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to22s Bio-Systems Systems Pharmacology Utility

Bio-Identical
Phytosterol Elicitors.

Engineered natural triterpenoid elicitors derived from domestic rice bran (Oryza sativa L.) for metagenomic BH3 pocket elicitation & cross-kingdom cell death modulation — targeting conserved apoptotic and Toxin-Antitoxin (TA) machinery without synthetic chemical residues.

// FUNGAL SUICIDE
≤ -14.0
ΔGbind kcal/mol
// INSECT ECDYSIS
≤ -14.85
ΔGbind kcal/mol
// ONCOLOGY ALLOSTERY
21 nM
Human Bcl-2 α5– Ki
// CROP SAFETY
100%
Selective ΔΔG ≥ +12.0 kcal/mol
// Systems Pharmacology Platform & IP Strategy

One Core Engine.
Four Research Hubs.

Anchored by a comprehensive patent portfolio spanning across these vast fields—from agricultural biosecurity and human oncology to broad-spectrum antivirals and closed-loop biomanufacturing—to22s Bio-Systems targets evolutionarily conserved structural allosteric hinges and metagenomic BH3 hydrophobic grooves (Leu-X-X-X-Asp-X-Leu).

Hub D • USDA NIFA SBIR 8.2

Agricultural Biosecurity & Crop Protection

Dual-action foliage elicitor spray driving fungal hyphal suicide (Magnaporthe, Phakopsora, Botrytis) and insect sterol auxotrophy disruption (Spodoptera, Aphis, Diabrotica) without synthetic chemical residues.

Testing Partners: UF/IFAS GCREC Core • USF ChBME
Hub A • NCI SBIR Phase I

Oncology & Venetoclax Resistance

Allosteric Cycloartanol therapy targeting the human Bcl-2 , overcoming G101V and D103Y resistance mutations in acute myeloid leukemia (AML).

Testing Partners: CRO • USF CPAS
Hub B • NIH STTR Phase I

Broad-Spectrum Toxin & Viral Shield

Modulation of host cell membrane lipid rafts and sterol transporters (ABCA2, NPC1) to inhibit viral envelope fusion and neutralize pore-forming bacterial toxins (PFTs).

Testing Partners: CRO
Hub C • NSF STTR Phase I

Green scCO2 Biomanufacturing

Supercritical CO2 refining at 69–70 MPa coupled with heterologous yeast feruloyl esterase (FAE) biocatalysis for high-purity, continuous phytosterol production.

Testing Partners: Supercritical Process Engineering Core
// USDA NIFA SBIR Phase I • Topic Area 8.2

Dual-Action Crop Protection:
Fungicide + Insecticide.

FOA: USDA-NIFA-SBIR-001001
Program Area: Plant Production & Protection
Target 1 • Phytopathogenic Fungi

Metagenomic Hyphal Suicide

  • Magnaporthe oryzae (Rice Blast)
  • Phakopsora pachyrhizi (Soybean Rust)
  • Botrytis cinerea (Gray Mold)
  • Fusarium oxysporum (Wilt)
EC50 ≤ 5.0 μM • ΔGbind ≤ -14.0 kcal/mol
Target 2 • Pest Insects

Sterol Auxotrophy & Molting Arrest

Ingested cycloartane sterols competitively bind midgut sterol transporters (SCP-2, NPC1b) and insect apoptotic regulators (Debcl/Buffy), triggering ecdysis failure.

  • Spodoptera frugiperda (Fall Armyworm)
  • Aphis gossypii (Melon Aphid)
  • Diabrotica virgifera (Corn Rootworm)
  • Midgut Epithelial Apoptosis
LC50 ≤ 10 μM • ΔGbind ≤ -14.85 kcal/mol
Target 3 • Crop Phytotoxicity

100% Host Crop Safety

Molecular docking against host plant cycloartenol synthases confirms zero steric engagement, ensuring complete crop seedling and yield safety without foliage burn.

  • Zero Steric Engagement
  • Rice & Soybean Seedling Safety
  • EPA Biorational MRL Exemption
  • 100% Biodegradable Carrier
Differential Affinity ΔΔG ≥ +12.0 kcal/mol
// Closed-Loop Formulation Engineering

The [C3G :: Ferulate]
π-π Photoprotective Stack.

Natural γ-oryzanol from domestic rice bran occurs as a ferulic acid ester of cycloartenol. Continuous supercritical CO2 refining followed by heterologous feruloyl esterase (FAE) biocatalysis cleanly liberates active Cycloartanol alongside free Ferulic Acid.

Rather than discarding the ferulate co-product, our closed-loop process co-formulates it with Cyanidin-3-Glucoside (C3G, purple rice anthocyanin) to form an intermolecular π-π stacked photoprotective & plant defense complex. Free Ferulic Acid serves as a potent endogenous elicitor—activating phenylalanine ammonia-lyase (PAL), reinforcing plant cell wall lignification, and priming Systemic Acquired Resistance (SAR) to synergize with the primary phytosterol active.

