On November 2, 2023 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the third quarter ended September 30, 2023, and provided an update on the Company’s operations (Press release, BridgeBio, NOV 2, 2023, View Source [SID1234636740]).

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"We continue to be extremely grateful to the patient and physician communities with whom we collaborate; their partnership has helped us to realize tremendous advancement recently across the programs that make up our portfolio," said Neil Kumar, Ph.D., founder and CEO of BridgeBio. "We are excited about the progress from our late-stage pipeline, and have begun to highlight areas of differentiation for the upcoming, potentially blockbuster launch of our ATTR-CM asset. In particular, recent real-world evidence on ATTR-CM therapies presented at the HFSA scientific sessions suggests that the survival levels observed on acoramidis treatment in our Phase 3 study are indeed differentiated even in the context of the contemporary care setting as compared to other agents in the field. This continues to reinforce our hypothesis that better stabilization leads to better outcomes for patients with ATTR-CM."

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM):
In August 2023, the Company presented detailed positive results from its Phase 3 ATTRibute-CM study of acoramidis for patients with ATTR-CM; a highly statistically significant result was observed on the primary endpoint with a Win Ratio of 1.8 (p<0.0001). This primary endpoint result consistently favored acoramidis treatment across key subgroups, including National Amyloidosis Center (NAC) ATTR stage 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 interventional studies of ATTR-CM to the Company’s knowledge, including real-world evidence presented at recent cardiology medical meetings.
The 81% survival rate on acoramidis approaches the survival rate in the age-matched U.S. database (~85%); the 0.29 mean annual CVH rate on acoramidis approaches the annual hospitalization rate observed in the broader U.S. Medicare population (~0.26).
Assessment of measures of disease progression in the trial suggest that on acoramidis, 45% of subjects experienced an improvement from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) versus 9% on placebo, and 40% of subjects experienced an improvement from baseline on 6-minute walk distance (6MWD) versus 24% on placebo. To the Company’s knowledge, the proportions of treated patients improving on these measures over 30 months are higher than have been observed in prior controlled studies in ATTR-CM.
We believe these points of differentiation observed in the ATTRibute-CM results are made possible by acoramidis achieving near-complete stabilization of transthyretin (TTR) in both wild-type and variant ATTR patients; serum TTR was promptly and consistently elevated throughout the study.
In an exploratory post-hoc analysis of the relationship between on-treatment serum TTR levels and on-treatment measures of CVH, NT-proBNP, and Kansas City Cardiomyopathy Questionnaire (KCCQ), there was an association between the mean on-treatment TTR level and each of these three variables, consistent with the premise that higher degrees of stabilization lead to better outcomes for patients.
Acoramidis was well-tolerated with no safety signals of potential clinical concern identified.
The Company intends to file an NDA for acoramidis with the FDA by the end of 2023 and marketing authorization applications with additional regulatory authorities globally in 2024.
Additional detailed results of ATTRibute-CM are planned for presentation at the American Heart Association Scientific Sessions and the American College of Cardiology Scientific Sessions.
Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia:
In September 2023, the Company completed positive regulatory meetings with the FDA and the EMA. Alignment from the FDA and EMA was reached on the adequacy of a one-year, 2:1 randomized, placebo-controlled Phase 3 pivotal trial for infigratinib to support a marketing application for the treatment of children with achondroplasia.
Based on the positive results to date, the Company has been enrolling children in the run-in for PROPEL3, the Phase 3 registrational study, and expects to initiate PROPEL3 by the end of 2023.
If approved, the Company believes that infigratinib has the potential to capture a significant share of the market based on blinded market research.
The Company is committed to exploring the potential of infigratinib on the wider medical and functional impacts of achondroplasia, hypochondroplasia and other skeletal dysplasias, which hold significant unmet needs for families.
BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9):
In October 2023, the Company shared new long-term data from its Phase 2 trial in patients with LGMD2I/R9 at the Annual Congress of World Muscle Society. 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 αDG levels at 3 months predicted ambulatory improvements at 9 months, providing support for the possible use of glycosylated αDG levels as a surrogate endpoint in the ongoing Phase 3 study for Accelerated Approval by the FDA.
FORTIFY, the global Phase 3 registrational trial of BBP-418, continues to enroll in the U.S. with clinical trial sites planned for Europe and Australia. The Company believes there is potential to pursue Accelerated Approval for BBP-418 based on recent interactions with the FDA on the use of glycosylated αDG levels as a surrogate endpoint.
The Company believes BBP-418 has the potential to address a population of 7,000 patients in the U.S. and Europe.
There are currently no disease-modifying treatments available for LGMD2I/R9.
Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1):
In September 2023, the Company announced proof-of-concept Phase 2b data evaluating the effects of encaleret on mineral homeostasis in patients with ADH1 were published in the New England Journal of Medicine in partnership with the NIH. The results highlighted that encaleret restored physiologic mineral homeostasis in 13 participants with ADH1, specifically correcting hypocalcemia and reducing hypercalciuria.
Population genetics analyses estimate approximately 25,000 carriers of gain-of-function variants of the CaSR, the underlying cause of ADH1, in the U.S. and European Union.
The Company has received approval to begin enrollment for CALIBRATE, its Phase 3 clinical trial of encaleret, in European Union and Japan, and anticipates sharing topline data from CALIBRATE in 2024.
If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1.
BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH):
The Phase 1/2 gene therapy trial of BBP-631 for CAH continues to progress, with the dose-escalation portion of the study (N=6) fully enrolled; the Company plans to share data from the program in early 2024.
CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the U.S. and European Union.
RAS cancer portfolio:
BBO-8520, an investigational, next-generation small molecule direct KRASG12C(ON) inhibitor candidate that is designed to directly bind and inhibit KRASG12C in both its ON (GTP-bound) and OFF (GDP-bound) conformations, remains on track to file an IND in 2023.
The novel, direct KRAS (ON) targeting mechanism of BBO-8520 was observed to be potentially superior to KRAS (OFF) by data presented at the recent Triple Meeting, suggesting scope for a potent, next-generation agent to have an effect.
The Company’s PI3Kα:RAS breaker candidate BBO-10203 and pan-KRAS program remain on track for an IND and a development candidate selection, respectively, in 2024.
Recent Corporate Updates:

