Onco3R Therapeutics Reports Positive Phase 1 Data for Novel SIK3 Inhibitor O3R-5671 in Autoimmune Disease Treatment
核心洞察
Onco3R Therapeutics (搜索) completed the first multiple ascending dose cohort of its Phase 1 trial for O3R-5671 (搜索), a novel SIK3 (搜索) inhibitor, with no drug-related adverse events reported.
The drug demonstrated approximately 90% TNF-α (搜索) inhibition at doses between 25-35mg, with sustained inhibition of more than 75% at 24 hours post-dosing.
O3R-5671 (搜索) showed favorable pharmacokinetic properties including a long half-life, low intersubject variability, and no food restrictions for future clinical studies.
Onco3R Therapeutics (搜索) announced the successful completion of the first multiple ascending dose (MAD) cohort in its Phase 1 trial of O3R-5671 (搜索), a novel SIK3 (搜索) inhibitor designed to treat autoimmune diseases (搜索). The Belgium-based clinical-stage biotech company reported no drug-related adverse events in the initial cohort, marking a significant milestone for the first-in-human study of this selective kinase inhibitor.
Trial Design and Dosing Results
The Phase 1 study evaluated O3R-5671 (搜索) in healthy volunteers using both single ascending dose (SAD) and multiple ascending dose designs. Four SAD cohorts have been completed, with six subjects in each cohort receiving single oral doses ranging from 5mg to 35mg. In the first MAD cohort, six subjects received 5mg O3R-5671 once daily for 14 days.
The safety profile proved highly encouraging, with no drug-related adverse events reported in the 25mg and 35mg SAD cohorts or the 5mg MAD cohort. Additionally, no clinically significant abnormalities were observed in ECG, vital signs, or physical examinations across all tested doses.
Pharmacokinetic and Pharmacodynamic Profile
O3R-5671 (搜索) demonstrated favorable pharmacokinetic properties that support its potential as a convenient therapeutic option. The drug exhibited a flat PK profile with a long half-life and dose-proportional exposure across the SAD cohorts with low intersubject variability. A food effect study confirmed that O3R-5671's pharmacokinetic profile remains consistent regardless of food intake, eliminating the need for food restrictions in future patient studies.
Data from the first MAD cohort showed that the attractive pharmacokinetic profile was maintained at day 14, with drug exposure approximately two times higher than the equivalent single 5mg dose.
The pharmacodynamic results proved particularly compelling, demonstrating potent TNF-α (搜索) inhibition in a dose-dependent manner. Maximal inhibition of approximately 90% was achieved at doses between 25mg and 35mg. Notably, drug levels measured 24 hours after dosing at the 25mg and 35mg doses maintained TNF-α inhibition of more than 75%, indicating sustained therapeutic activity.
Mechanism and Therapeutic Potential
O3R-5671 (搜索) represents a highly selective SIK3 (搜索) inhibitor designed based on more than 12 years of preclinical and clinical data on SIK inhibitors for autoimmune diseases (搜索). The drug has been specifically engineered to avoid toxicities associated with inhibiting SIK1 and SIK2, while demonstrating selectivity by not inhibiting other kinases in extensive safety panels.
Preclinical data showed that O3R-5671 (搜索) inhibits the release of pro-inflammatory cytokines TNF-α (搜索) and IL-23 (搜索) while promoting the release of the immunomodulatory cytokine IL-10. According to CEO and Founder Pierre Raboisson, non-clinical data also demonstrate that O3R-5671 potently inhibits IL-12 (搜索), which along with TNF-α and IL-23, plays a role in the pathogenesis of various autoimmune diseases (搜索).
Clinical Development Timeline
Based on the positive safety and pharmacokinetic data, Onco3R Therapeutics (搜索) plans to investigate a higher dose in the second MAD cohort, scheduled to initiate in early December. The current Phase 1 trial includes extensive biomarker testing to provide insights into how O3R-5671 (搜索) modulates immune responses.
"These data exceed the expectations we had for O3R-5671 (搜索) before we entered the clinic, and we are excited about the prospect of completing this important study and embarking on patient studies in 2026," said Raboisson.
The company has identified multiple potential indications for O3R-5671 (搜索), including ulcerative colitis (搜索), Crohn's disease (搜索), psoriasis (搜索), psoriatic arthritis (搜索), and rheumatoid arthritis (搜索). Patient trials across this range of autoimmune diseases (搜索) are planned to commence in 2026, with the current Phase 1 results informing the design of subsequent studies.
Company Background
Onco3R Therapeutics (搜索), based in Leuven, Belgium's biotech cluster, focuses on developing precision-designed therapies for autoimmune diseases (搜索) and cancer. The company's team brings over 150 years of combined R&D experience in disease biology, drug discovery and development, and translational science. The company's approach involves focusing on clinically validated targets and selecting appropriate therapeutic modalities to address underlying disease biology with best-in-class therapies.