Slide 1: PROPEL2 topline results
PROPEL2 topline results March 6th, 2023 Exhibit 99.2
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements. Statements in this presentation 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),
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
Slide 4: Infigratinib in cohort 5 has the strongest efficacy profile yet demonstrated in achondroplasia
Not available Infigratinib in cohort 5 has the strongest efficacy profile yet demonstrated in achondroplasia Source: Data on file; Savarirayan et al 2019 NEJM; Savarirayan et al 2020 Lancet; Vosoritide M12 data from summary basis of approval +3.03 + + +1.35 0.016-0.064 mg/kg/day 0.128 mg/kg/day 0.25
Slide 5: Big wheels keep on turning
Big wheels keep on turning ATTR-CM Idea $58M Phase 3 Achondroplasia Idea $75M Phase 3 LGMD2i Idea $38M ADH1 Idea $31M Phase 3 CAH Idea $68M Note: Costs represent total BBIO investment from Inception to POC/P3 Initiation. CAH POC expected in 2H 2023
Slide 6: Developing infigratinib for children with achondroplasia based on three key principles
We are developing infigratinib as a treatment option for children with achondroplasia based on three key principles Objectives Design principles Maximize efficacy For all the manifestations of ACH—not just height– which matter for families and physicians Target the condition directly at the source (
Slide 7: Achondroplasia and related FGFR-driven skeletal dysplasias represent a large unmet medical need
Achondroplasia and related FGFR-driven skeletal dysplasias represent a large unmet medical need Source: CDC birth estimates; EU Eurostats birth estimates; Foreman et al 2020 Am J Med Genet; Bober et al 2020 Gene Reviews; Wenger et al 2020 Gene Reviews; Al-Namman et al 2019 J Oral Biol Craniofac Res
Slide 8: Achondroplasia comes with risk of serious medical complications
Achondroplasia comes with risk of serious medical complications Source: Savarirayan et al. 2022 Nat Rev Endocrinol These medical complications represent a severe unmet need for people living with achondroplasia Life-threatening Sudden death (SIDS-like relative risk 50-fold in first 5 years) Foramen
Slide 9: Stenosis of the foramen magnum is of particular concern
Stenosis of the foramen magnum is of particular concern Source: White….Savarirayan 2015 Am J Med Genet The foramen magnum (FM) is the opening at the base of the skull which connects the brain with the spinal cord Stenosis of the FM can lead to compression in cervicomedullary structures, resulting in
Slide 10: Increased risk of sleep apnea is another medical complication of achondroplasia
Increased risk of sleep apnea is another medical complication of achondroplasia with unmet need Source: White….Savarirayan 2015 Am J Med Genet There is high prevalence of sleep apnea in children and adults living with achondroplasia It is best to use sleep labs/sleep studies Can present as obstructi
Slide 11: Increased risk of debilitating spinal complications in achondroplasia
Children and adults living with achondroplasia have increased risk of debilitating spinal complications which require expert monitoring & treatment Source: Fredwall et al 2021 Orphanet J Rare Dis Thoraco-lumbar kyphosis Spinal stenosis (all levels) Chronic back pain Monitoring Assessment Treatment/m
Slide 12: PROPEL clinical program trial design
The PROPEL clinical program trial design consists of an observational run-in, a dose-finding phase, and long-term follow-up Ph2 Dose-finding (n=70+) Observational run-in Open-label extension Children are followed for a minimum of six months to establish baseline annualized growth velocity (AGV) 0.12
Slide 13: PROPEL2 cohort participant demographics
PROPEL2 cohort 5 participant demographics Source: Data on file Note: race information was not collected in France Cohort 5 0.25 mg/kg/day N 12 Sex Female 7 (58.3%) Male 5 (41.7%) Age in years (Mean) Mean ± Std Dev 7.24 ± 1.9 Median (Range) 7.17 (4.9-11.3) 3 - <5 1 (8.3%) 5 - <8 years 7 (58.3%) ≥8 ye
Slide 14: Infigratinib in cohort 5 has the strongest efficacy profile yet demonstrated
Infigratinib in cohort 5 has the strongest efficacy profile yet demonstrated in achondroplasia Source: Data on file; Savarirayan et al 2019 NEJM; Savarirayan et al 2020 Lancet; Vosoritide summary basis of approval + + +1.35 +3.03 0.016-0.064 mg/kg/day 0.128 mg/kg/day 0.250 mg/kg/day Note: All cohort
Slide 15: Dose-responsive increases in annualized height velocity compared to baseline
Infigratinib demonstrates significant, dose-responsive increases in annualized height velocity compared to baseline Mean change from baseline in annualized height velocity at M6, cm/yr Source: Data on file + * + *** +3.03 0.016-0.064 mg/kg/day 0.128 mg/kg/day 0.250 mg/kg/day Note: Data shown is rest
Slide 16: 80% of children in cohort 5 responded to infigratinib
80% of children in cohort 5 responded to infigratinib, and responders had a mean AHV change from baseline of 3.81 cm/yr Responder rate1 at M6 % with an AHV increase of >25% from baseline 1Responder defined as having a change from baseline AHV of 25% or greater Source: Data on file. The response to t
Slide 17: Individual-level data shows breadth and strength of the response
Individual-level data for cohort 5 participants shows the breadth and strength of the response; baseline AHV for the cohort is just under 4 cm/yr Mean (1-10 only) 6.77 3 Individual absolute AHV, participants with at least six months follow up (N=10), cm/yr Individual absolute AHV, participants with
Slide 18: Median AHV exceeds 7 cm/yr, above 99th percentile growth rate
The median AHV exceeds 7 cm/yr, which is above the 99th percentile growth rate for children of comparable age with achondroplasia Source: Savarirayan et al, Genet Med 2022; cohort 5 data on file 60% of children in cohort 5 had an AHV equal to or greater than 7 cm/yr. The median AHV overall was 7.6 c
Slide 19: Collagen X biomarker supports the clinical results
Collagen X, a biomarker for growth in the long bone growth plates, supports the clinical results in suggesting a robust, dose-responsive effect Collagen X marker level % increase from baseline visit % The increase in CXM also supports a dose-responsive relationship with cohort 5 0.016-0.064 mg/kg/da
Slide 20: Infigratinib was well-tolerated with no study-drug related TEAEs in cohort 5
Infigratinib was well-tolerated, with no study-drug related treatment-emergent adverse effects seen in cohort 5 Source: Data on file With follow up out to 961 days, infigratinib continues to be well-tolerated, with no SAEs and no discontinuation due to AEs across all cohorts Cohort 5 had a well-tole
Slide 21: Next steps
Next steps Regulatory interactions planned for mid-2023 BridgeBio expects to complete an FDA End of Phase 2 meeting and an EMA scientific advice meeting in mid-2023 Committed to delivering the full potential of infigratinib Building on the promising results in achondroplasia, BridgeBio has initiated
Slide 22: What do these results mean for the achondroplasia community and physicians?
What do these results mean for the achondroplasia community and physicians? Significant increase in growth and a broad response rate The magnitude of effect we saw today could result in meaningful improvement in functional abilities Optimistic about impacts on severe medical complications of achondr
Slide 23: Thank you
bridael , bridgebio Thank you