Technoderma Medicines has announced positive results from its Phase 2a clinical trial of TDM-180935, a topical Janus kinase (JAK)-1/tyrosine kinase (TYK)-2 inhibitor, for the treatment of atopic dermatitis (AD). The study demonstrated the efficacy of the 2% formulation of the ointment, with favorable tolerability and minimal systemic absorption.
The Phase 2a trial (NCT06363461) was a randomized, vehicle-controlled, parallel-group study that included an open-label pharmacokinetic (PK) substudy. Twenty-four patients with mild to moderate AD were randomly assigned to receive TDM-180935 1%, TDM-180935 2%, or placebo for 8 weeks. An additional six patients were enrolled in the open-label PK substudy and treated with the 2% formulation.
The primary efficacy endpoint, change from baseline in modified Eczema Area and Severity Index (m-EASI) at week 8, was met in the 2% TDM-180935 group. Substantial m-EASI-75 and m-EASI-90 responses were observed across all active treatment groups. Specifically, 62.5% of patients in the 2% TDM-180935 group achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with a ≥ 2-point improvement from baseline at week 8, compared to 37.5% in the 1% group and 12.5% in the pooled placebo group.
Safety and Tolerability
The treatment was well-tolerated, with treatment-emergent adverse events deemed unremarkable. One patient in the placebo arm withdrew from the study due to flare-ups of the disease at the application sites. Plasma drug levels were low in the PK substudy, with only two of six patients showing measurable levels, and those were below 1 ng/mL. No serious adverse events were reported.
Clinical Significance
Atopic dermatitis is a chronic, relapsing inflammatory skin disorder affecting an estimated 15-20% of children and 1-3% of adults worldwide. The pathogenesis of AD involves skin barrier dysfunction, allergen exposure, microbial infection, and dysregulated immune function. Current treatments include topical corticosteroids, calcineurin inhibitors, and systemic therapies, but there remains an unmet need for safe and effective topical treatments, especially for long-term use and application to large body surface areas.
Expert Commentary
"The current study results demonstrate Proof-of-Concept for TDM-180935 regarding efficacy and guides choice of the 2% ointment formulation strength as appropriate for continued development in our AD program," said Arthur P. Bertolino, MD, PhD, MBA, Chief Medical Officer at Technoderma Medicines. "We remain encouraged by the selective advantages that may be provided by TDM-180935 as a potent JAK1/Tyk2 small molecule inhibitor."
About TDM-180935
TDM-180935 is a small molecule drug candidate being developed as a topical treatment for atopic dermatitis. As a potent JAK1/Tyk2 inhibitor, it may offer significant advantages regarding efficacy and safety compared to existing topical treatments. Functional cell assays demonstrate that TDM-180935 can effectively suppress both keratinocyte- and T cell-derived pathogenic pathways characteristic of atopic dermatitis. Phase 1 clinical testing of topical TDM-180935 ointment previously demonstrated excellent toleration and minimal systemic absorption.
