Clinical Risk Intelligence Report

Generated: 2025-11-25 13:17:18

1. Executive Summary

The integrated clinical-risk system highlights UNKNOWN_TARGET_CLASS, DNA, Epidermal growth factor receptor as the dominant mechanistic failure clusters, driven by aggregate toxicity and cross-portfolio propagation.

Clinical attrition remains concentrated in PHASE2 (3122), PHASE3 (1348), PHASE1 (1128), reflecting global R&D late-stage volatility and dose-limiting toxicity trends.

Regulatory observations indicate significant exposure to FDA 21 CFR–defined deviations: STERILITY_FAILURE (135), CONTAMINATION (21), LABELING_PACKAGING (11), signaling potential manufacturing and QA vulnerabilities.

Short-term biomedical evidence activity (7-day) reveals ongoing discussions across trial:148, tox:49, safety:114, withdraw:2, pointing to increased scrutiny around safety and withdrawal risks.

2. Clinical Failure Clusters

PhaseCount
PHASE23122
PHASE31348
PHASE11128
PHASE41027
PHASE1, PHASE2694
NA589
PHASE2, PHASE3211
UNKNOWN164
EARLY_PHASE1139

3. Mechanism Hotspot (Risk-Weighted)

Target ClassFreqAvg ScoreWeighted
UNKNOWN_TARGET_CLASS5190.49311.55
DNA1323.4880.24
Epidermal growth factor receptor941.2656.78
Tubulin921.6755.70
Bacterial penicillin-binding protein850.4751.14
Glucocorticoid receptor771.7546.73
Histamine H1 receptor720.3943.32
D(2) dopamine receptor681.0141.10
GABA-A receptor; anion channel671.2440.57
Bacterial 70S ribosome670.7240.42
Sodium-dependent noradrenaline transporter650.7839.24
Sodium channel alpha subunit581.2135.16
Cyclooxygenase571.2034.56
Beta-2 adrenergic receptor570.5534.37
5-hydroxytryptamine receptor 2A561.5134.05
Mu-type opioid receptor540.9532.68
Estrogen receptor490.8629.66
Receptor-type tyrosine-protein kinase FLT3451.8227.55
Muscarinic acetylcholine receptor M3450.6827.21
Androgen receptor431.1126.13
NON_TARGETED_VIRAL_VACCINE430.2525.88
Vascular endothelial growth factor receptor411.9725.19
Receptor tyrosine-protein kinase erbB-2411.2324.97
Hepatocyte growth factor receptor390.8623.66
Muscarinic acetylcholine receptor M1370.7222.41
Mast/stem cell growth factor receptor Kit352.7221.82
Human immunodeficiency virus type 1 reverse transcriptase350.7421.22
Sodium-dependent serotonin transporter350.6721.20
Mitogen-activated protein kinase 14350.3421.10
Progesterone receptor340.9820.69
Vascular endothelial growth factor receptor 2331.2820.18
Beta-1 adrenergic receptor330.6620.00
Peroxisome proliferator-activated receptor gamma311.0318.91
Topoisomerase IV300.8318.25
Insulin receptor300.7318.22
Bacterial DNA gyrase290.6817.60
5-hydroxytryptamine receptor 2C271.4916.65
Programmed cell death protein 1263.4516.64
Voltage-gated L-type calcium channel270.6616.40
Gonadotropin-releasing hormone receptor270.4916.35
5-hydroxytryptamine receptor 1A261.1715.95
Phosphodiesterase 4260.7915.84
Serine/threonine-protein kinase mTOR260.6415.79
PI3-kinase class I260.6215.79
Platelet-derived growth factor receptor252.4215.72
Tyrosine-protein kinase JAK2251.3315.40
Dihydropteroate synthase250.2815.08
DNA topoisomerase 1240.8714.66
Lanosterol 14-alpha demethylase240.8014.64
Sodium-dependent dopamine transporter231.5314.26

4. Regulatory Exposure Summary (FDA 21 CFR)

CategoryCount
STERILITY_FAILURE135
CONTAMINATION21
LABELING_PACKAGING11
MANUFACTURING_OTHER10
POTENCY_STABILITY10
GMP_DEVIATION7

