P0815 Oral alpha 4 beta 7 (α4β7) integrin antagonist EA1080 (NSHO-101) demonstrates target engagement and α4β7 integrin receptor occupancy following once-daily administration in healthy volunteers
Bibliographic record
Abstract
Abstract Background EA1080 (NSHO-101) is a selective, oral small molecule α4β7 integrin antagonist being advanced for the treatment of inflammatory bowel disease (IBD). EA1080 (NSHO-101) was safe and well tolerated and resulted in near complete inhibition of MAdCAM-1 binding to α4β7 integrin (receptor occupancy) on peripheral blood CD4+ T cells following twice-daily dosing with Formulation X in a healthy volunteer phase 1 study (DDW 2024: Su1789; NCT04223960). No effect on peripheral blood lymphocyte count was observed, confirming no specific engagement of α4β1 integrin. Here pharmacokinetics (PK) and pharmacodynamics (PD) results from a once-daily formulation are presented. Methods The PK and PD results from multiple ascending dose (MAD) cohorts with a formulation utilizing once-daily dosing were assessed in a healthy volunteer phase 1 study. Peripheral blood lymphocyte counts were assessed across the dosing period. Results Once-daily administration of EA1080 (NSHO-101) resulted in sustained, near-complete inhibition of MAdCAM-1 binding to α4β7 integrin on peripheral blood CD4+ T cells (≥95% receptor occupancy) across the dosing interval (24 hours). This correlated with plasma concentrations of active metabolite of EA1080 (EA1080-M) and approximated the level of receptor occupancy seen with twice-daily dosing with Formulation X. Plasma concentrations of EA1080-M reached steady-state levels within 3-4 days, and this correlated with maximal inhibition of MAdCAM-1 binding (receptor occupancy). No consistent trend in peripheral blood lymphocyte counts was observed across the dosing period. Conclusion These results demonstrate that once-daily oral administration of EA1080 (NSHO-101) results in near complete inhibition MAdCAM-1 binding to α4β7 integrin (≥95% receptor occupancy) across the dosing interval. No effect on peripheral blood lymphocyte counts was observed, confirming no specific engagement of α4β1. These results support continued development of a once-daily dosing formulation for future clinical studies.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".