encaleret (BBP-305) / BridgeBio - LARVOL DELTA

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

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 | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2025 ➔ Aug 2025

Enrollment closed • Trial primary completion date • Endocrine Disorders • CASR

BridgeBio Pharma Reports Fourth Quarter and Full Year 2024 Financial Results and Commercial Update (GlobeNewswire) - "FORTIFY, the Phase 3 clinical trial of BBP-418 in LGMD2I/R9...The Company expects to achieve last participant – last visit and report topline results of the interim analysis cohort in the second half of 2025...CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1...The Company expects to achieve last participant – last visit and report topline results in the second half of 2025...PROPEL 3, the Phase 3 clinical trial of infigratinib in achondroplasia, the most common form of disproportionate short stature, is fully enrolled with 114 participants randomized. The Company expects to achieve last participant – last visit in the second half of 2025."

P3 data: top line • Trial status • Endocrine Disorders • Hypoparathyroidism • Muscular Dystrophy • Rare Diseases

Encaleret (CLTX-305) Normalizes Mineral Homeostasis Parameters in Patients with Autosomal Dominant Hypocalcemia Type 1 over 24 months in a Phase 2 Study (NCT04581629) (ASBMR 2024) - P2 | No abstract available

Clinical • Late-breaking abstract • P2 data • Endocrine Disorders

The Oral Calcilytic Encaleret Decreased the Fractional Excretion of Calcium in Individuals with Post-surgical Hypoparathyroidism: Preliminary Findings from an Ongoing Open-label Phase 2 Study (ASBMR 2024) - No abstract available

Clinical • Late-breaking abstract • P2 data • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Preliminary Findings From An Ongoing Open-label Phase 2 Study Demonstrate That The Calcilytic Encaleret Can Improve The Relationship Between Blood And Urinary Calcium In Individuals With Post-surgical Hypoparathyroidism (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P2 data • Endocrine Disorders • Hypoparathyroidism • Renal Disease

A Rare Heterozygous CaSR Mutation in Patient with Autosomal Dominant Hypocalcemia (ENDO 2024) - "She was referred to the CALIBRATE study for potential candidacy for the calcilytic, Encaleret. Patients with ADH1 present with symptoms of hypocalcemia and lab work demonstrating low- or low-normal PTH, hypocalcemia, hypomagnesemia, hyperphosphatemia, and elevated urinary calcium levels...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO."

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

CALIBRATE: Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Trial primary completion date: Jun 2024 ➔ Apr 2025

Trial primary completion date • Endocrine Disorders • CASR

Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone. (PubMed, Endocrinol Metab (Seoul)) - "Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level."

Journal • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Study of the PTH-independent Effects of Encaleret on Mineral Homeostasis in Subjects With Postsurgical Hypoparathyroidism (PSH) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: National Institute of Dental and Craniofacial Research (NIDCR) | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Study of the PTH-independent Effects of Encaleret on Mineral Homeostasis in Subjects With Postsurgical Hypoparathyroidism (PSH) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: National Institute of Dental and Craniofacial Research (NIDCR) | N=20 ➔ 30

Enrollment change • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1 (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2 | Trial completion date: Jan 2024 ➔ Sep 2023 | Trial primary completion date: Jan 2024 ➔ Sep 2023

Phase classification • Trial completion • Trial completion date • Trial primary completion date • Endocrine Disorders • CASR

Efficacy and Safety of Encaleret in Autosomal Dominant Hypocalcemia Type 1. (PubMed, N Engl J Med) - No abstract available

Journal • Endocrine Disorders

CALIBRATE: Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company | Trial completion date: Dec 2028 ➔ Sep 2028 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Endocrine Disorders • CASR