Core Insights - Encaleret demonstrated significant efficacy in normalizing blood and urine calcium levels in post-surgical hypoparathyroidism patients, with 80% achieving normal levels within 5 days of treatment initiation compared to 0% on conventional therapy at baseline [1][6] - The treatment was well-tolerated, with no serious adverse events reported during the study [1] - BridgeBio plans to initiate a registrational clinical study for encaleret in chronic hypoparathyroidism in 2026 based on the promising Phase 2 results [1][3] Company Overview - BridgeBio Pharma, Inc. is focused on developing transformative medicines for genetic diseases, with a pipeline that includes early science to advanced clinical trials [5] - The company was founded in 2015 and aims to leverage advances in genetic medicine to expedite patient care [5] Study Details - The Phase 2 proof-of-concept study evaluated the PTH-independent effects of encaleret on renal calcium handling in ten participants with post-surgical hypoparathyroidism, administered at 162 mg twice daily for up to 5 days [2] - Calcitriol was stopped one day prior to the first dose, and calcium levels were titrated based on blood calcium after starting encaleret [2] Additional Findings - Encaleret treatment resulted in a rapid and sustained reduction in fractional excretion of calcium in nine participants, supporting its potential as an orally-administered treatment option for chronic hypoparathyroidism [6] - Data from preclinical studies of infigratinib were also presented, showing significant improvements in bone growth and skull development in relevant mouse models, indicating broad potential for treating skeletal conditions [4]

Summary of BridgeBio Pharma (BBIO) 2025 Conference Call Company Overview - **Company**: BridgeBio Pharma - **Key Products**: Acoramidis, Encaleret - **Focus Areas**: Limb-girdle muscular dystrophy, autosomal dominant hypocalcemia type 1 (ADH1) Key Points Acoramidis Launch and Performance - The launch of acoramidis is described as having a strong start, with increasing momentum in both treatment naive and switch settings [2][3] - Acoramidis is noted for its superior clinical profile, being the only near-complete stabilizer on the market [2] - Key clinical outcomes include: - 50% reduction in hospitalization at 30 months - 40% reduction in all-cause mortality (ACM) and hospitalization at 30 months [3] - Metrics such as gross-to-net revenue have stabilized in the 30% to 40% range, with compliance around 80% [3][5] - New patient additions have accelerated, with 3,751 patients reported by Q2, up from 2,072 in Q1, indicating a growth rate of approximately 90 to 100 patients per week [8][9] Market Dynamics and Competitive Landscape - The discontinuation of Pfizer's Vyndaqel in 2026 is seen as an opportunity for BridgeBio to capture patients who would have been prescribed Vyndaqel, as these physicians are already predisposed to using stabilizers [12] - The polymorph patent covering both Vyndaqel and Vyndamax is expected to protect acoramidis from generic competition, raising the bar for any potential generic manufacturers [13][14] Encaleret Development - Encaleret is being developed for ADH1, with a prevalence rate of about 1 in 25,000, translating to approximately 12,000 individuals in the U.S. [22] - The diagnosis rates for ADH1 are lagging behind prevalence due to the lack of indicated treatments [22][23] - Phase two results showed that 70% of patients normalized both blood and urine calcium levels, which is a significant improvement over conventional therapies [34][35] - The phase three study is designed to evaluate the concurrent normalization of blood and urine calcium over six months, informed by phase two results [35] Limb-Girdle Muscular Dystrophy Insights - Ribitol is crucial for muscle function as it is used by FKRP to glycosylate alpha-dystroglycan, a stabilizing protein in muscle fibers [45] - Phase two results indicated an approximate doubling of glycosylated alpha-dystroglycan levels in patients, with a significant reduction in creatine kinase (CK) levels [52][53] - The study aims for a 5% absolute change in glycosylated alpha-dystroglycan and a 40% reduction in CK for potential accelerated approval [56][57] Competitive Landscape for Hypoparathyroidism - Encaleret is positioned against Yorvipath, with potential advantages such as being an oral medication and offering a urine calcium benefit [43][44] - The treatment goals focus on normalization of blood calcium, urine calcium, and phosphate, rather than complete independence from conventional therapy [41] Future Outlook - The company is optimistic about the continued growth of acoramidis and the potential for encaleret to address unmet needs in hypoparathyroidism and ADH1 [14][44] - Upcoming data presentations and interim analyses are expected to provide further insights into the efficacy and market positioning of both acoramidis and encaleret [56][57] Additional Important Insights - The company emphasizes the importance of genetic testing for undiagnosed patients with ADH1, suggesting that many patients with hypoparathyroidism are not genotyped [28][23] - The phase three trial for encaleret is designed to be powered for success based on the promising phase two results, indicating a strong confidence in the product's potential [35][40]

