encaleret (BBP-305) / BridgeBio - LARVOL DELTA

RECLAIM-HP: Efficacy, Safety, and Tolerability of Encaleret in Participants With Chronic Hypoparathyroidism (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Not yet recruiting ➔ Recruiting

Enrollment open • Endocrine Disorders • Hypoparathyroidism

Hypoparathyroidism: translating science from the laboratory to the clinic. (PubMed, Lancet Diabetes Endocrinol) - "PTH analogues with extended action (eg, palopegteriparatide, eneboparatide, and canvuparatide) show sustained activation of PTH receptors with reduced requirements for active forms of vitamin D and calcium supplements. Calcilytics (eg, encaleret) normalise calcium-sensing receptor (CaSR) hyperactivation in patients with autosomal dominant hypocalcaemia type 1 and have the potential for broader application in other forms of hypoparathyroidism...Translational research is redefining the future of hypoparathyroidism management. Developments in receptor-targeted therapies, long-acting PTH analogues, negative allosteric modulators of CaSR, and regenerative approaches reflects a shift towards restoring mineral homoeostasis to a more physiological state."

Journal • Review • Endocrine Disorders • Hypoparathyroidism • Transplantation

RECLAIM-HP: Efficacy, Safety, and Tolerability of Encaleret in Participants With Chronic Hypoparathyroidism (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company

New P3 trial • Endocrine Disorders • Hypoparathyroidism

Participant-Reported Changes in Symptoms and Treatment Experience with Encaleret in Autosomal Dominant Hypocalcemia Type 1: 24-Week Findings From the Phase 3 CALIBRATE Trial (ASBMR 2026) - No abstract available

P3 data • Endocrine Disorders

Encaleret Restores Mineral Homeostasis And Increases Bone Turnover In Autosomal Dominant Hypocalcemia Type 1 (ADH1): 24-Week Results From Phase 3 CALIBRATE Trial (ASBMR 2026) - No abstract available

P3 data • Endocrine Disorders

BridgeBio is currently enrolling CALIBRATE-PEDS (NCT07080385), a global registrational Phase 2/3 study of encaleret in pediatric ADH1. (The Manila Times) - "The Company also plans to initiate RECLAIM-HP, a global Phase 3 study of encaleret in chronic hypoparathyroidism later this summer, building on the positive Phase 2 proof-of-concept findings of PTH-independent effects of encaleret on renal calcium handling and expanding the potential applications of encaleret beyond ADH1."

Enrollment status • New P3 trial • Genetic Disorders • Hypoparathyroidism

BridgeBio Pharma, Inc…announced the FDA has accepted for filing its New Drug Application (NDA) for encaleret for the treatment of individuals living with autosomal dominant hypocalcemia type 1 (ADH1). (The Manila Times) - "The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 8, 2027...CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1, successfully achieved all pre-specified primary and key secondary efficacy endpoints, supporting encaleret’s potential as a disease-modifying therapy by targeting the underlying genetic cause of ADH1...Additional results were presented at the European Congress of Endocrinology (ECE) 2026 and the Endocrine Society 2026 annual meeting (ENDO) in oral presentations...The Company also intends to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the use of encaleret in ADH1 in the second half of 2026."

EMA filing • FDA filing • PDUFA • Endocrine Disorders • Genetic Disorders

Defying Expectations: Low Urinary Calcium in Autosomal Dominant Hypocalcemia Type 1 (ENDO 2026) - "This case highlights the importance of determining the cause of hypoparathyroidism and pursuing genetic testing in patients with atypical features, as management of ADH-1 differs from other forms of hypoparathyroidism."

CNS Disorders • Endocrine Disorders • Gastrointestinal Disorder • Hypoparathyroidism • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Rare Diseases • Renal Calculi • Renal Disease • Sleep Disorder

Encaleret Restores Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Primary Results from the Phase 3 CALIBRATE Trial (ENDO 2026) - P3 | "Few serious adverse events (AE) were reported with frequency similar between treatment arms. These results establish encaleret as a potential disease-specific therapy for ADH1 with clinically meaningful efficacy, safety, and tolerability."

P3 data • Chronic Kidney Disease • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Renal Disease • CASR

Defying Expectations: Low Urinary Calcium in Autosomal Dominant Hypocalcemia Type 1 (ENDO 2026) - "This case highlights the importance of determining the cause of hypoparathyroidism and pursuing genetic testing in patients with atypical features, as management of ADH-1 differs from other forms of hypoparathyroidism."