5. Evidence Signals (7-Day PubMed)

KeywordCount
trial148
tox49
safety114
withdraw2

6. Dynamic Risk Engine — High-Risk Portfolio

DrugScoreSummaryStrategies
CYCLOPHOSPHAMIDE78.2731DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 195 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
CISPLATIN52.6667DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 131 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
CARBOPLATIN49.4659DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 123 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
DOCETAXEL43.4644Microtubule-associated toxicity cluster. Mechanism-based risk originates from interactions involving Tubulin. Clinical risk includes 108 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Tubulin."]
PEMBROLIZUMAB43.0643Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Programmed cell death protein 1. Clinical risk includes 107 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Programmed cell death protein 1."]
DEXAMETHASONE40.4485Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Glucocorticoid receptor. Clinical risk includes 97 historical terminated/withdrawn trials. Regulatory alerts detected in....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Review manufacturing and QA processes to eliminate future recall triggers.", "Reduce off-target risk; consider a more selective variant against Glucocorticoid receptor."]
CAPECITABINE40.3707DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving Thymidylate synthase, RNA, DNA. Clinical risk includes 99 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Thymidylate synthase, RNA."]
LENALIDOMIDE31.8615Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving CRL4(CRBN) E3 ubiquitin ligase. Clinical risk includes 79 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against CRL4(CRBN) E3 ubiquitin ligase."]
BEVACIZUMAB30.4998Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Vascular endothelial growth factor A, long form. Clinical risk includes 73 historical terminated/withdrawn trials. Regul....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Review manufacturing and QA processes to eliminate future recall triggers.", "Reduce off-target risk; consider a more selective variant against Vascular endothelial growth factor A, long form."]
NIVOLUMAB29.4609Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Programmed cell death protein 1. Clinical risk includes 73 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Programmed cell death protein 1."]
RITUXIMAB29.0608Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving B-lymphocyte antigen CD20. Clinical risk includes 72 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against B-lymphocyte antigen CD20."]
EVEROLIMUS22.6592Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Peptidyl-prolyl cis-trans isomerase FKBP1A. Clinical risk includes 56 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Peptidyl-prolyl cis-trans isomerase FKBP1A."]
TEMOZOLOMIDE20.6587DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 51 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
PACLITAXEL20.2586Microtubule-associated toxicity cluster. Mechanism-based risk originates from interactions involving Tubulin. Clinical risk includes 50 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Tubulin."]
CELECOXIB19.8585Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Prostaglandin G/H synthase 2. Clinical risk includes 49 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Prostaglandin G/H synthase 2."]
LIDOCAINE19.8047Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Sodium channel alpha subunit. Clinical risk includes 48 historical terminated/withdrawn trials. Regulatory alerts detect....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Review manufacturing and QA processes to eliminate future recall triggers.", "Reduce off-target risk; consider a more selective variant against Sodium channel alpha subunit."]
ATEZOLIZUMAB19.4584Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Programmed cell death 1 ligand 1. Clinical risk includes 48 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Programmed cell death 1 ligand 1."]
DASATINIB18.6582Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Bcr/Abl fusion protein. Clinical risk includes 46 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Bcr/Abl fusion protein."]
BUSULFAN17.4579DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 43 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
DURVALUMAB17.4579Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Programmed cell death 1 ligand 1. Clinical risk includes 43 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Programmed cell death 1 ligand 1."]
BUPIVACAINE16.6577Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Sodium channel protein type 4 subunit alpha. Clinical risk includes 41 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Sodium channel protein type 4 subunit alpha."]
TRANEXAMIC ACID16.6577Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Plasminogen. Clinical risk includes 41 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Plasminogen."]
AZACITIDINE16.6183DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA (cytosine-5)-methyltransferase 1, RNA, DNA. Clinical risk includes 39 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA (cytosine-5)-methyltransferase 1, RNA."]
CETUXIMAB16.2576Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Epidermal growth factor receptor. Clinical risk includes 40 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Epidermal growth factor receptor."]
OXYTOCIN16.2576Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Oxytocin receptor. Clinical risk includes 40 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Oxytocin receptor."]
ASPIRIN14.6572Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Cyclooxygenase. Clinical risk includes 36 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Cyclooxygenase."]
GABAPENTIN14.6572Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Voltage-gated calcium channel. Clinical risk includes 36 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Voltage-gated calcium channel."]
