FKRP

Atamyo has received approval to initiate a clinical trial of ATA-200 gene therapy in France and Italy ATA-200 is a single-injection gene therapy aimed to treat LGMD2C/R5 caused by mutations in the γ-sarcoglycan gene The phase 1b, dose-escalation study will evaluate the safety and efficacy of ATA-200 in children EVRY, France--(BUSINESS WIRE)-- Atamyo Therapeutics, a clinical-stage biotechnology company focused on the development of new-generation gene therapies targeting muscular dystrophies and cardiomyopathies, today announced the first authorization of a Clinical Trial Application (CTA) in Europe for ATA-200, its gene therapy for the treatment of the γ-sarcoglycan related limb-girdle muscular dystrophy Type 2C/R5 (LGMD2C/R5). This authorization was first granted by the Italian Medicines Agency (AIFA), then by the French Medicines Agency (ANSM). “We are thrilled to obtain our CTA approval in France and Italy for the devastating LGMD2C/R5 disease affecting primarily a pediatric population and for which there is no approved treatment,” said Dr Sophie Olivier, Chief Medical Officer of Atamyo. “Atamyo plans to initiate dosing in patients for ATA-200 in third quarter 2024.” “LGMD 2C/R5 is a severe muscular dystrophy with an onset in early childhood and loss of ambulation generally occurring before adolescence,” said Pr. Giacomo Comi, Full Professor of Neurology at the University of Milan (Italy), and principal investigator of this trial. “It is a great motivation to know that the work we are doing has the potential to make a life-changing difference for the patients affected by this disease.” “This is a significant milestone for LGMD-2C/R5 patients and for Atamyo as ATA-200 is the first treatment targeting LGMD-2C/R5 to enter clinical trials,” said Stéphane Degove, CEO of Atamyo Therapeutics. “With the ongoing clinical trial of ATA-100 in LGMD2I/R9, the initiation of the clinical program for ATA-200 confirms our unique capabilities in bringing to patients suffering from limb-girdle muscular dystrophies a new generation of safe and effective gene therapies.” This clinical trial (NCT05973630) is a multicenter, Phase 1b, open-label, dose escalation study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of intravenous ATA-200, a single-dose Adeno-Associated Virus (AAV) vector carrying the human γ-sarcoglycan transgene. LGMD2C/R5 is a rare genetic disease caused by mutations in the gene that produces γ-sarcoglycan, a transmembrane protein that is involved in the connection between muscle fibers and their environment. It affects an estimated 2,000 people in Europe. In the classical form, symptoms appear in early childhood and patients suffer from progressive muscular weakness leading to loss of ambulation before adulthood. Cardiac involvement, typically presenting as dilated cardiomyopathy is reported in approximately half of patients. There is no curative treatment. The management of LGMD2C/R5 is solely supportive. ATA-200, a gene therapy candidate for LGMD2C/R5, delivers a normal copy of the gene for production of γ-sarcoglycan protein. In preclinical models, a single systemic injection of ATA-200 demonstrated its tolerability and capability to correct symptoms and biomarkers of the pathology. ATA-200 has been granted Orphan Medicinal Product Designation by the European Medicines Agency (EMA). The therapy is based on the research of Atamyo Chief Scientific Officer Isabelle Richard, Ph.D., Research Director at National Center of Scientific Research (CNRS) in France and head of the Progressive Muscular Dystrophies Laboratory at Genethon. In addition to its LGMD2C/R5 gene therapy, Atamyo is developing a clinical trial with ATA-100 gene therapy for LGMD2I/R9, related to deficiencies in FKRP; and is in IND-enabling studies for LGMD2A/R1, related to deficiencies in calpain protein. 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 . View source version on businesswire.com: Contacts U.S. Contact: Charles Craig, Opus Biotech Communications Charles.s.craig@gmail.com, 404-245-0591 European Contact: contact@atamyo.com Source: Atamyo Therapeutics View this news release online at:

ATA-100 is being evaluated in a multi-center phase 1b/2b “ATA-001-FKRP” study Completion of enrollment of the first dose cohort of 3 patients First results of cohort one presented at ESGCT in oral presentation Good clinical and biological safety/tolerability in the first cohort Preliminary efficacy documented with biomarkers and functional assessments DSMB clearance to proceed with enrollment of the 2nd cohort with a 3-times higher dose EVRY, France--(BUSINESS WIRE)-- Atamyo Therapeutics, a biotechnology company focused on the development of new-generation gene therapies targeting muscular dystrophies and cardiomyopathies, today announced the presentation of the first clinical results obtained with ATA-100 in the on-going ATA-001 Phase 1b/2b clinical trial. ATA-100 is a one-time