NEW YORK and WALTHAM, Mass., August 4, 2026

Dianthus Therapeutics, Inc. announced the launch of DNTH312, an internally developed first-in-class, next-generation bifunctional fusion protein designed to treat severe autoimmune diseases by simultaneously targeting active C1s (aC1s) and BAFF/APRIL, two clinically validated pathways involved in autoimmune disease progression. Built upon the company’s lead complement inhibitor claseprubart, DNTH312 combines Classical Complement Pathway inhibition with B-cell modulation through a single therapeutic molecule, aiming to deliver broader disease control and superior clinical efficacy across multiple autoantibody-driven disorders. Preclinical studies demonstrated comparable in vitro potency and aC1s inhibition to claseprubart, while also achieving similar immunoglobulin (IgM, IgA, and IgG) reductions to the late-stage BAFF/APRIL inhibitor povetacicept following a single dose in non-human primates. The company expects DNTH312 to be Phase 1 ready by the end of 2027, further strengthening its autoimmune disease pipeline.

Dual Mechanism Designed to Address Multiple Autoimmune Pathways

DNTH312 was engineered to combine upstream B-cell inhibition and downstream Classical Complement Pathway blockade within a single molecule, targeting two complementary biological mechanisms responsible for tissue damage in autoantibody-mediated diseases. The therapy inhibits BAFF/APRIL, reducing the production of disease-causing autoantibodies, while simultaneously blocking active C1s, preventing activation of the complement cascade and reducing inflammatory damage caused by components such as the Membrane Attack Complex (MAC). According to Dianthus, this dual mechanism has the potential to produce deeper clinical responses, broader symptom control, and improved outcomes in diseases including generalized myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), systemic lupus erythematosus (SLE), Sjögren’s disease, rheumatoid arthritis, and IgA nephropathy, where both complement activation and B-cell dysfunction contribute to disease progression.

Preclinical Data Demonstrate Strong Pharmacology and Extended Half-Life

The company reported encouraging preclinical pharmacology data, showing that DNTH312 achieved comparable complement inhibition and potency to claseprubart across multiple functional assays evaluating Classical Complement Pathway activity. The investigational fusion protein also incorporates YTE half-life extension technology, enabling a 22-day half-life in non-human primates, comparable to claseprubart’s preclinical profile and supporting the potential for infrequent subcutaneous self-administration in humans. In addition, the molecule demonstrated similar reductions in IgM, IgA, and IgG levels compared with povetacicept, while potentially offering longer dosing intervals due to its extended pharmacokinetic profile. These findings suggest the therapy could combine the advantages of validated complement inhibition and BAFF/APRIL blockade within a single long-acting biologic designed for chronic autoimmune disease management.

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DNTH312 Expands Dianthus’ Autoimmune Leadership Strategy

With DNTH312, Dianthus Therapeutics is expanding beyond its lead candidate claseprubart to build a broader portfolio of next-generation autoimmune therapies targeting complementary disease pathways. The company believes the new fusion protein has the potential to become a pipeline-in-a-product, addressing a wider range of severe autoimmune disorders while extending its intellectual property portfolio with protection expected through at least 2047, beyond the existing protection for claseprubart. By leveraging its scientific expertise in complement biology and autoimmune diseases, Dianthus aims to position DNTH312 as a differentiated therapeutic capable of delivering best-in-disease efficacy across multiple indications. As development progresses toward Phase 1 readiness by year-end 2027, the company expects the candidate to play an important role in expanding treatment options for patients living with severe autoimmune and inflammatory diseases with significant unmet medical needs.

Source:Dianthus Therapeutics press release