Bridgebio Pharma, Inc. · NASDAQ:BBIO
Bridgebio Pharma — Investor Presentation (June 2021)
52 slides from Bridgebio Pharma's investor presentation, Jun 1, 2021
Slide 1: Corporate presentation June 2021
Exhibit 99.1 Corporate presentation June 2021Exhibit 99.1 Corporate presentation June 2021
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: BridgeBio Pharma: Hope through rigorous science
BridgeBio Pharma: Hope through rigorous science Our mission: To discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers 3BridgeBio Pharma: Hope through rigorous science Our mission: To discover, create, tes
Slide 4: Our 2025 vision – A leading player in genetic medicine
Our 2025 vision – A leading player in genetic medicine Multiple best-in-class or first-in-class products in blockbuster markets, with a total of 4+ NDAs on file Patient-centric global commercial infrastructure World-class drug discovery and development platform Broad network of >40 university partne
Slide 5: Context #1: 2021 is a critical year for BridgeBio
Context #1: 2021 is a critical year for BridgeBio Value to patients and investors Returns to scale 4 clinical trial readouts in $750 M+ markets: ADH1, ATTR, achondroplasia, CAH 2015 2020 2021 2022 2 NDAs accepted for priority review 8 new clinical trials initiated 4 later-stage trials fully enrolled
Slide 6: Context #2: The opportunity to help patients remains large
Context #2: The opportunity to help patients remains large 8,000 $1B+ opportunities in 8 the pipeline 1) Acoramidis for ATTR CM and PN 2) Low-dose infigratinib for achondroplasia >50 3) AAV5 gene therapy for congenital adrenal hyperplasia 4) High-dose infigratinib for adjuvant urothelial carcinoma 5
Slide 7: Context #3: Still Day 1 for innovation within genetic medicine
Context #3: Still Day 1 for innovation within genetic medicine New Therapeutic Macromolecules Molecular Systems Clinical Diagnosis Modalities • Whole genome sequencing of rare disease patients in UK • Antisense oligonucleotides • Mass spectrometry + DNA RNA Protein Biobank coming of age st metabolom
Slide 8: Product platform: Discover, Create, Test, Deliver
Product platform: Our drug engineering platform leverages and efficiently translates innovation to therapies that matter Discover Create Test Deliver Novel genetic Medicines with industry- Our drugs through global Our products to patients through disease targets leading research capabilities develop
Slide 9: Product platform: BridgeBio is a people and a process
Product platform: BridgeBio is a people and a process Scientific insight and judgment from industry leaders with a proven track record Discover Charles Homcy, MD Frank McCormick, PhD Richard Scheller, PhD Len Post, PhD Phil Reilly, MD, JD Founder and Chairman of Founder and Chairman of Advisor Advis
Slide 10: Our pipeline spans multiple therapeutic areas with numerous upside opportunities
Our pipeline spans multiple therapeutic areas with numerous upside opportunities Small molecule Topical small molecule Biologics Antisense oligo Gene therapy Preclinical Clinical Portfolio Patient pop. Program Drug mechanism Diseases Modality segment (US+EU) Discovery IND-enabling Phase1 Phase 2 Pha
Slide 11: Product pipeline: Layers of de-risking and upside
Product pipeline: Layers of de-risking and upside Future pipeline catalysts and Targeted oncology Common mendelian long-term growth (FGFR3 in UC, (LGMD2i, RDEB, SHP2, KRAS) PKAN, VM) Near-term major catalysts from Validation of asset picking 4 core value drivers and execution (ATTR, ADH1, achondropl
Slide 12: Significant milestones for BridgeBio in the next 12 months
