← Platform Overview

Senovia Biosciences · Scientific Brief · SNV-301

Metabolic Psychiatry: Complete Remissions in Treatment-Resistant Patients via Bioenergetic Restoration

A century of clinical observation. Documented remissions where pharmacotherapy failed. Never pharmaceuticalized.

Abstract

Emerging human evidence demonstrates that metabolic state correction produces complete psychiatric remissions in patients who have failed standard pharmacotherapy. Across independent case series and controlled inpatient studies, ketogenic metabolic therapy (KMT) has achieved PANSS reductions of 46% in refractory psychotic illness (p<0.001), complete PHQ-9 remission in treatment-resistant depression, and transdiagnostic symptom resolution across PTSD, ADHD, and binge-eating disorder. These effects occur in patients classified as treatment-resistant by conventional criteria. The mechanistic basis centers on correction of cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation, pathologies shared across psychiatric diagnostic categories. SNV-301 aims to deliver pharmaceutical-grade ketosis as an oral, titratable therapeutic, converting dietary observation into a registrational drug program.

46%
PANSS reduction in
refractory inpatients
Danan 2022
PHQ-9: 0
Complete remission
in lifelong TRD
PMID 40083888
27/27
Inpatients improved
on CGI-S
Danan 2022
505(b)(2)
Regulatory pathway
for known substrates
 
Evidence Context Human evidence: Multiple independent case series and controlled inpatient studies documenting complete remissions in treatment-resistant patients. No completed RCTs of exogenous ketone therapy for psychiatric indications. Mechanistic rationale supported by extensive preclinical and human neuroimaging data. Pipeline status: IND-enabling.

1. The Metabolic Basis of Psychiatric Illness

The ketogenic diet was first applied to psychiatric conditions in the 1920s, alongside its use in epilepsy. Mood stabilization, psychosis attenuation, and reduced agitation were documented before the first antipsychotic existed. A century later, the field is converging on a unifying explanation: major psychiatric disorders share metabolic pathology.

Glucose hypometabolism has been demonstrated on PET imaging in schizophrenia, bipolar disorder, and major depression. Insulin resistance occurs in psychiatric populations at 2-3x the rate of age-matched controls. Mitochondrial dysfunction, indexed by lactate elevation and reduced ATP production, has been identified across diagnostic categories. The brain consumes 20% of total body energy at 2% of body mass. When that energy supply fails, neural circuits fail.

The Insight

If psychiatric symptoms emerge downstream of metabolic failure, then correcting the metabolic state should produce symptom resolution independent of neurotransmitter manipulation. That is exactly what the clinical data show.

The gap between observation and therapy has persisted because dietary ketosis cannot be patented, prescribed, or titrated. Compliance rates for the ketogenic diet in psychiatric populations are low, and the intervention is incompatible with controlled clinical trial design. SNV-301 resolves this by delivering pharmaceutical-grade ketosis in an oral, titratable format.

2. Human Clinical Evidence: Remissions in Treatment-Resistant Patients

The following table summarizes published human clinical data. Each study involved patients classified as treatment-resistant by conventional pharmacological criteria. Effect sizes are reported as published; all citations link to indexed, peer-reviewed publications.

Condition Population Outcome Effect Source
Refractory psychiatric illness
(bipolar, schizoaffective)		 31 inpatients, 6-week KD PANSS 91.4 → 49.3 46% reduction
p<0.001		 Danan 2022
Treatment-resistant MDD 47yo female, lifelong TRD PHQ-9: 25 → 0 at 8 weeks Complete remission PMID 40083888
Schizoaffective disorder 17yo female, severe psychosis Cessation of hallucinations
and suicidal ideation		 Full remission @ 6 wk Laurent 2025
Schizoaffective disorder 32yo female, chronic Full remission; psychiatric
medication discontinued		 Deprescription Laurent 2025
Transdiagnostic
(PTSD, ADHD, binge-eating)		 Adult, all prior Tx failed PHQ-9, GAD-7, DASS-21
all reduced to 0 by week 12		 All scales → 0 PMID 40626225
MDD + GAD 3-patient case series Complete remission of MDD
and generalized anxiety		 Remission @ 7-12 wk Needham 2024
OCD + ulcerative colitis 37yo female Y-BOCS 0, FOCI 0,
UC clinical remission		 Dual remission @ 12 wk PMID 40248603
Bipolar, treatment-resistant Adult, failed ketamine KMT + ketamine →
sustained remission		 Failed ketamine; responded to KMT PMID 39188977
Treatment-resistant schizophrenia 48yo female, 5-week inpatient HOMA-IR ↓69%, CRP ↓61%,
extrapyramidal symptoms ↓80%		 Metabolic normalization PMID 41356674
Severe anorexia nervosa Enduring AN, KD + ketamine Weight restoration,
symptom cessation		 Complete remission PMID 32848935
Autism spectrum 15 children, 3-month KD ADOS-2 significant improvement p=0.006 at 3 mo;
sustained at 6 mo		 Lee 2018

Note: Published data derive from ketogenic diet interventions. SNV-301 aims to replicate these metabolic effects via exogenous ketone delivery with improved compliance, titratability, and exposure control. No clinical trials of SNV-301 have been completed.

