Bridgebio Pharma, Inc. · NASDAQ:BBIO
Bridgebio Pharma — Investor Day (September 2025)
30 slides from Bridgebio Pharma's investor day presentation, Sep 10, 2025
Slide 1: Autosomal Dominant Hypocalcemia Type 1 (ADH1) Investor Webinar
Autosomal Dominant Hypocalcemia Type 1 (ADH1) Investor Webinar September 10, 2025 Encaleret is an investigational drug. Its safety and efficacy Alexis and Jackson have not been fully evaluated by any regulatory authority. Living with ADH1
Slide 2: Forward-Looking Statements and Disclaimer
Forward-Looking Statements and Disclaimer Statements in this Presentation that are not statements of historical fact are considered 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 amend
Slide 3: Agenda
Agenda Ananth Sridhar 1 Introduction Chief Operating Officer BridgeBio Cardiorenal Rachel Gafni, M.D. 2 Overview of ADH1 & Encaleret National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIH) Scott Adler, M.D. Review of Encaleret Clinical 3 Chief Medical Office
Slide 4: Patient Video - Jessica’s Story
Patient Video - Jessica’s Story 4
Slide 5: Overview of ADH1 & Encaleret
Overview of ADH1 & Rachel Gafni, M.D. Senior Research Physician & Encaleret CALIBRATE Study Steering Committee Co-Chair National Institute of Dental and Craniofacial Research of the National Institutes of Health (NIH) Encaleret is an investigational drug. Its safety and efficacy have not been fully
Slide 6: Blood calcium is maintained by four organs regulated by the CaSR and parathyroid hormone
Blood calcium is maintained by four organs regulated by the CaSR and parathyroid hormone Ca2+ = ionized calcium; PTH = parathyroid hormone; CaSR = calcium-sensing receptor Source: Roszko KL et al., J Bone Miner Res 2022. 6 Used with permission of Oxford University Press, from Roszko et al., J Bone M
Slide 7: Activating variants in the CASR cause ADH1
Activating variants in the CASR cause ADH1 Activating variants in the CASR increase Hyperactive CaSR causes dysregulation Clinical Manifestations tissue sensitivity to Ca2+ of Ca homeostasis Acute symptoms Parathyroid Hypocalcemic seizures Wild Decreased parathyroid PTH Paresthesia PTH Secretion Typ
Slide 8: CASR variants associated with ADH1 are commonly inherited in an autosomal dominant pattern
CASR variants associated with ADH1 are commonly inherited in an autosomal dominant pattern A single altered copy of the gene is enough to cause the condition Change in Each child has a 50% chance of CASR gene inheriting the condition It is common for someone with ADH1 to be the first person in
Slide 9: Diagnosis of ADH1
Diagnosis of ADH1 Definitive diagnosis of ADH1 requires genetic testing1 Medical History Clinical Features2,3 Genetic Testing2,3 (Patient and Family)1,2 ADH1 prevalence is estimated to be 1 in 25K based on general population genetics evidence4,5 ADH1 can be difficult to diagnose based on symptom
Slide 10: Management of patients with ADH1 – Conventional therapy
Management of patients with ADH1 – Conventional therapy Includes calcium supplements and activated vitamin D Effects of conventional therapy – Calcium 3-4x/day on calcium excretion – Active vitamin D 1-2x/day Some patients also require magnesium and potassium supplements blood calcium = ur
Slide 11: Why is PTH replacement inadequate for ADH1?
Why is PTH replacement inadequate for ADH1? Most studies of PTH analogs have deliberately excluded ADH1 patients ADH1 patients have capacity to secrete endogenous parathyroid hormone; PTH analogs may suppress this response Cases of long-acting PTH analog use in ADH1 patients did not sufficient
Slide 12: Twice daily PTH 1-34 did not prevent nephrocalcinosis in this ADH1 patient
Twice daily PTH 1-34 did not prevent nephrocalcinosis in this ADH1 patient Baseline One year of PTH 1-34 BID Normal kidney ultrasound Medullary nephrocalcinosis Open label study of BID PTH 1-34 N=31, 4 participants with ADH1 Blood calcium levels maintained low/low normal (7.6-9 mg/dL/1.9-2.25
Slide 13: Encaleret, an investigational oral calcilytic, may be a potential treatment for ADH1
Encaleret, an investigational oral calcilytic, may be a potential treatment for ADH1 • Encaleret is an investigational negative allosteric modulator of the CaSR that can decrease CaSR sensitivity to extracellular calcium • Normalizing CaSR sensitivity could correct hypocalcemia, hypercalciuria, and
Slide 14: Encaleret Clinical Development Program
Encaleret Clinical Scott Adler, M.D. Development Chief Medical Officer Program Calcilytix Therapeutics, a BridgeBio Company Encaleret is an investigational drug. Its safety and efficacy have not been fully evaluated by any regulatory authority. 14
Slide 15: Encaleret is a first-in-class, disease-modifying investigational therapy
Encaleret is a first-in-class, disease-modifying investigational therapy that targets the underlying disease mechanism of ADH1 Mechanism Design Principles Normal CaSR senses and Encaleret is a CaSR antagonist regulates serum Ca levels to designed to decrease the sensitivity maintain homeostasis of C
Slide 16: Phase 2 study evaluated encaleret in 13 ADH1 patients