Value to patients and shareholders Significant milestones for BridgeBio in the next 12 months Mid ‘22 Gene therapy for CAH: Ph1 data ENDO 2021 data: 1H ‘22 100% response rate Low-dose infigratinib Q4 for achon: Ph2 data ‘21 Q1 Acoramidis for ATTR: ‘21 Ph3 data Encaleret for ADH1: Ph2 data Growth pot
Slide 13: Acoramidis (AG10) for transthyretin amyloidosis (ATTR)
Acoramidis (AG10) for transthyretin (TTR) amyloidosis (ATTR) ATTR overview Prevalence Genetic driver Pathophysiology 400,000+ worldwide, Destabilizing TTR Systemic disease most largely undiagnosed today variants or factors of commonly presenting as aging, leading to cardiomyopathy or peripheral amyl
Slide 14: ATTR is already a $2B+ market with major upside potential
In under two years, ATTR is already a $2B+ market with major upside potential 1 Global annual ATTR market sales $B Significant potential future ATTR market growth $2.3 driven by: +71% $1.7 ▪ Increasing diagnosis in established $1.7 geographies (23.5K patients diagnosed in US is a fraction of $0.8 $0
Slide 15: Acoramidis was designed to treat ATTR at its source
Acoramidis was designed to treat ATTR at its source Native TTR circulates Monomers aggregate, Dissociation into in blood as a tetramer causing disease monomers initiates pathogenesis ~130 known destabilizing mutations Disease mechanism Protective T119M mutation Therapeutic Acoramidis was designed to
Slide 16: Acoramidis well-tolerated with near-complete TTR stabilization
Acoramidis has been well-tolerated and demonstrated near-complete TTR stabilization in preclinical, Phase 1, and Phase 2 studies 1 2 Phase 2 safety summary Phase 2 TTR stabilization TTR stabilization at steady-state trough level Acoramidis Placebo %, mean ± SEM (pooled doses) N = 17 N = 32 140 Any A
Slide 17: Deaths and CV hospitalizations in Phase 2 OLE vs ATTR-ACT placebo
Deaths and CV hospitalizations reported in acoramidis Phase 2 OLE were lower than in placebo-treated ATTR-ACT participants All-cause mortality at 15 months Cardiovascular hospitalizations at 15 months Participants died or receiving transplant (%) Participants with ≥1 CV hospitalization (%) -44% -39%
Slide 18: ATTRibute-CM study design and endpoints
ATTRibute-CM will provide 12-month functional outcome data and 30-month mortality and CV hospitalization data 12-month endpoints: 30-month endpoints: Primary: Change in 6MWD Primary: Hierarchical composite Key Key secondary: Change in KCCQ Key secondary: Change in 6MWD, KCCQ inclusion criteria 800 m
Slide 19: Higher dose of tafamidis showed greater clinical benefit in ATTR-ACT
Higher dose of tafamidis demonstrated increased TTR stabilization and greater clinical benefit in ATTR-ACT + LTE Phase 3 ATTR-ACT study tested two doses of tafamidis (20 mg & 80 mg) vs. placebo ▪ In an analysis of ATTR-ACT combined with long-term extension (LTE), benefit of tafamidis 1 80 mg vs. 20
Slide 20: Ongoing and planned studies of acoramidis
Ongoing and planned studies of acoramidis aim to continually expand clinical evidence and addressable patient population 2025+ Prevention in high risk populations ATTRibute-CM Phase 3 study enrolled 2024 632 participants and is on track for Head-to-head comparisons topline data in 4Q 2021 2023 ATTR-
Slide 21: Encaleret for autosomal dominant hypocalcemia type 1 (ADH1)
Encaleret for autosomal dominant hypocalcemia type 1 (ADH1) overview ADH1 overview Prevalence Genetic driver Pathophysiology 12K individuals harboring Calcium-sensing receptor Decreased blood calcium, 1 variants in US (CaSR) hyperactivation elevated urine calcium, and lower 2 parathyroid hormone sec
Slide 22: Encaleret is designed to treat ADH1 by normalizing CaSR sensitivity
