UNION therapeutics announces publication of results from the OSIRIS Phase 2 study of orismilast in hidradenitis suppurativa in the Journal of the European Academy of Dermatology and Venereology

• Orismilast demonstrated clinically relevant improvements in patients with hidradenitis suppurativa (HS), confirming the relevance of orismilast for the treatment of HS
• 67% of patients completing 16 weeks of treatment achieved HiSCR50, and the mean reduction in AN-count in patients completing treatment with orismilast was 33.1%
• A 48.2% reduction in skin-related pain, which is one of the most bothersome symptoms for HS patients, was observed for the patients completing treatment
• Positive topline results have been reported with orismilast in psoriasis and is currently being tested in an ongoing Phase 2b study in atopic dermatitis (AD)

Hellerup, Denmark, March 15, 2024 – UNION therapeutics A/S (“UNION”), a privately held, clinical stage, pharmaceutical development company focused on immunology, announces publication of a paper presenting full results from the OSIRIS investigator-initiated Phase 2 study of orismilast for the treatment of mild, moderate and severe HS in the peer-reviewed Journal of the European Academy of Dermatology and Venereology (JEADV).

The paper, authored by the OSIRIS principal investigator and co-investigators, highlights the outcomes of the OSIRIS study. OSIRIS was an open-label, single-center, prospective, single arm, investigator-initiated proof-of-concept study exploring the efficacy, safety, and tolerability of orismilast taken twice daily for up to 16 weeks in adult patients with mild, moderate, and severe HS. 20 patients were enrolled in the study with patients receiving up to 40 mg (dose range 10-40 mg) of orismilast administered twice daily. 9 patients completed 16 weeks of treatment while 11 patients discontinued treatment prematurely. The dosing regimen was individualized with lower end-doses and slower titration for some patients.

The study demonstrated clinically relevant improvements in patients with HS. The percent change from baseline in abscess and inflammatory nodule count (AN-count) at week 16 was −33.1% in patients completing treatment and a decrease in the mean total lesion count from 8.8 to 5.3 was seen in patients completing treatment with orismilast. In contrast to changes in the AN-count, changes in the total lesion count, the International Hidradenitis Suppurativa Severity Score (IHS4-score), and the Hidradenitis Suppurativa Clinical Response (HiSCR), which also encompasses assessment of draining tunnels, may provide a more thorough assessment of the changes seen in the patients. Study completers experienced a decrease in the mean IHS4-score from 19.8 to 10, equating to a reduction of −43.8%. Additionally, 67% of patients completing treatment with orismilast achieved HiSCR50, 44% achieved HiSCR75 and 22% achieved HiSCR100. Three of the patients achieving HiSCR50 response after 16 weeks of orismilast treatment had previously failed one or more biologic therapies.

Pain is one of the most bothersome symptoms for patients with HS. It is therefore encouraging that patients who completed all 16 weeks of treatment exhibited reductions in skin-related pain (−48.2%) and improvements in disease-related quality of life (DLQI-score −39.6% and HiSQoL score −31.4%). Clinically meaningful reductions in skin-related pain were reported by patients already after week 2. These data indicate that PDE4-inhibition is a relevant mode of action for HS, and that at the right dose regimen, orismilast may be a promising treatment for HS.

No new safety signals were identified with orismilast which confirms the general safety profile of PDE4 inhibitors with a manageable, transient and well-characterized adverse event (AE) profile. This study found that the adverse drug reactions (ADR) most frequently reported were gastrointestinal, dizziness and headache and most of these were mild to moderate in severity. ADRs were most frequently reported during the first 4 weeks of treatment. The safety profile was similar to what was seen in the IASOS Phase 2b study with orismilast in psoriasis. 1)

Topline results from the OSIRIS study were reported in June 2023 and data was presented at a late-breaking oral presentation at the European Academy of Dermatology and Venereology (EADV) Congress in October 2023.

Professor Gregor B. Jemec, MD, DMedSci, Professor (Chair of Dermatology), Head of Research, Department of Dermatology, Zealand University Hospital, Denmark, and principal investigator of the study said: 

“Hidradenitis suppurativa is an inflammatory systemic skin disease where a strong unmet need remains for safe and effective oral treatments. Data from the Phase 2 study with orismilast in HS indicates PDE4-inhibition is a relevant mode of action for HS, and that at the right dose regimen, orismilast may be a promising treatment for HS.”

Kim Kjøller, Co-Chief Executive Officer of UNION therapeutics, said:

“It is encouraging that data from the OSIRIS investigator-initiated Phase 2 study with orismilast confirms the clinical relevance of orismilast for the treatment of a range of immune-dermatological diseases including hidradenitis suppurativa (HS). Preparations are ongoing for the next clinical studies with orismilast for the treatment of HS.”

About orismilast

Orismilast is a next generation, high potency PDE4 inhibitor targeting the PDE4B/D subtypes linked to inflammation, demonstrating potent inhibition of Th1, Th2 and Th17 pathways. It acts early in the inflammation cascade, inducing a broad range of anti-inflammatory effects across multiple cytokines involved in many dermatological and immunological diseases.2)

UNION is developing orismilast as an oral treatment, based on the well-known safety profile of the PDE4 class, across immunology, initially targeting best-in-class or first-in-class positions in atopic dermatitis, hidradenitis suppurativa, psoriasis and ulcerative colitis.

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 AD as well as for the treatment of moderate to severe HS.

Sources

1)       Frederiksen et al., JEADV 2023: https://pubmed.ncbi.nlm.nih.gov/38147438/

2)       Blauvelt A et al., Dermatology and Therapy 2023: Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review - PubMed (nih.gov) &

Silverberg J.I. et al., JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18818  &

Warren R.B. et al., JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18812 &

Contacts

Morten Boesen, Chief Financial Officer, UNION therapeutics A/S

+45 2381 5487

morten.boesen@uniontherapeutics.com

Sarah Toft-Jørgensen, Director of Communications and IR, UNION therapeutics A/S

+45 5385 3044

sarah.toft-joergensen@uniontherapeutics.com

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 more than fifteen marketed drugs. Read more at www.uniontherapeutics.com