Innovent and UNION Therapeutics Announce First Subject Dosed in a Chinese Clinical Phase I Study of the Novel PDE4 Inhibitor Orismilast (IBI353)

ROCKVILLE, Md. and SUZHOU, China, Dec. 4, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), 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.

About Orismilast

IBI353 (Orismilast) is a next-generation PDE4 inhibitor with high potency for the PDE4 subtypes linked to inflammation currently under development as an oral treatment for psoriasis, AD and HS. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE that is expressed by immune and inflammatory cells, including T lymphocytes, neutrophils, eosinophils, monocytes, dendritic cells, and macrophages^[10]. In these cells PDE4 is the predominant PDE form and PDE4 inhibitors increase cAMP levels. High cAMP levels tend to reduce proliferation and cytokine production, whereas low concentrations of cAMP have the opposite effects. PDE4 inhibition has previously been shown to downregulate production of a range of proinflammatory cytokines^[11]-[13]. Consistent with previously published work, orismilast demonstrates a potent and broad anti-inflammatory effect by inhibiting the secretion of Th1 (TNFα and IFNg, Th17 (IL-22 and IL-23), and Th2 (IL-4, IL-5 and IL-13) effector cytokines in human PBMCs. In addition, potent inhibition of innate cytokines (IL-1α and IL-1b ) was also observed. These results support further development of orismilast as a potential best-in-class or first-in-class PDE4 inhibitor for the treatment of chronic inflammatory skin diseases including psoriasis, HS and AD.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines in the fields of oncology, metabolic, autoimmune, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT (sintilimab injection), BYVASDA (bevacizumab biosimilar injection), SULINNO (adalimumab biosimilar injection), HALPRYZA (rituximab biosimilar injection), Pemazyre (pemigatinib oral inhibitor), olverembatinib （BCRABLTKI, Cyramza (ramucirumab) and selpercatinib. An additional 2 assets are under NMPA NDA review, 5 assets are in Phase 3 or pivotal clinical trials, and 20 more molecules are in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

^Note:

^{TYVYT® (sintilimab injection) is not an approved product in the United States.
BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.
TYVYT® (sintilimab injection, Innovent)
BYVASDA® (bevacizumab biosimilar injection, Innovent)
HALPRYZA® (rituximab biosimilar injection, Innovent)
SULINNO® (adalimumab biosimilar injection, Innovent)
Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.
CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.}
Selpercatinib (Eli Lilly). Selpercatinib was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer:

<sup>1. This indication is still under clinical study, which hasn't been approved in China.
2. Innovent does not recommend any off-label usage.</sup>

About UNION therapeutics

UNION therapeutics is a privately-held, multi-asset, clinical stage, pharmaceutical development company focused on immunology and infectious diseases. The company is currently working with two complementary chemistry classes, spanning immunology and microbiology with multiple candidates in clinical development. UNION is headquartered in Hellerup, Denmark, and led by an international team consisting of biotech entrepreneurs and senior pharma executives, with a collective track record of developing and launching more than fifteen marketed drugs. Read more at www.uniontherapeutics.com

Innovent's Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

Reference:

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[11].    Brideau C, Van Staden C, Styhler A, Rodger IW, Chan C-C. The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor-α and leukotriene B4 in a novel human whole blood assay. Br J Pharmacol 1999;126(4):979-88.
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SOURCE Innovent Biologics