CNS Disorders • Endocrine Disorders • Gastrointestinal Disorder • Hypoparathyroidism • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Rare Diseases • Renal Calculi • Renal Disease • Sleep Disorder

PTH-Independent CaSR Inhibition with the Oral Calcilytic Encaleret Improves Calcium Homeostasis in Post-Surgical Hypoparathyroidism: A Phase 2 Open-Label Proof-of-Concept Trial. (PubMed, Res Sq) - "Transient mild hypercalcemia and headache in 1 participant were the only treatment-related AEs. In PSH, encaleret reduced urinary Ca and increased serum Ca, demonstrating the PTH-independent role of CaSR signaling in renal calcium handling and supporting further study of encaleret as an oral treatment for patients with PSH."

Journal • P2 data • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Pain

BridgeBio Submits NDA for Encaleret for Autosomal Dominant Hypocalcemia Type 1 (HCPLive) - "Announced on May 12, 2026, this submission follows positive results from the CALIBRATE phase 3 trial, in which encaleret achieved all pre-specified primary and key secondary efficacy endpoints."

FDA filing • Endocrine Disorders

CALIBRATE-PEDS: Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1) (clinicaltrials.gov) - P2/3 | N=28 | Recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Not yet recruiting ➔ Recruiting | Initiation date: Aug 2025 ➔ Feb 2026

Enrollment open • Trial initiation date • Endocrine Disorders • Pediatrics

CALIBRATE: Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (clinicaltrials.gov) - P3 | N=67 | Active, not recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Trial completion date: Sep 2028 ➔ Aug 2029

Trial completion date • Endocrine Disorders • CASR

CALIBRATE-PEDS: A Phase 2/3, Multicenter, Single-Arm, Open-Label Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants with Autosomal Dominant Hypocalcemia Type1 (ENDO 2025) - P2, P3 | "CALIBRATE-PEDS is the first pediatric study of encaleret. It is under development and is expected to be initiated globally in 2025."

Clinical • P2/3 data • PK/PD data • Endocrine Disorders • Pediatrics

Therapeutic Management of ADH1 in a 16-year Old Boy Using Palopegteriparatide. (ENDO 2025) - "Previously, the patient was receiving alfacalcidol (1.25 mcg/day), CaCO3 (600 mg Ca/day), hydrochlorothiazide (12.5-6.25 mg), MgSO4 (260 mg Mg/day), and KCl (782 mg K/day)...Calcilytics (e.g., encaleret) should be the drugs of choice in the treatment of ADH1, but they are currently still the subject of/ under investigation (CALIBRATE trial)...The long-term effects of using long-acting PTHR1 analogs are currently unknown. However, this treatment should be considered in cases of severe abnormalities in calcium and phosphate levels that lead to calcium salt precipitation and subsequent organ dysfunction."

Cataract • Endocrine Disorders • Hypoparathyroidism • Infectious Disease • Metabolic Disorders • Nephrology • Ophthalmology • Pain • Renal Disease

The Oral Calcilytic Encaleret Reduced Urinary Calcium While Maintaining Blood Calcium in Individuals with Post-Surgical Hypoparathyroidism (ASBMR 2025) - P2 | No abstract available

Clinical • Endocrine Disorders • Hypoparathyroidism

Gain-of-Function CASR variants Identified as a Major Genetic Contributor of Non-Surgical Hypoparathyroidism: Findings from Over 300 Participants in a Sponsored Genetic Testing Program (ENDO 2025) - P3 | "An ongoing global Phase 3 study [NCT05680818] is investigating encaleret, an oral calcilytic, which has the potential to be the first targeted treatment for ADH1. The sponsored genetic testing program offers an efficient pathway for diagnosing genetic causes in patients with non-surgical hypoparathyroidism and, in accordance with consensus guidelines, enables improved care for those with an identified genetic etiology."

Endocrine Disorders • Hypoparathyroidism • Immunology • ACADM • ATP1A1 • CASR • DHCR7 • EGF • GATA3 • GNA11 • SLC2A3 • TBX1

Sustained Normalization of Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1: Results from a Phase 2 Study Over 42 Months of Encaleret (CLTX-305) Treatment (ENDO 2025) - P2, P3 | "Compared with screening, DXA Z-scores had decreased at LTEM24 but stabilized at LTEM36 (AP spine Z=2.6±1.5→2.2±1.6→2.2±1.6; Total hip Z=2.2±1.4→1.8±1.1→1.7±1.1; 1/3 radius Z=0.2±0.9→ -0.2±0.4→ -0.1±0.5, n=10-11 [p<0.05]).In patients with ADH1, encaleret corrected biochemical abnormalities and increased bone turnover, with stabilization of bone density by 42 months of continuous treatment. These consistent and sustained results are clinically meaningful and support ongoing efficacy and safety evaluation of encaleret as the first potential treatment for ADH1."

