Targeting the angiopoietin-like protein 3/8 complex with a monoclonal antibody in patients with mixed hyperlipidemia: a phase 1 trial
Bibliographic record
Abstract
The angiopoietin-like protein 3/8 complex (ANGPTL3/8) inhibits lipoprotein lipase (LPL) activity, primarily in oxidative tissues, and does so more potently than ANGPTL3, making ANPTL3/8 an attractive target for treating dyslipidemia. This study enrolled 48 adults (36 men, 12 women) with mixed hyperlipidemia to assess the primary outcome of safety and the secondary outcomes of pharmacokinetics and pharmacodynamics of ascending doses of LY3475766, a human monoclonal antibody that specifically blocks ANGPTL3/8-mediated inhibition of LPL activity. Participants received a single dose of LY3475766 or placebo. LY3475766 was well tolerated with no severe adverse events or adverse event-related discontinuations. Compared with placebo, LY3475766 dose-dependently reduced the concentration of triglycerides (-70%), remnant cholesterol (-86%), low-density lipoprotein cholesterol (-32%), non-high-density lipoprotein cholesterol (non-HDL-C) (-35%) and apolipoprotein B (-29%) while increasing HDL-C (+27%). LY3475766 thus significantly reduced atherogenic lipoprotein levels while increasing HDL-C levels; however, the effects on cardiovascular risk remain to be established. ClinicalTrials.gov registration: NCT04052594 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".