BridgeBio(US:BBIO)2025-09-10 13:02Summary of BridgeBio Pharma's Investor Webinar on Incalerit for ADH1 Company and Industry Overview - Company: BridgeBio Pharma (NasdaqGS:BBIO) - Industry: Pharmaceuticals, specifically focusing on treatments for genetic disorders, particularly Autosomal Dominant Hypocalcemia Type 1 (ADH1) Core Points and Arguments 1. Introduction of Incalerit: Incalerit is a small molecule being developed for the treatment of ADH1, a rare genetic disorder characterized by low calcium levels due to mutations in the calcium-sensing receptor [2][17] 2. Patient Experience: A video presentation highlighted the challenges faced by patients with ADH1, emphasizing the need for effective treatment options [3][4] 3. Mechanism of ADH1: ADH1 is caused by heterozygous activating variants in the calcium-sensing receptor, leading to decreased parathyroid hormone (PTH) secretion and low blood calcium levels [10][11] 4. Clinical Manifestations: Symptoms of ADH1 include neuromuscular irritability, muscle cramps, and long-term complications such as kidney stones and chronic kidney disease [11][12] 5. Current Treatment Limitations: Conventional therapies do not address the underlying pathophysiology of ADH1 and can worsen long-term complications [13][14] 6. Incalerit's Mechanism of Action: Incalerit acts as a negative allosteric modulator of the calcium-sensing receptor, aiming to restore normal PTH secretion and calcium metabolism [16][17] 7. Clinical Development Program: The Phase IIb study showed that Incalerit effectively restored mineral homeostasis in patients with ADH1, with significant improvements in blood calcium and PTH levels [22][23] 8. Market Opportunity: The prevalence of ADH1 is estimated at 1 in 25,000 individuals, translating to approximately 12,000 individuals in the U.S., with 3,000 to 5,000 currently addressable based on symptoms [27][28] 9. Genetic Testing Initiatives: BridgeBio is sponsoring genetic testing programs to identify potential genetic variants causing hypoparathyroidism, which may accelerate diagnosis rates for ADH1 [30][31] 10. Regulatory Pathway: The company has had fruitful discussions with the FDA and international regulators regarding the trial design and is confident in its ability to file for approval based on Phase III results [71][72] Additional Important Content 1. Safety and Tolerability: Incalerit was well tolerated in the Phase II study, with few adverse events reported, primarily transient low blood phosphate concentrations [21][22] 2. Long-term Efficacy: Nearly 70% of patients achieved normal blood and urine calcium levels after 42 months of treatment with Incalerit, a significant improvement over standard care [23][24] 3. Phase III Study Design: The ongoing Phase III Calibrate study aims to confirm the efficacy of Incalerit, with top-line results expected in the fall [24][25] 4. Differentiation from PTH Therapy: Incalerit offers advantages over PTH replacement therapy, including oral administration and a focus on reducing urinary calcium excretion, which is crucial for preventing kidney complications [35][55] 5. Genetic Variants and Treatment Response: The Phase III study will include a broader range of genetic variants, allowing for a better understanding of treatment responses across different genotypes [66][82] This summary encapsulates the key points discussed during the investor webinar, highlighting the potential of Incalerit as a groundbreaking treatment for ADH1 and the strategic direction of BridgeBio Pharma in addressing this rare genetic disorder.