P2 data • Endocrine Disorders • Metabolic Disorders • Nephrology • Pain • Renal Disease • CASR

Study of the PTH-independent Effects of Encaleret on Mineral Homeostasis in Subjects With Postsurgical Hypoparathyroidism (PSH) (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: National Institute of Dental and Craniofacial Research (NIDCR) | Recruiting ➔ Completed | N=30 ➔ 13 | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ May 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Endocrine Disorders • Hypoparathyroidism

CALIBRATE-PEDS: Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1) (clinicaltrials.gov) - P2/3 | N=28 | Not yet recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company

New P2/3 trial • Endocrine Disorders • Pediatrics

A Rare CaSR Gene Variant Causing Autosomal Dominant Hypocalcemia Type 1 (ENDO 2025) - "A novel selective antagonist of CaSR, Encaleret, is currently being studied in qualifying patients with ADH1 in a Phase 3 clinical trial...To our knowledge, this variant has not been reported in literature or in a large population database indicating this variant is rare. This case highlights some of the complexities in the diagnosis and management of non-surgical hypoparathyroidism, while also contributing to the body of knowledge regarding genotype-phenotype expression of CaSR and raising awareness of novel therapeutic options for this condition."

Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • CASR

Gain-of-Function CASR variants Identified as a Major Genetic Contributor of Non-Surgical Hypoparathyroidism: Findings from Over 300 Participants in a Sponsored Genetic Testing Program (ESPE-ESE 2025) - P3 | "An ongoing global Phase 3 study [NCT05680818] is investigating encaleret, an oral calcilytic, which has the potential to be the first targeted treatment for ADH1. The sponsored genetic testing program offers an efficient pathway for diagnosing genetic causes in patients with non-surgical hypoparathyroidism and, in accordance with consensus guidelines, enables improved care for those with an identified genetic etiology."

Endocrine Disorders • Hypoparathyroidism • Immunology • ACADM • ATP1A1 • CASR • DHCR7 • EGF • GATA3 • GNA11 • SLC2A3 • TBX1

CALIBRATE-PEDS: A Phase 2/3, Multicenter, Single-Arm Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants with Autosomal Dominant Hypocalcemia Type 1 (ESPE-ESE 2025) - P2, P3 | "The primary endpoint is the composite endpoint of a) cCa within 2.1 to 2.6 mmol/L in participants aged ≥1 year, and within 2.0 to 2.8 mmol/L in participants aged <1 year and b) UCa <0.1 mmol/kg/d in toilet-trained participants or spot ratio of UCa/UCr within the age-specific reference range in non-toilet-trained participants. Participants meeting both criteria at the end of Period 3 will be considered responders. Key secondary endpoints include safety and tolerability, mineral homeostasis, renal ultrasound, bone density, and self- reported outcomes."

Clinical • P2/3 data • PK/PD data • Endocrine Disorders • Pediatrics

Sustained Normalization of Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1: Results from a Phase 2 Study Over 42 Months of Encaleret (CLTX-305) Treatment (ESPE-ESE 2025) - P2, P3 | "Baseline P3W24 LTEM12 LTEM24 LTEM36 CTx (value/ULN) 0.4±0.3 1.15±1.0* 1.45±1.23* 0.73±0.48* 0.71±0.53* P1NP (value/ULN) 0.3±0.1 1.22±1.05* 1.04±0.57* 1.1±0.68* 1.37±0.98* AP spine Z-score 2.6±1.5 2.3 ± 1.7 2.5 ± 1.7 2.2±1.6* 2.2±1.6* Total Hip Z-score 2.2±1.4 2.0 ± 1.4* 2.0 ± 1.3* 1.8±1.1* 1.7±1.1* 1/3 Radius Z-score 0.2±0.9 0.3 ± 0.9 0.5 ± 0.5 -0.2±0.4* -0.1±0.5* * p< 0.05 compared with Baseline In patients with ADH1, encaleret corrected biochemical abnormalities and increased bone turnover, with stabilization of bone density by 42 months of continuous treatment. These consistent and sustained results are clinically meaningful and support ongoing efficacy and safety evaluation of encaleret as the first potential treatment for ADH1."

P2 data • Endocrine Disorders • Metabolic Disorders • Nephrology • Pain • Renal Disease • CASR