On December 29, Sino Biopharmaceutical Limited (1177.HK) announced that the Phase II clinical trial of TQH3906 (a TYK2/JAK1 JH2 allosteric inhibitor), a Class 1 innovative drug independently developed by CTTQ Pharma for moderate-to-severe Plaque Psoriasis (PsO), has met its primary endpoint. Study results showed that at the recommended Phase 2 dose (RP2D), after 12 weeks of treatment, the PASI 75 (Psoriasis Area and Severity Index score reduction of at least 75% from baseline) response rate exceeded 90%, and the PASI 90 (Psoriasis Area and Severity Index score reduction of at least 90% from baseline) response rate exceeded 70%. All dose groups demonstrated good safety and tolerability. 

PASI 75 Response Rate Over 90%, PASI 90 Response Rate Over 70%

This study is a randomized, double-blind, placebo-controlled, multi-center Phase II clinical trial (NCT06542614), led by Professor Xinghua Gao of the First Affiliated Hospital of China Medical University, designed to evaluate the efficacy and safety of TQH3906 in subjects with moderate-to-severe plaque psoriasis. A total of 209 patients were enrolled in this study, including a placebo group and five different TQH3906 dose groups, administered orally once daily. 

In terms of clinical efficacy, TQH3906 demonstrated a good dose-response relationship and reached a plateau in efficacy at the primary endpoint. At the expected RP2D, after 12 weeks of treatment, over 90% of subjects achieved PASI 75 and over 70% achieved PASI 90. The clinical benefit is comparable to that of biologic IL-17/IL-23 inhibitors and shows a significant advantage over other marketed oral psoriasis treatments. 

Safety results showed that TQH3906 has a good overall safety profile. The overall incidence of adverse reactions was comparable to the placebo group. The main treatment-emergent adverse events (TEAEs) were Grade 1-2, similar to the safety profile of other TYK2 inhibitors, with no new safety signals observed. The detailed results of this study will be presented at upcoming international academic conferences. 

Targeting the JH2 Domain, Balancing High Selectivity and Safety

TQH3906 works by targeting the pseudokinase domain (JH2) of TYK2/JAK1. Compared to previous JAK inhibitors that target the active kinase domain (JH1), it can effectively maintain high selectivity against JAK2, JAK3, and other kinases, thereby reducing potential inhibitory effects on off-target proteins. This high selectivity can enhance therapeutic effects and reduce side effects, demonstrating significant therapeutic potential. In addition to plaque psoriasis, exploratory studies for TQH3906 will continue for several new indications in autoimmune and dermatological fields, including inflammatory bowel disease and psoriatic arthritis. 

Psoriasis is a chronic inflammatory skin disease caused by a combination of genetic, immune, and environmental factors, affecting about 2%-3% of the global population. The most common type is plaque psoriasis, accounting for about 80%-90% of all psoriasis patients^[1], of which 30%-40% progress to moderate-to-severe disease^[2]. Although psoriasis typically manifests as inflammatory skin plaques, growing evidence suggests that it is a multi-system chronic inflammatory disease with multiple comorbidities, including obesity, metabolic syndrome, cardiovascular and cerebrovascular diseases, and autoimmune diseases. Psoriasis seriously affects patients' quality of life due to recurrent and worsening conditions, adverse drug reactions, and comorbidities. 

Traditional systemic therapeutic drugs (such as methotrexate and cyclosporine) can control symptoms in the short term but have dose-dependent risks such as liver toxicity and bone marrow suppression^[3]. Biologics (such as TNF-α, IL-17/IL-23 inhibitors) have significantly improved efficacy, but the need for long-term injection administration and the potential risk of infection limit their clinical application^[4]. In recent years, with breakthroughs in the molecular mechanisms of psoriasis, oral small-molecule targeted drugs have become a research hotspot due to their advantages of precise blockade, convenient administration, and good tolerability. 

Currently, approved oral small-molecule targeted drugs for plaque psoriasis in China include PDE-4 inhibitors and TYK2 JH2 allosteric inhibitors. Their global multi-center registration studies show a 16-week PASI 75 response rate of nearly 60% and a PASI 90 response rate of nearly 40%^[5-7], indicating a clinical need for small-molecule targeted drugs with higher efficacy and manageable safety. Based on the excellent data and good safety profile demonstrated in this Phase II clinical trial, TQH3906 is expected to provide a new treatment option for psoriasis patients that is convenient, effective, and safe. 

References:
[1] Committee on Psoriasis of Chinese Society of Dermatology. Guidelines for the Diagnosis and Treatment of Psoriasis in China (2023 Edition) [J]. Chinese Journal of Dermatology, 2023, 56(7): 573-625. 
[2] Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? [J]. Br J Dermatol, 2020, 182(4): 840-848.
[3] Bochncke WH, Brembilla NC.Unmet needs in the field of psoriasis: pathogenesis and treatment[J]. Clin Rev Allergy Immunol, 2018, 55(3): 295-311.
[4] Committee on Psoriasis of Chinese Society of Dermatology. Expert Consensus on Treat-to-target Approach for the Treatment of Psoriasis with Biological Agents[J]. Chinese Journal of Dermatology, 2023, 56(3): 191-203. 
[5] Armstrong AW, Gooderham M, Warren RB,et al.Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol.2023 Jan; 88(1): 29-39.
[6] Strober B, Thaçi D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023 Jan; 88(1): 40-51.
[7] Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul; 73(1): 37-49.
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This press release contains certain forward-looking statements, including statements regarding the clinical development plan, expected clinical benefits and advantages, commercialization prospects, the possibility of clinical benefit to patients, and potential commercial opportunities for [TQH3906]. Words such as "expect", "believe", "continue", "may", "estimate", "hope", "intend", "plan", "potential", "predict", "project", "should", "will", "propose", and similar expressions are intended to identify forward-looking statements, but not all forward-looking statements contain these identifying words. These forward-looking statements are predictions or expectations made by the company based on currently available data and information, and actual results may differ materially from these forward-looking statements due to uncertainties or risks such as policy, R&D, market, and regulatory factors. Current or potential investors are advised to carefully consider the potential risks and should not place undue reliance on the forward-looking statements in this press release, which contain information only as of the date of this press release. Unless required by law, the company undertakes no obligation to update or revise any forward-looking statements in this press release as a result of new information, future events, or other circumstances.