Slide 1: CALIBRATE Phase 3 Topline Results of Encaleret in ADH1
CALIBRATE Phase 3 Topline Results of Encaleret in ADH1 October 29, 2025 Alexis and Jackson Living with ADH1 Encaleret is an investigational drug. Its safety and efficacy have not been fully evaluated by any regulatory authority.
Slide 2: Forward-Looking Statements and Disclaimer
Forward-Looking Statements and Disclaimer Statements made or presented in this Presentation may include statements that are not historical fact and 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
Slide 3: Agenda
Agenda Neil Kumar, Ph.D. 1 Introduction Chief Executive Officer, BridgeBio Ananth Sridhar 2 ADH1 Overview Chief Operating Officer, BridgeBio Cardiorenal CALIBRATE Phase 3 Scott Adler, M.D. 3 Topline Results Chief Medical Officer, Calcilytix Therapeutics, a BridgeBio Company 4 Mary Scott Roberts, M.D
Slide 4: A sincere THANK YOU to the patients, families, advocates, investigators
encaleret for Autosomal Dominant Hypocalcemia Type 1 (ADH1) A sincere THANK YOU to the patients, families, advocates, investigators, clinical research staff, referring providers, and collaborating research partners 4
Slide 5: We have built a sustainable, high velocity engine to deliver medicines
We have built a sustainable, high velocity engine to deliver medicines Obtained Approval for 3 Medicines > 2,000 > 30 trials 3 fully + 2 Positive patients in > 30 countries enrolled Phase 3 Results trials > 500 sites pivotal trials > 70 > 35 < $10M and 19 papers academic < 3 yrs to INDs created publ
Slide 6: Encaleret is an exemplar of BridgeBio's model of partnering with leading academics
Encaleret is an exemplar of BridgeBio’s model of partnering with leading academics to translate beautiful science to patient impact “Connect the dots” Genetic disease represents Meaningful clinical data1 therapeutic hypothesis the just the tip of the iceberg ADH1 Potential Expansion Opportunity in C
Slide 7: ADH1 Overview
ADH1 Overview Ananth Sridhar Chief Operating Officer, BridgeBio Cardiorenal 7 7
Slide 8: CALIBRATE achieved & exceeded all criteria set forth as an upside target
CALIBRATE achieved & exceeded all criteria set forth as an upside target, with a 76% responder rate following 24 weeks of encaleret treatment Upside Target Clinical Profile Outcome Observed Statistically significant primary analysis result Primary endpoint met (p <0.0001) demonstrating compared to
Slide 9: There are no therapies currently indicated to treat ADH1
There are no therapies currently indicated to treat 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 populati
Slide 10: Activating variants in the CASR cause ADH1
Activating variants in the CASR cause ADH1 Activating variants in the CASR Hyperactive CaSR causes Clinical Manifestations increase tissue sensitivity to Ca2+ dysregulation of Ca homeostasis Acute symptoms Parathyroid Hypocalcemic seizures Wild Decreased parathyroid PTH Paresthesia PTH Secretion Typ
Slide 11: Encaleret is an investigational, potential first-in-class therapy targeting ADH1
Encaleret is an investigational, potential first-in-class therapy that targets the underlying disease mechanism of ADH1 Design Principles Only investigational treatment directly targeting ADH1 at its source Potential to restore physiologic mineral homeostasis that is disrupted by CaSR oversensitivit
Slide 12: CALIBRATE Phase 3 Topline Results
CALIBRATE Phase 3 Scott Adler, M.D. Chief Medical Officer Topline Results Calcilytix Therapeutics, a BridgeBio Company 12 12
Slide 13: Encaleret phase 3 registrational study design
Encaleret phase 3 registrational study design Screening and SOC Encaleret Optimization Period Encaleret Titration Period (N=45) Maintenance Period • Age > 16 years of age Participants randomized to encaleret stopped SoC prior to Long-Term • Documented first dose SoC Randomization 2:1 Extension patho
Slide 14: Study Participant Disposition
Study Participant Disposition Enrolled Population N=70 N=3 participants discontinued prior to randomization SoC Encaleret Randomized Randomized N=22 N=45 N=1 withdrawal by participant SoC Encaleret Completed Period 3 Completed Period 3 N=21 N=45 N=1 participant elected not to continue in long-term e
Slide 15: Baseline demographic characteristics
Baseline demographic characteristics SoC Encaleret All Participants Characteristic (N=22) (N=45) (N=67) Demographics Age, yr, mean (range) 37 (16-63) 44 (16-76) 42 (16-76) Female, n (%) 11 (50%) 24 (53%) 35 (52%) Race, n (%)1 White 20 (91%) 38 (84%) 58 (87%) Asian 2 (9%) 5 (11%) 7 (10%) Other 1 (5%)