gene therapy for the treatment of fukutin-related protein (FKRP) limb-girdle muscular dystrophy Type 2I/R9 (LGMD2I/R9). Atamyo also announced today that Data Safety Monitoring Board (DSMB) authorized the enrollment of the second dose cohort of the ATA-001 clinical trial. ATA-100 is being evaluated in a multi-center phase 1b/2b in Denmark, France, and the United Kingdom, and has received IND clearance by FDA. Preliminary results in the first cohort show: No unexpected safety signal identified Marked decline in levels of creatine kinase in all three patients Improved velocity, sustained at one year Disappearance of symptoms (cramps, myalgia) and improved quality of life Correction of centronucleation and evidence of transgene expression on the 3-month muscle biopsy Pr. John Vissing, principal investigator of the study, noted that “the preliminary results from cohort 1 with the first dose tested already show encouraging results from a safety and efficacy perspective. ATA-100 treatment has a life-changing potential in an indication where there is no approved treatment.” These first results will be presented during oral communications in two forthcoming conferences: 1) The 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) that will take place on October 24-27, 2023 in Brussels, (Belgium): “Gene therapy for LGMDR9: preliminary results of a dose-escalation study” • Oral presentation by Nicolai Preisler, MD, Rigshospitalet, Copenhagen, during the Cardiovascular and muscular diseases session, on Friday, October 27, 11h30-13h00 – Le BEL, Tour & Taxis 2) The 2023 International Limb-Girdle Muscular Dystrophy Conference, which will take place on 28-29 October 2023, Washington, DC. “Preliminary experiences with Atamyo’s FKRP gene therapy” • Oral presentation by John Vissing, MD, Rigshospitalet, Copenhagen, during the Clinical Trials Updates (Part 1) Session, on October 29, 11h00am-12h10pm – Constitution Ballroom, Grand Hyatt “These first results, in particular those related to transgene expression in muscle fibers are really exciting,” said Dr. Sophie Olivier, Atamyo’s Chief Medical Officer. “With the DSMB clearance to start the 2nd cohort, we are looking forward to enrolling new patients in Europe and in the US.” LGMD2I/R9 is a rare genetic disease caused by mutations in the gene that produces fukutin-related protein (FKRP). It affects an estimated 5,000 people in the US and Europe. In the most common form, symptoms appear around late childhood or early adulthood. Patients suffer from progressive muscular weakness leading to loss of ambulation. They are also prone to respiratory impairment. There are currently no curative treatments for LGMD2I/R9. ATA-100, a single-administration gene therapy candidate for LGMD2I/R9, delivers a normal copy of the gene for production of FKRP proteins. The therapy is based on the research of Atamyo Chief Scientific Officer Isabelle Richard, Ph.D., Research Director at CNRS who heads the Progressive Muscular Dystrophies Laboratory at Genethon. 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 muscular dystrophies and cardiomyopathies. 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 one clinical-stage program targeting LGMD-R9. Atamyo is committed to improve the life of patients affected by neuromuscular diseases with life-long efficient treatments. For more information visit . View source version on businesswire.com: Contacts U.S. Contact: Charles Craig, Opus Biotech Communications charles.s.craig@gmail.com, 404-245-0591 European contact: contact@atamyo.com Source: Atamyo Therapeutics View this news release online at:

- Early assessment of increased glycosylated ⍺DG levels at 3 months predicted subsequent ambulatory improvements at 9 months, supporting the use of glycosylated ⍺DG levels as a potential surrogate endpoint in LGDM2I/R9 - Long-term data from the ongoing Phase 2 study of BBP-418 in patients with LGMD2I/R9 at Month 21 demonstrate a well-tolerated safety profile, and stabilization in 10 meter walk test (10MWT), 100-m timed test (100mTT), and the North Star Assessment (NSAD) scores - A sustained decrease of ≥80% in creatine kinase (CK), a marker of muscle breakdown, was observed with BBP-418 treatment at 21 months - The Phase 3 study continues to enroll in the U.S. and BridgeBio believes there is potential to pursue Accelerated Approval for BBP-418 based on recent interactions with the U.S. Food and Drug Administration (FDA) on the use of glycosylated αDG levels as a surrogate endpoint PALO ALTO, Calif., Oct. 09, 2023 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, shared new long-term data from its Phase 2 trial in patients with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) at the Annual Congress of World Muscle Society (WMS) in Charleston, South Carolina. 