*) IIT: Investigator initiated trial

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Orismilast

A potential first-in-class or best-in-class treatment for immunological diseases

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.

Orismilast has been selected as lead molecule based on its attractive therapeutic window (i.e., the combination of improved efficacy and tolerability) and because of its potential to inhibit many inflammatory pathways involved in immunologic diseases due to the broad range of anti-inflammatory effects.

Over the course of Phase 1 and Phase 2 trials, orismilast has been demonstrated to be safe in both oral and topical dosage forms and the PDE4 mode-of-action has been verified as an effective, well-tolerated approach to treatment of patients across multiple diseases, with no need for monitoring.

UNION is developing orismilast as an oral formulation for the treatment of AD, HS, psoriasis and ulcerative colitis.

Orismilast development programs

The current development status of oral orismilast is the following:

• Atopic dermatitis (AD): The FDA has granted Fast Track designation to oral orismilast for the treatment of moderate to severe AD. Succesful completion of the ADESOS Phase 2b dose finding study was reported in June 2024 prior to presentation of data at the RAVE Conference in June 2024. The ClinicalTrials.gov Identifier is NCT05469464

• Hidradenitis suppurativa (HS): The FDA has granted Fast Track designation to oral orismilast for the treatment of moderate to severe HS. Positive topline results reported on June 21, 2023, for OSIRIS (PoC, IIT) study for oral orismilast in HS and data presented at EADV in October 2023. The study demonstrated clinically relevant improvements in HS for patients who completed the planned 16 weeks of treatment with oral orismilast. Importantly, the improvements included reduction of pain (Global Pain Assessment) and improvement in patient-reported quality of life (DLQI). ClinicalTrials.gov Identifier: NCT04982432

• Psoriasis: Phase 2b topline results were reported on January 9, 2023, supporting the target product profile of orismilast and confirming the well-established favorable safety profile of PDE4 inhibition. Data from the study has been presented at AAD. In November 2020, the US Food and Drug Administration (FDA) approved UNION’s Investigational New Drug Program (IND) for advancing oral orismilast into a Phase 2b trial in patients with moderate to severe psoriasis. ClinicalTrials.gov Identifier: NCT05190419

• Ulcerative colitis (UC): Phase 2, investigator-initiated study of orismilast in patients with moderate to severe ulcerative colitis was initiated in January 2024.