BridgeBio Pharma : BBIO – Encaleret – ADH1 – ENDO 2025 – CALIBRATE-PEDS Phase 2/3 Study Design

Published: 2025-07-13 15:17:05 ET BBIO

Published on 07/13/2025 at 15:17

Peter J Tebben MD1, Todd Alexander MD2,, Stefano Mora MD3, Raja Padidela MBBS, MRCPCH, MD4,5, Mary Scott Roberts MD6, Dingfeng Li MD, MSc6, Scott Adler MD6, Rachel I. Gafni MD7

1. Departments of Internal Medicine and Pediatrics, Section of Endocrinology, Yale University, New Haven, CT, USA; 2. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 3. Pediatric Endocrinology, Department of Pediatrics, IRCCS San Raffaele Hospital, Milano, Italy; 4. Department of Paediatric Endocrinology, Manchester University NHS Foundation Trust Hospital, Manchester, UK ; 5. Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.; 6. Calcilytix Therapeutics, Inc. a company of BridgeBio Pharma, Inc, San Francisco, CA, USA; 7. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

Background

Key Eligibility Criteria

Key Endpoints & Analyses

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by activating variants in the calcium-sensing receptor gene (CASR)1, presenting with low/inappropriately normal parathyroid hormone (PTH), hypocalcemia, and hypercalciuria1 (Figure 1).

Children with ADH1 often experience severe symptoms such as seizures in early childhood1.

Encaleret is an investigational oral negative allosteric

Age: birth to < 18 years

Documented activating variant of CASR

Biochemical diagnosis of hypoparathyroidism

Documented history of signs or symptoms of ADH1

On SoC and/or PTH treatment for at least 3-6 months prior to Screening

cCa within 8.4 to 10.4 mg/dL in ≥ 1y, or within 8.2 to 11.4 mg/dL in < 1y

UCa < 4 mg/kg/d in toilet-trained participants or spot ratio of UCa/UCr within the age-specific reference range in non-toilet-trained participants

Additional endpoints include PK, safety and tolerability, mineral homeostasis parameters, renal ultrasound, bone health, and self-reported outcomes.

modulator of the calcium-sensing receptor (Figure 2), with five strength tablets available. A pediatric formulation is under development for younger children who cannot swallow tablets or those who require finer dose adjustments.

In a Phase 2b study in 13 adults with ADH1,

4

1αOHase, 1α-hydroxylase; 1,25(OH)2D, 1,25dihydroxyvitamin D; 25(OH)D, 25hydroxyvitamin D; Ca2+, calcium; PTH, parathyroid hormone; PTH1R, PTH

History of thyroid or parathyroid surgery

History of conditions within 5 years that are associated with increased risk of osteosarcoma

Blood 25-OH Vitamin D cannot be corrected to 20 ng/mL or greater

Estimated glomerular filtration rate < 30 mL/minute/1.73 m2

PK parameters

blood iPTH

blood phosphate

blood magnesium

1,25-(OH)2Vitamin D

renal function

bone turnover markers

bone mineral density

renal ultrasound

10-item short form health survey

pediatric ADH1 questionnaire

palatability assessment

encaleret led to sustained normalization in PTH,

type-1 receptor, PO 3-, phosphate; VDR, vitamin D receptor. (Adapted from

The statistical analyses will be descriptive; no statistical testing is planned.

PTH Secretion

albumin-corrected calcium (cCa), phosphate, magnesium, and 24-hr urine calcium (UCa) excretion over 24 weeks, without serious adverse events reported2.

ADH1

Wild type

Encaleret

Parathyroid

Roskzo et al, 20221)

ADH1

Wild type

Encaleret

Kidney

Ca2+ Excretion

A Phase 3 study [NCT05680818, CALIBRATE] in adults with ADH1 is ongoing.

Blood Ca2+ Blood Ca2+

(Adapted from Tfelt-Hansen J et al, 20023)

Study Design

Approximately 28 children will be enrolled in 4 age cohorts (n=7 per cohort, Figure 3) sequentially, starting with the Cohort 1 (12 - <18y), followed by Cohort 2 (6 -

<12y), Cohort 3 (2 - <6y), and Cohort 4 (birth - <2y).

References

Roszko KL, Stapleton Smith LM, et al. Autosomal Dominant Hypocalcemia Type 1: A Systematic Review. J Bone Miner Res. 2022 Oct;37(10):1926-1935. doi: 10.1002/jbmr.4659

Gafni RI, Hartley IR, Roszko KL, et al. Efficacy and Safety of Encaleret in Autosomal Dominant Hypocalcemia Type 1. N Engl J Med. 2023;389(13):1245-1247. doi:10.1056/NEJMc2302708

Tfelt-Hansen, J., et al. The Role of the Calcium-Sensing Receptor in Human Pathophysiology. Curr Med Chem 2002;2(3):175-193: - 175-193. DOI: https://doi.org/10.2174/1568013023358870

Summary

CALIBRATE-PEDS is the first pediatric study of encaleret as a potential treatment for ADH1.

It is under development and is expected to be initiated globally in 2025.

Disclaimer

BridgeBio Pharma Inc. published this content on July 13, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on July 13, 2025 at 19:16 UTC.