Coultreon's COL-5671 shows mAb-comparable TNFα inhibition in Phase 1
Coultreon Biopharma has released final safety, pharmacokinetic and pharmacodynamic data from the Phase 1 study of COL-5671, its highly selective oral SIK3 inhibitor, at the United European Gastroenterology Week in Barcelona. The readout covers both single ascending dose and multiple ascending dose cohorts in healthy volunteers and marks the completion of the first-in-human programme that began in September 2025.
The drug was reported as well tolerated across all doses evaluated, with treatment periods of up to 14 days. The pharmacokinetic profile included a long half-life, low interparticipant variability and a consistent dose-to-exposure relationship, attributes that the company says support once-daily or infrequent dosing in future patient studies. At the 15 mg multiple ascending dose cohort, TNFα inhibition remained above 90% at the 24-hour mark, and doses up to 40 mg were evaluated across the MAD arm.
Mechanism and target breadth
The pharmacodynamic data are notable for what they suggest about the mechanism's scope. COL-5671 inhibits TNFα release in blood samples from dosed participants at a level the company says is comparable to that of monoclonal antibodies, a meaningful benchmark given the therapeutic standard set by established anti-TNF biologics such as adalimumab. The compound also inhibited IL-23 and IL-12 in human myeloid cells with greater potency than its TNFα suppression, and is expected to achieve strong tissue penetration.
This dual cytokine profile positions COL-5671 across a wide range of potential indications: the company lists ulcerative colitis, Crohn's disease, psoriasis, psoriatic arthritis, and hidradenitis suppurativa. The breadth of that target list is commercially attractive but means the company faces sequencing decisions about which indication to prioritise beyond the planned Phase 2 psoriasis study.
Pierre Raboisson, PhD, chief executive and founder of Coultreon, said COL-5671 "has significant potential to transform the lives of patients with debilitating inflammatory diseases" and confirmed that the psoriasis Phase 2 study would begin recruiting before the end of 2026.
Market context and competitive landscape
The SIK inhibitor class represents a newer approach to inflammatory disease compared with the large-molecule biologics that currently dominate the market. Oral small-molecule alternatives to anti-TNF and anti-IL-23 biologics have attracted considerable industry interest, with JAK inhibitors such as upadacitinib and tofacitinib demonstrating that patients and clinicians will accept oral immunomodulators when the efficacy and tolerability data support it. SIK3-selective inhibition is a more nascent strategy: COL-5671's design aims to sidestep the toxicities historically associated with broader SIK inhibition, which has been a limiting factor for the class.
The decision to present at UEGW, a gastroenterology-focused congress, alongside the primary commercial pivot toward psoriasis reflects the breadth of the inflammatory disease opportunity. Coultreon's ability to demonstrate differentiation from approved JAK inhibitors and from late-stage selective TYK2 inhibitors will be critical as COL-5671 moves into patient populations. Investors and potential partners will be watching Phase 2 psoriasis data closely for the safety signals and efficacy endpoints that Phase 1 biomarker data cannot yet confirm in disease.
The company was founded on more than 12 years of preclinical research in SIK biology, and this Phase 1 readout represents the first clinical validation of that programme. Full poster materials have been posted to the company's website.