BridgeBio Pharma Stock

BridgeBio Pharma, Inc. (BridgeBio) operates as a commercial-stage biopharmaceutical company.

BridgeBio's pipeline of development programs ranges from early science to advanced clinical trials. The company works across over 20 disease states at various stages of development.

The company focuses on genetic diseases because they exist at the intersection of high unmet patient need and tractable biology. The company's approach is to translate research pioneered at academic laboratories and leading medical institutions into products that the company hope will ultimately reach patients. The company is able to realize this opportunity through a confluence of scientific advances, including: (i) the identification of the genetic underpinnings of disease as more cost-efficient genome and exome sequencing becomes available; (ii) progress in molecular biology; and (iii) the development and maturation of longitudinal data and retrospective studies that enable the linkage of genes to diseases. This early-stage innovation represents one of the greatest practical sources for new drug creation.

The company has developed a world-class product platform that supports the continued growth of the company and the advancement of the company's pipeline.

Late-Stage Pipeline

The company's late-stage pipeline has delivered positive Phase 3 results for acoramidis, the New Drug Application (NDA), for which has been accepted for review by the FDA with the deadline for the FDA to review such NDA, or the Prescription Drug User Fee Act (PDUFA) date, set on November 29, 2024. This pipeline is expected to deliver Phase 3 results in three additional programs in potential markets of $1.0 billion dollars or more (low-dose infigratinib for achondroplasia, encaleret for ADH1, and BBP-418 for LGMD2I/R9) over the next two years.

Acoramidis (Eidos): TTR Amyloidosis

The company is developing acoramidis, also known as AG10, a next-generation oral small molecule near-complete TTR stabilizer, for the treatment of TTR amyloidosis, or ATTR. Acoramidis has the potential to demonstrate greater potency than first-generation partial stabilizers based on results from comparative nonclinical studies.

On July 17, 2023, the company announced positive data from its Phase 3 ATTRibute-CM clinical trial of acoramidis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The primary endpoint (a hierarchical analysis inclusive of all-cause mortality and frequency of cardiovascular-related hospitalization) was met (Win Ratio of 1.8) with a highly statistically significant p-value (p<0.0001). This primary endpoint result consistently favored acoramidis treatment across key subgroups, including across both variant and wild-type ATTR patients as well as across New York Heart Association (NYHA) Class I, II, and III patients. Absolute values observed across all-cause mortality (ACM), cardiovascular mortality (CVM) and CVH showed that over 30 months, patients survived more and were hospitalized less than has been seen in prior controlled studies of ATTR-CM to the company's knowledge. Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified. In additional results from ATTRibute-CM presented by the company on November 12, 2023, the placebo and acoramidis time-to-first event Kaplan-Meier curves for a composite of ACM and CVH separated beginning at Month 3, representing the most rapid and sustained clinical benefit on the composite endpoint of ACM and CVH in ATTR-CM patients through Month 30 to the company's knowledge.

On December 5, 2023, the company announced that it had submitted an NDA for acoramidis for the treatment of ATTR-CM to the FDA. On February 5, 2024, the company announced that the NDA for acoramidis for the treatment of ATTR-CM had been accepted by the FDA, with a PDUFA date of November 29, 2024, and that the Marketing Authorization Application (MAA) had been accepted by the European Medicines Agency (EMA).

Clinical Data

Phase 2 Data

In November 2018, the company announced Phase 2 data for acoramidis in symptomatic patients with ATTR-CM. The randomized, placebo-controlled, dose-ranging clinical trial included 49 patients with symptomatic ATTR-CM, of which 14 had ATTR-CM. Eligible patients were randomized in a 1:1:1 ratio to placebo or 400 milligrams or mg, or 800 mg of acoramidis twice daily over 28 days. Overall, acoramidis was well-tolerated in symptomatic ATTR-CM subjects with no safety signals of potential clinical concern attributed to study drug.

