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Record W4381377492 · doi:10.2337/db23-91-lb

91-LB: COVALENT-111, a Phase 1/2 Trial of BMF-219, a Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus—Preliminary Results

2023· article· en· W4381377492 on OpenAlexaboutno aff
José E. Rodríguez, Alexander Abitbol, FATHI ABUZGAYA, CESAR PEREZ, Sanchita Mourya, Brian Munneke, STEPHAN W. MORRIS, Thomas Butler

Bibliographic record

VenueDiabetes · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsnot available
Fundersnot available
KeywordsMedicineGlycemicDiabetes mellitusRegimenClinical trialPlaceboInternal medicineType 2 Diabetes MellitusHypoglycemiaEndocrinologyPediatricsAlternative medicinePathology

Abstract

fetched live from OpenAlex

Type 2 Diabetes Mellitus (T2DM) is characterized by impaired glycemic control caused by insulin resistance and progressive beta cell failure. Menin, a scaffold protein, drives beta cell proliferation when inhibited. We have reported BMF-219, an oral covalent menin inhibitor, elicits durable glycemic control following a short treatment in a ZDF Rat model. COVALENT-111, a randomized, double-blind, placebo-controlled study is evaluating BMF-219 in healthy adults and adults with T2DM diagnosed ≤15 yrs (NCT05731544). Here we report initial results from the first cohort of T2DM patients treated with BMF-219. Patients with poor glycemic control (HbA1C ≥7%) on their current antidiabetic regimen were enrolled. Twelve patients were randomized 5:1 (10 BMF-219, 2 placebo) to receive 100 mg QD for 4 weeks while continuing their existing treatment. BMF-219 was well tolerated; no subjects discontinued treatment or exited the trial during the 4-week treatment and all subjects continue in follow-up to assess durability of the treatment effect. There were no dose reductions, SAEs, or severe AEs. All TRAEs were mild and observed in 3 of 12 subjects. No subjects showed symptomatic hypoglycemia. These data demonstrate preliminary proof of concept for the novel disease-modifying effect of BMF-219 in T2DM. Enrollment is ongoing at higher doses; additional follow-up data will be presented. Disclosure J. E. Rodriguez: None. A. Abitbol: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Dexcom, Inc., Novo Nordisk Canada Inc., Janssen Pharmaceuticals, Inc., Research Support; Abbott Diabetes, Lilly Diabetes, Zucara Therapeutics, Novo Nordisk Canada Inc., Moderna, Inc., Senseonics, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Amgen Canada, Dexcom, Inc., Novo Nordisk Canada Inc., HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi. F. Abuzgaya: None. C. Perez: None. S. Mourya: Employee; Biomea Fusion, Inc. B. Munneke: Employee; Biomea Fusion, Inc., Corvus Pharmaceuticals. S. W. Morris: Employee; Biomea Fusion, Inc. T. Butler: Board Member; Biomea Fusion, Inc., Employee; Biomea Fusion, Inc., Stock/Shareholder; Biomea Fusion, Inc. Funding Not applicable

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0040.001

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.

Opus teacher head0.011
GPT teacher head0.250
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2023
Admission routes1
Has abstractyes

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