First-in-human, phase I, randomized, safety, pharmacokinetic, food-effect and pharmacodynamic study of a tyrosine kinase 2/Janus kinase 1 inhibitor, SDC-1801.

Authors

Chris Brearley, Sam Francis, John Reader, Judi Proctor

Published in

British journal of clinical pharmacology. Jun 21, 2026. Epub Jun 21, 2026.

Abstract

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (PK), food-effect (FE) and pharmacodynamics (PD) of an oral tyrosine kinase-2 (TYK2)/Janus kinase-1 (JAK1) inhibitor, SDC-1801, in healthy adult participants.
This first-in-human study randomized 95 male and female participants. Parts one and two were double-blind, placebo-controlled escalation designs, investigating single (5, 10, 30, 75, 150 mg) and multiple (30, 100, 75, 140 mg/day) doses of SDC-1801 or matching placebo. Part three evaluated the FE of 75 mg SDC-1801 in an open-label, crossover design.
There were no deaths or treatment-related serious adverse events (AEs) following SDC-1801, up to 150 mg; no treatment-emergent AEs (TEAEs) were severe with non-related headache most frequently reported. PK showed low to moderate variability and no consistent dose-exposure relationship; T_max occurred 3-5 h post-dose with a geometric mean (GM) t_1/2 of 15.2-27.0 h. Bioavailability appeared solubility limited, with lower exposure from the higher strength capsule and modestly higher exposure in the fed state. No safety stopping criteria were met. PD assessments demonstrated anti-inflammatory activity, with IFN-gamma induced protein-10 (IP-10), high sensitivity C reactive protein (hsCRP), and signal transducer and activator of transcription (STAT3/5) phosphorylation reductions with increasing exposure giving greater inhibition. At the highest exposure, there was a clear reduction of IP-10 levels at pre-dose on day 9, which rebounded following drug withdrawal.
SDC-1801 was well tolerated to 150 mg; all TEAEs were mild or moderate, with unrelated headache most frequently reported. The PK profile supports the potential for a once- or twice-daily regimen, with evidence of target engagement for both TYK2 and JAK1.

PMID:
42324886
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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