Datasets:

ClarusC64
/

clarus-preclinical-decision-coherence-v0.1

case_id stringlengths 8 8	modality stringclasses 6 values	indication stringlengths 5 20	mechanism stringlengths 13 31	target stringlengths 3 13	model_system stringclasses 10 values	study_design stringlengths 17 45	efficacy_summary stringlengths 28 65	safety_summary stringlengths 30 50	pk_pd_summary stringlengths 17 63	biomarker_summary stringlengths 11 47	confounders stringlengths 25 56	data_gaps stringlengths 33 59	decision_options stringclasses 1 value	expected_best_decision stringclasses 3 values	expected_rationale_bullets stringlengths 71 139	red_flags_expected stringlengths 31 71	risk_level stringclasses 3 values
PDC-0001	Small molecule	NAFLD	PPAR modulation	PPAR-delta	Mouse DIO	8w; n=12/arm; 3 doses; vehicle control	Liver fat -18% at top dose; no dose-response; ALT unchanged	No deaths; mild weight loss at top dose; AST +22%	Exposure high variance; Tmax delayed; trough below EC50 in 2/12	FGF21 +5% (ns); inflammatory panel mixed	Food intake not controlled; weight loss may drive effect	No histology scoring; no blinded readout	GO\|HOLD\|KILL	HOLD	Effect lacks dose-response\|Possible confound from weight loss\|AST rise needs clarification\|PK variability undermines interpretation	No dose-response\|Confounded efficacy\|Liver enzyme signal\|PK variability	Medium
PDC-0002	mAb	Oncology solid tumor	Receptor blockade	EGFR	PDX model	21d; n=8; weekly dosing; comparator anti-EGFR	Tumor growth inhibition 48% vs control; consistent across animals	No clinical signs; cytokines stable	Exposure consistent; target occupancy 85%	pERK down 60% post-dose; rebounds by day 7	PD sampling timing may bias rebound	No immunogenicity assessment; no combo data	GO\|HOLD\|KILL	GO	Efficacy consistent\|Clean safety\|Strong target engagement\|PD matches MoA\|PK stable	PD rebound risk\|Missing immunogenicity	Low
PDC-0003	Small molecule	Alzheimer's	Kinase inhibition	GSK3beta	Rat	4w; n=10; oral daily; two doses	Cognitive score improved 9% (p=0.08); no clear dose separation	Sedation reported in 4/10 high dose; falls in 2/10	Brain exposure adequate; peripheral exposure high	pTau down 12% (ns); neuroinflammation unchanged	Sedation may inflate cognitive test artifacts	No chronic tox; no female animals	GO\|HOLD\|KILL	KILL	Efficacy weak and not significant\|Dose separation absent\|CNS side effects prominent\|Biomarker shift minimal\|Risk of symptomatic masking	Weak efficacy\|CNS adverse effects\|No dose separation	High
PDC-0004	siRNA	Hypercholesterolemia	RNA silencing	PCSK9	Non-human primate	Single dose; n=4; follow 8w	LDL -52% sustained to week 6	Platelets stable; mild injection reactions	Exposure consistent; durable effect	PCSK9 protein down 80% at week 2	Small n limits confidence	No repeat-dose tox; no off-target transcriptome	GO\|HOLD\|KILL	GO	Large durable LDL reduction\|Safety acceptable\|Mechanism confirmed\|Clear translational precedent	Small n\|Missing repeat-dose tox	Low
PDC-0005	Small molecule	Asthma	Inflammation modulation	CRTH2	Guinea pig	2w; allergen challenge; n=9	Airway resistance improved 25% at mid dose only; high dose worse	No deaths; mild diarrhea at high dose	Exposure increases with dose; high dose peak high	Eosinophils down 10% (ns)	High dose paradox suggests off-target	No receptor occupancy assay; no metabolite ID	GO\|HOLD\|KILL	HOLD	Non-monotonic efficacy suggests off-target\|High dose worsening is concerning\|Need occupancy and off-target profiling\|GI tolerability issues	Non-monotonic response\|Worsening at high dose\|Missing occupancy	Medium
