The effect of the novel SHIP1 activator AQX-1125 on allergen-induced responses in mild to moderate asthma
Bibliographic record
Abstract
Rationale: SH2-containing inositol phosphatase-1 (SHIP1) is an endogenous inhibitor of the phosphoinositide-3-kinase pathway that is involved in the activation of inflammatory cells. AQX-1125 is a first in class oral SHIP1 activator with a novel anti-inflammatory mode of action and safety profile in pre-clinical studies. Objectives: To determine the effect of once daily AQX-1125 on lung function, airway responsivness to methacholine, sputum eosinophils and fractional exhaled nitric oxide (FeNO) in asthmatic patients after IAC. Methods: A randomized, double-blind, placebo-controlled, 2-way cross-over study was performed in 22 steroid-naive patients with mild asthma. AQX-1125 or placebo were administered orally for 7 days. IAC was performed on day 6 (2 h post-dose), followed by methacholine challenge (day 7) and induced sputum collection. Results: AQX-1125 significantly abrogated the late phase response compared with placebo (FEV1 4-10h: mean difference 150ml; p>0.027); and increased minimum FEV1 during LAR (mean difference 180ml; p=0.014); increased FEV1 0-10h (mean difference 97.5ml; p>0.05) but had no effect on the early phase response. AQX-1125 showed a trend in reduction of sputum eosinophils & macrophages & also reduced methacholine responsiveness but these did not achieve significance. There was no effect on FeNO. AQX-1125 was well tolerated with mild self limited GI side effects described in 5/22 subjects on active treatment. Conclusion: AQX-1125, a novel oral SHIP1 activator, significantly reduces the late phase response to IAC, with trends to reduce airway inflammation and hyperresponsiveness.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".