In November 2019, the company announced data from its Phase 2 open-label extension, or OLE, suggesting long-term tolerability of acoramidis and stabilization of ATTR-CM disease measures. Acoramidis was well-tolerated in the OLE and no safety signals of potential clinical concern were attributed to study drug. The rate of all-cause mortality (including either death or cardiac transplantation, 8.5%) and cardiovascular-related hospitalizations (proportion experiencing at least one event, 25.5%) observed in an exploratory analysis of OLE participants following a median of 15 months since Phase 2 initiation were lower than those observed at 15 months in placebo-treated patients in the ATTR-ACT study (all-cause mortality including death or cardiac transplantation, 15.3%; cardiovascular-related hospitalizations, 41.8%).

In October 2023, the company presented updated results from its Phase 2 OLE, demonstrating continued long-term tolerability of acoramidis and stabilization of ATTR-CM disease measures. With a median of 55 months of continuous treatment, acoramidis was generally well-tolerated in the OLE and no safety signals of potential clinical concern were attributed to study drug. In patients with symptomatic ATTR-CM, long-term treatment with acoramidis is associated with both stable median NT-proBNP levels and sustained increases in serum TTR. In this ongoing open-label study, at least 53% of patients with ATTR-CM and NYHA Class II or III at entry to the phase 2 trial have survived for a median follow-up of 4.6 years.

Phase 3 Data

In February 2019, the company initiated ATTRibute-CM, a global Phase 3 randomized, placebo-controlled clinical trial of acoramidis in ATTR-CM. ATTRibute-CM enrolled 632 subjects with symptomatic ATTR-CM, associated with either wild-type or variant TTR and New York Heart Association, or NYHA, Class I-III symptoms. Subjects were randomized 2:1 between treatment (acoramidis 800 mg) and placebo twice daily in a two-part trial. In Part A, change in 6MWD at 12 months was compared between treatment and placebo groups as a potential registrational endpoint. In Part B, the hierarchical composite primary endpoint including all-cause mortality and cardiovascular hospitalizations will be compared between treatment and control groups at 30 months. Secondary endpoints include quality of life as assessed by the KCCQ-OS, safety parameters, serum TTR levels, a measure of TTR stabilization, and NT-proBNP levels, a cardiac biomarker. In Part B, concomitant use of tafamidis is allowed.

On December 27, 2021, the company reported topline data from Part A of the ATTRibute-CM trial which did not meet its primary endpoint of change from baseline in 6MWD (p = 0.76). Mean observed 6MWD decline for the acoramidis and placebo arms were 9 meters and 7 meters, respectively. Decline observed in both arms of ATTRibute-CM was similar to expected functional decline in healthy elderly adults at 12 months. The company observed improvements in acoramidis-treated participants relative to placebo-treated participants at Month 12 on secondary and exploratory endpoints, including NT-proBNP, serum TTR concentration and KCCQ-OS.

On July 17, 2023, the company announced positive data from its Phase 3 ATTRibute-CM clinical trial of acoramidis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The primary endpoint (a hierarchical analysis inclusive of all-cause mortality and frequency of cardiovascular-related hospitalization) was met (Win Ratio of 1.8) with a highly statistically significant p-value (p<0.0001). This primary endpoint result consistently favored acoramidis treatment across key subgroups, including across both variant and wild-type ATTR patients as well as across New York Heart Association (NYHA) Class I, II, and III patients. In particular, consistency against cardiovascular-related hospitalizations (CVH) was observed across all prespecified subgroups at 30 months. Absolute values observed across all-cause mortality (ACM), cardiovascular mortality (CVM) and CVH showed that over 30 months, patients survived more and were hospitalized less than has been seen in prior controlled studies of ATTR-CM to the company's knowledge. Assessment of measures of disease progression in the trial suggest that of participants assigned to receive acoramidis treatment who completed a Month 30 visit, 45% experienced an improvement from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 40% experienced an improvement from baseline on 6-minute walk distance (6MWD), and 13% experienced an improvement from baseline in NYHA class. The placebo and acoramidis time-to-first event Kaplan-Meier (K-M) curves for a composite of all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) separated beginning at Month 3, representing rapid and sustained clinical benefit on the composite endpoint of ACM and CVH in ATTR-CM patients through Month 30 (Hazard Ratio = 0.645, 95% CI: 0.500-0.832). Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified.

