TransThera Sciences (Nanjing), Inc. (TransThera) released new translational and preclinical findings at the 2026 American Association for Cancer Research (AACR) Annual Meeting, identifying lineage reprogramming as a key mechanism of resistance to endocrine therapy in hormone-receptor-positive (HR+) breast cancer and presenting supportive data for its multi-kinase inhibitor, tinengotinib (TT-00420).

The company’s poster, titled “Convergent FGFR-JAK signaling reprograms luminal identity and drives endocrine resistance in HR+ breast cancer,” detailed single-cell transcriptomic analyses showing a luminal-to-basal transition with estrogen- and progesterone-receptor down-regulation in resistant tumors. This plasticity originated in primary lesions and intensified in metastatic sites, particularly malignant pleural effusions.

Laboratory models demonstrated that both therapy-induced and microenvironment-driven resistance converge on activation of fibroblast growth factor receptor (FGFR) and Janus kinase (JAK) pathways, which suppress luminal markers ESR1 and PGR. Tinengotinib, a dual FGFR/JAK inhibitor, re-established luminal identity and restored sensitivity to endocrine agents in vitro and in vivo. These data underpin an ongoing Phase II study evaluating tinengotinib combined with endocrine therapy in advanced HR+ breast cancer.

Tinengotinib is TransThera’s internally discovered, New Drug Application (NDA)-stage, multi-kinase inhibitor targeting FGFRs, VEGFRs, Aurora A/B, and JAK. The molecule holds U.S. FDA Orphan Drug and Fast Track designations for cholangiocarcinoma, EMA Orphan Drug status for biliary tract cancer, and is listed for Priority Review and Breakthrough Therapy Designation by China’s NMPA.

The company reiterated that, in accordance with Hong Kong Listing Rule 18A.08(3), there is no assurance that tinengotinib or related candidates will successfully reach the market.