PREDNISONE14.6572Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Glucocorticoid receptor. Clinical risk includes 36 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Glucocorticoid receptor."]
PROPOFOL14.6572Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving GABA-A receptor; anion channel. Clinical risk includes 36 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against GABA-A receptor; anion channel."]
AVELUMAB14.2571Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Programmed cell death 1 ligand 1. Clinical risk includes 35 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Programmed cell death 1 ligand 1."]
CYTARABINE13.9641DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA polymerase (alpha/delta/epsilon), RNA, DNA. Clinical risk includes 33 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA polymerase (alpha/delta/epsilon), RNA."]
OXALIPLATIN13.8570DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA. Clinical risk includes 34 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA."]
GEMCITABINE HYDROCHLORIDE13.7105DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving Ribonucleoside-diphosphate reductase RR1, DNA polymerase (alpha/delta/epsilon). Clinical risk includes 33 historical ter....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Ribonucleoside-diphosphate reductase RR1, DNA polymerase (alpha/delta/epsilon)."]
VORINOSTAT13.4175Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Histone deacetylase 3, Histone deacetylase 2, Histone deacetylase 6. Clinical risk includes 31 historical terminated/wit....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Histone deacetylase 3, Histone deacetylase 2."]
AZITHROMYCIN13.0568Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Bacterial 70S ribosome. Clinical risk includes 32 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Bacterial 70S ribosome."]
PEMETREXED12.3637Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Thymidylate synthase, Trifunctional purine biosynthetic protein adenosine-3, Dihydrofolate reductase. Clinical risk incl....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Thymidylate synthase, Trifunctional purine biosynthetic protein adenosine-3."]
IPILIMUMAB12.2566Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Cytotoxic T-lymphocyte protein 4. Clinical risk includes 30 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Cytotoxic T-lymphocyte protein 4."]
SIROLIMUS12.2566Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Peptidyl-prolyl cis-trans isomerase FKBP1A. Clinical risk includes 30 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Peptidyl-prolyl cis-trans isomerase FKBP1A."]
ZOLEDRONIC ACID12.2566Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Farnesyl pyrophosphate synthase. Clinical risk includes 30 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Farnesyl pyrophosphate synthase."]
TACROLIMUS12.0414Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Peptidyl-prolyl cis-trans isomerase FKBP1A. Clinical risk includes 26 historical terminated/withdrawn trials. Regulatory....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Review manufacturing and QA processes to eliminate future recall triggers.", "Reduce off-target risk; consider a more selective variant against Peptidyl-prolyl cis-trans isomerase FKBP1A."]
ARSENIC TRIOXIDE11.8565Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Thioredoxin reductase 1, cytoplasmic. Clinical risk includes 29 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Thioredoxin reductase 1, cytoplasmic."]
EPOETIN ALFA11.8565Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Erythropoietin receptor. Clinical risk includes 29 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Erythropoietin receptor."]
METHYLPREDNISOLONE11.8027Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Glucocorticoid receptor. Clinical risk includes 28 historical terminated/withdrawn trials. Regulatory alerts detected in....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Review manufacturing and QA processes to eliminate future recall triggers.", "Reduce off-target risk; consider a more selective variant against Glucocorticoid receptor."]
ARIPIPRAZOLE11.5635Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 1A. Clinical risk includes 27 hist....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A."]
DECITABINE11.5635DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving DNA (cytosine-5)-methyltransferase 1, DNA, DNA (cytosine-5)-methyltransferase 3A. Clinical risk includes 27 historical t....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against DNA (cytosine-5)-methyltransferase 1, DNA."]
PREGABALIN11.4564Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Voltage-gated calcium channel. Clinical risk includes 28 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Voltage-gated calcium channel."]
SIMVASTATIN11.4564Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Clinical risk includes 28 historical terminated/withdrawn trials..["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against 3-hydroxy-3-methylglutaryl-coenzyme A reductase."]
IMATINIB MESYLATE11.4170Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Platelet-derived growth factor receptor beta, Bcr/Abl fusion protein, Mast/stem cell growth factor receptor Kit. Clinica....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Platelet-derived growth factor receptor beta, Bcr/Abl fusion protein."]
ACETAMINOPHEN11.1634Mechanism-driven vulnerability. Mechanism-based risk originates from interactions involving Fatty-acid amide hydrolase 1, Transient receptor potential cation channel subfamily V member 1, Cyclooxygenase. Clinical....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Fatty-acid amide hydrolase 1, Transient receptor potential cation channel subfamily V member 1."]
CLOFARABINE11.1634DNA-damage / genotoxicity cluster. Mechanism-based risk originates from interactions involving Ribonucleoside-diphosphate reductase RR1, DNA polymerase (alpha/delta/epsilon), DNA. Clinical risk includes 26 historica....["Reassess clinical trial design; strengthen enrollment & monitoring.", "Reduce off-target risk; consider a more selective variant against Ribonucleoside-diphosphate reductase RR1, DNA polymerase (alpha/delta/epsilon)."]