Encaleret is designed to treat ADH1 at its source by normalizing CaSR sensitivity CaSR senses and regulates Hyperactive CaSR causes Acute symptoms and serum Ca levels dysregulation of Ca homeostasis long-term complications Presenting symptoms 2+ Increased urinary calcium Ca Hypocalcemic seizures ADH
Slide 23: Majority of ADH1 patients are symptomatic
Majority of ADH1 patients are symptomatic including one third with severe symptoms Meta-analysis of published ADH1 case reports Size proportional to study sample number 100% Pagan, 2004 Mancilla, 1997 Hendy, 2003 80% Pearce, 1996 Watanabe, 1998 Uckun-Kitapci, 2005 Tan, 2003 60% Hirai, 2001 Livadariu
Slide 24: Current therapy for ADH1 does not address disease mechanism
Current therapy for ADH1 (oral calcium, activated Vitamin D) raises blood Ca but does not address disease mechanism; increases UCa, suppresses PTH Without supplementation Summary of key disease measures in ADH1 patients with and without supplementation With supplementation Blood calcium Urine calciu
Slide 25: Encaleret Phase 2 study design
Encaleret Phase 2 study design Complete Ongoing Phase 2 Period 2 Phase 2 Period 3 Phase 2 Period 1 Individualized dose adjustment Outpatient extension Individualized dose escalation 5 days, inpatient 5 days, inpatient 6 months, outpatient (N=6) (N=11-16) (N=11-16) Program Overview March 2021: 2H 202
Slide 26: All trial participants had normal blood and urine calcium by Day 5
All trial participants had normal blood and urine calcium by Day 5 Baseline Value (Day 1) Mean Value (Day 5) Blood calcium Urine calcium Blood parathyroid hormone mg/dL mg/day pg/mL 1000 11 120 800 10 90 600 9 60 400 8 30 200 7 0 0 6 † * * All Subjects Average All Subjects Average Average All Subjec
Slide 27: Encaleret Ph2 baseline characteristics
Encaleret Ph baseline characteristics Encaleret Characteristic Normal Range N = 6 Age, mean (range) 40 (22-60) Female, n (%) 3 (50%) Nephrocalcinosis, n (%) 4 (67%) ECG QT B (msec) 452 ± 9 < 440 c Corrected Calcium (mg/dL)* 7.6 ± 0.6 8.4 –10.2 Intact PTH (pg/mL)* 3.4 ± 4.5 15 – 65 Phosphate (mg/dL)*
Slide 28: Encaleret generally well-tolerated with no serious adverse events
Encaleret was generally well-tolerated with no serious adverse events reported after 5 days N = 6 Number of subjects experiencing any Serious Adverse Event 0 (0%) Number of subjects experiencing any Adverse Event 5 (83%) Mild 5 (83%) Moderate 0 (0%) Severe 0 (0%) Number of Adverse Events Reported 9
Slide 29: Dose dependent increases in PTH mirrored encaleret levels
Dose dependent-increases in PTH mirrored encaleret levels * 90 180 180 180 180 180 30 8 mg mg mg mg mg mg mg 6 4 2 0 250 200 150 100 50 0 Day 1 Day 2 Day 3 Day 4 Day 5 29 Data shown as mean ± SD *One subject reduced second dose on Day 5 to 120 mg *Dashed line reflects normal range of PTH 15-65 pg/mL
Slide 30: Encaleret normalized blood and urine calcium
Encaleret normalized blood and urine calcium * 30 90 180 180 180 180 180 11 mg mg mg mg mg mg mg ULN 10 9 LLN 8 7 6 1200 800 400 ULN 0 Day 1 Day 2 Day 3 Day 4 Day 5 Data shown as mean ± SD *Values below limit of assay quantitation were marked as “0” *One subject reduced second dose on Day 5 to 120 m
Slide 31: Conclusions
Conclusions ▪ Encaleret was well-tolerated when administered in escalating oral doses once or twice daily over 5 days, with no serious adverse events reported and no adverse events of moderate or severe intensity ▪ Blood calcium, PTH, and phosphate were normalized and maintained within the normal ra
Slide 32: Next steps for encaleret
Next steps for encaleret include generating further evidence in ongoing Phase 2 study Planned activities ✓ Initiate Phase 2 study in ADH1 2020 ▪ Phase 3 registrational study in ADH1 ✓ Receive ODD from FDA for ADH ▪ Pediatric development program in ADH1 ▪ Evaluation of encaleret in non-genetic ✓ Repo
