Belgium has approved a first‑in‑human study of Onco3R Therapeutics’ SIK3‑selective inhibitor O3R‑5671, clearing a single‑ and multiple‑ascending dose trial in healthy volunteers at SGS’s Clinical Pharmacology Unit in Antwerp. The protocol layers extensive pharmacodynamic biomarker work onto standard safety and PK, with first dosing expected later in September and an initial data package targeted for the first half of 2026.
The core move is a regulatory green light that shifts Onco3R into the clinic with an oral agent aiming at a broad autoimmune footprint, including ulcerative colitis, Crohn’s disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis. O3R‑5671 is positioned to avoid liabilities linked to first‑generation pan‑SIK approaches by dialing selectivity to SIK3 and away from SIK1/2 and other kinases. Preclinical work suggests suppression of pro‑inflammatory cytokines (TNFα, IL‑23) and elevation of IL‑10, a profile the company will now test for translation in humans via a biomarker‑rich SAD/MAD design at a single CPU site.
Strategically, this is a calculated re‑entry into a mechanism with prior setbacks, framed around specificity and an operationally tight early clinical plan. The use of a centralized Belgian unit reflects a speed‑to‑signal approach common among small biotechs: contain variability, collect dense PK/PD, and generate a clear dose‑response to support indication selection and financing or partnering. It also reflects the current dynamics of the autoimmune market. Orals remain attractive, but recent classwide scrutiny on JAK safety and payer pressure on chronic immunology agents elevate the bar for tolerability and clean target engagement. If SIK3 selectivity demonstrably separates from the off‑target toxicities that hampered earlier efforts, the mechanism could regain relevance as sponsors seek alternatives to immunosuppression‑heavy regimens and complex biologic combinations.
For sites and CROs, the immediate impact is narrow but instructive. SGS Antwerp gains another first‑in‑human program with deep biomarker sampling, reinforcing demand for CPU‑plus‑translational lab capabilities and rapid bioanalytical turnaround. If the PD signal is coherent, the 2026 patient trials will likely span gastroenterology, dermatology, and rheumatology networks, challenging sponsors and CROs to coordinate cross‑indication screening, endpoint diversity, and centralized lab logistics. Vendors with immunomonitoring, cytokine panels, and PK/PD modeling expertise should expect early engagement as dose selection and schedule optimization move to the foreground. Regulators will focus on whether a selective SIK3 profile avoids the safety liabilities that previously constrained development in this pathway, with the durability of tolerability being a gating factor for multi-year, chronic use indications.
What matters next is the quality of the human translational readout. Watch for dose proportionality, food‑effect clarity, and a clean AE slate alongside consistent reductions in pro‑inflammatory cytokine signals and sustained IL‑10 modulation in healthy volunteers—any inconsistency there will complicate indication prioritization. A once‑daily PK profile with minimal drug–drug interaction potential would simplify Phase 2 operations in polypharmacy populations. Onco3R will also need to declare where it goes first; UC, psoriasis, and PsA present different timelines, biomarkers, and competitive benchmarks, with TYK2 and next‑gen biologics setting efficacy and safety expectations. A multi‑arm adaptive Phase 2 spanning two indications could conserve capital but increase operational complexity. Finally, expect an IND filing and potential multi-region expansion if the Belgian study yields a clear exposure-response relationship and tolerability window. The risk remains classic mechanism translation and class perception; the opportunity is a differentiated oral with a cleaner safety narrative in a market increasingly sensitive to long‑term risk.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
