Target Workspace

NaV1.7 / SCN9A

Voltage-gated sodium channel·Moderate-HighImproving·Review recommended·TSTranslational Science· Updated 3 days ago

Overview Evidence Patient Segments Risks Options Decision Brief Sources

Risk register

Tracked risks with owners, evidence basis, and resolution paths.

AI risk synthesisAI-assisted

The most decision-sensitive risk is isoform selectivity. Internal chemistry data would reduce uncertainty most. CNS exclusion and on-target sensory effects remain monitor-only based on current evidence.

Risk	Category	Sev	Lik	Evidence basis	Resolution path	Owner	Status
Insufficient isoform selectivity in clinic	Off-target safety	High	Moderate	Literature + class precedent	Phase I PK/PD with isoform-specific biomarkers	Chemistry	Open
Inadequate CNS exclusion	Off-target safety	Moderate-High	Moderate	Preclinical PK/PD pending	Brain penetration data; relevant biomarkers	Translational Science	Needs internal data
On-target sensory adverse effects	On-target safety	Moderate	Moderate	Class safety profile	Dose-response in healthy volunteer or POC	Safety	Monitoring
Magnitude of analgesia insufficient at safe doses	Translational	Moderate-High	Moderate	Model-informed projection	Model-informed dose selection; biomarker-anchored POC	Translational Science	Open
Competitor accelerates with selective design	Competitive	Moderate	Moderate	Public pipeline scan	Public pipeline monitoring	Competitive Intelligence	Source check required

Decision impact

Current convictionModerate-High

Active stress-test0 scenarios

Projected conviction—

Most sensitive risk

Isoform selectivity in clinic

Next data needed

Phase I PK/PD with isoform-specific biomarkers

Stress-test scenarios

Insufficient selectivity
Inadequate CNS exclusion
Insufficient analgesia at safe dose

Trigger watch list

Monitoring configuration

Trigger	Source monitored	Impact	Alert threshold	Status
Public NaV1.7 competitor reports cleanly differentiated POC	ClinicalTrials.gov; conference abstracts	Strengthens build case	Phase II POC reported	Active
New large-cohort genetic study modifies expected effect size of NaV1.7 inhibition	GWAS Catalog; UK Biobank; FinnGen	Recalibrates conviction	Cohort > 100k	Active
Regulatory precedent established for non-opioid chronic pain endpoint	FDA briefing materials	Improves trial feasibility	FDA guidance update	Idle
Class-wide failure due to on-target safety not previously characterized	Public safety reports	Reduces conviction across class	Any class-wide SAE	Active