Muscular Dystrophy, Limb-Girdle, Type 2I

- Study exceeded target enrollment, with an expected topline data readout from the interim analysis expected in 2025 - BridgeBio believes there is an opportunity to pursue Accelerated Approval in the U.S. for BBP-418 in LGMD2I/R9 based on a potential biomarker surrogate endpoint of glycosylated alpha-dystroglycan (αDG) at time of the interim analysis - If successful, BBP-418 could be the first approved therapy for individuals living with LGMD2I/R9 in the U.S. - Enrollment completion announced on 10th annual LGMD Awareness Day, a collaborative yearly effort on September 30th to globally raise awareness of individuals living with LGMD PALO ALTO, Calif., Sept. 30, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases, announced, on LGMD Awareness Day, the completion of enrollment of FORTIFY, the Company’s Phase 3 registrational study of BBP-418 in individuals with LGMD2I/R9. FORTIFY is a randomized, double-blind, placebo-controlled Phase 3 study evaluating the safety and efficacy of BBP-418, an investigational oral therapy in development for the treatment of individuals living with LGMD2I/R9. The study includes a planned interim analysis at 12 months focused on assessing glycosylated αDG as a surrogate endpoint to potentially support Accelerated Approval. The primary endpoint, to be evaluated at 36 months, is the North Star Assessment (NSAD) for limb-girdle type muscular dystrophies and is designed to provide confirmatory clinical data supporting the efficacy of BBP-418. More information about the Phase 3 clinical trial of BBP-418 (NCT05775848) can be found here on clinicaltrials.gov. A topline data readout from the interim analysis is expected in 2025. “Living with a progressive muscle wasting condition like LGMD2I/R9 means that individuals are continually losing the ability to perform daily activities independently and relying on friends and family to support them as they experience a continued decline in strength and health. For patients with LGMD2I/R9, there are currently no approved treatment options, but the promise seen in the rapid enrollment of this clinical trial provides hope for patients and their families that this may change in the future,” said Kelly Brazzo, CEO of CureLGMD2i Foundation. “Completing rapid enrollment of FORTIFY is an important milestone and underscores the need for a therapeutic option for patients,” said Douglas Sproule, M.D., M.Sc., Chief Medical Officer of ML Bio Solutions, a BridgeBio company developing BBP-418 for LGMD2I/R9. “Based on multiple encouraging discussions with the FDA, we believe there is an opportunity to pursue Accelerated Approval in the U.S. for BBP-418 in LGMD2I/R9 based on a potential surrogate endpoint biomarker of glycosylated αDG at time of the interim analysis. If successful, BBP-418 could be the first approved disease-modifying therapy for individuals living with LGMD2I/R9 in the U.S. We’re immensely grateful to the patients, their families, and the trial site investigators participating in our study and look forward to sharing pivotal data with the community.” BBP-418 has previously received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the FDA and Orphan Drug Designation from the European Medicines Agency (EMA). Consistent with the Rare Pediatric Designation from the FDA, if BBP-418 is approved, BridgeBio may qualify for a Priority Review Voucher. About Limb-girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9)LGMD2I/R9 is a monogenic autosomal recessive disease caused by partial loss of function mutations in the fukutin-related protein (FKRP) gene, and FKRP mutations impair glycosylation of alpha-dystroglycan (αDG), a protein associated with stabilizing muscle cells. Clinical manifestations typically present as a skeletal myopathy affecting the lower and then upper limbs, which is commonly later accompanied by respiratory muscle and cardiac muscle involvement. Individuals who harbor a homozygous L276I genotype typically develop disease manifestations during late childhood with progression to loss of independent ambulation (25%), assisted ventilation (10%), and cardiomyopathy (30%) in adulthood. Cardiomyopathy is progressive, with an annual loss of 0.4% of left ventricular ejection fraction (LVEF). Individuals with other FKRP genotypes typically have an earlier childhood onset with a more severe clinical course, rapid loss of mobility by 20 years of