SinoMab BioScience Limited has announced breakthrough results from its completed Phase 1b clinical study of SM17, a novel therapy targeting the IL-25 receptor pathway for moderate to severe atopic dermatitis (AD). The study demonstrated remarkable efficacy in both itch relief and skin healing, potentially addressing critical unmet needs in AD treatment.
SM17 is a first-in-class humanized monoclonal antibody that uniquely binds to the co-receptor for IL-25, blocking downstream signaling and disrupting the inflammatory cascade. This mechanism differs significantly from existing therapies by targeting the receptor rather than the ligand, allowing for faster and more sustained therapeutic effects.
Exceptional Efficacy in Phase 1b Trial
The 16-week, randomized, placebo-controlled, double-blind study evaluated two dose levels of SM17 (200mg and 600mg) in 32 adults with moderate-to-severe AD. Most participants had previously shown inadequate response to topical corticosteroids, with some having prior exposure to biologics or JAK inhibitors.
At week 12, the higher dose group showed remarkable results:
- 75.0% of patients achieved EASI-75 (≥75% reduction in Eczema Area and Severity Index score) compared to 0.0% in the placebo group
- 91.7% of patients achieved NRS-4 (≥4-point reduction in peak pruritus numeric rating scale) versus 0.0% in the placebo group
- 41.7% of patients reached vIGA-AD 0/1 (clear or almost clear skin with ≥2-point reduction from baseline)
Even the lower dose group demonstrated significant efficacy, with 50.0% achieving EASI-75 and 66.7% achieving NRS-4.
Rapid Onset and Sustained Relief
One of SM17's most notable advantages is its rapid onset of action. Anti-pruritus effects were observed as early as week 2 after initial dosing in both treatment groups, compared to weeks 4-6 typically seen with anti-IL-4/13 agents. This quick relief addresses a critical unmet need for AD patients, for whom itch is often the most distressing symptom.
The improvement in pruritus reached mean reductions of 68% and 57% from baseline at week 12 for the higher and lower dose groups, respectively, compared to just 18% for the placebo group. Importantly, these benefits were maintained until week 16, which was 6 weeks after the final dose at week 10.
Favorable Safety Profile
SM17 demonstrated excellent tolerability with no serious adverse events (SAEs) or treatment-related adverse events of grade 3 or above. The most frequent treatment-emergent adverse events were nasopharyngitis and urinary tract infection, with incidence rates only marginally higher than in the placebo group (less than 5% difference).
This safety profile compares favorably to JAK inhibitors, which carry boxed warnings for serious infections and major adverse cardiovascular events.
Competitive Advantages in the AD Landscape
Dr. Shui On Leung, Executive Director, Chairman and CEO of SinoMab, highlighted SM17's unique position in the AD treatment landscape: "SM17 has the potential to become a first- and best-in-class therapy for atopic dermatitis, a market where a single transformative therapy can achieve multibillion-dollar annual revenue."
SM17 offers several distinct advantages over existing therapies:
- Dual efficacy in both itch relief and skin healing, with over 60% responder rates for both NRS-4 and EASI-75 simultaneously
- Faster and deeper itch relief than anti-IL-4/13 agents like dupilumab
- Better safety profile than JAK inhibitors such as upadacitinib
Market Potential and Future Development
The global AD market represents a significant opportunity. With at least 230 million AD patients worldwide and the market projected to reach $31.44 billion by 2034, effective new therapies have substantial commercial potential. For context, dupilumab's global sales surpassed $14 billion in 2024.
SinoMab is accelerating its clinical programs for SM17, with plans to initiate Phase 2 trials in adults with moderate-to-severe AD. The company is also exploring partnerships to maximize the drug's global impact.
Beyond AD, preclinical studies have shown promising results for SM17 in treating other Type 2 allergic diseases, including asthma, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), and idiopathic pulmonary fibrosis (IPF). This suggests SM17 could become a versatile therapeutic for a range of Th2-driven diseases.
Mechanism of Action: Targeting the Receptor vs. the Ligand
SM17's approach of targeting the IL-25 receptor rather than the ligand itself offers key advantages. In AD, stimulated skin continuously releases IL-25, making it difficult for anti-IL-25 antibodies to neutralize all ligand molecules effectively.
By blocking the limited number of IL-25 receptors on cell surfaces, SM17 can stop signaling regardless of IL-25 levels. This allows for faster, long-lasting inhibition without requiring high doses to "mop up" continuously released IL-25.
SinoMab's in-house data shows that SM17 blocks receptor signal transduction without affecting IL-25 engagement with the receptor, providing rapid anti-pruritic and anti-inflammatory effects.
As the company moves forward with Phase 2 trials, SM17 appears well-positioned to potentially redefine the standard of care for this debilitating condition that affects millions worldwide.