Low-dose Infigratinib: Achondroplasia

The company is developing low-dose infigratinib, an oral FGFR1-3 selective tyrosine kinase inhibitor, or TKI, as a treatment option for children with achondroplasia. The company is enrolling patients in PROPEL, a prospective observational study in children with achondroplasia and PROPEL 3, a Phase 3 double-blinded, placebo-controlled pivotal study of low-dose infigratinib at a dose level of 0.25 milligrams per kilogram per day (mg/kg/day) in children with achondroplasia.

On June 20, 2023, the company announced positive topline results from PROPEL2, its Phase 2 clinical trial of infigratinib in children with achondroplasia. In the highest dose level (Cohort 5, 0.25mg/kg once daily), the mean change from baseline in annualized height velocity ('AHV') at six months was +3.38 centimeters per year (cm/yr) (p = 0.001). Infigratinib demonstrated clear dose-responsiveness when given as a single daily oral dose and was well-tolerated with no treatment-related adverse events ('AEs') assessed in Cohort 5.

Clinical Development Plan

The company is enrolling patients in PROPEL, a prospective observational study in children with achondroplasia. The study will establish annualized height velocity, or AHV, for each child for a minimum period of six months. PROPEL is designed to provide baseline measurements for children that the company anticipate enrolling in PROPEL 3, the pivotal Phase 3 trial.

Following positive feedback on the regulatory path to approval from FDA and EMA, the company initiated PROPEL 3, a phase 3 double-blinded, 2:1 randomized, placebo-controlled pivotal study of low-dose infigratinib at a dose level of 0.25 mg/kg/day in children with achondroplasia. The primary endpoint is change from baseline in AHV and the secondary endpoints include safety, proportionality, and height for age z-score. On December 12, 2023, the company announced the first child randomized in PROPEL 3.

Low-dose Infigratinib: Hypochondroplasia

The company is also developing low-dose infigratinib as a treatment option for children living with hypochondroplasia, a skeletal dysplasia closely related to achondroplasia and similarly driven by FGFR3 gain-of-function variants. ACCEL, an observational study for infigratinib in hypochondroplasia, is expected to initiate in the first half of 2024. The company is also committed to exploring the potential of infigratinib on the wider medical and functional impacts of hypochondroplasia, which hold significant unmet needs for families.

Encaleret: Autosomal Dominant Hypocalcemia Type 1 and Hypoparathyroidism

Encaleret is an oral small molecule antagonist of the calcium sensing receptor, or CaSR, that the company is developing for the treatment of Autosomal Dominant Hypocalcemia Type 1, or ADH1. The company is studying encaleret in an ongoing Phase 3 clinical trial as a potential treatment for patients with ADH1. The company reported results from the Phase 2b study in 2022 and published the results from the same study in the New England Journal of Medicine in September 2023. In 13 participants in the Phase 2b trial, treatment with encaleret resulted in rapid and sustained restoration of normal mineral homeostasis, with mean values of blood calcium, urinary calcium, and blood parathyroid hormone, or PTH within the normal range by day 5 of therapy and sustained at 24 weeks, and was well-tolerated without any reported serious adverse events. Encaleret has been granted orphan drug and fast track designations by the FDA for the treatment of autosomal dominant hypocalcemia. Encaleret has also been granted orphan designation by the European Commission as a treatment for hypoparathyroidism, inclusive of ADH1.

Clinical Data

On June 13, 2022, the company reported positive data from its Phase 2b clinical trial of encaleret in patients with ADH1. Thirteen adults with ADH1 caused by nine unique CASR variants participated in the three-period, Phase 2b, open-label, dose-ranging clinical trial. Oral calcium and activated vitamin D supplements were discontinued prior to encaleret initiation. Periods 1 and 2 each evaluated encaleret over the course of five inpatient days and Period 3 included a 24-week outpatient evaluation.

The participants who completed Period 3 of the Phase 2b study were eligible to continue in an open-label extension of up to 25 months. The results of the study were published in the New England Journal of Medicine in September 2023.