Financial Data and Key Metrics Changes - The company announced a significant increase in the number of treatment-naive patients on acoramidis, indicating positive commercial execution [47][48] - The gross-to-net ratio is expected to stabilize in the range of 30% to 40%, reflecting a more representative payer mix [56][57] Business Line Data and Key Metrics Changes - The ADH-1 program is transitioning from a single-center phase two study to a global phase three study with over 25 sites, which may lead to a more heterogeneous patient population [3][4] - In the phase two study of ADH-1, 70% of patients responded to encaleret, and the company aims to replicate this success in phase three [15][38] Market Data and Key Metrics Changes - The prevalence of ADH-1 was estimated at 1 in 25,000 based on data from multiple biobanks, indicating a consistent finding across different cohorts [18][19] - The company is learning that many patients diagnosed with hypoparathyroidism may actually have ADH-1, which highlights the need for better disease education and genetic testing [19] Company Strategy and Development Direction - The company is focused on driving disease education and increasing the utilization of genetic testing to improve diagnosis rates for ADH-1 [19] - The strategy includes leveraging compelling clinical data and new treatment guidelines to enhance awareness and diagnosis of the condition [12][13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the launch of acoramidis, noting that the share of treatment-naive patients has been increasing month over month [47][48] - The company believes that any treatment that stops or slows the progressive loss of function will be well-received by patients, given the lack of current options [43] Other Important Information - The company plans to present full phase two data for chronic hypoparathyroidism at an upcoming medical meeting, which may address skepticism regarding efficacy [26] - The phase three study for 418 is designed to show trends in clinical measures rather than statistically significant benefits, aligning with FDA requirements for accelerated approval [38][40] Q&A Session Summary Question: What are the risks in translating phase two findings to phase three for ADH-1? - The main difference is the number of sites and patients, with phase three being a global study involving over 25 sites [3] Question: How does the company view the use of PTH replacement therapy in ADH-1 patients? - Management indicated that PTH replacement is not ideal for these patients due to the intact parathyroid glands and the need for a more biologically appropriate treatment [9][10] Question: What factors will drive physicians to pursue genetic testing for ADH-1? - Compelling clinical data, new treatment guidelines recommending genetic testing, and the implementation of a new ICD-10 code for ADH-1 are key drivers [12][13] Question: How does the company plan to differentiate encaleret in the market? - The company aims to demonstrate urine calcium benefits and long-term safety, which are not currently addressed by other treatments [27] Question: What is the expected impact of competition on the market? - The company believes that its strategy of parity access and best-in-class hospitalization data will maintain its market position despite competition [60][61] Question: What is the company's stance on the potential for generic competition for tafamidis? - Management expressed confidence that the existing patents provide strong protection against generics entering the market [62][63]

Financial Data and Key Metrics Changes - The company reported a significant increase in the number of treatment-naive patients on acoramidis, indicating a positive trend in commercial execution [47][53] - The gross-to-net ratio is expected to stabilize in the range of 30% to 40%, reflecting a more representative payer mix as of Q2 [55][56] Business Line Data and Key Metrics Changes - The ADH-1 program is transitioning from a single-center phase two study to a global phase three study with over 25 sites, which may lead to a more heterogeneous patient population [3][4] - In the phase two study of ADH-1, approximately 70% of patients responded to encaleret, and the company aims to replicate this success in phase three [16][38] Market Data and Key Metrics Changes - The prevalence of ADH-1 has been estimated at about 1 in 25,000 based on data from multiple biobanks, indicating a consistent finding across different cohorts [18][19] - The company is comparing the patient identification and market development strategies for ADH-1 to those used in the ATTR field, which has seen significant improvements in diagnosis rates [22] Company Strategy and Development Direction - The company is focused on driving disease education and the utilization of genetic testing to improve diagnosis rates for ADH-1 [19] - The strategy for encaleret includes differentiating the product through urine calcium reduction and long-term safety, aiming to establish it as a standard of care [27][28] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the launch of acoramidis, noting that the share of treatment-naive patients continues to increase, which is a positive indicator for long-term success [47][48] - The company is optimistic about the upcoming data presentations that may address skepticism regarding the efficacy of encaleret in chronic hypoparathyroidism [25][26] Other Important Information - The company is preparing for a webinar to provide more details on the ADH-1 program, indicating a commitment to transparency and stakeholder engagement [3] - Management highlighted the importance of compelling clinical data and new treatment guidelines in driving diagnosis rates for ADH-1 [13][14] Q&A Session Summary Question: What are the risks in translating phase two findings to phase three for ADH-1? - The main difference is the number of sites and patients, with phase three being a global study involving over 25 sites [3] Question: Why is PTH replacement therapy not optimal for ADH-1 patients? - PTH replacement does not address the root cause of the condition, and urine calcium levels remain high even with treatment [10][11] Question: How is the company addressing patient identification for ADH-1? - The company is focusing on compelling clinical data, new treatment guidelines recommending genetic testing, and increased awareness through ICD-10 coding [13][14][18] Question: What is the expected impact of competition on acoramidis? - The company has not seen significant pressure from competitors and maintains a strategy of parity access without needing to offer larger rebates [57][59] Question: What is the confidence level regarding the safety profile of infigratinib? - The phase two data provided confidence in a clean safety profile, and the company expects to continue monitoring safety closely in phase three [65][66]