Slide 16: Baseline clinical characteristics
Baseline clinical characteristics SoC Encaleret All Participants Characteristic (N=22) (N=45) (N=67) Baseline Characteristics Serum Calcium1, mg/dL, mean (SD) 7.9 (0.7) 8.4 (0.8) 8.2 (0.8) 24hr Urine Calcium, mg/day, mean (SD) 331 (195) 397 (178) 376 (185) Intact PTH, ng/L, mean (SD) 6.0 (4.5) 6.8 (
Slide 17: 76% of participants randomized to encaleret met the primary endpoint
76% of participants randomized to encaleret met the primary endpoint achieving serum calcium1 and 24-hour urine calcium in the target ranges Week 4 Week 24 Primary Analysis – Within Group SoC Encaleret p-value4 (N=45) (N=45) Number of Participants Meeting The Primary 2 34 Endpoint (Responder status)
Slide 18: 91% of participants achieved intact PTH above the lower limit
91% of participants randomized to encaleret achieved intact PTH above the lower limit of the reference range Week 4 Week 24 Key Secondary Analysis – Within Group SoC Encaleret p-value1 (N=45) (N=45) Number of Participants With iPTH ≥ LL Reference 3 41 Range Proportion, % 7% 91% Difference in Proport
Slide 19: Rapid and sustained increase in serum calcium into the normal range
Encaleret demonstrated a rapid and sustained increase in serum calcium1 into the normal range over 24 weeks Mean difference of change from Encaleret baseline = 0.82 mg/dL (p<0.0001)* SoC Target Range Mean difference Mean of change from Corrected baseline = Calcium 0.65 mg/dL (mg/dL)1 (p=0.009)** Wee
Slide 20: Robust effect on urine calcium reduction into the normal range
Encaleret demonstrated a robust effect on urine calcium reduction into the normal range over 24 weeks Mean difference of change from Encaleret baseline = -200 mg/day (p<0.0001)* SoC Target Range Mean Mean difference 24-hr Urine of change from Calcium baseline = (mg/day) -221 mg/day (p<0.0001)** Week
Slide 21: Encaleret was well-tolerated with no TEAEs resulting in discontinuation
Encaleret was well-tolerated with no TEAEs resulting in encaleret or study discontinuation Period 1 Periods 2 and 3 SoC SoC Encaleret N=67 N=22 N=45 Participants experiencing any Serious TEAE 2 (3%) 3 (14%) 4 (9%) Serious Related TEAE 1 (2%) 0 (0%) 1 (2%) Participants experiencing any TEAE 30 (45%)
Slide 22: Encaleret restored physiologic mineral homeostasis through its action on the CaSR
Encaleret was found to restore physiologic mineral homeostasis through its action on the CaSR • 76% of participants randomized to encaleret achieved serum and urine calcium in the target range compared to the same individuals on conventional therapy (difference 71%, p<0.0001)1,2 • Among encaleret re
Slide 23: Program Next Steps
Program Next Mary Scott Roberts, M.D. Steps VP, Clinical Development Calcilytix Therapeutics, a BridgeBio Company 23 23
Slide 24: NDA submission planned in the first half of 2026
NDA submission planned in the first half of 2026 with two additional registrational studies planned for initiation next year Advance encaleret towards registration in Generate clinical evidence for encaleret in ADH1 additional patient populations Submit New Drug Application to Initiate Phase 2/3 stu
Slide 25: Launch Readiness
Launch Matt Outten, M.B.A. Readiness Chief Commercial Officer BridgeBio 25 25
Slide 26: Leveraging our proven commercial infrastructure to launch encaleret
Leveraging our proven commercial infrastructure to successfully launch encaleret Built on the foundation of Attruby’s® global commercial success and tailored to the unique ADH1 market opportunity Proven launch playbook Targeted resource deployment Established commercial infrastructure Enabling faste
Slide 27: Data-driven commercial precision to accelerate ADH1 diagnosis and treatment
Data-driven commercial precision to accelerate ADH1 diagnosis and treatment State of Market ADH1 patients predominantly managed by Concentration of HCPs Managing Patients endocrinologists Endocrinology Nephrology Primary Care Concentrated prescriber base enabling targeted engagement How we will capi
Slide 28: A proven market access strategy built for a successful planned encaleret launch
A proven market access strategy built for a successful planned encaleret launch in ADH1 Market Access strategy designed to support logistics for patients and providers and payer coverage Strategic area Objective Rapid and seamless titration Infrastructure in place to ensure dose adjustments can be i
Slide 29: Q&A Session
Q&A Session 29 29