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

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 25
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ratinib, while reducing or eliminating the decrease in potency observed with N550K/H/D and E566A molecular brake, V565F/L/I gatekeeper, and K660E/N A-loop activator resistance mutations. In a preclinical allograft model of an FGFR2-driven Ba/F3 cell line with the V565F gatekeeper mutation, we observed 96% and 98% tumor growth inhibition by TYRA-200 versus 62% tumor growth inhibition in an allograft treated with futibatinib.

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Development plans for TYRA-200 in ICC 

In December 2023, we commenced our Phase 1 clinical trial of TYRA-200, SURF201, a multi-center, open label study designed to evaluate the safety, tolerability, and PK of TYRA-200 and determine the optimal dose for further development, the MTD and RP2D, as well as evaluate preliminary antitumor activity.  SURF201 is currently enrolling participants with ICC with acquired kinase domain mutations. Positive data in this setting, where other FGFR inhibitors have not succeeded, would potentially provide confidence in our belief that addressing acquired resistance may prolong the duration of responses, and ultimately PFS, in the FGFR-naive setting. 

Beyond FGFR-resistant and FGFR-naive ICC, there is potential for TYRA-200 to extend into metastatic endometrial carcinoma as well as advanced colorectal, breast, ovarian, gastric, and lung cancer. 

Our FGF19+ Program

TYRA-430 for Hepatocellular Carcinoma

FGF19 is a post-prandial enterohepatic hormone that signals through FGFR4 and its associated co-receptor KLB to exert its normal cellular functions. In a subset of certain cancers, such as HCC, gastric adenocarcinoma, and squamous esophageal carcinoma, FGF19 is aberrantly expressed due to focal chromosomal amplifications or epigenetic mechanisms, promoting tumor cells to become dependent on the FGFR4/KLB/FGF19 oncogenic axis.	

An experiment run by Tao et al (2022) demonstrated a greater dependence of HCC JHH-7 cells on KLB, the common co-receptor for FGFR3 and FGFR4, than on either receptor alone. This is also consistent with the results of the double knock down of FGFR3 and 4 being more deleterious than knock down of either receptor alone, suggesting the