Rationale and Design of a Phase 1b Trial Evaluating APG279, the Combination of Half-Life-Extended Anti-IL-13 and Anti-OX40L Monoclonal Antibodies, Compared With Dupilumab in Moderate-to-Severe Atopic Dermatitis
Bibliographic record
Abstract
Introduction: Atopic dermatitis (AD) is a chronic skin disease primarily driven by Type 2 inflammation. Other pathways, including Type 1 and Type 3 inflammation, are known to contribute to disease heterogeneity. Monoclonal antibodies (mAb) targeting the IL-13, IL-4/IL-13, or OX40/OX40L pathway have demonstrated therapeutic potential for improving the signs and symptoms of AD, although current therapies require ongoing injections every 2-4 weeks. There remains an unmet need to address the multiple drivers of inflammation in this disease while minimizing injection burden for patients. Rationale: APG279 is a combination of APG777, a half-life-extended anti-IL-13 mAb, and APG990, a half-life-extended anti-OX40L mAb. APG777 was designed for deep and sustained inhibition of IL-13-driven Type 2 inflammation, while APG990 targets the upstream OX40/OX40L interaction with the potential for broad inhibition of Types 1, 2, and 3 inflammation. In phase 1 studies, both mAbs demonstrated favorable safety and pharmacokinetics (PK), with APG777 exhibiting a half-life of 75.3-77.5 days and APG990 demonstrating a half-life of ~60 days (interim results). Objective: This phase 1b, open-label, assessor-blinded, randomized, multicenter, active comparator study (NCT07027527) evaluates the safety, PK, pharmacodynamics (PD), and efficacy of APG279 in adults with moderate-to-severe AD, in comparison to dupilumab. Study Design: Adults (≥18 years) are eligible to participate if they have a diagnosis of AD for ≥1 year and exhibit moderate-to-severe AD (EASI≥16, vIGA-AD≥3, BSA≥10%) at screening and baseline. Participants will be randomized 1:1 to APG279 or dupilumab. The study consists of a 24-week treatment period and a 52-week follow-up. The primary endpoint is the incidence of treatment-emergent adverse events through week 24. Secondary endpoints include PK of APG777 and APG990. Exploratory endpoints include biomarkers, ADA, and efficacy (e.g., EASI-75, vIGA-0/1) throughout the study including the follow-up period. The study is currently enrolling in Canada, Australia, and New Zealand and aims to include ~50 participants. Funding: Apogee Therapeutics, Inc.
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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 | 0.011 | 0.007 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.006 |
| Insufficient payload (model declined to judge) | 0.016 | 0.005 |
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".