Onco3R Therapeutics has received approval from Belgian regulatory authorities for its Clinical Trial Application (CTA) to begin first-in-human testing of O3R-5671, a novel SIK3 inhibitor targeting multiple autoimmune diseases. The approval marks a significant milestone for the Leuven-based biotech company, transitioning it into a clinical-stage organization focused on immunology and oncology therapeutics.
Novel Approach to SIK Inhibition
O3R-5671 represents a next-generation approach to SIK (salt-inducible kinase) inhibition, developed based on more than 12 years of preclinical and clinical data on SIK inhibitors for autoimmune diseases. The compound has been specifically designed to overcome the limitations that hindered first-generation SIK inhibitors, demonstrating improved toxicity profile, enhanced efficacy, and greater SIK isoform specificity.
The targeted SIK3 inhibitor has been engineered to avoid the toxicities associated with inhibiting SIK2 and SIK1, while maintaining selectivity by not inhibiting other kinases. Preclinical data demonstrate that O3R-5671 has shown a highly attractive profile in extensive safety panels, addressing key shortcomings that previously limited the development of SIK inhibitors for autoimmune applications.
Mechanism and Therapeutic Potential
Preclinical studies reveal that O3R-5671 modulates immune responses through multiple pathways. The compound inhibits the release of inflammatory cytokines TNFα and IL-23 while promoting the release of the immunomodulatory cytokine IL-10. These immunomodulatory effects, combined with data from animal models of autoimmune diseases and an attractive pharmacokinetic profile, indicate broad therapeutic potential.
The drug is expected to have applications across a range of autoimmune conditions, including ulcerative colitis, Crohn's disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis. This broad applicability positions O3R-5671 as a potential oral treatment option for patients across multiple autoimmune indications.
Clinical Trial Design and Timeline
The first-in-human trial will be conducted at the SGS Clinical Pharmacology Unit in Antwerp, Belgium, using a single ascending dose (SAD) and multiple ascending dose (MAD) design in healthy volunteers. Beyond standard safety and pharmacokinetic assessments, the trial includes extensive biomarker testing to provide insights into how O3R-5671 modulates immune responses.
Subject enrollment is expected to begin in the coming weeks, with dosing of the first participant anticipated later in September 2025. Final data from the study are expected to be available in the first half of 2026, which will inform the design of subsequent patient trials across various autoimmune diseases planned to commence in 2026.
Addressing Unmet Medical Needs
"While effective therapies exist for many autoimmune diseases, too many patients relapse or cannot tolerate treatments due to toxicities," said Pierre Raboisson, PhD, CEO and Founder of Onco3R Therapeutics. "With O3R-5671, we believe we are uniquely positioned to develop a well-tolerated, effective, and convenient oral therapy for these patients."
The company's approach focuses on addressing current treatment limitations in autoimmune diseases, where existing therapies may cause patient intolerance or treatment failure. O3R-5671's oral administration route and improved safety profile could provide a more convenient and tolerable option for patients requiring long-term immunomodulatory therapy.
Company Background and Expertise
Onco3R Therapeutics brings over 150 years of combined R&D experience through its multidisciplinary team, with deep expertise in disease biology, drug discovery and development, and translational science. The company focuses on clinically validated targets and selects appropriate therapeutic modalities to address underlying disease biology with best-in-class therapies.
Based in the biotech cluster in Leuven, Belgium, Onco3R aims to de-risk clinical development and accelerate the delivery of innovative treatments by integrating learnings from past clinical challenges and applying cutting-edge technologies. The company's mission centers on developing safer, more effective medicines in immunology and oncology that deliver real-world impact for patients.
