Company: TYRA
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0000950170-25-046124
Chunk: 21

Company: Tyra Biosciences, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 21
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 age of 18 in the United States and approximately 23,000 addressable, affected individuals under the age of 18 worldwide. Approximately 80% of ACH cases arise through a spontaneous mutation of FGFR3, whereas 20% of cases are familial. 

FGFR3 is implicated in multiple additional skeletal conditions, including HCH, which is most commonly caused by the N540K mutation (~70-80%) in the FGFR3 gene, as well as SHOX Deficiency, where SHOX is a transcription factor for FGFR3.

Current treatment landscape and unmet need

ACH had been managed primarily through surgical and physical therapy intervention until the accelerated approval of Voxzogo (vosoritide) in 2021. Voxzogo is a daily injected C-natriuretic peptide (CNP) analog, which acts downstream of FGFR3.  In a pivotal study, children treated with 15mg/kg of Voxzogo achieved 5.66cm/year in average height velocity (AHV), a 1.40cm improvement over 4.26cm baseline. Children in the Phase 2 trial treated with 15mg/kg achieved 5.91cm/year AHV, 1.87cm improvement over 4.04cm baseline. Children treated with 30mg/kg saw a lower change from baseline, suggesting the CNP pathway activity is potentially dose-limited in 

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FGFR3-driven conditions. TransCon CNP, a prodrug of CNP administered to children with ACH by injection on a weekly basis, showed similar efficacy in Phase 3 and a New Drug Application (NDA) filing is expected in the first quarter of 2025. BridgeBio is developing infigratinib, a daily oral, low-dose FGFR1/2/3 inhibitor, which achieved 6.0 cm/yr AHV and a 2.51 cm/yr improvement over 3.51cm/yr baseline for the 0.25 mg/kg cohort in Phase 2 studies. BridgeBio previously published that doses above 0.33mg/kg are limited by hyperphosphatemia and they have communicated they do not plan to exceed the 0.25 mg/kg dose in pediatric skeletal conditions. BioMarin disclosed that prolonged treatment with Voxzogo could result in a final adult height improvement of 17cm or more in ACH, potentially 29cm less than average height for adult males without ACH, pointing to remaining un