Slide 1: Investor webcast: PROPEL 2 data update and ACCEL program initiation
Investor webcast: PROPEL 2 data update and ACCEL program initiation June 4th 2024
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements. Statements made or presented may include statements that are not historical facts and are considered forward- looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), an
Slide 3: Thank you to the children, families, advocates, and physicians
To the children, families, advocates, and physicians who have been a part of this program: Thank you Developing new treatment options relies entirely on your guidance, dedication, and effort 3
Slide 4: Achondroplasia, hypochondroplasia, and related FGFR-driven genetic conditions represent a large unmet medical need
Achondroplasia, hypochondroplasia, and related FGFR-driven genetic conditions represent a large unmet medical need Children eligible for FGFR inhibitor treatment in the US and Europe 1.5-2.5K 7-10K 15-25K children 7-10K Achondroplasia Hypochondroplasia Other FGFR-driven Total children potentially ge
Slide 5: We are developing infigratinib as a treatment option based on three key principles
We are developing infigratinib as a treatment option based on three key principles Objectives Design principles Maximize efficacy Target the condition For all the manifestations of ACH—not just directly at the source height– which matter for families and physicians (FGFR3) Demonstrate safety Avoidin
Slide 6: Infigratinib directly targets the underlying cause: FGFR3 overactivity
Infigratinib addresses the first design principle by directly targeting the underlying cause of achondroplasia and hypochondroplasia: FGFR3 overactivity FGFR3 NPR2 ▪Infigratinib targets achondroplasia Gain-of-function and hypochondroplasia directly at variant the source: FGFR3 overactivity ▪Infigrat
Slide 7: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing 1Insert source / footnote
Slide 8: Cohort 5 of PROPEL2: Infigratinib continues to be well-tolerated, with no related AEs
Cohort 5 (0.25 mg/kg) of the PROPEL2 Trial: Infigratinib continues to be well- tolerated, with no related AEs • In Cohort 5 (the highest dose escalation level of 0.25 mg/kg): • No serious adverse events (SAEs), no AEs that required treatment discontinuation • Most TEAEs were grade 1 in severity and
Slide 9: Reported AEs across all cohorts are common in the pediatric population
Reported AEs across all cohorts are common in the pediatric population, especially in children with achondroplasia AEs occurring in ≥10% of study participants Total (%) N = 72 Nasopharyngitis 29 (40.3%) COVID-19 24 (33.3%) Headache 24 (33.3%) Vomiting 22 (30.6%) Pain in extremity 20 (27.8%) Ear infe
Slide 10: Cohort 5: The best-in-class change from baseline in AHV at M6 is sustained at M12 and M18
Cohort 5: The best-in-class change from baseline in AHV at M6 is sustained at M12 and M18 Mean change from baseline in annualized height velocity (AHV) +3.38 cm/yr Baseline demographics +2.51 cm/yr +2.50 cm/yr Female:Male ratio 7:5 Mean age at screening (yr) 7.24 3.51 cm/yr <5 8% 5 - <8 58% 8 - <11
Slide 11: The response to infigratinib was broad, with most kids having an increase in AHV at M18
The response to infigratinib was broad, with 10 out of 11 kids having an increase from baseline in AHV at M18 compared to baseline Absolute AHV individual values, cm/yr 11 10 9 8 91% of participants had an increase Absolute AHV (cm/yr) 7 in AHV from Baseline to M18 6 5 4 3 73% of participants had an
Slide 12: Infigratinib shows a persistent decrease in upper/lower body segment ratio
Infigratinib shows a persistent decrease in upper/lower body segment ratio at the cohort 5 dose Upper body to lower body segment ratio 2.05 2.02 2.00 P=0.001 1.95 1.95 (Mean change from Lower value 1.95 means baseline) improved proportionality 1.90 1.88 1.85 1.80 Baseline M6 M12 M18 (n=12) (n=12) (n
Slide 13: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing
Slide 14: Proportionality links changes in linear growth to potential benefits beyond height
Proportionality links changes in linear growth to potential benefits beyond height Avg stature ▪ Achondroplasia is a disproportionate skeletal dysplasia (upper body segment to lower body segment ratio of ~2.0 versus ~1.0 in average ACH statured children) ▪ Disproportionality is associated with delay
Slide 15: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing
Slide 16: PROPEL 3, the phase 3 trial of infigratinib for achondroplasia, is underway
PROPEL 3, the phase 3 trial of infigratinib for achondroplasia, is underway with last participant in expected by end of 2024 PROPEL 3: Ph3 randomized, double-blinded pivotal PROPEL OLE: PROPEL: Observational run-in trial (n=~110) Open-label extension 0.25 mg/kg/day Infigratinib Observational Childre
Slide 17: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing 1Insert source / footnote
Slide 18: Hypochondroplasia is a FGFR3-related skeletal dysplasia with a need for treatment options
Hypochondroplasia is a FGFR3-related skeletal dysplasia with a need for treatment options • Autosomal dominant condition • Similar incidence to achondroplasia Infigratinib directly targets FGFR3 signaling • Greater genetic heterogeneity in FGFR3 pathogenic variants (e.g. N540K in addition to others)
Slide 19: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing 1Insert source / footnote
Slide 20: The ACCEL clinical program consists of an observational run-in and an interventional study
Similar to the PROPEL program in ACH, the ACCEL clinical program consists of an observational run-in and an interventional study with long-term follow-up Observational Phase 2/3 Open-Label Phase followed by a Double-Blinded, Open-Label Run-in Randomized, Placebo-Controlled Study Extension (planned)
Slide 21: Agenda
Agenda Cohort 5 in ACH: Data Update Cohort 5 in ACH: Context (Dr. Savarirayan) PROPEL 3 for ACH Hypochondroplasia: Overview (Dr. Savarirayan) ACCEL program for Hypochondroplasia: Overview Closing 1Insert source / footnote
Slide 22: Conclusions
Conclusions Best-in-class efficacy and well-tolerated safety profile of infigratinib in achondroplasia are sustained through 18 months in the current data, now with a statistically-significant improvement in proportionality PROPEL 3 pivotal study of infigratinib in achondroplasia is enrolling quickl
Slide 23: Thank you
Bridoal . bridgebio Thank you