Avidity Biosciences, Inc.

— Unprecedented data from FORTITUDE™ dose escalation cohorts for del-brax treated participants, compared to placebo, demonstrate improvement in function, strength and PROs as well as rapid and significant reduction in biomarkers — — Data support planned accelerated approval BLA submission in H2 2026 — — Data being presented at the 32nd Annual FSHD Society International Research Congress (IRC); Investor and analyst webcast event today, Monday, June 9 at 8:00 a.m. ET — SAN DIEGO, CA, USA I June 9, 2025 I Avidity Biosciences, Inc. (Nasdaq: RNA ), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™) to profoundly improve people’s lives, today announced positive topline data from the dose escalation cohorts of the delpacibart braxlosiran (del-brax) Phase 1/2 FORTITUDE™ program in Facioscapulohumeral Muscular Dystrophy (FSHD). These data as well as research supporting KHDC1L as a novel DUX4 regulated circulating biomarker will be presented in oral and poster presentations at the 32nd Annual FSHD Society International Research Congress (IRC), being held June 12-13, 2025, in Amsterdam, the Netherlands. Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD by directly targeting the disease-causing gene, double homeobox 4 (DUX4). Currently, there are no approved therapies for the treatment of FSHD, a rare, hereditary disorder marked by life-long, relentless loss of muscle strength and function, significant pain, fatigue, and progressive disability. FSHD affects approximately 45,000 to 87,000 people in the United States and Europe. “The positive topline del-brax results from FORTITUDE being presented at FSHD IRC this week are remarkable and consistent across multiple functional measures as well as biomarkers,” said Sarah Boyce, president and chief executive officer at Avidity. “Based on these unprecedented data, we are rapidly advancing del-brax as we pursue accelerated approval and prepare to submit a BLA in the second half of 2026. We are incredibly grateful for the continued trust and support from study participants, their caregivers, investigators and their staff, which are paramount to the success of this program.” Avidity today also announced that the accelerated approval regulatory pathway in the U.S. is open for del-brax and that the company has initiated the global, confirmatory Phase 3 FORWARD™ study in FSHD. “Del-brax data from the FORTITUDE study continue to demonstrate consistent reductions in a novel circulating biomarker across two cohorts at 12 months. I am particularly encouraged that del-brax shows favorable safety and tolerability with early and consistent trends towards benefit with del-brax compared to placebo across multiple functional and participant-reported outcome measures,” said Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE trial investigator. “These data indicate that by directly targeting DUX4, del-brax may be able to improve the lives of patients with FSHD and potentially meaningfully control their disease. I look forward to continued evaluation of del-brax in the FORWARD Phase 3 study and remain hopeful that it is on track to become the potentially first approved drug for FSHD.” Topline Data from the Phase 1/2 FORTITUDE™ Dose Escalation Cohorts The FORTITUDE™ clinical development program includes a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate multiple doses of del-brax in participants with FSHD as well as an open-label extension study. The two dose escalation cohorts evaluated 39 participants on either 2 mg/kg or 4 mg/kg of del-brax versus placebo over a period of 12 months. In these cohorts, del-brax was given every six weeks for the first three months and then every 13 weeks thereafter. Topline data from these cohorts for del-brax treated participants, compared to placebo, demonstrated: Topline data from the ongoing, fully enrolled del-brax Phase 1/2 FORTITUDE biomarker cohort are anticipated in Q2 2026. The primary endpoint of the FORTITUDE biomarker cohort is reduction of KHDC1L, a novel DUX4-regulated circulating biomarker. Avidity collaborated with Stephen Tapscott, M.D., Ph.D., Professor of Human Biology and Clinical Research at the Fred Hutchinson Cancer Center around the identification of the KHDC1L circulating biomarker in people living with FSHD. Video Webcast Information The Company is hosting an investor and analyst event today, June 9, 2025 at 8:00 a.m. ET. Avidity management will be joined by Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE™ trial investigator, to discuss these updates relating to del-brax in FSHD. The virtual event will be available via a live video webcast and can be accessed here or from the “ Events and Presentations ” page in the “Investors” section of Avidity’s website. A replay of the webcast will be archived on