Our TYK2 program with GLPG3667
GLPG3667 is a reversible and selective TYK2 kinase domain inhibitor discovered by us.
In 2020, we tested the molecule in a healthy volunteer study. This Phase 1 study was a randomized, double-blind, placebo-controlled dose escalation study evaluating safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending oral doses of GLPG3667 for 13 days. Blood was drawn at multiple time points on Day 1 and on Day 10 and stimulated ex vivo with several cytokines, including IFNα, to analyze the level of inhibition in pSTAT signaling. The Phase 1 data showed an encouraging PK profile for once-daily dosing and PD activity of GLPG3667:
Following these results, we initiated a randomized, placebo-controlled, double-blind Phase 1b study in 31 patients with moderate to severe plaque psoriasis. Patients were randomized in a 1:1:1 ratio to a daily oral dose of GLPG3667 (low dose or high dose) or placebo, for a total of 4 weeks.
In July 2021, we announced positive topline results demonstrating that GLPG3667 was generally well tolerated with a positive efficacy signal at week 4:
- At week 4, four out of 10 patients in the high dose group had a PASI 50 response, defined as at least a 50% improvement in PASI from baseline, compared to one out of 10 subjects on placebo. There were no subjects with a PASI 50 response on the low dose of GLPG3667. The 4 responders in the high dose group of GLPG3667 achieved a 52%, 65%, 74% and 81% improvement respectively in their PASI scores from baseline, while the subject randomized to placebo improved by 52%. Positive efficacy signals were also observed with the high dose for other endpoints, including affected Body Surface Area and physician and patient global assessment, versus placebo at week 4.
GLPG3667: clinical activity in Pso at week 4
- One subject in the low dose group interrupted participation in the study for one day for exacerbation of psoriasis. The majority of treatment related adverse events (AEs) were mild in nature and transient. There were no deaths or serious adverse events (SAEs) in this 4-week study.
We are currently completing a dose escalation Phase 1 study to determine the optimal dose to progress into a Phase 2 program, which is planned in 2022.