Hellerup, Denmark, October 31, 2025 – UNION therapeutics A/S (“UNION”), a privately held, clinical stage, pharmaceutical development company focused on immunology, announces publication of a paper documenting the ability of orismilast, a potent selective PDE4 B/D inhibitor, to modulate key disease driving cytokines measured via a pioneering combination of extensive tape-stripping and Olink® technology from the IASOS study in psoriasis published in Experimental Dermatology.1)
The paper, authored by the IASOS principal investigator and co-investigators, reports the first data to date exploring biomarker data obtained from non-invasive tape-stripping and analyzed using the Olink® technology. 71 different skin proteins were analyzed, of which 32 were upregulated in psoriatic skin at baseline.
At Week 16, an immunomodulatory effect of orismilast across several immune axes was observed as demonstrated by a significant reduction in lesional protein levels related to TH17 (e.g. IL-23, IL-17A, CCL20 and IL-12B), TH1 (e.g. TNFα, IFNγ, CXCL9 and CXCL10) and epithelial inflammation (e.g. IL-17C). In particular, key markers of the psoriasis disease pathology were significantly reduced in the two active arms (20mg/30mg) reaching an improvement of 51-%52% (IL-17A), 41-54% (CCL20) and 60-66% (TNFα) at Week 16.
While most patients had a good immunomodulatory effect of orismilast, achieving a PASI75 response was associated with an IL17A reduction of 98% at week 16 indicating a threshold for clinical effect. Other TH1 and TH17 immune axis biomarkers showed a similar trend. In PASI75 non-responders reductions of up to 60% of IL17A was observed in line with the clinical findings that most patients experience clinical benefits upon orismilast treatment.
The broad anti-inflammatory effect seen in psoriasis patients after treatment with orismilast is in alignment with preclinical data of orismilast in vitro and in vivo and supports the mechanistic hypothesis of PDE4 inhibition impacting T cell receptor activation through the cAMP signaling pathway and keratinocyte activation, which support the value of potent and selective PDE4 B/D inhibition. The broad biomarker response observed in psoriasis patients indicate PDE4 B/D inhibition could be a potential treatment for diseases caused by more complex inflammation such as Hidradenitis Suppurativa.
Kim Kjøller, Co-Chief Executive Officer of UNION therapeutics, said:
“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. The strong immunomodulatory effects reported across TH17, TH1 and epithelial inflammation combined with similar effects for TH2 reported in the ADESOS dose ranging study of orismilast in moderate to severe Atopic Dermatitis (AD), support the broader potential of orismilast treatment in inflammatory disease with multiple axis involved such as Hidradenitis Suppurativa (HS), where a Phase 2b study is currently being planned.”
About IASOS
IASOS was a Ph2b study investigating the effect of three doses of orismilast vs. placebo in 202 subjects with moderate to severe psoriasis with the primary endpoint at wk16. All three doses separated statistically significantly from placebo, with 20 and 30 mg being selected for future studies in a weight-based dosing regimen.
UNION is developing orismilast, a high-potency PDE4 inhibitor targeting the PDE4B/D subtypes linked to inflammation, demonstrating potent inhibition of Th1, Th2 and Th17 pathways. It operates early in the inflammation cascade, inducing a broad range of anti-inflammatory effects across multiple cytokines involved in many dermatological and immunological diseases.2)
Orismilast holds the potential to become a safe and efficacious oral treatment for several immunological diseases3), and UNION is currently developing oral orismilast for the treatment of hidradenitis suppurativa (HS).
The FDA has cleared UNION’s Investigational New Drug (IND) application for oral orismilast and granted Fast Track designation for oral orismilast for the treatment of moderate to severe HS as well as for the treatment of moderate to severe atopic dermatitis.
Sources
1) Warren R.B. et al, Orismilast, a potent and selective PDE4B/D inhibitor, reduces protein levels of key disease driving cytokines in the skin of patients with plaque psoriasis, Experimental Dermatology 2025, https://pubmed.ncbi.nlm.nih.gov/40970551/
2) Silverberg J.I. et al., Pharmacology of orismilast, a potent and selective PDE4 inhibitor, JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18818 & Warren R.B. et al., Efficacy and safety in moderate-severe psoriasis and development of modified release tablets, JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18812
3) Warren R.B. et al., Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS), J Am Acad Dermatol 2024: https://pubmed.ncbi.nlm.nih.gov/37951245/ & Silverberg J.I. et al., Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS), Br J Dermatol 2025: https://pubmed.ncbi.nlm.nih.gov/39847538/. Frederiksen et al., JEADV 2023: https://pubmed.ncbi.nlm.nih.gov/38147438/.
Contacts
Morten Boesen, Chief Financial Officer, UNION therapeutics A/S
+45 2381 5487
About UNION therapeutics
UNION therapeutics is a privately held, clinical stage, pharmaceutical development company focused on immunology. UNION is headquartered in Hellerup, Denmark, and led by an international team combining biotech entrepreneurs and seasoned pharma executives, with a track record of developing and launching multiple marketed drugs. Read more at http://www.uniontherapeutics.com