Avidity’s website following the event. About the Phase 1/2 FORTITUDE™ and Phase 2 FORTITUDE-OLE™ trials The FORTITUDE™ trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate single and multiple doses of delpacibart braxlosiran or del-brax in 90 participants with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Activity of del-brax is being assessed using key biomarkers, including DUX4-regulated muscle and circulating biomarkers and magnetic resonance imaging (MRI) measures of muscle volume and composition. Though the Phase 1/2 trial is not statistically powered to assess functional benefit, it explores the clinical activity of del-brax including measures of functional mobility and muscle strength as well as patient reported outcomes and quality of life measures. The trial has a total of three dose cohorts. The first two dose escalation cohorts evaluated 2 mg/kg or 4 mg/kg of del-brax versus placebo and were designed to assess safety as well as inform the dose and dose regimen of del-brax for additional studies. Avidity has completed enrollment in the dose escalation cohorts and identified 2 mg/kg every six weeks of del-brax as the dose for future clinical trials. The third, ongoing biomarker cohort in the FORTITUDE trial assesses the impact of del-brax 2 mg/kg every six weeks versus placebo for 12 months in people living with FSHD, ages 16-70. The primary endpoint of the biomarker cohort is reduction of KHDC1L, a novel DUX4-regulated circulating biomarker. Enrollment in the biomarker cohort is complete and blinded treatment is ongoing. Participants who complete FORTITUDE have the option to enroll in the ongoing FORTITUDE open-label extension (FORTITUDE-OLE™) study evaluating the long-term safety and tolerability of del-brax in participants living with FSHD. For more information about the FORTITUDE trial, visit the FORTITUDE study website or visit http://www.clinicaltrials.gov and search for NCT05747924. For more information on the FORTITUDE-OLE study click here or visit http://www.clinicaltrials.gov and search for NCT06547216. About Del-brax Del-brax is designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the life-long, progressive loss of muscle function in patients with FSHD. Del-brax aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people with FSHD. Del-brax consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DUX4 mRNA. Del-brax is currently in registrational-stage studies including FORTITUDE biomarker cohort and the global, confirmatory, Phase 3 FORWARD trial in individuals with FSHD. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted Orphan designation for del-brax and the FDA has granted del-brax Fast Track designation. About Facioscapulohumeral Muscular Dystrophy (FSHD) Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. It is characterized by progressive and often asymmetric skeletal muscle loss that initially causes weakness in muscles in the face, shoulders, arms and trunk and progresses to weakness in muscles in the lower body. FSHD is an autosomal dominant disease caused by the aberrant expression of the DUX4 (double homeobox 4) gene in the skeletal muscle, which activates genes that are toxic to muscle cells and leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function. Skeletal muscle weakness results in physical limitations throughout the whole body, including an inability to lift arms for more than a few seconds, loss of ability to show facial expressions and serious speech impediments. These symptoms cause many people affected by FSHD to become dependent on the use of a wheelchair for mobility. Currently, there are no approved treatments for people living with FSHD. About Avidity Avidity Biosciences, Inc.’s mission is to profoundly improve people’s lives by delivering a new class of RNA therapeutics – Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare neuromuscular diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is also advancing two wholly-owned precision cardiology development candidates addressing rare genetic cardiomyopathies. In addition, Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit www.aviditybiosciences.com and engage with us on LinkedIn and X . SOURCE: Avidity Biosciences

