Tyra Biosciences Advances FGFR Inhibitor Pipeline with Multiple Clinical Trials
核心洞察
Tyra Biosciences is developing TYRA-300, a selective FGFR3 (搜索) inhibitor, for bladder cancer (搜索) and skeletal dysplasia, with Phase 2 trials for achondroplasia (搜索) expected to begin in Q1 2025.
SURF201, a Phase 1 clinical study, is evaluating TYRA-200, an oral FGFR1/2/3 inhibitor, in patients with advanced cholangiocarcinoma (搜索) and other solid tumors harboring FGFR2 (搜索) alterations.
The FDA has cleared Tyra Biosciences' IND for TYRA-430, a FGFR4 (搜索)/3-biased inhibitor, allowing a Phase 1 study in advanced hepatocellular carcinoma (搜索) and other solid tumors with FGF/FGFR pathway aberrations.
Tyra Biosciences is making significant strides in its pipeline of Fibroblast Growth Factor Receptor (FGFR) inhibitors, targeting a range of cancers and skeletal dysplasias. The company's portfolio includes TYRA-300, TYRA-200, and TYRA-430, each designed to address specific FGFR mutations and resistance mechanisms.
TYRA-300: Targeting FGFR3 in Bladder Cancer and Achondroplasia
TYRA-300 is an investigational inhibitor of FGFR3 (搜索), engineered for potency and selectivity. It aims to overcome limitations of existing FGFR inhibitors, particularly treatment-emergent resistance mutations like the V555 gatekeeper mutation, and to selectively target FGFR3 over FGFR1 and other FGFR isoforms, reducing off-target side effects.
In bladder cancer (搜索), activating FGFR3 (搜索) mutations are estimated to occur in up to 75% of non-muscle invasive bladder cancer (NMIBC) and up to 20% of muscle invasive bladder cancer (MIBC). TYRA-300 is being developed for both bladder and solid tumors harboring these mutations.
Beyond oncology, TYRA-300 is also being investigated for skeletal dysplasia, including achondroplasia (搜索), a genetic condition caused by mutations in the FGFR3 (搜索) gene. Dosing for the Phase 2 trial in achondroplasia is expected to commence in Q1 2025. Greater than 99% of achondroplasia cases arise through spontaneous mutation of FGFR3.
TYRA-200: Pan-FGFR Inhibitor for Cholangiocarcinoma and Solid Tumors
TYRA-200 is an investigational, oral FGFR1/2/3 inhibitor demonstrating in vitro potency against activating FGFR2 (搜索) gene alterations and resistance mutations. It is currently being evaluated in the SURF201 Phase 1 clinical study (NCT06160752), a multi-center, open-label trial designed to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TYRA-200, as well as to assess its preliminary antitumor activity. The SURF201 study is enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma (搜索) (ICC) and other advanced solid tumors with activating alterations in FGFR2. Approximately 15-20% of patients with ICC have genetic alterations in FGFR2, primarily gene fusions and activating mutations.
TYRA-430: FGFR4/3-Biased Inhibitor for FGF19+/FGFR4-Driven Cancers
TYRA-430 is an investigational, FGFR4 (搜索)/3-biased inhibitor targeting FGF19+/FGFR4-driven cancers. In August 2024, the FDA cleared Tyra Biosciences' Investigational New Drug (IND) application for TYRA-430, allowing the company to proceed with a Phase 1 clinical study. This first-in-human study will be a multicenter, open-label trial of TYRA-430 in advanced hepatocellular carcinoma (搜索) (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431).