Kairos expands lung resistance strategy

Kairos Pharma continues its journey of tackling resistance mechanisms in lung cancer, moving to sign a deal to acquire two targeted inhibitors from the private biotech Celyn Therapeutics. The transaction aims to bring in CL-273, a pre-IND reversible pan-EGFR inhibitor, and CL-741, a phase 1-ready type IIb cMet inhibitor, into Kairos's pipeline. Celyn was founded in 2021, operating largely under the radar with backing from OrbiMed and Torrey Pines Investment; it says its inhibitors were discovered with the aid of the AI-focused companies Molsoft and Chemdiv. At present the potential tie-up is the subject of a term sheet, but Kairos told ApexOnco that a formal deal was expected to close within three months. However, it declined to disclose its financial terms. Overcoming resistanceThe move reflects Kairos's focus: tackling the resistance mechanisms that emerge in patients with EGFR-mutant non-small cell lung cancer. Combining EGFR and cMet-targeting assets has already become a widely adopted approach to overcome resistance, and Kairos appears to be positioning itself to pursue multi-drug combinations. The assets being acquired might ultimately fit alongside Kairos’ lead programme, carotuximab, an anti-CD105 monoclonal antibody that the company is attempting to resurrect after earlier clinical setbacks. Carotuximab was originally developed by Tracon Pharmaceuticals but fell apart in oncology after the phase 3 Tappas angiosarcoma trial was stopped for futility when Votrient, the drug in its control cohort, outperformed the carotuximab combination.Tracon subsequently licensed the asset in 2021 to Enviro, a subsidiary of Kairos, for $100,000. Kairos has since repositioned carotuximab, reporting early prostate cancer data, including an 86% response rate and 13-month median progression-free survival in eight castration-resistant prostate cancer patients given a carotuximab and Erleada combo. In lung cancer, the CD105-targeting MAb is being tested in combination with Tagrisso in an investigator-initiated trial, with data expected this year. CD105 is said to be expressed on lung tumours and is believed to contribute to resistance against EGFR inhibitors. So, if the results of the ongoing trial are positive, Kairos could incorporate carotuximab into combinations with the newly acquired EGFR and cMet inhibitors. Still, unless Kairos can raise money its ambitions might be constrained by its balance sheet. The company had just $5m as of November, projecting a runway into late 2026. That projection might be shorter still following the acquisition, although further clarity is not expected until Kairos reports its first-quarter results.   Kairos Pharma's oncology pipelineProjectMechanismStatusCarotuximabCD105-targeting MAbLicensed from Tracon in 2021; several trials ongoingKROS-201T-cell therapy Phase 1 trial in glioblastoma withdrawn owing to "lack of funding"CL-741cMet inhibitorBeing licensed from Celyn; phase 1 readyKROS-101GITR agonistIn preclinical development for solid tumoursKROS-301RelA inhibitorIn preclinical development for triple-negative breast cancerKROS-401IL-4/13 receptor complex inhibitor In preclinical development for solid tumoursENV-205mtDNA-targeting MAbIn preclinical development for chemotherapy resistanceCL-273Reversible pan-EGFR inhibitorBeing licensed from Celyn; pre-INDSource: OncologyPipeline.