3. Published Clinical Data

CGI-S improvement trajectories in 27 psychiatric inpatients on ketogenic diet
CGI-S trajectories, 27 psychiatric inpatients. All patients showed clinical improvement; 12 of 27 (44%) reached CGI-S = 1, indicating clinical remission. Mean time to remission approximately 50 days. Danan et al., Front Psychiatry 2022. PMID: 35873236
PANSS scores across psychiatric inpatients on ketogenic diet
PANSS total scores, controlled inpatient setting. Mean PANSS decreased from 91.4 to 49.3 (46% reduction, p<0.001) over 6 weeks of ketogenic metabolic therapy in treatment-resistant inpatients. Danan et al., Front Psychiatry 2022. PMID: 35873236
Transdiagnostic psychiatric symptom remission on ketogenic therapy
Transdiagnostic remission: all validated scales reduced to zero. PHQ-9, GAD-7, and DASS-21 scores resolved completely by week 12 in a patient with comorbid PTSD, ADHD, and binge-eating disorder who had failed prior pharmacotherapy. PMID: 40626225
PHQ-9 trajectory in treatment-resistant depression
PHQ-9 trajectory in lifelong treatment-resistant depression. 47-year-old female with decades of failed pharmacotherapy achieved complete PHQ-9 remission (25 → 0) within 8 weeks of ketogenic metabolic therapy. PMID: 40083888
Schizoaffective disorder remission timeline on ketogenic diet
Schizoaffective disorder: full remission and deprescription. Two independent cases of schizoaffective disorder achieving complete remission with subsequent psychiatric medication discontinuation under clinical supervision. Laurent et al., Front Nutr 2025. PMID: 39990610
Glucose and ketone levels in treatment-resistant schizophrenia
Metabolic normalization in treatment-resistant schizophrenia. Daily glucose and beta-hydroxybutyrate levels over 5 weeks of inpatient KMT. Insulin resistance reversed (HOMA-IR ↓69%), systemic inflammation reduced (CRP ↓61%), extrapyramidal symptoms decreased 80%. PMID: 41356674
Complete remission of MDD and GAD on ketogenic therapy
MDD + GAD complete remission: 3-patient case series. All three patients achieved complete remission of both major depressive disorder and generalized anxiety disorder within 7 to 12 weeks of ketogenic metabolic therapy. Needham et al., Front Nutr 2024. PMID: 38887496
ADOS-2 improvement in children with autism on ketogenic diet
Autism spectrum: ADOS-2 improvement in pediatric cohort. Significant improvement on the Autism Diagnostic Observation Schedule at 3 months (p=0.006) with sustained social affect gains at 6 months (p=0.019) in 15 children on modified ketogenic diet with MCT supplementation. Lee et al., Physiol Behav 2018. PMID: 29421589

4. Mechanism: Why Metabolic Correction Resolves Psychiatric Symptoms

The therapeutic effect of ketone bodies in psychiatric illness operates through multiple convergent mechanisms, each independently validated in human or preclinical systems:

Mechanism Pathway Psychiatric Relevance
Bioenergetic restoration Beta-hydroxybutyrate bypasses impaired glycolysis; direct mitochondrial substrate via succinyl-CoA:3-ketoacid CoA transferase Corrects cerebral glucose hypometabolism documented in schizophrenia, bipolar, MDD
NLRP3 inflammasome blockade BHB directly inhibits NLRP3 assembly, reducing IL-1beta and IL-18 Youm 2015 Neuroinflammation implicated in treatment resistance across diagnoses; CRP reduced 61% in TRS case
Insulin sensitization Reduces hepatic glucose output; improves peripheral and central insulin signaling HOMA-IR reduced 69% in TRS; insulin resistance 2-3x more prevalent in psychiatric populations
GABA/glutamate modulation Acetoacetate inhibits vesicular glutamate transport (VGLUT); shifts excitatory/inhibitory balance Juge 2010 Glutamate excitotoxicity implicated in psychosis, mood instability, and seizure- psychiatric comorbidity
Epigenetic reprogramming BHB acts as endogenous HDAC inhibitor; lysine beta-hydroxybutyrylation modulates gene expression Xie 2016 Epigenetic dysregulation documented in bipolar disorder, schizophrenia, and MDD
BDNF upregulation Ketosis increases brain-derived neurotrophic factor via beta-hydroxybutyrylation of BDNF promoter regions BDNF deficiency is among the most replicated findings in depression and schizophrenia
Gut-brain axis Shifts microbiome composition; reduces gut permeability and systemic endotoxemia Gut dysbiosis and LPS translocation documented in depression, bipolar, and alcohol use disorder

The Convergence

These are not seven separate drug targets. They are seven downstream consequences of a single upstream intervention: restoring bioenergetic capacity in metabolically compromised neural tissue. This is why a single metabolic correction produces remissions across diagnostic categories that share no neurotransmitter target but all share metabolic pathology.

