SNV-401
Drug-Resistant Epilepsy
The most validated mechanism in the portfolio. Cochrane RR 5.80. Over 100 years of clinical observation. 3,462 papers analyzed. The pharmacology to deliver this mechanism as a medicine has never existed. SNV-401 changes that.
Therapeutic rationale
A proven mechanism without a drug.
Drug-resistant epilepsy (DRE) affects approximately 30% of epilepsy patients. After failing two adequately trialed anti-seizure medications, the probability of achieving seizure freedom with a third drops below 5%. For an estimated 85,000 patients in the US alone with developmental and epileptic encephalopathies (DEEs), conventional pharmacology has reached its ceiling.
The ketogenic diet has been used for seizure control since 1921. It is standard of care at every major pediatric epilepsy center. It outperforms 9 of 11 approved anti-seizure medications by responder rate. The Cochrane meta-analysis (RR 5.80) represents one of the strongest treatment effects in any neurological condition.
The gap is not evidence. It is delivery. The ketogenic diet requires extreme dietary restriction (75\u201390% fat calories), continuous dietitian support, and produces adherence rates ranging from 23.5% to 100% across studies. For children with developmental disabilities, for adults with comorbidities, for patients in resource-limited settings, the diet is impractical.
SNV-401 is an oral prodrug designed to achieve the same sustained metabolic state that 100 years of clinical observation associate with seizure control, delivered as a titratable medicine with pharmaceutical-grade consistency.
Clinical evidence
Cochrane-validated, dose-responsive, multi-syndrome.
Human evidence from RCTs, meta-analyses, and biomarker studies establishing the ketone-seizure relationship.
Martin-McGill et al., Cochrane 2020 (4 RCTs, n=385)
Relative risk 5.80 (95% CI: 3.48–9.65, p<0.001) for ≥50% seizure reduction with ketogenic interventions vs. control. This is the largest Cochrane-validated treatment effect in the Senovia portfolio and one of the largest in drug-resistant epilepsy.
Neal et al., Lancet Neurol 2008 (RCT, n=145)
38% responder rate (≥50% seizure reduction) vs. 6% control (p<0.0001). The definitive randomized trial establishing efficacy of metabolic intervention in drug-resistant epilepsy. Effect size exceeds most approved anti-seizure medications.
Zuo et al., 2025 (Meta-analysis, 15+ studies, n=726)
63% pooled seizure reduction rate across heterogeneous epilepsy populations. At extended follow-up: 65% responder rate, 54% infantile spasm control, 57% EEG normalization. Durable, multi-endpoint improvement.
Qiao et al., 2025 (Retrospective, n=213)
Optimal blood BHB range for seizure control: 1.1–4.9 mM. Below 1.1 mM, efficacy drops significantly. This defines a pharmacologically targetable therapeutic window with clear dose-response boundaries.
Dahlin et al., 2024 (Metabolomics)
Blood ketone levels are the top PERMANOVA predictor of clinical response (R²>0.10, p=0.0017), outperforming all other metabolic and clinical variables. Microbiota composition correlates with seizure outcomes, suggesting gut-brain axis engagement.
Indication basket
Six rare epilepsy syndromes. One metabolic platform.
Each DEE syndrome has published evidence supporting metabolic intervention. Orphan drug designation potential for each indication, with 7-year market exclusivity per approval.
GLUT1 Deficiency
~4,000 US
Standard of care. Metabolic therapy is first-line, not adjunctive.
Consensus guidelines recommend ketogenic diet as primary treatment.
Dravet Syndrome
~16,000 US
32.5% seizure-free with metabolic intervention
Multiple retrospective series; FDA orphan pathway available.
Lennox-Gastaut
~48,000 US
40% responder rate (≥50% reduction)
Retrospective data; largest addressable DEE population.
Doose Syndrome
~5,000 US
54% seizure-free
Highest seizure freedom rate in the DEE basket.
Angelman Syndrome
~15,000 US
5/6 patients achieved >80% seizure reduction
Small series with dramatic responder signal.
Mitochondrial Epilepsy
~2,000 US
74% responder rate
Mechanistically direct: bypasses the mitochondrial defect.
Mechanism of action
Multi-pathway anti-seizure activity.
Unlike conventional ASMs that target single ion channels, SNV-401 engages 6+ validated anti-epileptic pathways simultaneously. Each is independently published.
VGLUT1/2 inhibition
Ketone bodies (specifically acetoacetate) directly inhibit vesicular glutamate transporters, reducing excitatory neurotransmitter loading into synaptic vesicles. This dampens glutamate-mediated excitotoxicity at the pre-synaptic level.
Juge et al., Neuron 2010
NLRP3 inflammasome blockade
BHB inhibits NLRP3 inflammasome assembly, reducing IL-1β and IL-18. Neuroinflammation lowers seizure thresholds and drives the kindling phenomenon that makes drug-resistant epilepsy progressive. Inflammasome inhibition addresses this directly.
Youm et al., Nature Medicine 2015
K-ATP channel activation
Ketone metabolism alters the ATP/ADP ratio at neuronal K-ATP channels, promoting hyperpolarization and raising seizure thresholds. This is mechanistically distinct from every approved anti-seizure drug.
Ma et al., 2007; Lutas & Bhatt, 2021
HCAR2/GPR109A signaling
BHB activates the hydroxycarboxylic acid receptor 2, triggering anti-inflammatory cascades and neuroprotective gene expression programs independent of its metabolic effects.
Rahman et al., 2014
Epigenetic regulation (HDAC inhibition)
BHB acts as an endogenous Class I HDAC inhibitor, modulating transcription of oxidative stress resistance genes (FOXO3a, MT2) and neurotrophic factors (BDNF) that support neuronal survival.
Shimazu et al., Science 2013
Gut-brain axis modulation
Metabolic state shifts restructure the gut microbiome, altering GABA/glutamate precursor availability and vagal afferent signaling. Dahlin 2024 showed gut microbiota composition predicts seizure response (PERMANOVA p=0.0017).
Olson et al., Cell 2018; Dahlin et al., 2024
The pharmacological gap
Existing products fail on duration and consistency.
The Qiao 2025 data defines the target: sustained blood BHB of 1.1\u20134.9 mM. No existing commercial product achieves this without dietary restriction.
Development pathway
505(b)(2) with orphan drug strategy.
SNV-401 pursues a 505(b)(2) regulatory pathway referencing established ketone body safety data, with precedent from Dojolvi (triheptanoin) for metabolic disorders. Each DEE indication qualifies for orphan drug designation, providing 7-year market exclusivity per approved indication.
Phase 1b directly in DRE patients with seizure frequency as the primary endpoint, enriched for rare DEE syndromes. The biomarker strategy is straightforward: blood ketone levels correlate with seizure outcomes (Dahlin 2024, PERMANOVA p=0.0017), enabling real-time PK/PD monitoring.