SNV-901
Infectious Disease & AMR
Metabolic host defense. Gram-negative membrane permeabilization via putrescine depletion. ICU feasibility established. Complete malaria protection in vivo. A host-directed adjuvant that restores antibiotic efficacy without adding selective pressure for new resistance.
The crisis
The antibiotic pipeline is collapsing. The death toll is not.
48.9M
Sepsis cases per year globally
11M
Sepsis-related deaths annually
1.27M
Direct AMR deaths per year
<5
Novel-mechanism antibiotics per decade
Bacteria evolve resistance faster than the pharmaceutical industry can produce new antibiotics. The economic model for antibiotic development is broken: high development costs, low pricing, and limited treatment duration make ROI unattractive. Fewer than 5 novel-mechanism antibiotics have reached market in the last decade.
The alternative: instead of finding new weapons to attack the pathogen, strengthen the host. A host-directed metabolic approach that restores antibiotic sensitivity doesn't compete with existing antibiotics. It makes them work again. And it does so through a mechanism (host metabolite-mediated membrane permeabilization) that does not create new selective pressure for resistance.
Published evidence
From membrane permeabilization to ICU feasibility.
Mechanism, feasibility, and efficacy data across bacterial, viral, parasitic, and fungal pathogens.
Cui et al., Cell Metabolism 2025 (PMID: 40315854)
Specific ketone metabolites deplete putrescine in Gram-negative bacteria, destabilizing the outer membrane and restoring antibiotic lethality. This is a host-derived mechanism that permeabilizes the bacterial membrane without requiring a new antibiotic. MIC reduction demonstrated for multiple antibiotic classes against resistant strains.
Rahmel et al., Science Translational Medicine 2024
Ketogenic feeding achieves stable therapeutic ketosis in critically ill septic ICU patients. Clinical feasibility demonstrated in the most challenging treatment setting: mechanically ventilated, hemodynamically unstable, multi-organ failure. The metabolic intervention is compatible with standard critical care protocols.
Wei et al., 2025 (PMID: 40410577)
Complete protection in murine P. berghei malaria model with metabolic intervention. Direct parasite arrest at elevated BHB levels, suggesting both host immune enhancement and direct anti-parasitic metabolic activity. 282 million malaria cases annually; current prophylaxis has adherence and resistance challenges.
Palmucci et al., mBio 2024
Metabolic intervention combined with fluconazole produced a 2.66 log10 reduction in brain fungal burden in invasive candidiasis model. Dramatically outperformed antifungal monotherapy. Invasive candidiasis carries 20–85% mortality; current antifungal options are limited.
Goldberg et al., 2020 (γδ T-cell activation)
Metabolic intervention activated γδ T-cells, improving survival in an influenza model. γδ T-cells provide rapid innate-like immune defense against diverse pathogens. 9–41 million annual US influenza illnesses; pandemic preparedness requires host-directed approaches.
Karagiannis et al., 2022 (COVID/T-cell rescue)
Metabolic rescue of T-cell function in SARS-CoV-2 infection model. Ketone bodies restored anti-viral T-cell effector function that was impaired by the metabolic demands of acute viral infection.
Mechanism of action
Three-node host defense: sensitize, modulate, rescue.
SNV-901 engages anti-infective host defense through three simultaneous, complementary mechanisms.
1. Pathogen sensitization
Specific ketone metabolites deplete bacterial putrescine, a polyamine required for outer membrane stability in Gram-negative bacteria. Putrescine depletion destabilizes the lipopolysaccharide layer, restoring permeability to antibiotics that were previously excluded. This mechanism does not create new selective pressure for resistance because it operates through a host metabolite, not a synthetic antibiotic.
Cui et al., Cell Metabolism 2025
2. Immune modulation (anti-cytokine storm)
BHB inhibits the NLRP3 inflammasome, preventing the cytokine storm that drives sepsis mortality. Sepsis kills through immune dysregulation, not pathogen burden. By modulating the innate immune response, the metabolic intervention addresses the inflammatory cascade that causes organ failure without suppressing pathogen clearance.
Youm et al., Nature Medicine 2015
3. Bioenergetic rescue (organ support)
Sepsis induces organ-level metabolic failure: mitochondrial dysfunction, ATP depletion, and metabolic paralysis in liver, kidney, heart, and immune cells. Ketone bodies provide an alternative energy substrate that bypasses the glycolytic blockade, supporting organ function during the critical acute phase.
Multiple preclinical studies; Rahmel 2024 (ICU feasibility)
Competitive positioning
Host-directed vs. pathogen-directed.
SNV-901 operates through a fundamentally different paradigm than conventional antibiotics.
Global health thesis
Extending the life of existing antibiotics worldwide.
The AMR crisis disproportionately impacts low- and middle-income countries (LMICs) where access to novel antibiotics is limited, cold-chain logistics are challenging, and IV administration infrastructure is scarce. SNV-901 is designed as a shelf-stable, oral/NG-tube-compatible small molecule that works with existing antibiotics.
Rather than racing to develop new antibiotics that bacteria will eventually resist, SNV-901 extends the useful life of the existing antibiotic arsenal. For the global health community, a host-directed adjuvant that restores sensitivity without generating new resistance represents a fundamentally different approach to the AMR crisis.
Lead indication: Gram-negative sepsis (AMR adjunct), where the Cell Metabolism 2025 mechanism data and the Rahmel 2024 ICU feasibility data converge. Expansion into viral ARDS, malaria (282M cases/year), and invasive fungal infections based on published efficacy signals.