Preprint Watch 2026-05-20: 1 Clinical Failures Flagged for TNF | Claidex

Q: Why was this TNF preprint flagged?

1 prior Claidex failure claim matched the target-disease mechanism. This preprint reports a mechanistic claim about TNF that aligns with the documented Claidex failures inb03-soluble-tnf-covid19-ards-futility. The reported observations should be read against the field-level evidence that targeting TNF alone has produced limited durable activity in the indications studied to date.

Q: Which clinical failure claims match TNF in COVID-19 acute respiratory distress?

INB03 in COVID-19 ARDS: Why a Selective Soluble TNF Strategy Did Not Separate From Placebo (NCT04370236)

Claidex Preprint Watch

doi:10.64898/2026.05.17.725749

Preprint WatchModerateMay 20th, 2026

An 8 Gene Bevacizumab Resistance Signature Predicts Prognosis and Reveals Immunosuppressive Microenvironment in Colorectal Cancer

Niu, Z.; Qiu, D.; Xu, P.

An 8 Gene Bevacizumab Resistance Signature Predicts Prognosis and Reveals Immunosuppressive Microenvironment in Colorectal Cancer

Moderate contradiction

1 prior failure

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

This preprint reports a mechanistic claim about TNF that aligns with the documented Claidex failures inb03-soluble-tnf-covid19-ards-futility. The reported observations should be read against the field-level evidence that targeting TNF alone has produced limited durable activity in the indications studied to date.

Abstract excerpt

Background Bevacizumab resistance severely limits long term efficacy in metastatic colorectal cancer (CRC). This study aimed to develop and validate a bevacizumab resistance associated gene signature for prognosis prediction and immune microenvironment characterization in CRC. Methods Two GEO datasets (GSE19862, GSE86582) with bevacizumab response data and TCGA COAD/READ RNA seq data were analyzed. Overlapping differentially expressed genes (DEGs) linked to both CRC progression and bevacizumab resistance were identified. An 8 gene signature (AXIN2, PSORS1C1, KRT74, SLC2A3, STIL, IL33, GALNT6, HSD11B2) was constructed via univariate Cox and LASSO Cox regression. Results In the TCGA cohort, high risk patients had shorter overall survival (OS; log rank P < 0.0001). Time dependent ROC yielded 1 year AUC = 0.638, 3 year AUC = 0.657, and 5 year AUC = 0.757. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. External validation in GSE39582 (optimal cutoff = -1.49) replicated these findings: high risk patients had inferior OS (P = 0.0016) with acceptable 1/3/5 year AUCs and retained independent prognostic value (HR = 1.634, P = 0.00415). CIBERSORT and ESTIMATE analyses showed that the high risk group was characterized by increased M2 macrophages and neutrophils, higher immune and stromal scores, and reduced activated memory CD4 T cells, monocytes, and activated dendritic cells (all P < 0.05). GSEA highlighted enrichment of TNF /NF {kappa}B, IL 6/JAK/STAT3, and immune checkpoint pathways in the high risk group. AXIN2 (HR = 0.829, P = 0.032) was an independent protective factor, while PSORS1C1 (HR = 1.356, P = 0.048) was an independent risk factor. Conclusion The 8 gene bevacizumab resistance signature robustly predicts prognosis and reflects an immunosuppressive microenvironment closely linked to bevacizumab failure in CRC. These findings provide novel insights into immune mediated resistance and support clinical risk stratification.

Matching Claidex post-mortems

1 of 1 indexed

May 20, 2026INB03 in COVID-19 ARDS: Why a Selective Soluble TNF Strategy Did Not Separate From PlaceboINB03 (XPro1595, pegipanermin)EfficacyMRS 43

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.