Slide 33: Low-dose FGFR inhibitor (infigratinib) for achondroplasia
Low-dose FGFR inhibitor (infigratinib) for achondroplasia Achondroplasia overview Prevalence Genetic driver Pathophysiology 55,000 (US+EU) – FGFR3 activation Up-regulation of STAT1 and MAPK one of the most common in the growth plate cause cranial, genetic conditions spinal, and stature symptoms Feat
Slide 34: Targeting achondroplasia directly at its genetic source
Potential best-in-class approach targeting achondroplasia directly at its genetic source ACH FGFR3 gain-of-function mutation causes: FGF ▪ 2-3x over-activation of the receptor FGFR3 G380R ▪ Up-regulation of downstream pathways STAT1 mutation Growth plate chondrocyte and MAPK ▪ Aberrant growth plate
Slide 35: Low-dose infigratinib improves key drivers in ACH mouse model
Low-dose infigratinib improves all the key drivers of clinical symptomology in validated ACH mouse model Y367C/+ Y367C/+ FGFR3 WT FGFR3 FGFR3 No treatment No treatment Infigratinib tx Cranial bone issues 1 May lead to decrease 17% 6% in foramen magnum increase in increase in AP stenosis and fewer FM
Slide 36: Potential best-in-class preclinical profile in achondroplasia
Low-dose infigratinib showed potential best in-class preclinical profile in validated achondroplasia mouse model Company/ Foramen MOA Route Status Mouse model Tibia length Femur L4-L6 height Asset magnum area Selective Y367C/+ 32.6% 20.9% 17.0% 12.1% Oral Ph2 FGFR3 FGFR1-3i Infigratinib Pivotal Y367
Slide 37: Wide anticipated therapeutic index in achondroplasia
We have a wide anticipated therapeutic index in achondroplasia Infigratinib has been tested in >700 humans in our oncology program, providing significant data on PK, tolerability and safety Most common and dose-limiting side effect is phosphorus elevation (on-target through FGFR1 inhibition), which
Slide 38: The PROPEL clinical program is enrolling
The PROPEL clinical program is enrolling with data expected in 2H 2021 Ph2 Dose-finding (n=40) Long-term extension Observational run-in Children are followed for a minimum of 6 months to establish baseline 0.128 mg/kg annualized growth velocity (AGV) n=10 0.064 mg/kg n=10 12 month Select dose long-t
Slide 39: BBP-631: AAV5 gene therapy for CAH
BBP-631: AAV5 gene therapy for congenital adrenal hyperplasia (CAH) Program overview Prevalence Genetic driver Pathophysiology 75,000 (US+EU) – One of 21-hydroxylase Inability to produce cortisol causes need the largest known AAV inactivation for supraphysiologic doses of synthetic gene therapy mark
Slide 40: Gene therapy is the only modality designed to treat CAH at its source
Gene therapy is the only modality designed to treat CAH at its source and allow for production of endogenous cortisol Hormonal dysregulation with 21OHD; no cortisol “brake” on Healthy Hypothalamic-Pituitary-Adrenal Axis ACTH, shunting of 17OHP to androgens CRF Hypothalamus CRF Hypothalamus ACTH ACTH
Slide 41: CAH: NHP study showed durable transgene expression
CAH: NHP study showed durable transgene expression; 5-10% of WT enzyme may be sufficient for clinical impact Genotype-phenotype studies show that Mouse studies show a VGC of only 0.13 NHP studies show sustained VGC and RNA >5-10% of enzyme activity results in at 18 wks was sufficient for phenotypic
Slide 42: NHP protein data suggests potentially therapeutic enzyme levels
NHP protein data using mass spec methods suggests potentially therapeutic levels of 21-hydroxylase enzyme Human 21-hydroxylase protein as a % of NHP 21-hydroxylase protein (Mass Spec quantification) ▪ We have developed mass- 24% spec methods to quantify protein expression by identifying differential