Phase 2 study evaluated encaleret in 13 ADH1 patients Program Overview Complete Period 1 Period 2 Period 3 LTE Individualized dose Individualized dose Long-term extension Outpatient extension (LTE) escalation titration1 5 days, inpatient (N=6) cv 5 days, inpatient (N=13) 6 months, outpatient cv (N=1
Slide 17: Baseline Characteristics
Baseline Characteristics Characteristic Study Population (N = 13) Normal Range Age, mean, yr (range) 39 (22-60) Female, n (%) 8 (62%) Corrected Calcium1,2 (mg/dL) 7.1 ± 0.4 8.4 –10.2 Intact PTH (pg/mL) 6.3 ± 7.8 15 – 65 Phosphate (mg/dL) 4.5 ± 1.1 2.3 – 4.7 Magnesium (mg/dL) 1.7 ± 0.2 1.6 – 2.6 24h
Slide 18: Encaleret was generally well-tolerated over 42 months of outpatient administration
Encaleret was generally well-tolerated over 42 months of outpatient administration Periods 2 and 3 LTE N=13 N=13 Number of subjects experiencing any Serious Adverse Event 0 (0%) 2 (15%) Post-operative right shoulder pain 1 Chest pain 1 Number of subjects experiencing any Treatment-Emergent 13 (100%)
Slide 19: Phase 2 results showed rapid and sustained normalization of serum Ca, urine Ca, and PTH
Phase 2 results showed rapid and sustained normalization of serum Ca, urine Ca, and PTH Normal Range Blood Calcium Urine Calcium 11 800 Blood cCa (mg/24 h) Urine Ca 10 (mg/dL) ** ** 600 9 400 8 ** ** 7 200 6 0 0 8 16 24 48 6 72 12 96 18 24 120 30 144 168 36 0 8 16 24 6 48 12 72 18 96 24 120 30 144 3
Slide 20: 69% of participants responded to encaleret as defined by the planned Phase 3 primary analysis
69% of participants responded to encaleret as defined by the planned Phase 3 primary analysis Individuals achieving both blood Ca and urine Ca in the target range SoC vs Encaleret (n=13) 100% 80% 69% % of Participants 60% 40% 20% 0% 0% SoC Encaleret Screening Week 24 Ca = calcium; SoC = standard of
Slide 21: Summary of encaleret Phase 2 results and ongoing development
Summary of encaleret Phase 2 results and ongoing development Existing treatment regimens for patients with ADH1 focus on symptom management rather than addressing the underlying disease mechanism Patients with ADH1 face significant unmet needs that may be addressed by precision therapies targeti
Slide 22: Topline results of the CALIBRATE Phase 3 study of encaleret in ADH1 are anticipated in Fall 2025
Topline results of the CALIBRATE Phase 3 study of encaleret in ADH1 are anticipated in Fall 2025 Encaleret Screening and SoC Encaleret Titration Period Maintenance Optimization Period Period • Age > 16 years of age SoC Long-Term Extension • Documented pathogenic or Maintenance Randomization 2:1 like
Slide 23: Preliminary data demonstrate rapid, PTH-independent, effect on blood and urine calcium
Preliminary data demonstrate rapid, PTH-independent, effect on blood and urine calcium Proof-of-principle phase 2 study of encaleret in post-surgical hypoparathyroidism (PSH), N=10 0.04 0.03 FECa 0.02 * * ULN 100% % of Participants with blood & 24- 80% hr urine Ca in reference range 0.01 80% 0.00 -2
Slide 24: Proof-of-concept study findings suggest a potential path for improved calcium control in a convenient pill form
Proof-of-concept study findings are suggestive of a potential path for improved calcium control in a convenient pill form Potential Differentiating Features For Encaleret • Orally administered tablet • Benefit in 24-hour urinary calcium excretion • Avoidance of long-term PTH-mediated impact on bone
Slide 25: ADH1 Market Opportunity
ADH1 Market Ananth Sridhar Opportunity Chief Operating Officer, BridgeBio Cardiorenal 25
Slide 26: There are no therapies specifically indicated for ADH1, a serious and rare genetic condition
There are no therapies specifically indicated for ADH1, a serious and rare genetic condition An analogous ADH1 market is XLH 12K Individuals with ADH1 XLH ADH1 ~12K ADH1 prevalent Prevalence (US) 12K5 12K population in the US based on Acute - hypocalcemia Disease burden Hypophosphatemia 4 population
Slide 27: ADH1 is emerging as the leading isolated cause of nonsurgical hypoparathyroidism
ADH1 is emerging as the leading isolated cause of nonsurgical hypoparathyroidism1 Results – Sponsored Genetic Testing Program Variants in Nonsurgical Relative Number of Individuals 2 HP Individuals with Detected Variants Sample Characteristics Population (N=169) 100 No Variants Mean Age (range) 23.4
Slide 28: Evolution in the diagnosis and management of hypoparathyroidism may further accelerate ADH1 market development
Evolution in the diagnosis and management of hypoparathyroidism may further accelerate ADH1 market development Established ICD-10 Code Management Guidelines Sponsored Genetic Testing dedicated to ADH1 & Specify Need for Genetic Program ADH2 Testing1 “Genetic testing is advised for all patients with
Slide 29: The primary analysis of CALIBRATE will assess the relative improvement of blood and urine calcium on encaleret compared to SoC
The primary analysis of CALIBRATE will assess the relative improvement of blood and urine calcium on encaleret compared to SoC Base Case Target Upside Target • Statistically significant primary • Statistically significant primary analysis result compared to SoC analysis result compared to SoC • Rest
Slide 30: Q&A Session
Q&A Session 30