age, more frequent cardiac involvement (60%), and eventual respiratory failure by 30 years of age in nearly all cases. About BridgeBio Pharma, Inc.BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn, Twitter and Facebook. BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements BridgeBio makes in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “seeks,” “should,” “will,” and variations of such words or similar expressions. BridgeBio intends these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the clinical and therapeutic and market potential of BridgeBio’s programs and product candidates, including BBP-418 for the treatment of LGMD2I/R9, the potential benefits of BBP-418, including its potential to address unmet need for patients with LGMD2I/R9, the potential and the opportunity to pursue Accelerated Approval Pathway for BBP-418 in LGMD2I/R9 in the U.S., the potential that BridgeBio may qualify for a Priority Review Voucher based on receipt of the Rare Pediatric Designation from the FDA, the expected timeline of announcing the topline data from the interim analysis of FORTIFY in individuals with LGMD2I/R9 in 2025, the statements regarding the potential benefit of our clinical trial or of our product candidate in the quotes of Dr. Sproule and Kelly Brazzo, and the progress, timeline and success of BridgeBio’s ongoing and planned clinical trials of BBP-418, among others, reflect BridgeBio’s current views about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to BridgeBio and on assumptions BridgeBio has made. Although BridgeBio believes that its plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, BridgeBio can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, BridgeBio’s ability to continue and complete its ongoing and planned clinical trials of BBP-418 for the treatment of LGMD2I/R9, initial and ongoing data from its clinical trials not being indicative of final data, the design and success of ongoing and planned clinical trials, difficulties with enrollment in our clinical trials, adverse events that may be encountered in our clinical trials, the FDA or other regulatory agencies not agreeing with BridgeBio’s regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the ability of BBP-418 to retain Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the FDA and Orphan Drug Designation from the European Medicines Agency and potential adverse impacts due to global health emergencies, including delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine and in Israel and the Gaza Strip, increasing rates of inflation and rising interest rates, on our business operations and expectations as well as those risks set forth in the Risk Factors section of BridgeBio’s most recent Annual Report on Form 10-K, and BridgeBio’s other filings with the U.S. Securities and Exchange Commission. Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio’s management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact:Vikram Balicontact@bridgebio.com (650)-789-8220

EVRY, France--( BUSINESS WIRE )-- Atamyo Therapeutics , a biotechnology company focused on the development of new-generation gene therapies targeting neuromuscular disease, today announced its participation in six upcoming conferences in the US and Europe to highlight recent developments in its programs targeting limb-girdle muscular dystrophies (LGMDs). Atamyo CEO Stephan Degove will provide a corporate overview at Sach’s 20 th Annual Biotech in Europe Forum, Chardan's 8th Annual Genetic Medicines Conference and the Cell & Gene Meeting on the Mesa 2024. • Sach’s 20th Annual Biotech in Europe Forum, held in Basel, Switzerland, on September 25-26, 2024: Presentation on September 25, at 11:40 am (CEST), in the Ruby Room. • Chardan's 8th Annual Genetic Medicines Conference, held in New York City, on September 30 and October 1, 2024: Presentation on September 30 at 11:00 am (US EDT), in the Embassy Room. • Cell & Gene Meeting on the Mesa, held in Phoenix, AZ, on October 7-9, 2024: Presentation on October 8, at 5:45 pm (US MST), at the FLW Ballroom F. Two communications at the 29th Annual Congress of the World Muscle Society, October 8-12, 2024, in the Prague Congress Centre, Prague, Czech Republic, will describe Atamyo’s LGMD programs. • “Preliminary results from a Phase 1-2 gene therapy study of ATA-100, AAV9 vector encoding FKRP, in patients with Limb Girdle Muscular Dystrophy R9.” Oral presentation