The company also announced the initiation of its Phase 3 registrational trial of encaleret in ADH1 in December 2022.

BBP-418: Limb Girdle Muscular Dystrophy Type 2I

BBP-418 is an investigational, orally administered, small molecule substrate supplementation therapy that the company is developing for the treatment of LGMD2I, also known as LGMDR9. In October 2023, the company shared positive long-term data from its Phase 2 trial in patients with LGMD2I, including that early assessment of increased glycosylated alphaDG predicted subsequent ambulatory improvements at later time points, supporting the use of glycosylated alphaDG levels as a potential surrogate endpoint in LGMD2I. The company is studying BBP-418 in FORTIFY, an ongoing global registrational Phase 3 clinical trial in patients with LGMD2I. There is potential to pursue accelerated approval in the U.S. for BBP-418 based on recent interactions with the FDA on the use of glycosylated alphaDG as a surrogate endpoint.

Clinical Data

On October 9, 2023, the company shared positive long-term results from the company's ongoing Phase 2 clinical trial of BBP-418 in patients with LGMD2I at the Annual Congress of the World Muscle Society. The open-label, dose-ascending Phase 2 trial enrolled 14 participants, including both ambulatory and non-ambulatory patients with LGMD2I, across three cohorts. The new long-term data remains consistent with earlier data from the Phase 2 study showing a well-tolerated safety profile and encouraging preliminary efficacy. Additionally, early changes in glycosylated alphaDG levels at 3 months appear to be associated with ambulatory improvements at 9 months, providing support for the possible use of glycosylated alphaDG levels as a surrogate endpoint in the ongoing Phase 3 study for accelerated approval.

Clinical Development Plan

The company's Phase 2 clinical trial investigating BBP-418 in LGMD2I is ongoing. Following the release of top-line data from the company's Phase 2 trial, the company has engaged with regulatory authorities to align on a Phase 3 trial design. The company's Phase 3 trial, FORTIFY, was initiated in the U.S., with the first patient enrolled in June 2023.

Sales and Marketing

The company intends to build a commercial infrastructure in the United States and selected other territories to support the commercialization of the company's product candidates when a regulatory approval in a particular territory is likely. As of December 31, 2023, the company received regulatory approval for two products that the company previously developed, TRUSELTIQ (infigratinib) for the treatment of patients with previously-treated locally advanced or metastatic cholangiocarcinoma, or CCA harboring an FGFR2 fusion or rearrangement, and NULIBRY (fosdenopterin) for injection as the first therapy to reduce the risk of mortality in patients with MoCD Type A. Sentynl Therapeutics, Inc., or Sentynl, acquired global rights to NULIBRY in the first quarter of 2022 and is now responsible for the ongoing development and commercialization of NULIBRY in the United States and developing, manufacturing and commercializing fosdenopterin globally. Following FDA approval of TRUSELTIQ (infigratinib) in May 2021, the company was the principal selling party of this product in the United States. Commencing in January 2022, the company sold the remaining transitional supply of TRUSELTIQ to Helsinn Healthcare S.A. and Helsinn Therapeutics (U.S.), Inc., or collectively, Helsinn, and Helsinn became the principal selling party. Helsinn permanently discontinued the distribution of TRUSELTIQ and requested a withdrawal of the NDA in May 2023, additionally, all clinical investigations under the associated IND are discontinued. In December 2022, the company entered into a mutual termination agreement with Helsinn concerning, among other things, steps to wind down the commercialization of infigratinib in oncology indications.

Intellectual Property

As of February 13, 2024, the company's intellectual property portfolio was composed of 133 issued patents and 108 patent applications that the company licenses from academic and research institutions and other third parties, and 56 issued patents and 424 pending patent applications that the company owns or co-owns, including through its subsidiaries. These patents and patent applications generally provide the company with the rights to develop the company's product candidates in the United States and worldwide.