master1305/Getty Images Avidity has been given the go-ahead by the FDA to request accelerated approval of delpacibart braxlosiran—potentially the first disease-modifying treatment for facioscapulohumeral muscular dystrophy—with an application in the second half of 2026. Avidity Biosciences’ antibody-oligonucleotide conjugate improved mobility and muscle strength in a type of muscular dystrophy in an early-stage trial, and the FDA is open to receiving an application for accelerated approval of the drug, the San Diego–based biotech revealed Monday. “Today’s updates are significantly positive for [Avidity],” BMO Capital Markets analysts wrote in a note Monday, adding that the “FDA’s “endorsement of [delpacibart braxlosiran] AA pathway is a big win.” Nevertheless, Avidity’s shares declined more than 11% to $32.14 as of 11:17 a.m. ET. Avidity plans to launch a global confirmatory Phase III study called FORWARD for facioscapulohumeral muscular dystrophy (FSHD) to support the submission, according to a separate announcement on Monday. This is on top of an ongoing registrational study to obtain more biomarker data. The company plans to biologics license application for delpacibart braxlosiran in FSHD in the second half of 2026. Monday’s topline data comes from the Phase I/II FORTITUDE study of patients with FSHD, a variant of muscular dystrophy that primarily weakens muscles in the face and upper body but can spread to the rest of the body. Patients who received delpacibart braxlosiran saw improvements in mobility and muscle strength across a number of tests, including the 10-meter walk-run test, timed up and go and quantitative muscle testing, compared to patients who received placebo. Patients who received delpacibart braxlosiran also had reduced levels of KHDC1L and creatine kinase, biomarkers of muscle damage. The trial had no discontinuations and no serious or severe adverse effects were reported. The company will present more details at the 32nd Annual FSHD Society International Research Congress, June 12-13 in Amsterdam. FSHD is caused by abnormal expression of a protein called DUX4. Using similar concepts to an antibody-drug conjugate, Delpacibart braxlosiran uses an antibody to target a transferrin receptor that delivers an siRNA molecule that targets and destroys DUX4 mRNA. Delpacibart braxlosiran is the first therapy designed to treat this underlying cause of FSHD, according to Avidity. A much-watched company in the muscular dystrophy space, Avidity’s pipeline also includes an exon-skipper, delpacibart zotadirsen, for Duchenne muscular dystrophy, which in August 2024 boosted dystrophin production by an “ unprecedented ” 25% in a Phase I/II trial. Also last year, the FDA granted breakthrough status to its myotonic dystrophy type I treatment, and in 2023 Bristol Myers Squibb bet up to $2.3 billion that Avidity’s antibody-oligonucleotide technology could be applied to five different cardiovascular targets.

PepGen on Wednesday said it will shutter its Duchenne muscular dystrophy (DMD) programme after an underwhelming performance of its exon-skipping therapy PGN-EDO51 in the mid-stage CONNECT1 study; the biotech will instead refocus resources on its promising myotonic dystrophy type 1 (DM1) programme.The company is set to wind down all DMD-related research and development activities following analysis of data from CONNECT1’s 10 mg/kg cohort involving 4 participants, where total dystrophin levels only reached 0.59% of normal levels — inadequate for a meaningful therapeutic benefit in patients amenable to exon 51 skipping. In March, the company announced it was temporarily pausing the parallel Phase II CONNECT2 study in anticipation of the CONNECT1 10 mg/kg cohort readout."We are disappointed by the dystrophin results…in the 10 mg/kg dose cohort…as it was our hope that we could improve upon existing therapies for patients in a more profound way," said James McArthur, chief executive of PepGen.In the competitive DMD space featuring triumphs and disappointments, another exon-skipping therapy — Avidity Biosciences’ delpacibart zotadirsen (del-zota/AOC 1044) recently showed encouraging biomarker data in an early-stage trial. Pivot to DM1Meanwhile, in a strategic pivot, PepGen will redirect its efforts to advancing its DM1 candidate PGN-EDODM1 — developed using the same Enhanced Delivery Oligonucleotide technology platform as PGN-EDO51. The DM1 asset — which aims to restore the normal splicing function of MBNL1 — “has already demonstrated [in FREEDOM-DM1] robust target engagement after a single 10 mg/kg dose in patients that resulted in mean mis-splicing correction of 29% with a favourable emerging safety profile," remarked Paul Streck, R&D head at PepGen.Highlighting the development timelines for PGN-EDODM1, PepGen said it expects data from the Phase I FREEDOM-DM1 15 mg/kg cohort in the second half of the year. The study’s key outcomes include safety, 28-day splicing correction, and functional benefit endpoints. Additionally, the company anticipates the 5 mg/kg cohort of the Phase II FREEDOM2-DM1 study to read out in the first quarter of 2026.PGN-EDODM1, however, has had its own share of troubles before entering the clinic. In May 2023, the FDA issued a clinical hold notice regarding an IND application to commence the FREEDOM-DM1 trial. The hold was subsequently lifted in October the same year.