by S. Olivier (Atamyo), at Congress Hall on Saturday, October 12, 2024, 8 am - 8:15 am (CEST) • “MRI characterization of the cardiac involvement in LGMD2i/R9.” JY Hogrel (Institute of Myology, Paris) et al., Poster Board Number 87P at Forum Hall, on Wednesday, October 9, 2024, 5:15 pm - 6:15 pm (CEST). Two communications at the European Society of Gene & Cell Therapy 31 st Annual Congress, October 22-25, 2024 in La Nuvola, Rome, Italy, will describe Atamyo’s LGMD programs. Both posters will be presented during Poster Session II on Wednesday 23 October, 1:30 pm to 3 pm (CEST). • “Development of a quantitative alpha-dystroglycan glycosylation test in patients with Limb Girdle Muscular Dystrophy R9 treated in ATA-001-FKRP open-label multicenter AAV trial.” E Thevenot (Genethon) et al., Poster number P0088 • “Natural history of limb girdle muscular dystrophy R9: two-year follow-up of a European cohort.” S Olivier (Atamyo) et al., Poster number P0264 Two communications on Atamyo’s LGMD-R9 program will be presented at the ASGCT’s Breakthroughs in Muscular Dystrophy Conference, November 19-20, 2024, in Chicago, IL. • “Development of Gene Therapy for LGMD-R9.” Oral presentation by E. Gicquel (Genethon), on November 19, 2024, 5:15 p.m. - 5:30 p.m. (US CDT), Great Lakes East Ballroom at the Westin Michigan Avenue Hotel. • “Overcoming Phenotypic Variability in Dystrophic Models: A Machine Learning Method for Refined Gene Therapy Evaluation.” E. Brureau (Genethon) et al. Poster P27. Session on November 16, 2024, 8 a.m. - 7 p.m. (US CDT), Great Lakes East Ballroom at the Westin Michigan Avenue Hotel Publication in Nature Communications of a Next-Generation Gene Therapy Vector for Muscle Diseases, Using AI Predictive Methodology to Improve Efficacy and Safety. • “An engineered AAV targeting integrin alphaV beta 6 presents improved myotropism across species,” by Ai Vu Hong (Genethon), et al., was published in Nature Communications ( https://doi.org/10.1038/s41467-024-52002-4 ). The paper describes development of the next-generation LICA-1 capsid by Isabelle Richard, Ph.D., Atamyo’s Chief Scientific Officer, and her Progressive Muscular Dystrophies Team at Genethon. Atamyo has rights to the LICA-1 capsid for cardiomyopathies indications. About Atamyo Therapeutics Atamyo Therapeutics is a clinical-stage biopharma focused on the development of a new generation of effective and safe gene therapies for neuromuscular diseases. A spin-off of gene therapy pioneer Genethon, Atamyo leverages unique expertise in AAV-based gene therapy and muscular dystrophies from the Progressive Muscular Dystrophies Laboratory at Genethon. Atamyo’s most advanced programs address different forms of limb-girdle muscular dystrophies (LGMD), with two clinical-stage programs targeting respectively LGMD2I/R9 and LGMD2C/R5. The name of the company is derived from two words: Celtic Atao which means “Always” or “Forever” and Myo which is the Greek root for muscle. Atamyo conveys the spirit of its commitment to improve the life of patients affected by neuromuscular diseases with life-long efficient treatments. For more information visit www.atamyo.com

iStock/ jauhari1 As it nears a crucial FDA action date for its transthyretin amyloid cardiomyopathy candidate, BridgeBio focuses on its late-stage pipeline. Bay area–based biotech BridgeBio, founded in 2015 to be a bridge between promising early-stage academic work and patients with genetic diseases, is now a growing commercial enterprise, with two products on the market and another expecting an FDA decision by the end of November. As such, the company is making strategic moves, spinning out some assets into two new companies, cutting an entire gene therapy program and focusing its remaining resources on its late-stage programs in transthyretin amyloid cardiomyopathy and achondroplasia, which analysts say are key to BridgeBio’s success. “We have the capability, by our tenth birthday, to have had six approved products for a billion-plus dollar market,” Neil Kumar, the company’s charismatic founder and CEO told BioSpace . “So that’s a very, very productive engine.” However, commercial success requires the company to make some adjustments, Kumar continued. “Our investors would like to see us focus our resources to show that we can commercialize,” Kumar said, with a specific focus on the company’s later-stage pipeline. “We’ve shown we can do R&D, but now we have to show