Company: TYRA
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0000950170-25-046124
Chunk: 27

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 27
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 ramucirumab have been approved in this setting based on ORR ranging from 4-7%, PFS ranging from 2.5-5.2 months and OS ranging from 8.5-10.6 months. Use of sorafenib and lenvatinib, initially approved for treatment-naïve patients, is anticipated to rise in the second line, but randomized data is not available for these agents in this setting. Several FGFR4-selective inhibitors have been developed and achieved clinical proof of concept with ORR of 17%-21%, in FGF19+ patients. However, FGFR4-specific approaches have shown limited durability, potentially due to an FGFR3-mediated bypass mechanism as well as acquired drug resistance in some cases. We believe TYRA-430 has the potential to address the shortcomings of prior FGFR4-specific approaches as well as the overall unmet need in FGF19+ HCC, where no biomarker-driven, targeted therapy has been approved.

Our Solution, TYRA-430 in HCC

TYRA-430 was selected for development based in part on its bias for FGFR4 and FGFR3 over the FGFR1 and FGFR2 isoforms specifically to address the aberrant FGF19 signaling pathway, while also potentially limiting side effects due to inhibition of FGFR1 and FGFR2. In addition to the activity toward FGFR3, TYRA-430 is further distinguished from the highly specific FGFR4 inhibitors by its relative resistance to clinically observed mutations at the gatekeeper (550) and cysteine (552) positions.

In preclinical models, TYRA-430 demonstrated bias for FGFR4 and FGFR3 over FGFR1 and FGFR2 isoforms in Ba/F3 cells. Additionally, in a JHH7 FGF19+ HCC xenograft, TYRA-430 (28 mg/kg BID), demonstrated 99% tumor growth inhibition while roblitinib (FGFR4-specific inhibitor, 100 mg/kg BID) and lenvatinib (30 mg/kg QD) demonstrated 86% and 53% tumor growth inhibition, respectively.

Development plans for TYRA-430 in HCC 

In August 2024, we announced that the FDA cleared our IND to proceed with a Phase 1 clinical trial of TYRA-430. SURF431 will be a Phase 1, multicenter, open-label, first-in-human study of TYRA-430 in advanced HCC and other