Financial Data and Key Metrics Changes - The company reported a significant increase in the number of treatment-naive patients on acoramidis, indicating a positive trend in commercial execution [47][53] - The gross-to-net ratio is expected to stabilize in the range of 30% to 40%, reflecting a more representative payer mix as of Q2 [55][56] Business Line Data and Key Metrics Changes - The ADH-1 program is transitioning from a single-center phase two study to a global phase three study with over 25 sites, which may lead to a more heterogeneous patient population [3][4] - In the phase two study of ADH-1, approximately 70% of patients responded to encaleret, and the company aims to replicate this success in phase three [16][38] Market Data and Key Metrics Changes - The prevalence of ADH-1 has been estimated at about 1 in 25,000, consistent across multiple biobanks, indicating a stable understanding of the patient population [18][19] - The company is comparing its market potential to that of ATTR and X-linked hypophosphatemia, suggesting a similar trajectory in patient identification and market development [22][23] Company Strategy and Development Direction - The company is focused on driving disease education and the utilization of genetic testing to improve diagnosis rates for ADH-1 [19] - The strategy includes leveraging compelling clinical data and new treatment guidelines to enhance awareness and diagnosis of the condition [13][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the launch of acoramidis, noting that the share of treatment-naive patients continues to increase, which is a positive indicator for long-term success [47][52] - The company is optimistic about the upcoming data presentations that may address skepticism regarding the efficacy of encaleret in chronic hypoparathyroidism [25][66] Other Important Information - The company is preparing for a webinar to provide more details on the ADH-1 program, indicating a commitment to transparency and stakeholder engagement [3] - Management highlighted the importance of long-term safety and efficacy data for encaleret, particularly in relation to urine calcium reduction, which could differentiate it in the market [27][66] Q&A Session Summary Question: What are the risks in translating phase two findings to phase three for ADH-1? - The main difference is the number of sites and patients, with phase three being a global study involving over 25 sites [3] Question: Why is PTH replacement therapy not optimal for ADH-1 patients? - PTH replacement does not address the root cause of the condition, and urine calcium levels remain high even with treatment [10][11] Question: How is the company addressing patient identification for ADH-1? - The company is focusing on compelling clinical data, new treatment guidelines recommending genetic testing, and increased awareness through ICD-10 coding [13][14][18] Question: What is the expected impact of competition on acoramidis? - The company has not seen significant pressure from competitors and maintains a strategy of parity access without needing to offer larger rebates [57][58] Question: How does the company view the potential for generic competition for tafamidis? - The company believes that the existing patents provide strong protection against generics, and the discontinuation of Vyndaqel complicates entry for potential competitors [60][61]

Pipeline and Approvals - Attruby (acoramidis) is now FDA approved in the US for Transthyretin Amyloidosis (ATTR-CM)[8, 40, 42] - Beyonttra (acoramidis) is approved in the EU, Japan, and UK[11, 32] - Three Phase 3 trials are fully enrolled: BBP-418 for Limb-Girdle Muscular Dystrophy 2I/R9 (112 patients), encaleret for Autosomal Dominant Hypocalcemia Type 1 (71 patients), and infigratinib for Achondroplasia (114 participants)[12] Attruby (acoramidis) Clinical and Commercial Performance - Attruby demonstrated a 42% reduction in the composite of all-cause mortality and recurrent cardiovascular-related hospitalization events at Month 30[44] - Attruby showed a 50% reduction in the cumulative frequency of cardiovascular-related hospitalization events at Month 30[44] - In Q1 2025, Attruby generated $36.7 million in total U S revenue[51] - Attruby has achieved 77% Medicare lives in equal formulary position to tafamidis[51] Market and Financial Outlook - The global annual ATTR market is projected to reach $15-$20 billion at its peak[30, 66] - BridgeBio envisions a vision for 2030 with >$8 billion in revenue[35] - The company estimates the market opportunity for Infigratinib in Achondroplasia and Hypochondroplasia to be $2B+ each[30] - The company estimates the market opportunity for BBP-418 in Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) to be $1B+[30, 146] - The company estimates the market opportunity for Encaleret in Autosomal Dominant Hypocalcemia Type 1 (ADH1) to be $1B+[30, 121]