we can commercialize and build a business against these products.” To satisfy these investors, BridgeBio has adopted a hub-and-spoke model. In May 2024, it spun out its KRAS-focused cancer portfolio into BridgeBio Oncology Therapeutics , which it endowed with $200 million in initial funding. And last month, BridgeBio debuted GondolaBio to further develop early-stage assets for tuberous sclerosis complex, erythropoietic protoporphyria and alpha-A1 antitrypsin deficiency. Then this week, the company announced that it is discontinuing development of its gene therapy candidate BBP-631 after it failed to show “transformational results” in a mid-stage study in congenital adrenal hyperplasia (CAH). “The data we generated did not suggest that our efforts would result in a meaningful step forward for patients as compared to what we think standard of care will be in the coming years,” Kumar said. “Therefore, we felt our efforts would be better applied to other areas of unmet need,” though the company is seeking a partnership to continue development of BBP-631 and other next-generation gene therapies for CAH. That leaves the company’s two approved products— Nulibry for molybdenum cofactor deficiency type A and the targeted cancer treatment Truseltiq (infigratinib), both approved in 2021—and four assets in late-stage development. First and foremost, BridgeBio is gearing up for a Nov. 29 FDA action date on its transthyretin amyloid cardiomyopathy (ATTR-CM) hopeful, acoramidis. At the same time, the company is continuing Phase III development on three more drug candidates —infigratinib for achondroplasia, BBP-418 for limb-girdle muscular dystrophy type 21/R9 and encaleret for autosomal dominant hypocalcemia type 1. Kostas Biliouris, director of biotech equity research at BMO Capital Markets, noted that the primary interest in BridgeBio is in acoramidis and infigratinib. “The other spinout companies are probably increasing efficiency” for these late-stage products because they effectively remove from BridgeBio’s portfolio “something that investors are not focused on,” he told BioSpace . The Path to Success If approved in November, acoramidis will be going up in the ATTR-CM market against Pfizer’s tafamidis, sold as Vyndaqel and Vyndamax, which Biliouris said is well-established in the market. Like tafamidis, acoramidis is a transthyretin stabilizer. Biliouris said that while acoramidis may be “incrementally better” than tafamidis, it needs to be dosed twice per day, compared to once per day for Pfizer’s drugs, which may limit uptake. In addition, Biliouris said, Pfizer has demonstrated that tafamidis can reduce the risk of mortality, whereas acoramidis did not show a statistically significant effect on this measure. In a survey of 30 physicians conducted by BMO Capital Markets, 50% of doctors said the efficacy is similar between acoramidis and tafamidis, while 40% believed acoramidis to be incrementally better, Biliouris shared. “That’s why it’s not an easy story.” If BridgeBio does secure FDA approval for acoramidis, the company will then need to beat sales expectations in 2025, Biliouris said, estimating these to be about $165 million in the U.S. “If BridgeBio can beat that number, it will be great,” he told BioSpace . “It will help the stock and the story. If not, it will be challenging.” Some of the drug’s success could also be tied to whether or not tafamidis goes generic in 2028 or 2035, Biliouris noted, adding that this won’t be known until 2028. Another piece of the puzzle, according to Biliouris, is infigratinib, which if approved, will go up against BioMarin’s Voxzogo in the achondroplasia space. BridgeBio is anticipating a readout for the drug in late 2025, according to Biliouris. This trial needs to meet its primary endpoint and show a good safety profile, he said. “Usually, this drug treats kids and safety is very sensitive here.” It also “needs to be at least as good, if not better, than its main competitor,” Voxzogo, Biliouris continued, and like acoramidis, will also need to beat sales expectations. Kumar, for one, is confident in BridgeBio’s future success, noting that its ultimate goal is “to serve as many patients as possible across as many indications that effectively allow us to do high probability drug discovery development. What some companies would do [in BridgeBio’s position] is they would push pause,” he said. “But I don’t believe in pushing pause.”