Company: TYRA
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0000950170-25-046124
Chunk: 26

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 26
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 need for dual inhibition of FGFR3 or FGFR4.  

TYRA-430 is an investigational FGFR4/3 biased inhibitor for FGF19+/FGFR4-driven cancers that is designed to be agnostic to acquired resistance mechanisms originating from the V550 gatekeeper and the C552 mutations. In August 2024, we announced that the FDA cleared our IND to proceed with the global Phase 1 SURF431 clinical trial of TYRA-430 in advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations.

Disease background

Liver cancer is the third leading cause of cancer related mortality worldwide (Bray et al). Abnormal activation of FGF19 has been implicated as an oncogenic driver in approximately 30% of HCC. Data suggests that in this subtype, excessive FGF19 may over-activate the receptor tyrosine kinases FGFR4 and FGFR3 thus drive cancer cell proliferation, survival, and resistance to apoptosis. 

We estimate that in 2022, approximately 6,000 frontline FGFR19+ HCC patients were addressable for treatment with an FGFR4/3 inhibitor and over 3,000 FGFR19+ HCC patients were addressable in the post-frontline setting in the United States. 

Current treatment landscape and unmet need

Between 2014 and 2020, the five-year relative survival for liver cancer patients in the US was 21.7%. Most HCC patients are diagnosed with unresectable disease and are not eligible for potentially curable treatments, including surgery, transplant or ablation. For patients with advanced, unresectable HCC, immunotherapies have become standard of care in the frontline since the 2020 approval of Tecentriq/Avastin (atezolizumab/bevacizumab), based on a 28% ORR and 6.8 month PFS, with follow up analysis in the intent to treat population showing a 19.2 month OS. Promising phase 2 datasets have been released for agents in development as part of a triplet combination regimen atezolizumab/bevacizumab. 

In the post-frontline setting, non-targeted approaches including multi-kinase inhibitors approved for the second and third lines have shown modest therapeutic benefit. Bayer’s Stivarga (regorafenib), Exilixis’ Cabometyx 

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(cabozantinib) and Eli Lilly’s