Atopic dermatitis

Devonian Health Group Inc. has completed a phase II clinical trial in mild-to-moderate atopic dermatitis using Thykamine™ in a cream formulation. The phase II trial was a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of Thykamine™ cream monotherapy (0.05%, 0.1% and 0.25%) compared to placebo in skin clearance as assessed by the Investigator Global Assessment (IGA) in adult patients with mild-to-moderate atopic dermatitis. Efficacy and safety were assessed every week over a four-week dosing treatment (twice a day). A total of 162 patients, spread over several sites in Canada, were recruited for this study.

Compared to placebo, Thykamine™ at 0.1% demonstrated significant improvement of the primary endpoint, i.e., skin clearance (IGA) at all measured timelines (week 1: p = 0.006; week 2: p < 0.001; week 3: p < 0.001; week 4: p = 0.002), resulting in a fast onset of the therapeutic effect.

IGA success rates at week 4 were 6.7% for placebo (vehicle cream), 19.0% for Thykamine™ cream 0.05% (p = 0.053 vs placebo), 30.8% for Thykamine™ cream 0.10% (p = 0.014 vs placebo), and 12.1% for Thykamine™ cream 0.25% (p = 0.461 vs placebo). The success rate over placebo of Thykamine™ cream 0.1% was not only reached at week 4 but also at week 3 (p = 0.04), resulting in a fast onset of the therapeutic effect. As such, Thykamine™ cream 0.10% has been retained for phase III trials.

In addition, Thykamine™ achieved statistically significant differences, compared to placebo, in its key secondary efficacy endpoints, i.e., BSA, pruritus, POEM, and Quality of Life measurement.

Thykamine™ was shown to be safe and well tolerated during the study.

Development Stage: Ready for phase III in adults with mild-to-moderate atopic dermatitis. Ready for phase II/III in the pediatric population with mild-to-moderate atopic dermatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of hepatic disorders characterized by excess fat accumulation in the liver (hepatic steatosis) in the presence of at least one cardiometabolic risk factor, such as obesity, type 2 diabetes, hypertension, or dyslipidemia. It includes simple steatosis but can progress to metabolic dysfunction-associated steatohepatitis (MASH, previously non-alcoholic steatohepatitis or NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Criteria for histological diagnosis of MASH include steatosis, lobular inflammation, and hepatocellular injury (typically hepatocyte ballooning). While MASH may be evident histologically, a lack of clear symptoms and public awareness means it often goes undiagnosed. Among adults in the United States, the prevalence of MASH was estimated to be 5.8% in 2020 and is expected to rise to 7.9% by 2050.

A study investigated the effects of Thykamine™ on liver disease progression in the widely used STAM mouse model of MASH/fibrosis. In this model, diabetic mice were fed a high-fat diet and rapidly developed fatty liver disease caused by inflammation and fat accumulation in the organ. Resmetirom, the first drug approved by the US FDA for the management of MASH, was used as a positive control at an oral dose of 3.0 mg/kg once a day for 3 weeks. Thykamine™, administered orally at doses of 0.5 mg/kg, 5.0 mg/kg, and 50.0 mg/kg once a day for 3 weeks, provided a hepatoprotective effect preventing liver disease progression compared to the control group (vehicle). Specifically, Thykamine™ treatment resulted in a significant reduction of the liver NAFLD activity score (NAS), a composite measure of fatty liver disease composed of steatosis, inflammation, and hepatocyte ballooning. α-SMA, a marker used to evaluate liver fibrosis, was also significantly decreased. Thykamine™ treatment reduced liver collagen type I expression, collagen type III score, F4/F80 expression, Ly-6G expression, and MARCO (macrophage receptor with collagen structure) expression. The effects on these markers were comparable to those of Resmetirom. Overall, progression of liver fibrosis was reduced by Thykamine™ treatment. These data demonstrate an exciting proof of concept of Thykamine™’s anti-inflammatory and anti-fibrotic effects in MASH.

Development Stage: Differentiating preclinical work ongoing.

Eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is characterized by symptoms associated with dysfunction of the esophagus due to chronic mucosal eosinophilia and inflammation. It is a complex disease with heterogeneous clinical presentation classified, based on endoscopic features, into inflammatory, fibrostenotic, or mixed inflammatory/fibrostenotic phenotypes. EoE has emerged over the past two decades as a major cause of upper gastrointestinal morbidity. The reported prevalence of EoE has been increasing worldwide, with a recent meta-analysis estimating 34.2 cases per 100,000 persons. Subgroup analysis of North American adults reveals similar rates, at 31.9 cases per 100,000 adults, with individual studies on U.S. adults ranging from 9.45 to 58.9 cases per 100,000. The incidence of EoE has been increasing over the past several decades, and while this phenomenon is at least partially due to increased awareness and interest in the condition, some studies report that the rate of EoE has disproportionately risen with the increased rate of biopsies during the same study periods, suggesting a true increase in EoE.

Several in vitro and in vivo pharmacology studies with Thykamine™—using biochemical and cellular pathway assays as well as animal models—have consistently demonstrated its anti-inflammatory, antioxidant, and immunomodulatory properties. In a MASH mouse model, Thykamine™ significantly downregulated inflammation- and fibrosis-related genes, underscoring its potential as a novel therapeutic candidate for eosinophilic esophagitis.

Development Stage: Mucoadhesive formulation in development.