Clinical Trial Update

Innovent And UNION Therapeutics Announce First Subject Dosed In A Chinese Clinical Phase I Study Of The Novel PDE4 Inhibitor Orismilast (IBI353)

December 06,2022 04:56 AM
- By Admin

 Innovent Biologics, Inc. a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and UNION therapeutics A/S (UNION), a privately-held, multi-asset, clinical stage, pharmaceutical development company focused on immunology and infectious diseases, today announced that the first Chinese healthy volunteer has been successfully dosed in the Phase I study of orismilast (Innovent R & D code: IBI353), a potential best-in-class PDE4 inhibitor in global clinical Phase II stage.

This study (CTR 20222393) is a multiple dose escalation Phase I study in healthy volunteers aiming to evaluate the pharmacokinetic (PK) profile, safety and tolerability of orismilast in healthy Chinese subjects after multiple doses to support the subsequent clinical development of orismilast in multiple indications such as psoriasis and atopic dermatitis (AD).

Orismilast is a next-generation PDE4 inhibitor with high potency for the PDE4 subtypes linked to inflammation. In 2021, Innovent reached a strategic cooperation with UNION to obtain exclusive rights to the research, development and commercialization of orismilast in China (including mainland China, Hong Kong, Macao and Taiwan). Orismilast has generated positive proof of concept (PoC) data in psoriasis (administered orally) and in AD (administered topically) and is being developed as a potential best- or first-in-class oral treatment option in both diseases. Compared to other PDE4 inhibitors, the selectivity of orismilast for PDE4 subtypes B and D and the novel modified release delivery is expected to generate a favorable therapeutic window, potentially resulting in improved efficacy and tolerability.Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: 'There is currently no cure for psoriasis, and there is a great unmet clinical need in this field. Orismilast is a new target molecule Innovent laid out in the field of autoimmunity by co-development with UNION. It is potentially one of the best candidates in the mid-stage of clinical development at Innovent. The results of ex-China clinical studies have demonstrated that orismilast has good safety profile and biological activity. The ongoing Phase I study will evaluate the safety and tolerability of orismilast in Chinese healthy volunteers and provide the basis for further clinical development. We will accelerate the clinical development of orismilast in Chinese subjects with psoriasis or AD in order to obtain regulatory approval as soon as possible in China and to fulfill the needs of safe, effective and convenient long-term oral treatment for patients, thus significantly reducing the disease burden of patients and their pain. We will truly uphold our mission of "To develop and commercialize high-quality biopharmaceuticals that are affordable to ordinary people".'

Kim Kjøller, CEO of UNION therapeutics, stated: 'We are excited by the strong advancement of orismilast by Innovent, which is essential in our joint efforts to provide this novel treatment to patients with dermatological diseases globally. We have seen good progress in our three late-stage clinical trials with orismilast for treatment of psoriasis, atopic dermatitis, and hidradenitis suppurative, respectively. This, together with the now ongoing Phase I study in China, is important steps in the development of orismilast.'

About Psoriasis and atopic dermatitis (AD)

Psoriasis is a multisystem disease characterized by well-defined erythematous scaly plaques that are often pruritic. Estimates of psoriasis prevalence range from 0.51% to 11.43% in adults and 0% to 1.37% in children[1].Psoriasis is a common disease that occurs more frequently with age. The most common clinical type of psoriasis is psoriasis vulgaris (plaque psoriasis). The involvement of inflammatory cells (e.g., T cells and myeloid dendritic cells) and pro-inflammatory cytokines (e.g., tumor necrosis factor-α, interleukin (IL) -12, and IL-17) in the pathogenesis of psoriasis has been well documented [2].

There is currently no cure for psoriasis. Psoriasis vulgaris can be managed with local therapy, phototherapy, or systemic therapy or any combination of these.

It is estimated that around 80% of psoriasis patients have mild to moderate psoriasis[3] [4] , for those patients topical therapy is used first line. About one-third of psoriasis patients experience moderate-to-severe disease, systemic medications (biologic or nonbiologic) or phototherapy are preferred regimens for such patients[5]. However, long term treatment of psoriasis with topical therapies (e.g. TCS), biologic therapies (eg, antibodies) is often limited by safety and tolerability issues, with decreasing efficacy over time, thus resulting in poor patient adherence due to inconvenient routes of administration (eg, injections) [6]. Therefore, there is an unmet need for safe, effective, and convenient long-term oral therapy for patients with psoriasis.

Atopic Dermatitis (AD) is a chronic inflammatory disease characterized by eczematous lesions and intense pruritus, affecting up to 20% of children and up to 3% of adults[7].Inflammatory infiltrates in these skin lesions include T lymphocytes, neutrophils, eosinophils, monocytes, macrophages, and mast cells[8].High levels of PDE4 activity have also been identified in leukocytes of these patients[9].AD is usually treated with topical therapies, primarily intermittent prophylactic use of topical corticosteroids and/or topical calcineurin inhibitors, along with daily emollients. Intermittent corticosteroid use poses minimal risk of corticosteroid-related adverse effects such as skin atrophy, striae formation in sensitive or thin skin areas, and systemic effects. However, long-term adherence to topical therapy was low. Off-label use of other conventional systemic oral immunomodulators such as cyclosporine, azathioprine, and methotrexate may be effective in adult AD patients, but patients discontinue treatment due to adverse events or lack of efficacy. Use of these agents has known safety limitations and requires regular laboratory monitoring. Therefore, better systemic treatment options are needed, particularly for AD patients who do not respond well to topical treatment. Dupilumab, a subcutaneous biologic therapy targeting IL-4 and IL-13 receptors, is approved by the US Food and Drug Administration for the treatment of moderate to severe AD in adults. The need for oral treatment options remains imperative in this disease state.