, RALGDS, SOS1, K27 and K55.
Replay Holdings LLC has entered into an exclusive, worldwide license agreement with the National Institutes of Health (NIH) for intellectual property related to a library of T-cell receptors (TCRs) directed against multiple cancer neoantigens.
Immuneering Corp. has obtained FDA clearance of its IND application for IMM-6-415, an oral, twice-daily small molecule in development for the treatment of advanced RAF or RAS mutant solid tumors.
Medigene AG has announced a prioritization of its pipeline as it advances its differentiated T-cell receptor engineered T cell (TCR-T) therapies for solid tumors.
The mRNA technology used in vaccines against viral infections could also be developed for cancer therapies. A group of scientists has designed a circular RNA (circRNA) encapsulated in lipid nanoparticles (LNPs) that acts in the mitochondria of tumor cells through the protein gasdermin-D (GSDMD) and reduces adenocarcinoma. The work was published on Oct. 16, 2023, in Nature Cancer.
The dark cloud of what the U.S. FDA called potential “systemic bias” rained on Amgen Inc.’s bid for full approval of Lumakras (sotorasib), a KRAS-G12C inhibitor that was granted accelerated approval in May 2021 for locally advanced or metastatic non-small-cell lung cancer after at least one systemic therapy.