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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