UNION Therapeutics Publishes Biomarker Data Showing Orismilast's Multi-Pathway Anti-Inflammatory Effects in Psoriasis
Key Insights
UNION therapeutics (search) published biomarker data from the IASOS psoriasis (search) study demonstrating orismilast's ability to significantly reduce key inflammatory cytokines across TH17, TH1, and epithelial pathways using novel tape-stripping and Olink technology.
The PDE4 (search) B/D inhibitor achieved substantial reductions in disease markers, with 51-52% improvement in IL-17A, 41-54% in CCL20 (search), and 60-66% in TNFα (search) at Week 16 in active treatment arms.
Patients achieving PASI75 response showed 98% IL-17A reduction, establishing a clear biomarker threshold for clinical efficacy and supporting orismilast's potential for treating complex inflammatory diseases like hidradenitis suppurativa (search).
UNION therapeutics (search) announced publication of biomarker data from its IASOS psoriasis (search) study, revealing orismilast's broad anti-inflammatory effects across multiple immune pathways. The study, published in Experimental Dermatology, represents the first use of non-invasive tape-stripping combined with Olink technology to analyze biomarker modulation in psoriasis patients.
Novel Biomarker Analysis Reveals Multi-Pathway Effects
The research analyzed 71 different skin proteins, identifying 32 that were upregulated in psoriatic skin at baseline. At Week 16, orismilast demonstrated significant immunomodulatory effects across several immune axes, with notable reductions in lesional protein levels related to TH17 (IL-23, IL-17A, CCL20 (search), IL-12B), TH1 (TNFα (search), IFNγ, CXCL9, CXCL10), and epithelial inflammation (IL-17C).
The two active treatment arms (20mg and 30mg) achieved substantial improvements in key psoriasis (search) disease markers: 51-52% reduction in IL-17A, 41-54% reduction in CCL20 (search), and 60-66% reduction in TNFα (search) at Week 16.
Clinical Response Threshold Identified
A critical finding emerged regarding the relationship between biomarker reduction and clinical response. Patients achieving PASI75 response demonstrated a 98% reduction in IL-17A at week 16, establishing a clear threshold for clinical effect. Other TH1 and TH17 immune axis biomarkers showed similar trends. Even PASI75 non-responders experienced IL-17A reductions of up to 60%, consistent with clinical observations that most patients benefit from orismilast treatment.
"The biomarker data from IASOS are very encouraging as they show a clear link between reduction of the TH17 axis and clinical results including the existence of a clear threshold for IL17A reduction needed to achieve a PASI75 response," said Kim Kjøller, Co-Chief Executive Officer of UNION therapeutics (search).
Mechanistic Validation and Broader Therapeutic Potential
The broad anti-inflammatory effects align with preclinical data and support the mechanistic hypothesis that PDE4 (search) inhibition impacts T cell receptor activation through the cAMP signaling pathway and keratinocyte activation. This validates the therapeutic value of potent and selective PDE4 B/D inhibition.
The comprehensive biomarker response observed in psoriasis (search) patients suggests PDE4 (search) B/D inhibition could effectively treat diseases involving more complex inflammation patterns, such as Hidradenitis Suppurativa (search). Kjøller noted that the strong immunomodulatory effects across TH17, TH1, and epithelial inflammation, combined with similar TH2 effects reported in the ADESOS atopic dermatitis (search) study, support orismilast's broader therapeutic potential.
Development Program and Regulatory Status
The IASOS study was a Phase 2b trial investigating three orismilast doses versus placebo in 202 subjects with moderate to severe psoriasis (search), with the primary endpoint at week 16. All three doses achieved statistically significant separation from placebo, with 20mg and 30mg doses selected for future studies using a weight-based dosing regimen.
UNION is developing orismilast as a high-potency PDE4 (search) inhibitor targeting PDE4B/D subtypes linked to inflammation. The compound demonstrates potent inhibition of Th1, Th2, and Th17 pathways, operating early in the inflammation cascade to induce broad anti-inflammatory effects across multiple cytokines involved in dermatological and immunological diseases.
The FDA has cleared UNION's Investigational New Drug application for oral orismilast and granted Fast Track designation for treating moderate to severe hidradenitis suppurativa (search) and moderate to severe atopic dermatitis (search). The company is currently planning a Phase 2b study in hidradenitis suppurativa.