Company: TYRA
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0000950170-25-046124
Chunk: 14

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 14
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 leveraged our SNÅP approach to develop novel small molecules designed to overcome the toxicity and resistance liabilities of prior generation pan-FGFR inhibitors. Four FGFR targeted therapies have been approved by the FDA for oncology: erdafitinib for locally advanced or mUC, or bladder cancer, and pemigatinib, infigratinib, and futibatinib for ICC with FGFR2-fusions or gene rearrangements (infigratinib was later withdrawn from the market effective March 31, 2023). These inhibitors have demonstrated clinical responses, however response rates and duration of response are limited and come with toxicities driven by the inhibition of FGFR receptors 1, 2 and 4. FGFR1 is expressed in kidney cells where it regulates phosphate and calcium reabsorption, and consequently, inhibition of FGFR1 results in hyperphosphatemia. Inhibition of FGFR2 can result in toxicities that significantly impact quality of life, such as skin and nail toxicities (e.g., onycholysis and hand-foot syndrome), stomatitis, and ocular toxicities such as keratitis and blurred vision. Inhibition of FGFR4 disrupts bile acid metabolism and can result in diarrhea and elevated liver enzymes (AST and ALT).  Hyperphosphatemia was a dose-limiting toxicity (DLT) of erdafitinib and was reported in over 70% of patients in the Phase 3 clinical trial conducted in mUC. Overall, Phase 3 adverse events resulted in 72% dose interruptions, 69% dose reductions, and 14% treatment discontinuations. By way of example, we believe the safety and tolerability profile of erdafitinib is a key limitation to its efficacy, as demonstrated by the dosing instructions to start at a daily 8 mg dose, and only increase to 9 mg if hyperphosphatemia is not observed. A similarly high rate of FGFR-related toxicities has been reported in clinical trials of other non-isoform selective FGFR inhibitors including pemigatinib, infigratinib and futibatinib in pivotal studies for ICC. In addition to being limited by toxicity, patients can develop acquired drug resistance, ultimately resulting in disease progression and discontinuation of therapy.

Our FGFR3 Program for Bladder Cancer 

TYRA-300 for mUC and NMIBC 

FGFR3 is a protein receptor expressed on the cell surface that stimulates cellular proliferation upon binding of fibroblast growth