Bridgebio Pharma, Inc. · NASDAQ:BBIO
Bridgebio Pharma — Investor Day (July 2025)
29 slides from Bridgebio Pharma's investor day presentation, Jul 11, 2025
Slide 1: Limb-girdle Muscular Dystrophy Type 2I/R9 Investor Webinar
Limb-girdle Muscular Dystrophy Type 2I/R9 Investor Webinar July 11, 2025
Slide 2: Forward Looking Statements and Disclaimer
Forward Looking Statements and Disclaimer Statements in this Presentation that are not statements of historical fact are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such fo
Slide 3: Agenda
Agenda Matthew Wicklund, MD, FAAN LGMD2I/R9 Professor of Neurology 01 disease background Vice Chair of Research, Dept. of Neurology University of Texas at San Antonio Douglas Sproule, MD, MSc BBP-418 02 program overview Chief Medical Officer ML Bio Solutions, a BridgeBio Company Looking ahead: Chris
Slide 4: LGMD2I/R9 is one of ~30 subtypes of limb-girdle muscular dystrophy
LGMD2I/R9 (FKRP-related) is one of ~30 subtypes of limb-girdle muscular dystrophy, each driven by mutations in distinct genes impacting muscle function Old nomenclature Affected gene New nomenclature LGMD 1D DNAJB6 LGMD D1 DNAJB6-related LGMD 1F TNP03 LGMD D2 TNP03-related LGMD 1G HNRNPDL LGMD D3 HN
Slide 5: Updated LGMD nomenclature defined in 2018; many still use old nomenclature
An updated set of nomenclature for LGMDs was defined in 2018; however, many patients and HCPs still utilize the old nomenclature Limb-girdle muscular dystrophy type 2I/R9: Nomenclature Old nomenclature New nomenclature Affected gene/protein Fukutin-related protein LGMD2I LGMDR9 (FKRP-related) (FKRP)
Slide 6: LGMD2I/R9 is caused by FKRP mutations reducing glycosylation of alpha-dystroglycan
LGMD2I/R9 is caused by mutations in FKRP that result in reduced glycosylation of alpha-dystroglycan (αDG), leading to progressive muscle damage Molecular pathogenesis of LGMD2I/R9 • In healthy muscle cells, alpha-dystroglycan (αDG) plays an important role in linking the muscle cell membrane (sarcole
Slide 7: Without glycosylated αDG, LGMD2I/R9 muscle tissue is susceptible to damage
Without glycosylated αDG playing its role as a “shock absorber,” LGMD2I/R9 muscle tissue is susceptible to damage and eventually forms fibrotic tissue Healthy muscle tissue LGMD2I/R9 muscle tissue Source: https://bridgebio.com/lgmd2i-r9/ 7
Slide 8: LGMD2I/R9 genotype/phenotype association; ~2/3 homozygous for L276I
LGMD2I/R9 has an established genotype/phenotype association; ~2/3 of patients are homozygous for the most common founder effect mutation (L276I) Birth Early Childhood Late Childhood Adolescence to adulthood L276I Loss of ambulation: 25% by age 40 ▪ Age of symptom onset homozygous 18 ± 3 years old Re
Slide 9: Diagnosis via genetic testing; standard of care limited to supportive care
Diagnosis is confirmed through sponsored genetic testing, and SoC is limited to supportive care, making disease-modifying therapies the key unmet need Diagnosis Standard of care • There are no approved therapies for any form of LGMD today, including LGMD2I/R9 • SoC is limited to supportive care, inc
Slide 10: Summary: LGMD2I/R9 disease background
Summary: LGMD2I/R9 disease background • LGMD2I/R9 (FKRP-related) is one of many genetically distinct subtypes of limb-girdle muscular dystrophy and causes progressive muscle weakness, including loss of ambulation, cardiomyopathy, and respiratory dysfunction • The foundational defect of LGMD2I/R9 is
Slide 11: The BBP-418 program builds on decades of scientific progress
The BBP-418 program builds on multiple decades of scientific progress 2023 2016 2019 pre-2000 2005 LGMD determined to L276I identified as Discovery Initiation of Initiation of be separate entity a founder mutation of FKRP’s natural randomized, from Duchenne and in LGMD2I/R9 primary history placebo-c
Slide 12: BBP-418 targets the disease at its source by restoring glycosylation of αDG
BBP-418 is being investigated to target the disease at its source by driving residual activity of the affected FKRP enzyme and restoring glycosylation of αDG Disease mechanism Proposed BBP-418 therapeutic approach FKRP glycosylates alpha-dystroglycan (αDG) which stabilizes muscle Supply supraphysiol
Slide 13: Proprietary, validated Western Blot assay to measure glycosylated αDG
We have developed a proprietary, validated Western Blot assay to accurately and reliably measure glycosylated αDG directly in skeletal muscle tissue Validated Western Blot evaluates change from baseline in glycosylated alpha-dystroglycan (αDG)1,2 untreated + 3 months + 6 months LGMD2I/R9 patient BBP
Slide 14: Studies characterizing natural history and safety of BBP-418
We have conducted several studies to characterize natural history of LGMD2I/R9 and evaluate safety of BBP-418; following an encouraging Ph. 2, we have fully enrolled a Ph. 3 Study Phase Description Key takeaways ▪ Natural history study to characterize ▪ Defined disease trajectory over ~1 year Natura
Slide 15: Natural history: reduced glycosylated αDG levels in LGMD2I/R9 patients
