Company: TYRA
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0000950170-25-046124
Chunk: 24

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 24
---
2 inhibitors. 

Current treatment landscape and unmet need

Currently, surgical recession is the only curative option available to ICC patients. However, only up to one-third of patients are eligible for surgery at diagnosis and up to 70% of patients experience a recurrence largely within the first two years following surgery. Patients with unresectable tumors are typically treated with frontline immunotherapy in combination with cisplatin-based chemotherapy which have shown 12.7-12.8 month OS. Upon disease progression, patients with somatic alternations in FGFR2 are eligible to be treated with approved pan-FGFR inhibitors including Pemazyre (pemigatinib) and Lytgobi (futibatinib) which have generated ORR of 36-42% and mean duration of response of 9.1-9.7 months. The investigational FGFR2-specific inhibitor lirafugratinib has reported ~80% response rates in a small dataset of patients who have not received an FGFR inhibitor previously, though showed limited activity in patients whose tumors have developed these acquired resistance mutations. 

The currently approved pan-FGFR inhibitors as well as several investigational agents are not active against the entire spectrum of clinically important acquired resistance mutations that develop in response to FGFR inhibition. Polyclonal resistance (multiple resistance mutations that occur in the same patient) is a common feature in this patient population, with one dataset showing Over 50% of patients who recur on FGFR therapy have gatekeeper and molecular brake mutations. We believe the ability to demonstrate clinically beneficial activity in the FGFR inhibitor-resistant setting will provide proof of concept and validate the design principles behind TYRA-200.  

Our solution, TYRA-200 in ICC

We believe the critical unmet need for patients with FGFR2 fusion or FGFR2-altered ICC is balancing the potency for the wild type and the numerous on-target resistance mutations that confer resistance to the currently approved FGFR inhibitors. We believe maintaining potency against all of these clinically important mutations as well as wild-type FGFR2 could potentially improve efficacy and duration of response. Additionally, we designed TYRA-200 with greater selectivity for FGFR1-3 versus FGFR4 to potentially improve upon tolerability of pan-FGFR inhibitors that are potent for FGFR4.

In preclinical models, TYRA-200 has demonstrated potency in FGFR2-driven Ba/F3 cells similar to erdafitinib, pemigatinib, futibatinib or infig