Avidity Biosciences, Inc.

PepGen Inc. (Nasdaq: PEPG) announced that the US FDA has placed a partial clinical hold on the FREEDOM2-DM1 Phase II study of PGN-EDODM1, a peptide-conjugated antisense oligonucleotide under development for the treatment of myotonic dystrophy type 1 (DM1). The partial clinical hold applies to US trial activity only, while dosing continues at international sites. The FDA’s partial clinical hold relates to questions about previously submitted preclinical pharmacology and toxicology studies. The agency did not cite concerns regarding blinded clinical data from the earlier Phase I FREEDOM study, which PepGen had submitted to support initiation of FREEDOM2 in the United States. No US patients had been enrolled in the FREEDOM2 trial at the time of the hold. PepGen stated it is submitting additional analyses to the FDA, including recently unblinded FREEDOM data, and intends to work with the agency to resolve the questions. A partial clinical hold permits ongoing treatment of already-enrolled patients but restricts new enrollment at affected sites. FREEDOM2 is designed as a multiple ascending dose, randomized, placebo-controlled study. Regulatory holds related to safety or preclinical data are not uncommon in the oligonucleotide field. For example, the FDA placed a partial hold on Avidity Biosciences’ AOC-1001 program in 2022 and paused Amylyx’s AMX0114 antisense therapy during early clinical review, both of which were later resolved after additional safety analyses. PGN-EDODM1 uses PepGen’s proprietary Enhanced Delivery Oligonucleotide (EDO) platform, which conjugates cell-penetrating peptides to antisense oligonucleotides to improve cellular uptake in muscle tissue. The molecule binds to pathogenic CUG trinucleotide repeat expansions in DMPK mRNA, disrupting sequestration of the MBNL1 splicing protein and restoring normal RNA splicing function. DM1 is a severe neuromuscular disease with no FDA-approved disease-modifying therapies. Current management is limited to symptomatic treatment. The FDA has granted PGN-EDODM1 both Orphan Drug Designation and Fast Track Designation for DM1, and the European Medicines Agency has granted Orphan Designation. PepGen was founded in 2018 as a spinout from the University of Oxford, where the EDO platform technology was developed. The company holds a license agreement with Oxford for the foundational intellectual property. PepGen completed its initial public offering on Nasdaq in May 2022 and has retained full development and commercial rights to PGN-EDODM1 without entering into any disclosed partnership or sublicensing arrangement. Outside the United States, PepGen received regulatory clearance to initiate FREEDOM2 in South Korea, Australia, and New Zealand. Dosing of the 10 mg/kg cohort continues in the United Kingdom and Canada, following a Data Safety Monitoring Board recommendation to dose escalate. Patients from the FREEDOM and FREEDOM2 studies in Canada are continuing into an Open Label Extension study, and PepGen has received regulatory clearance for the OLE in the UK. PGN-EDODM1 is among several clinical-stage candidates in development for DM1, including Dyne Therapeutics’ DYNE-101 and Avidity Biosciences’ AOC 1044, both of which use alternative delivery approaches to target DMPK mRNA. None of these programs has yet reached a regulatory filing stage. PepGen reiterated its guidance for reporting data from the FREEDOM2 5 mg/kg cohort in the first quarter of 2026 and from the 10 mg/kg cohort in the second half of 2026. The company stated it is committed to addressing the FDA’s preclinical questions and maintaining trial progress at sites outside the United States. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

San Diego–based Atrium Therapeutics launched as a publicly traded biotechnology company (Nasdaq: RNA) with approximately USD 270 million in cash to develop RNA therapeutics for rare genetic cardiomyopathies. The company was created as a spinoff tied to Novartis’ acquisition of Avidity Biosciences, with Atrium emerging as an independent entity focused on cardiac applications of RNA medicines. Unlike a traditional venture-backed biotech launch, Atrium’s initial capital base was allocated through the corporate transaction that formed the company. The funding will support advancement of two lead candidates through IND-enabling studies, manufacturing development, and early clinical trials, alongside additional undisclosed research-stage programs. Atrium’s pipeline centers on two RNA-based therapies targeting rare inherited heart diseases. ATR-1072 is being developed for PRKAG2 syndrome, a genetic cardiomyopathy caused by mutations that increase activity of AMP-activated protein kinase (AMPK). The resulting glycogen accumulation in heart cells can lead to cardiac hypertrophy, arrhythmias, and