5. Indication Coverage

Published human evidence now spans seven psychiatric categories. The transdiagnostic nature of the metabolic effect is consistent with the mechanistic hypothesis: if the upstream pathology is metabolic, the downstream symptom category is secondary.

Documented Human Remissions

Treatment-resistant depression (complete PHQ-9 remission)

Schizoaffective disorder (full remission, deprescription)

Bipolar disorder (PANSS 46% reduction; sustained remission)

OCD (Y-BOCS 0, FOCI 0)

Anorexia nervosa (weight restoration, symptom cessation)

Transdiagnostic (PTSD + ADHD + BED: all scales to 0)

Significant Improvement Documented

Autism spectrum (ADOS-2 improvement, p=0.006)

Alcohol use disorder (craving reduction; metabolic normalization)

Treatment-resistant schizophrenia (metabolic + EPS improvement)

GAD (GAD-7 remission in multiple case series)

PTSD (PCL-5 reduction documented)

ADHD (symptom resolution as part of transdiagnostic response)

6. Clinical Development Plan

Lead Indication: Treatment-Resistant Bipolar Depression

Treatment-resistant bipolar depression was selected as the lead indication based on strength of existing clinical signal (46% PANSS reduction in controlled inpatient setting), high unmet need (current options limited to ECT, ketamine, or clozapine), and regulatory precedent for 505(b)(2) pathways in metabolic therapeutics. Fast Track and Breakthrough Therapy designations may be available given documented remissions in patients who failed standard of care.

Phase 1a
SAD/MAD safety and PK in healthy volunteers. Establish dose range producing sustained BHB ≥ 1.5 mM for ≥ 8 hours.
Phase 1b
Open-label in treatment-resistant bipolar depression (n=20-30). Primary: MADRS change from baseline. Secondary: CGI-S, metabolic biomarkers (HOMA-IR, CRP, ketone AUC).
Phase 2
Randomized, placebo-controlled in TR bipolar depression (n=80-120). 12-week treatment. Co-primary: MADRS and CGI-S. Biomarker-stratified analysis by baseline insulin resistance.
Expansion
Schizoaffective disorder (PANSS), alcohol use disorder (heavy drinking days), and autism spectrum (ADOS-2) as follow-on indications based on Phase 2 signal.

Regulatory Pathway

505(b)(2) leveraging established safety of ketone bodies and extensive dietary intervention literature. The known safety profile of beta-hydroxybutyrate as an endogenous metabolite and GRAS-status food ingredient de-risks early clinical development. Orphan Drug Designation may apply to treatment-resistant subtypes.

The Ask

Development partner for treatment-resistant psychiatric disorders.

Seeking a CNS-focused pharma partner to co-develop SNV-301 through Phase 2 proof-of-concept in treatment-resistant bipolar depression. Estimated program cost through Phase 2 readout: ~$20-30M. Structure: co-development partnership with option to license, or strategic co-lead.

Contact: joel@senoviabiosciences.com

References

1. Danan A, Westman EC, Saslow LR, Ede G. The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Front Psychiatry. 2022;13:951376. PMID: 35873236

2. Laurent N, Bellamy EL, Tague KA, Hristova D, Houston A. Ketogenic metabolic therapy for schizoaffective disorder: a retrospective case series. Front Nutr. 2025. PMID: 39990610

3. Needham N, et al. Complete remission of depression and anxiety using a ketogenic diet: case series. Front Nutr. 2024. PMID: 38887496

4. Lee RWY, et al. A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiol Behav. 2018;188:205-211. PMID: 29421589

5. Youm YH, et al. The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015;21(3):263-269. PMID: 25686106

6. Juge N, et al. Metabolic control of vesicular glutamate transport and release. Neuron. 2010;68(1):99-112. PMID: 20920794

7. Xie Z, et al. Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation. Mol Cell. 2016;62(2):194-206. PMID: 27105115

8. Laurent N, Bellamy EL, Hristova D, Houston A. Ketogenic metabolic therapy in the remission of chronic major depressive disorder: a retrospective case study. Front Nutr. 2025. PMID: 40083888

9. Transdiagnostic remission of comorbid PTSD, ADHD, and binge-eating disorder following ketogenic metabolic therapy. 2025. PMID: 40626225

10. OCD and ulcerative colitis remission with ketogenic diet. 2025. PMID: 40248603

11. Metabolic normalization in treatment-resistant schizophrenia. 2025. PMID: 41356674

12. Evangeliou A, et al. Application of a ketogenic diet in children with autistic behavior. J Child Neurol. 2003;18(2):113-118. PMID: 12693778

Senovia Biosciences · joel@senoviabiosciences.com

SNV-301 is investigational. No clinical trials of SNV-301 have been completed. Published evidence derives from ketogenic diet interventions.

Last updated: February 2026 | Version 4.0