Natural history reflects that LGMD2I/R9 patients have reduced glycosylated αDG levels, and L276I homozygous patients have higher levels than other genotypes 100 Healthy control tissue levels Glycosylated αDG levels (% of control) • Both L276I homozygous and other FKRP 75 genotype patients have reduc
Slide 16: Open-label, dose-finding Ph. 2 study with long-term extension
BBP-418 is being investigated in an open-label, dose-finding Ph. 2 study that has continued in a long-term extension Key Endpoints Dose Maximum Long-term ▪ NSAD1 escalation dose extension ▪ Ambulatory measures ‒ 10-meter walk test 90 days (N=14) 90 days (N=14) 24 months ‒ 100-meter timed test ▪ Pulm
Slide 17: BBP-418 well tolerated with only minor GI adverse events in Ph. 2
BBP-418 continues to be well tolerated, with only minor GI related adverse events recorded in the Ph. 2 study Treatment-related # of incidents # of patients (%) TEAE Diarrhea 8 6 (43%) • Most of the reported TEAEs in the Ph. 2 Dehydration 1 1 (7%) were Grade 1 (mild) or Grade 2 (moderate) in severit
Slide 18: Sustained increases in glycosylated αDG and decreases in serum CK in Ph. 2
Sustained increases in levels of glycosylated αDG in muscle and decreases in serum creatine kinase were observed in Ph. 2 study of BBP-418 Increase in glycosylated αDG in muscle observed post dosing with Reduction in mean serum CK observed post BBP-418 (median ± 95% CI) dosing with BBP-418 L276I hom
Slide 19: Stabilization in ambulatory measures observed in Ph. 2
Stabilization in ambulatory measures has also been observed after treatment with BBP-418 in Ph. 2 study, suggesting change in trajectory from natural history Change from baseline in 10-meter walk test (m/s) Change from baseline in 100-meter timed test (s) Blue lines denote natural history data and r
Slide 20: Fully enrolled Phase 3 FORTIFY study; topline interim data 2H 2025
We have fully enrolled a Phase 3 study (FORTIFY) of BBP-418 in LGMD2I/R9 and expect topline interim analysis data readout in 2H 2025 BBP-418 (N ~ 75) BBP-418 (N ~ 75) Screening Interim Analysis • Genetically Randomization (N ~ 70) Open Label confirmed, 2:1 (N ~ 112) Extension symptomatic Topline Dat
Slide 21: Positive FDA feedback on potential accelerated approval via glycosylated αDG
We have received positive feedback from FDA on potential for accelerated approval in the U.S. based on the surrogate endpoint of glycosylated αDG FDA may grant accelerated approval based on a …such as glycosylated αDG in LGMD2I/R9 surrogate endpoint… Definition “A surrogate endpoint, or ‘marker,’ is
Slide 22: Summary: BBP-418 program overview
Summary: BBP-418 program overview • BBP-418 aims to target LGMD2I/R9 at its source by restoring glycosylation of alpha- dystroglycan (αDG), which we measure by a proprietary, validated assay • In a small, open-label Ph. 2 study, BBP-418 was well tolerated, and sustained improvements on glycosylated
Slide 23: Momentum from regulatory interactions and rapid Ph. 3 enrollment
Continuing momentum from successful regulatory interactions and rapid Ph. 3 enrollment, we anticipate topline data from the Ph. 3 interim analysis in 2H Multiple encouraging discussions with the FDA support plan to pursue ✓ accelerated approval in U.S. for BBP-418 based on a surrogate endpoint 2023
Slide 24: Primary endpoint for interim analysis is glycosylated αDG at 3 months
The primary endpoint for the interim analysis is glycosylated αDG at 3 mo. with additional biomarkers and clinical measures as secondary endpoints at 12 mo. Ph. 3 FORTIFY interim analysis Type Endpoint Timepoint N Base case target Upside target • Statistically significant increase vs. • Statisticall
Slide 25: LGMD2I/R9 represents a $1B+ market opportunity across U.S. and EU
LGMD2I/R9 represents a $1B+ market opportunity across the U.S. and EU Addressable patients by indication LGMD2I/R9 market opportunity 9K Fukuyama congenital First-to-market to address high unmet need 2K muscular dystrophy Opportunity to treat debilitating progressive (Japan) neuromuscular disease wi
Slide 26: Estimated prevalence of LGMD2I/R9 ~6-7 per million in the U.S.
Based on prevalence of pathogenic variants in public sequencing databases and U.S. demographics, the prevalence of LGMD2I/R9 is ~6-7 per million in the U.S. Summary of LGMD2I/R9 prevalence rate, by ancestry Est. U.S. prevalence rate European: 8.4 per million U.S. weighted average: 6-7 per million Po
Slide 27: Natural history studies and patient advocacy groups accelerated Ph. 3 enrollment
Natural history studies and highly engaged patient advocacy organizations accelerated Ph. 3 enrollment and provide support for patient identification Natural history studies1 Patient advocacy organizations1 U.S. University of Iowa Clinical Trial Readiness MLB-01-0013 for Dystroglycanopathies2 (N=96)
Slide 28: Tailwinds in the LGMD landscape ahead of potential U.S. launch
Several tailwinds in the LGMD landscape may further accelerate market development in advance of a potential U.S. launch of BBP-418 in LGMD2I/R9 Potential approvals in Sponsored genetic Approved ICD-10 code other LGMDs to drive testing programs diagnosis • Established complimentary • ICD-10 code spec
Slide 29: Q&A
Q&A