For the company's subsidiary, QED Therapeutics, Inc. ('QED'), the company licenses rights from Novartis to two issued U.S. patents, and related pending and issued foreign patents and patent applications in Australia, Canada, China, Europe, Japan and Mexico, as well as in other countries in Asia and in South America, that are directed to compositions of matter of infigratinib. The foreign patents and patent applications, if issued, are expected to expire between 2025 and 2030. The issued U.S. patents are expected to expire between 2028 and 2029, which takes into account patent term adjustments granted by the USPTO, as well as a terminal disclaimer of one issued patent to another U.S. patent. Upon the initial approval of infigratinib, QED applied for 1,516 days of patent term extension, or PTE, for the U.S. patent covering the infigratinib compound; assuming grant of the PTE application, the term of this patent may be extended from August 25, 2029, to October 19, 2033.

The company also licenses rights from Novartis to two issued U.S. patents and related pending and issued foreign patents and patent applications in Australia, Canada, China, Europe, Japan and Mexico, as well as in other countries in Asia and in South America, that are directed to pharmaceutical formulations containing infigratinib. The issued patents and patent applications, if issued, are expected to expire in 2034. In addition, the company license rights from Novartis to one issued U.S. patent, one pending U.S. patent application, and related pending and issued foreign patents and patent applications in Australia, Canada, China, Europe, Japan and Mexico, as well as in other countries in Asia, that are directed to methods of treating hypophosphatemic disorders. The issued patents and patent applications, if issued, are expected to expire in 2033.

The company also licenses rights from Inserm Transfert ESA and Assistance Publique-HÔpitaux de Paris to two issued U.S. patents and one pending U.S. patent application, and one granted patent in Europe, that are directed to methods of treating skeletal dysplasias using infigratinib. The issued U.S. patents, granted patent in Europe, and the pending patent application, if issued, are expected to expire in 2032.

In addition, QED owns five pending U.S. patent applications, one pending Patent Cooperation Treaty, or PCT, patent application, and related pending foreign patent applications in Australia, Canada, China, Europe, Japan and Mexico, as well as in other countries in Asia, that are directed to methods of treating various cancers or skeletal disorders using infigratinib. If any patents issue from these patent applications, such patents would be expected to expire between 2040 and 2044.

For the company's subsidiary Eidos Therapeutics, Inc., the company licenses rights from the Board of Trustees of the Leland Stanford Junior University, or Stanford, to ten issued U.S. patents, two pending U.S. patent applications, one issued European patent, and one issued Japanese patent with claims directed to composition of matter and methods of use relating to acoramidis. These patents are expected to expire in 2031 or 2033.

In addition, the company owns five issued U.S. patents, six pending U.S. patent applications, and 67 related foreign patents issued or patent applications pending in various jurisdictions, including Australia, Canada, Europe, China, Japan, and Mexico, with claims directed to salt and solid forms, methods of manufacturing, dosing methods, and/or formulations relating to acoramidis. The issued U.S. and foreign patents are expected to expire in 2038 or 2039. The pending U.S. and foreign patent applications, if issued, are also expected to expire between 2038 and 2044.

For the company's subsidiary, Calcilytix, Inc., the company licenses rights from Japan Tobacco Company to one issued U.S. patent and two foreign patents in Europe and Japan that are directed to compositions of matter of encaleret. The U.S. patent is expected to expire in 2025, and the foreign patents are expected to expire in 2024. In addition, Calcilytix owns four pending U.S. patent applications, and thirty one related foreign patent applications pending in various jurisdictions, including Australia, Canada, Europe, China, Japan, and Mexico with claims to formulations, dosing methods, and patient selection methods relating to encaleret. The pending U.S. and foreign patent applications, if issued, are expected to expire between 2041 and 2044.

For the company's subsidiary, ML Bio Solutions, Inc., the company licenses rights from the Charlotte-Mecklenburg Hospital Authority d/b/a Atrium Health to five issued U.S. patents, three pending U.S. patent applications, and thirty three related foreign patent applications pending in various jurisdictions, including Australia, Canada, Europe, China, Japan, and Mexico with claims to methods of treatment, dosing methods, and compositions relating to BBP-418. The issued U.S. patents are expected to expire in 2037. The pending U.S. and foreign patent applications, if issued, are expected to expire in 2040 or 2041. In addition, ML Bio owns two pending U.S. patent applications relating to assays. The pending U.S. patent applications, if issued, are expected to expire in 2042 or 2044.

