J INTS BIO, a South Korean biopharmaceutical company, announced on February 12, 2026, that research findings on its fourth-generation EGFR tyrosine kinase inhibitor (TKI) JIN-A02 have been published in the journal Clinical Cancer Research. The publication (Impact Factor 10.2) describes a potential therapeutic approach against the common resistance mutation EGFR C797S, which occurs after treatment with the third-generation inhibitor Tagrisso (Osimertinib).
EGFR-mutated non-small cell lung cancer (NSCLC) initially responds well to targeted therapies, but acquired resistance – particularly C797S – limits efficacy. Currently, there are no approved treatments specifically for this mutation. JIN-A02 was developed as an orally available, selective fourth-generation inhibitor that specifically inhibits resistance mutations such as C797S and T790M while minimizing activity against wild-type EGFR.
Preclinical models of patients with EGFR E19del/T790M/C797S-mutated NSCLC, who were resistant to Tagrisso, showed a maximum tumor growth inhibition of 168.2% with JIN-A02 – significantly stronger than with Tagrisso – and led to tumor regression. Tumor tissue analyses revealed significant reductions in phosphorylated EGFR (p-EGFR) and the proliferation marker Ki-67, confirming effective inhibition of the EGFR signaling pathway at the molecular level. In intracranial models (brain metastases), JIN-A02 achieved rapid and sustained reductions in tumor burden, indicating good penetration of the blood-brain barrier.
Initial clinical observations come from an ongoing Phase 1/2 study (NCT05394831) in patients with EGFR-mutated NSCLC who had progressed after EGFR TKI and chemotherapy. By the data cutoff, 23 patients had been treated; partial remissions and stable diseases occurred. Particularly noteworthy is one patient in the 300 mg dose group with a partial remission: the lung lesion shrank by 39.7% at the beginning of the third cycle and reached a maximum of 44.9% by the seventh cycle. Brain metastases reduced by 25% by the fifth cycle, with a sustained response.
ctDNA (circulating tumor DNA) analyses showed complete elimination of the EGFR C797S mutation and exon 19 deletion, as well as a reduction of the T790M mutation by over 90% in this patient. This indicates effective molecular target inhibition, which is reflected clinically in a significant response.
J INTS BIO plans to accelerate the clinical development of JIN-A02: dose optimization, expansion of data in brain metastases, and validation of molecular response biomarkers are the focus. The long-term goal is to establish a new treatment option for patients with EGFR-mutated NSCLC who have exhausted current standard therapies.
