Massachusetts-based Soufflé Therapeutics, Inc. has registered a Phase I/II clinical trial of SFL-0821, an antibody-siRNA conjugate designed to silence DUX4 expression in skeletal muscle, in adults with facioscapulohumeral muscular dystrophy (FSHD). FSHD has no approved therapy, however the field is now being contested by multiple companies pursuing the same molecular target with closely related modalities .
The study (NCT07798609), sponsored by Soufflé, is listed as "not yet recruiting" with an estimated start date of September 2026. It is structured in two sequential parts: Part A is a single ascending dose phase and Part B a multiple ascending dose phase, both randomized, double-blind, and placebo-controlled. SFL-0821 will be administered by intravenous infusion. The trial plans to enroll 90 adults aged 18–65 with genetically confirmed FSHD 1 or 2, and sites span Australia and New Zealand, including The Alfred Hospital in Melbourne, Mater Hospital Brisbane, and Pacific Clinic Research Network in Auckland. Primary completion is expected by March 2028. Secondary endpoints extend beyond pharmacokinetics to include DUX4-regulated gene expression in skeletal muscle biopsy, quantitative muscle MRI, and functional mobility measures.
SFL-0821 uses a proprietary myocyte-targeting antibody conjugated to a DUX4-specific small interfering RNA (siRNA), delivering the payload directly into skeletal muscle cells via receptor-mediated uptake. According to preclinical data presented at the 2026 MDA Clinical and Scientific Conference, a single administration produced potent DUX4 transcript knockdown — with an IC50 below 0.05 mg/kg — in the Acta1-MCM; FLExDUX4 mouse model, and muscle-specific delivery was confirmed in non-human primates. The company said the data supported clinical advancement.
Novartis (SWX: NOVN.SW) is furthest ahead with delpacibart braxlosiran (del-brax; AOC 1020), an antibody oligonucleotide conjugate (AOC) acquired through its approximately USD 12 billion purchase of Avidity Biosciences, completed in February 2026. Del-brax uses a transferrin receptor 1 (TfR1)-targeting monoclonal antibody to deliver a siRNA that suppresses DUX4 expression in skeletal muscle. In June 2026, the biomarker cohort of the Phase I/II FORTITUDE study met its primary and key secondary endpoints, demonstrating reductions in the DUX4-regulated circulating biomarker KHDC1L and creatine kinase, a marker of muscle damage. Novartis is now enrolling approximately 200 patients in the pivotal Phase III FORTITUDE-3 study, using del-brax 2 mg/kg every six weeks. The company said in July that its base-case regulatory strategy is a submission based on Phase III data in 2028, while it continues discussions with health authorities over whether the Phase I/II dataset could support an earlier pathway.