conduction abnormalities. The company estimates 1,000–2,000 patients in the United States may have the disorder. IND-enabling studies and manufacturing work are underway, with an FDA IND filing expected in H2 2026. ATR-1086 targets phospholamban (PLN) cardiomyopathy, a progressive condition driven by mutations affecting regulation of the SERCA2a calcium pump in cardiomyocytes. The disease can lead to dilated or arrhythmogenic cardiomyopathy and carries a significant risk of heart failure and sudden cardiac death. Atrium estimates 2,000–4,000 affected individuals in the United States. Preclinical studies are expected to begin in 2026, with a potential IND submission in 2027. Both programs remain in the pre-IND stage, and no clinical trials have yet been registered publicly. Atrium’s technology originates from Avidity Biosciences, which developed an antibody-oligonucleotide conjugate (AOC) platform. The approach links a monoclonal antibody targeting a tissue-specific receptor with an oligonucleotide payload, enabling targeted delivery of RNA therapeutics outside the liver. Avidity previously validated this strategy in skeletal muscle for diseases such as Duchenne muscular dystrophy and myotonic dystrophy. Atrium is applying a related concept to deliver siRNA therapies to cardiac tissue, with the aim of selectively silencing disease-causing genes in cardiomyocytes. If successful, the approach could offer advantages over viral gene therapies, including repeat dosing and reversible gene silencing. However, targeted RNA delivery to the heart remains clinically unproven. Atrium is led by President and CEO Kathleen Gallagher, while Sarah Boyce, former CEO of Avidity Biosciences, serves as chair of the board. The company begins operations with two clinical candidates in development, additional research programs, and a platform aimed at expanding RNA medicines into precision cardiology. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Atrium’s path to existence, budding off a Big Pharma’s absorption of another biotech, is uncommon but not unprecedented.\n A new biotech has taken flight as a result of Novartis’ red-hot $12 billion acquisition of muscular dystrophy specialist Avidity Biosciences. A spinout planned since that deal’s October announcement has now officially debuted as Atrium Therapeutics, with two preclinical cardio candidates in tow.Atrium is led by Kathleen Gallagher, who previously spent five years at Avidity, most recently as chief program officer. To start, Gallagher will guide two small interfering RNA assets through investigational-new-drug-application-enabling studies, Atrium announced in a Feb. 27 release.Atrium’s debut was timed to coincide with the closing of Novartis’ Avidity acquisition. Atrium has inherited Avidity’s spot in the stock market, albeit with a tweaked ticker symbol (\"RNAM\" instead of \"RNA\"). As of 10:30 a.m. ET, Atrium shares were trading at about $13.71.The fledgling San Diego biotech has $270 million in cash in its pockets and is also investigating two undisclosed research targets.“Building on Avidity\'s pioneering work in targeted RNA delivery, Atrium is positioned to advance precision medicines designed to directly target the biologic drivers of cardiac disease,” Gallagher said in the release.Atrium’s ATR 1072 is being developed for PRKAG2 syndrome, a rare genetic condition that causes arrythmia and thickening of the heart muscle. ATR 1086, meanwhile, is in the works for PLN cardiomyopathy, where calcium regulation goes haywire and heart failure can occur as a result.Atrium plans to launch a phase 1 trial of ATR 1072 in the second half of this year and for ATR 1086 in 2027, according to the release.“Patients and families facing these genetically driven rare cardiomyopathies have few if any options that address the underlying cause,” Gallagher said. “Atrium has the opportunity to help pave the way for a new era for RNA therapies in precision cardiology.” Atrium is not alone in pursuing RNA medicines for cardiovascular diseases. Corsera Health launched last fall with $50 million and a preventive RNA interference asset for heart disease, along with the expertise of industry titans Clive Meanwell, M.D., formerly of The Medicines Company, and John Maraganore, Ph.D., founding CEO of Alnylam Pharmaceuticals.Atrium’s path to existence, budding off a Big Pharma’s absorption of another biotech, is uncommon but not unprecedented. When Scorpion Therapeutics’ PI3Kα program was snagged by Eli Lilly in January 2025, the biotech spun out Antares Therapeutics to advance three precision medicine candidates.When Johnson & Johnson maneuvered to buy Swiss biotech Actelion for $30 billion about a decade ago, Idorsia emerged from the deal with $1 billion in the bank, multiple clinical-stage assets and a partnership with the Big Pharma already in place.