UV-B Stabilization
Absorbs 310–350 nm UV-B, preventing foliage photo-degradation.
SAR Defense Elicitor
Activates PAL enzymes, driving cell wall lignification & SAR priming.
Rain-Fast Traversal
Contact angle <45° for rapid waxy cuticle penetration.

Foliage Micellar Spray Composition

Active Engine (150 mg)
Cycloartanol / Saturated 24-MCA
Hyphal Suicide + IGR
Photoprotective & SAR Stack (50 mg)
[C3G :: Ferulate] Intermolecular Stack
UV-B Shield + SAR Elicitor
Biodegradable Shell (37.5 mg)
Rice Wax & Lecithin Micellar Shell
Rain-Fast Cuticle Traversal
100% Synthetic Residue Free • Organic Farming Compatible • Zero-Waste Biorefinery
// Intermolecular π-π Stacking Geometry (310-350 nm UV-B Absorbance)
C3G π-π stack (3.4 Å) FA UV-B Shield SAR Elicitation PAL Enzyme Activation
// Active Research Pipeline & Patent Stack

Active Platform Programs.
Broad Multi-Target Coverage.

to22s Bio-Systems is actively researching and validating our systems pharmacology platform across rare hematologic cancers, oncoviral malignancies, broad agricultural crop protection, and waveform supercritical biomanufacturing. Protected by our proprietary patent portfolio (Patents A01–A27), our platform is open to field co-development and licensing interest.

// ONCOLOGY & RARE MALIGNANCIES Patents A01–A06

Hematologic Malignancies & Resistance

Targeting Bcl-2 (α5–α8) to overcome G101V and D103Y clinical resistance mutations.

// Active Malignancy Targets:
  • MV4-11 (AML)
  • HL-60 (AML)
  • MEC-1 (CLL)
  • NCI-H69 (SCLC)
Mechanism: G101V Allosteric Resiliency
// ONCOVIRAL CANCERS & DECOYS Patents A19–A24

Viral Oncoprotein & Decoy Neutralization

Neutralizing viral anti-apoptotic decoys (BHRF1, vBcl-2) while modulating host cell membrane lipid raft entry portals (ABCA2, NPC1) against viral envelope fusion.

// Active Oncoviral Targets:
  • Raji / Daudi (EBV+ BHRF1)
  • C666-1 (EBV+ Carcinoma)
  • BC-3 / BCBL-1 (KSHV+ vBcl-2)
  • Host Lipid Raft Fusion Shield
Mechanism: Viral Decoy Neutralization
// BROAD AGRICULTURAL BIOSECURITY Patents A12, F25

Crop Protection & Biorational Elicitation

Dual-action bio-identical phytosterol foliage elicitor driving fungal hyphal suicide and insect molting arrest across major row crops and specialty fruits.

// Active Crop & Pathogen Categories:
  • Rice Blast (M. oryzae)
  • Soybean Rust (P. pachyrhizi)
  • Gray Mold (B. cinerea)
  • Fall Armyworm (S. frugiperda)
Mechanism: Hyphal Suicide + Ecdysis Arrest
// BIOMANUFACTURING & EXTRACTION Patents A27, WDSE

Yeast Fermentation & Waveform scCO2

Stabilizes yeast vacuolar membranes (S. cerevisiae) preventing autolysis during high-density fermentation, and Waveform-Driven Supercritical Electrostatic Extraction.

// Active Process Stack:
  • S. cerevisiae Autolysis Shield
  • Vacuolar VMP Stabilization
  • Waveform scCO2 (WDSE 70 MPa)
  • Electrostatic Deposition
Mechanism: WDSE + Autolysis Prevention
// Institutional Research & Testing Core

Academic Partnerships & Subaward Infrastructure.

APPLICANT SBC

to22s Bio-Systems, Inc.

Safety Harbor, FL

PI management, OpenMM explicit-solvent MD simulations, platform architecture & target validation.

FORMULATION CORE

Process Engineering Core

University Chemical Engineering Core

Supercritical scCO2 bioprocess extraction, micellar foliage spray formulation, particle sizing.

ANALYTICAL CORE

Mass Spectrometry & NMR Core

University Analytical Instrumentation Core

High-resolution Agilent LC-MS QToF, NMR cyclopropane structural verification (δ 0.33, 0.55).

AGRICULTURAL TESTING

UF/IFAS GCREC Core

Plant Pathology & Entomology

Land-grant testing core executing fungal hyphal suicide panels and insect molting arrest bioassays.

// Partner & Investor Diligence

Request Executive Proposal Package.

Access our clean, non-markdown Executive Summaries, Phase I Specific Aims, Phase II computational binding trajectory datasets, and patent claim dossiers.