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 ⍺DG levels at 3 months appear to be associated with ambulatory improvements at 9 months, providing support for the possible use of glycosylated ⍺DG levels as a surrogate endpoint in the ongoing Phase 3 study for accelerated approval. BridgeBio presented 21-month results from its ongoing Phase 2 trial, including: Large (≥80%), sustained reduction in creatine kinase observed over an extended (up to 21-months) treatment periodStabilization in NSAD scores and ambulatory measures observed over 21-months of BBP-418 treatmentBBP-418 continues to be well-tolerated with longer-term treatmentNo treatment-related SAEs or dose limiting toxicities observed with 21-months of BBP-418 dosing “There is a serious unmet need for those with LGMD2I/R9. The consistent improvement observed in biomarkers as well as stabilization in ambulatory measures are encouraging and help predict the clinical benefit for patients. The data for BBP-418 give me hope that similar results will be carried through in the currently enrolling Phase 3 trial, FORTIFY, for patients with LGMD2I/R9,” said Amy Harper, M.D., professor in the department of neurology at Virginia Commonwealth University (VCU) and primary investigator of the Phase 2 clinical trial in LGMD2I/R9. BridgeBio recently announced the first patient dosed in FORTIFY, its Phase 3 registrational study in patients with LGMD2I/R9 and is continuing to enroll throughout the U.S. with clinical trial sites planned for Europe and Australia. The Phase 3 FORTIFY registrational study is a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of BBP-418. FORTIFY has a planned interim analysis at 12 months focused on assessing glycosylated αDG as a surrogate endpoint to potentially support an accelerated approval. The NSAD and secondary endpoints will be evaluated at 36 months, and results are expected to provide confirmatory clinical data. “To see that our therapy is potentially providing clinical improvements to people who otherwise could be non-ambulatory is deeply heartening for us,” said Douglas Sproule, M.D., M.Sc., chief medical officer of ML Bio Solutions, a BridgeBio affiliate that is focused on developing BBP-418 for LGMD2I/R9. “LGMD2I/R9 is a severely progressive disease and, inevitably, the weakening of the muscles causes many affected people to become fully dependent on a caregiver. Current treatments for LGMD2I/R9 are purely supportive. BBP-418 has the potential to be the first disease-modifying orally administered therapy available for patients.” More information about FORTIFY, the ongoing Phase 3 clinical trial of BBP-418 (NCT05775848) can be found here on the ClinicalTrials.gov website. 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 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. Patients who harbor a L276I homozygous 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). Patients with other (non-L276I homozygous) genotypes 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 and cancers with clear genetic drivers. 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 and Twitter. 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,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “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 potential of BridgeBio’s programs and product candidates, including BBP-418 for the treatment of LGMD2I, the potential benefits of BBP-418, including that the early assessment of increased glycosylated ⍺DG levels at 3 months predicted subsequent ambulatory improvements at 9 months, supporting the use of glycosylated ⍺DG levels as a potential surrogate endpoint in LGDM2I/R9 and that BBP-418 continues to be well-tolerated with longer-term treatment , the progress of BridgeBio’s ongoing and planned clinical trials of BBP-418, including the continued enrollment of the Phase 3 study in the U.S. with clinical trial sites planned for Europe, UK, and Australia, the potential and the opportunity to pursue Accelerated Approval Pathway for BBP-418 in LGMD2I/R9 in the U.S. based on recent interactions with the FDA on the use of glycosylated αDG levels as a surrogate endpoint, the statement regarding the potential benefit of FORTIFY trial for patients with LGMD2I/R9 and of BBP-418 in the quotes of Dr. Harper and Dr. Sproule, the expectation that the results of the evaluation of secondary endpoints at 36 months will provide confirmatory clinical data, and the timing and success of BridgeBio’s clinical trials and development pipeline, 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, initial and ongoing data from clinical trials not being indicative of final data, the design and success of BridgeBio’s ongoing and planned 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, as well as those risks set forth in the Risk Factors section of BridgeBio’s Annual Report on Form 10-K for the year ended December 31, 2022, and BridgeBio’s other SEC filings. 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 Media Contact:Vikram Balicontact@bridgebio.com (650)-789-8220