Dianthus Advances DNTH312 Dual-Target Approach for Severe Autoimmune Diseases

Dianthus Therapeutics has announced DNTH312, an investigational bifunctional fusion protein being developed to treat severe autoimmune diseases.

DNTH312 combines claseprubart, which inhibits the classical complement pathway through aC1s, with TACI-mediated inhibition of BAFF and APRIL. 

By targeting both pathways, the therapy is designed to address complementary mechanisms involved in autoantibody-driven diseases, including myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN).

Preclinical studies showed that DNTH312 achieved aC1s inhibition and potency comparable with claseprubart across several in vitro assays. 

The molecule also incorporates YTE half-life extension technology. In non-human primate studies, it demonstrated a 22-day half-life, similar to claseprubart.

Following a single dose, DNTH312 produced reductions in IgM, IgA and IgG levels comparable with povetacicept, a clinically validated BAFF/APRIL inhibitor. 

The extended half-life could support infrequent subcutaneous administration.

Dianthus believes the dual mechanism could deliver deeper immune responses, broader symptom control and potential access to larger patient populations.

DNTH312 is expected to be Phase 1 ready by the end of 2027. The programme is investigational and has not been approved for any indication worldwide.