Slide 43: BridgeBio oncology research
BridgeBio oncology research World-class oncology team drives our discovery and development Eli Wallace CSO Oncology Research Pedro Beltran SVP Oncology Frank McCormick Chairman of Oncology Richard Scheller Chairman of R&D Basia, pancreatic cancer patient (>90% KRAS-driven) 43BridgeBio oncology resea
Slide 44: Three disclosed oncology research targets
Three disclosed oncology research targets SHP2 (BBP-398) KRAS GPX4 Receptor tyrosine kinase signals Receptor tyrosine kinase signals (EGFR, ALK, TRK, RET) (EGFR, ALK, TRK, RET) Cell membrane damage Cancer cell membrane Cancer mutations lock Cancer mutations lock KRAS in its active state KRAS in its
Slide 45: Partnerships afford us exceptional collaborators and resources
Partnerships afford us exceptional collaborators and resources rd ▪ Partnership with the National RAS Initiative, ▪ Home to Sierra: the world’s 3 fastest computing including 60 of the world’s foremost academic RAS system researchers ▪ Enables multi-microsecond molecular dynamics ▪ Cutting edge RAS s
Slide 46: Crystal structure enables a static understanding of the target
Crystal structure enables a static understanding of the target … KRAS4b model based on crystal One therapeutic approach is to inhibit KRAS4b membrane localization by targeting hypervariable region Static model reveals only a subset of potential binding sites for pharmacological compounds G-domain sw
Slide 47: Molecular dynamics simulation reveals transient conformations
… whereas molecular dynamics simulation reveals transient conformations and interactions KRAS4b simulation Reveals possible KRAS4b HVR transient localization to G-domain Elucidates potential transient druggable pocket where compounds could react covalently with C185 Enables in silico SAR to inhibit
Slide 48: KRAS: multiple shots on goal with pan-mutant inhibitor programs
KRAS: multiple shots on goal with our pan-mutant inhibitor programs – each with a unique MOA targeting a novel pocket Targets Crystal Molecular KRAS pathway in cancer Program MOA KRAS GTP Pan-mutant structure Dynamics ▪ Directly binds activated KRAS Program 1: H95 Receptor tyrosine kinase signals (E
Slide 49: SHP2: Compound shows best-in-class potential in a large cancer market
SHP2: Our compound shows best-in-class potential in a large cancer market Our SHP2i blocks downstream MAPK signaling We believe BBP-398 has the ideal properties for combination and abrogates T cell exhaustion with a multitude of other therapeutic classes 1 Human half life: ~10-15 hours Potentially d
Slide 50: BBP-398 PK/PD profile
DUSP6 mRNA (Fold Change) DUSP6 mRNA (Fold Change) BBP-398 displays a PK/PD profile that may allow for daily pathway recovery and 100 1.5 improve SHP2 inhibitor tolerability 1 BBP-398 PK/PD data BBP-398 steady state PK simulation 10 1.0 BBP-398 predictions are based on allometric scaling and preclini
Slide 51: SHP2: BBP-398 monotherapy study initiated in 2020; combo trials to follow
SHP2: BBP-398 monotherapy study initiated in 2020; combo trials to follow Clinical development timeline First patient treated 4Q20 2020 2021 2022+ Monotherapy Combo Therapy ▪ Monotherapy study initiated 2H 2020▪ Partnered with Perceptive-backed LianBio in China to expand exploration of potential com
Slide 52: Major catalysts across the pipeline anticipated over the next 12 months
Major catalysts across the pipeline anticipated over the next 12 months ANTICIPATED Execution in 2021 4 core value drivers Pipeline upside BBIO / EIDX merger closure: Encaleret (CaSRi) for ADH1: Ph2 COL7 replacement for RDEB: Data th Completed January 26 proof-of-concept data (March ’21) from Ph2 st