Material Agreements

Acoramidis

License Agreement with Alexion

In September 2019, through the company's subsidiary Eidos Therapeutics, Inc., or Eidos, the company entered into a license agreement, or the Alexion License Agreement, with Alexion Pharma International Operations Unlimited Company, a subsidiary of Alexion Pharmaceuticals, Inc., or together, Alexion, to develop and commercialize acoramidis in Japan.

License Agreement with the Board of Trustees of the Leland Stanford Junior University

In April 2016, through Eidos, the company entered into an exclusive license agreement with Stanford for rights relating to novel transthyretin aggregation inhibitors. Under the company's agreement, Stanford has granted the company an exclusive worldwide license to make, use and sell products that are covered by the licensed patent rights. This license grant expires when the last licensed patent expires.

Infigratinib: License Agreement with Novartis International Pharmaceutical Ltd.

In January 2018, through the company's subsidiary QED, the company entered into a license agreement with Novartis International Pharmaceutical Ltd., or Novartis, for certain intellectual property rights, including patents and know-how, related to infigratinib for the treatment of patients with FGFR-driven diseases, including CCA, UC and achondroplasia. The company refers to this agreement as the Novartis License.

Pursuant to the Novartis License, the company obtained a license to research, develop, make, have made, use, import, offer for sale, sell, have sold and otherwise commercialize infigratinib, as well as therapeutic products incorporating infigratinib that would, but for the license grant, infringe Novartis' license patent rights, or that were developed using or that incorporate or embody Novartis' licensed know-how, in all fields of use worldwide. The license grant to the company includes the right to sublicense through multiple tiers. The company also has certain rights to intellectual property licensed to Novartis' affiliate under a materials transfer agreement with a third party.

The Novartis License is subject to Novartis' existing obligations to supply a third party with infigratinib to support the third party's clinical trials, and the company has an ongoing obligation to inform Novartis of the company's or its sublicensees' intent to seek regulatory approval for and commercialize infigratinib for various indications, with potential reversionary rights to Novartis in the event of a subsequent decision not to seek regulatory approval and commercialization, or a determination by Novartis that the company has failed to sufficiently pursue regulatory approval and commercialization, for Novartis to grant such third party limited rights to develop and commercialize infigratinib.

Under the Novartis License, the company is required to use commercially reasonable efforts to develop infigratinib, and to obtain regulatory approval for and commercialize infigratinib in the United States and the European Union.

Fosdenopterin: Asset Purchase Agreement with Alexion Pharma Holding Unlimited Company

In June 2018, through the company's subsidiary Origin Biosciences, Inc., the company entered into an asset purchase agreement with Alexion Pharma Holding Unlimited Company, or Alexion Pharma, pursuant to which the company acquired Alexion's right, title and interest in certain assets relating to fosdenopterin, including patents and other intellectual property rights.

BBP-398: License Development and Commercialization Agreement with Bristol-Myers Squibb Company

On May 12, 2022, BridgeBio and the company's subsidiary, Navire Pharma, Inc., or Navire, entered into an exclusive license development and commercialization agreement with Bristol-Myers Squibb Company, or BMS, pursuant to which Navire granted BMS exclusive rights to develop and commercialize Navire's product candidate, BBP-398, in all indications worldwide, except for the People's Republic of China, Macau, Hong Kong, Taiwan, Thailand, Singapore, and South Korea, or collectively, the Asia Region. The company refers to this agreement as the Navire-BMS License Agreement.

Government Regulation

The company's product candidates must be approved by the FDA through either a New Drug Application, or NDA or a Biologics License Application, or BLA, process before they may be legally marketed in the United States.

The company relies on third parties for the production of clinical and commercial quantities of any approved products in accordance with cGMP regulations. If the company's products, once approved, are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply.

The Foreign Corrupt Practices Act obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

History

BridgeBio Pharma, Inc., a Delaware corporation, was founded in 2015. The company was incorporated in 2019.