Dianthus Shares Preclinical Data for Phase II Neuromuscular Candidate

Dianthus Therapeutics, a clinical-stage biotechnology company, has unveiled promising preclinical data for its investigational drug DNTH103, currently being tested for generalized myasthenia gravis (gMG) and chronic demyelinating polyneuropathy (CIDP). The data were presented at the European Academy of Neurology (EAN) 2024 Congress in Helsinki, Finland.

Investigations into the blood samples of three gMG patients revealed that DNTH103 achieved a reduction in the fatigue index by 24.8% to 27.8% from baseline. This index is crucial as it reflects improvements in neurotransmission and muscle contraction. Myasthenia gravis is an autoimmune disorder characterized by muscle weakness and fatigue due to impaired communication between nerves and muscles.

Another dataset examined the blood of CIDP patients, indicating that the highest dose of DNTH103 tested successfully restored neuronal conduction velocity. CIDP is a neurological condition marked by progressive weakness and deteriorating sensory function in the limbs due to inflammation in peripheral nerves.

The preclinical findings also suggested that DNTH103 could be developed into a patient-friendly treatment, allowing infrequent subcutaneous (SC) self-administration. DNTH103 is a fully human IgG4 monoclonal antibody that inhibits C1s, a protein active in the inflammation-promoting classical complement pathway. This pathway typically helps clear microbes and damaged cells but is implicated in some autoimmune diseases.

These promising results support Dianthus’s ongoing Phase II clinical study, known as the MaGic trial (NCT06282159). Launched in February 2024, this trial plans to enroll 60 gMG patients who are positive for anti-acetylcholine receptor (AChR) antibodies. Participants will receive DNTH103 via SC injections every two weeks, with topline data anticipated in the second half of 2025.

Additionally, the US Food and Drug Administration (FDA) recently approved Dianthus to launch a Phase II trial of DNTH103 for treating multifocal motor neuropathy (MMN), with initial results expected in the second half of 2026. Dianthus is also planning another Phase II study for CIDP in the latter half of 2024.

In a related development, in October 2023, the FDA approved UCB’s ZILBRYSQ (zilucoplan) for treating adults with gMG who are AChR antibody-positive. ZILBRYSQ acts as a targeted peptide inhibitor of complement component 5 (C5). However, according to Dianthus CEO Marino Garcia, C5 inhibitors carry an increased risk of serious bacterial infections.

Garcia stated, “We aim to demonstrate that DNTH103 may become a best-in-class classical complement pathway inhibitor. Our goal is to provide effective and consistent symptom control for individuals with neuromuscular conditions through infrequent self-administration, without inhibiting the alternative and lectin pathways that play a critical role in infection defense.”

DNTH103’s ability to potentially offer a less frequent, self-administered treatment option could significantly enhance the quality of life for patients suffering from these debilitating neuromuscular conditions.