BridgeBio (BBIO) Study Result summary

Study design, rationale, and disease background

• Infigratinib is an oral FGFR1-3 inhibitor targeting FGFR3-driven skeletal dysplasias, including achondroplasia and hypochondroplasia, aiming for efficacy, safety, and convenience by avoiding daily injections.

• The program addresses MAPK and JAK/STAT pathways, impacting chondrocyte hypertrophy and proliferation for maximal height and proportionality improvements.

• Achondroplasia and hypochondroplasia affect 15,000–25,000 children in the US and Europe, causing disproportionate short stature and functional impairments.

• No approved treatments exist for hypochondroplasia in the US.

Phase II results: safety and efficacy

• Infigratinib at 0.25 mg/kg daily was well-tolerated over 18 months, with no serious or drug-related adverse events or discontinuations; most adverse events were mild and common in pediatrics.

• No hyperphosphatemia, ocular events, or accelerated bone age progression were observed.

• Annualized height velocity increased by 2.5–3.4 cm/year at 6, 12, and 18 months, statistically significant (p=0.0015 at month 18), with 91% of participants showing improvement and 73% having at least a 25% increase from baseline.

Proportionality and functional outcomes

• Statistically significant improvement in upper to lower body segment ratio at month 18 (from 2.02 to 1.88, p=0.001), more than double that seen in other treatments.

• Improvement in proportionality is functionally meaningful, addressing key quality-of-life issues for children.

• Proportionality effects are expected to be cumulative with longer treatment.