PDC-0006	Cell therapy	Oncology hematologic	Engineered T cells	BCMA	Mouse xenograft	n=10; single infusion; 30d follow	Complete response in 6/10; partial in 2/10	Cytokine spike day 2; 1 death likely CRS	Cells expand 50x then contract	IL6 high in responders and non-responders	Supportive care inconsistent	No dose-ranging; no mitigation strategy tested	GO\|HOLD\|KILL	HOLD	Strong efficacy but safety event\|Need CRS mitigation plan\|Dose-ranging required\|Supportive care variability confounds safety read	Treatment-related death\|CRS risk\|No dose-ranging	High
PDC-0007	Small molecule	Type 2 diabetes	GLP1 agonism (oral)	GLP1R	Dog	4w; n=6; fed vs fasted arms	HbA1c trend -0.3; glucose AUC improved 12% only fasted	Nausea in 3/6; vomiting in 1/6	Huge food effect; exposure drops 70% fed	Insulin secretion markers mixed	Fed/fasted imbalance across groups	No formulation optimization; no exposure-response model	GO\|HOLD\|KILL	HOLD	Efficacy depends on fasting\|Food effect undermines real-world use\|Need formulation work\|GI AEs present\|Exposure-response unclear	Severe food effect\|Real-world feasibility risk\|GI AEs	Medium
PDC-0008	mAb	Autoimmune	Pathway inhibition	IL-23	NHP	Repeat dose q4w x3; n=5	Inflammation score down 40% sustained	No serious AEs; mild infections in 2/5	Exposure stable; ADA detected low titer	IL-17A down 55%	Mild infections may signal immunosuppression depth	No opportunistic infection panel; small n	GO\|HOLD\|KILL	GO	Clear efficacy\|Manageable safety\|PK stable\|ADA low\|Mechanism consistent	Infection signal\|Limited infection workup	Low
PDC-0009	Small molecule	Oncology	DDR inhibition	ATR	Cell line + mouse	In vitro IC50 strong; in vivo 14d; n=10	Tumor reduction 15% only in one line; others none	Weight loss 12% in treated; neutropenia noted	Exposure exceeds IC90; narrow margin	pCHK1 down 70%	In vivo model may not match biomarker-defined population	No patient stratification hypothesis; limited combo testing	GO\|HOLD\|KILL	KILL	In vivo efficacy poor despite target engagement\|Toxicity significant\|Therapeutic window weak\|No clear responder hypothesis	Poor efficacy\|Toxicity\|Narrow window	High
PDC-0010	Protein	Rare disease	Enzyme replacement	IDUA	NHP	Single dose; n=3; 6w follow	Substrate down 35% in plasma; tissue unknown	Hypersensitivity reaction in 1/3	Exposure adequate; half-life short	Biomarker response transient	Premedication not standardized	No tissue biodistribution; no repeat dosing	GO\|HOLD\|KILL	HOLD	Some biomarker effect but transient\|Hypersensitivity risk needs plan\|Need tissue readouts\|Need repeat-dose data	Hypersensitivity\|No tissue efficacy data	Medium
PDC-0011	Small molecule	Depression	NMDA modulation	NR2B	Rat	2w; n=12; behavioral assays	Behavioral improvement 20% across tests	No deaths; locomotor hyperactivity at high dose	Exposure OK; brain penetration high	BDNF up 30%	Hyperactivity may inflate behavioral outcomes	No chronic tox; abuse liability not explored	GO\|HOLD\|KILL	HOLD	Signal present but confounded by hyperactivity\|Need assay controls\|Need longer tox\|Need liability assessment	Behavior confound\|CNS activation risk	Medium
PDC-0012	Vaccine	Infectious disease	Neutralizing antibody induction	Spike antigen	Mouse	Prime-boost; n=15	Neutralization titers high; challenge protection 80%	Local reactogenicity moderate; no severe AEs	PK not applicable	Th1 skew; cytokines acceptable	Challenge model variability	No durability beyond 8w; no variant panel	GO\|HOLD\|KILL	GO	Strong protection\|Safety acceptable\|Immune profile supports protection\|Clear next experiments identified	Durability unknown\|Variant coverage unknown	Low