Highly selective, allosteric inhibition of TYK2 with oral ESK-001 in patients with moderate-to-severe plaque psoriasis: Results from STRIDE, a 12-week, randomized, double-blinded, placebo-controlled, dose-ranging phase 2 study
Bibliographic record
Abstract
BACKGROUND: ESK-001, a novel allosteric, highly selective oral tyrosine kinase 2 inhibitor in development for treatment of immune-mediated disorders, was well-tolerated and achieved high levels of target inhibition in phase 1 studies with healthy volunteers. OBJECTIVE: To assess clinical efficacy, safety, and pharmacokinetics of ESK-001 compared to placebo in patients with moderate-to-severe plaque psoriasis. METHODS: STRIDE (NCT05600036, EudraCT Number 2022-002633-34) was a phase 2, double-blinded, 16-week study with patients randomized to 6 treatment groups for 12 weeks of placebo or ESK-001, ranging from 10 mg QD to 40 mg BID. RESULTS: ESK-001 demonstrated a dose-dependent improvement across all end points, with maximal efficacy observed in the highest dose arm (40 mg BID). At week 12, more patients achieved Psoriasis Area and Severity Index-75 in each ESK-001 dose arm compared to placebo: 64% in the 40 mg BID arm vs 0% with placebo (P < .0001). ESK-001 was well-tolerated, with no dose-limiting safety findings and a 2.6% rate of ESK-001 discontinuation due to adverse events. LIMITATIONS: Small sample size per treatment group and 16-week study duration. CONCLUSION: ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose in patients with psoriasis and was well-tolerated.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".