Multi-year partnership with Resilience to advance BBP-631, BBP-812 and future gene therapy treatments: The Company and Resilience signed an agreement to transfer the manufacturing process for the Company’s lead AAV-based gene therapy candidates, BBP-631 and BBP-812, to Resilience’s network of gene therapy manufacturing sites. Resilience will also be the primary manufacturer for future clinical projects across the Company’s gene therapy portfolio. The deal is intended to reduce manufacturing costs, which have historically accounted for approximately 50%-60% of the Company’s gene therapy budget.
$316 million gross proceeds raised between ATM and PIPE financing: The PIPE financing (as detailed in the forthcoming S-3 filing) included significant participation from four of the largest investment management firms in the U.S., as well as a number of large institutional investors and existing investors.
Third Quarter 2023 Financial Results:

Cash, Cash Equivalents, Marketable Securities and Short-Term Restricted Cash

Cash, cash equivalents and short-term restricted cash, totaled $521.9 million as of September 30, 2023, compared to cash, cash equivalents, marketable securities and short-term restricted cash of $466.2 million as of December 31, 2022. The net increase of $55.7 million in cash, cash equivalents, marketable securities and short-term restricted cash was primarily attributable to net proceeds received of $450.3 million from various equity financing offerings, and $5.2 million from stock option exercises, primarily offset by net cash used in operating activities of $402.9 million during the nine months ended September 30, 2023.

Revenue

Revenue for the three and nine months ended September 30, 2023 was $4.1 million and $7.6 million, respectively, as compared to $0.3 million and $75.8 million for the same periods in the prior year, respectively. The net decrease of $68.2 million for the nine months ended September 30, 2023, compared to the same period in the prior year, was primarily attributable to the timing of revenue recognized from the Navire-BMS License Agreement which was entered into in May 2022.

Operating Costs and Expenses

Operating costs and expenses for the three and nine months ended September 30, 2023 were $161.8 million and $437.5 million, respectively, compared to $129.5 million and $458.7 million, for the same periods in the prior year, respectively.

The overall increase of $32.3 million in operating costs and expenses for the three months ended September 30, 2023, compared to the same period in the prior year, was primarily due to an increase of $32.6 million in research and development and other expenses (R&D) to advance the Company’s pipeline of development programs, an increase of $4.6 million in selling, general and administrative (SG&A) expenses to support commercialization readiness efforts, offset by a decrease of $4.7 million in restructuring, impairment and related charges.

The overall decrease of $21.2 million in operating costs and expenses for the nine months ended September 30, 2023, compared to the same period in the prior year, was primarily due to a decrease of $28.9 million in restructuring, impairment and related charges given that the majority of the restructuring initiatives occurred in the prior year, a decrease of $8.3 million in SG&A expenses as a result of restructuring initiatives, offset by an increase of $16.0 million in R&D expenses to advance the Company’s pipeline of development programs.

Restructuring, impairment and related charges for the three and nine months ended September 30, 2023, amounted to $0.3 million and $7.2 million, respectively. These charges primarily consisted of winding down, exit costs, and severance and employee-related costs. Restructuring, impairment and related charges for the same periods in the prior year were $5.0 million and $36.1 million, respectively. These charges primarily consisted of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. The Company expects that the remaining restructuring, impairment and related charges will be immaterial through the end of 2023.

Stock-based compensation expenses included in operating costs and expenses for the three months ended September 30, 2023 were $27.2 million, of which $14.1 million is included in R&D expenses, and $13.1 million is included in SG&A expenses. Stock-based compensation expenses included in operating costs and expenses for the three months ended September 30, 2022 were $18.7 million, of which $6.2 million is included in R&D expenses, and $12.5 million is included in SG&A expenses.

Stock-based compensation expenses included in operating costs and expenses for the nine months ended September 30, 2023 were $77.9 million, of which $39.2 million is included in R&D expenses, and $38.7 million is included in SG&A expenses. Stock-based compensation expenses included in operating costs and expenses for the nine months ended September 30, 2022 were $71.2 million, of which $29.0 million is included in R&D expenses, $41.0 million is included in SG&A expenses, and $1.2 million is included in restructuring, impairment and related charges.

"We were pleased to partner with leading institutional investors on our PIPE financing last quarter," said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. "We continue to take advantage of our optionality in exploring less-dilutive forms of financing and anticipate that these, in conjunction with the PIPE financing, could capitalize us to profitability."