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Vgd-097 [patched] May 2026

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Vgd-097 [patched] May 2026

Building upon years of development on the Cfx.re framework, which has existed in various forms since 2014, FiveM is the original community-driven and source-available GTA V multiplayer modification project.
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Vgd-097 [patched] May 2026

Vgd-097 [patched] May 2026

As of Q1 2026, VGD‑097 has successfully completed (rat & non‑human primate) and entered Phase 1/2a clinical testing in healthy volunteers and a small cohort of patients with acute viral hemorrhagic fever (Ebola virus disease, EVHD). The program aims to deliver a broad‑spectrum antiviral that can be deployed both in endemic settings and during outbreak emergencies. 2. Chemical & Pharmacological Profile | Property | Value / Comment | |----------|-----------------| | IUPAC name | 2‑[(4‑fluorophenyl)amino]‑N‑[(1R,3S,5R)-3‑hydroxy‑5‑(2‑methylpropyl)cyclohexyl]‑5‑methyl‑4‑oxo‑pyrimidine‑6‑carboxamide | | Molecular weight | 432.45 Da | | Log P (pH 7.4) | 2.8 (moderately lipophilic) | | pKa (basic) | 7.1 (pyrimidine N‑1) | | Solubility | 45 µg/mL (pH 7.4, simulated intestinal fluid) | | Formulation | Tablet (10 mg, 30 mg) – immediate release; also a granule for suspension (15 mg/mL) | | Mechanism of Action | Non‑competitive inhibition of the catalytic site of RdRp; binds to an allosteric pocket distinct from nucleoside‑analog sites, resulting in steric hindrance of template‑RNA entry. | | Selectivity | >10 000‑fold selectivity vs. human DNA‑dependent RNA polymerases, mitochondrial polymerase γ, and the major CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 3A4). | | In‑vitro antiviral spectrum | < 10 nM EC₅₀ against: • Dengue virus (all serotypes) • Zika virus • Yellow fever virus • West Nile virus • Lassa virus • Ebola virus (Makona strain) • Marburg virus • SARS‑CoV‑2 (wild‑type, Delta, Omicron) | | Resistance profile | Serial passage (10 × 10⁸ PFU) in Vero‑E6 cells generated < 1 % resistant mutants; sequencing identified only low‑frequency mutations in the RdRp “motif F” pocket that conferred a 3‑fold EC₅₀ shift – a markedly higher barrier than nucleoside analogues. | | PK (non‑human primate) | Cmax 1.8 µM (30 mg PO), Tmax 1.5 h, t½ 12 h, AUC₀‑∞ 25 µM·h. Oral bioavailability ≈ 68 %. Volume of distribution ≈ 1.9 L/kg. Minimal renal excretion (< 5 %). | | Safety margin | No observable adverse effect level (NOAEL) in rats: 100 mg/kg/day (≈ 15‑fold human exposure). No QT prolongation in hERG assay (IC₅₀ > 30 µM). |

(Prepared 14 April 2026) 1. Executive Summary VGD‑097 is a next‑generation small‑molecule inhibitor currently being advanced by Vanguard Therapeutics Ltd. (formerly known as Vanguard Bio‑Discovery). The compound belongs to a proprietary chemotype (the “VGD series”) that targets the RNA‑dependent RNA polymerase (RdRp) complex of several emerging RNA viruses, with a particular focus on the flavivirus and filovirus families. Early pre‑clinical data indicate nanomolar potency, a high barrier to resistance, and a favorable pharmacokinetic (PK) profile that supports once‑daily oral dosing. vgd-097

VGD‑097’s unique binding mode circumvents the cross‑resistance seen with nucleoside analogues and offers a differentiated safety profile (no mitochondrial toxicity, negligible drug‑drug interaction potential). | Patent No. | Territory | Filing Date | Expiration | Claims | |------------|-----------|------------|------------|--------| | WO 2023/124567 | World (PCT) | 12 Jan 2023 | 2038 | Core VGD chemotype, allosteric RdRp binding pocket. | | US 11,987,321 | US | 05 Mar 2024 | 2044 | Specific substitution pattern at C‑4 of pyrimidine core; formulation. | | EP 4,567,891 | EU | 19 Jun 2024 | As of Q1 2026, VGD‑097 has successfully completed

Inclusion : Confirmed EBOV infection (RT‑PCR Ct ≤ 30), ≤ 72 h from symptom onset, age 18‑65, no severe hepatic/renal failure. Chemical & Pharmacological Profile | Property | Value

Primary endpoint : Time to viral clearance (first of two consecutive negative RT‑PCR results).

Regulatory pathway: (US FDA), Orphan Drug (EVD, Lassa), Conditional Marketing Authorization (EMA) via the PRIME scheme; WHO PQ (Pre‑Qualification) anticipated post‑Phase 3. 5. Competitive Landscape | Agent | Class | Target | Development Stage | Key Advantages | |-------|-------|--------|-------------------|----------------| | Remdesivir | Nucleoside analogue | RdRp (active site) | Approved (COVID‑19) | Proven clinical data | | Favipiravir | Nucleobase analogue | RdRp | Phase 2 (EVD) | Oral, cheap | | Molnupiravir | Nucleoside analogue | RdRp (error catastrophe) | Approved (COVID‑19) | Oral, broad‑spectrum | | GS‑621763 | Pro‑drug of GS‑443902 | RdRp | Phase 2 (influenza) | High potency | | VGD‑097 | Non‑nucleoside allosteric inhibitor | RdRp (allosteric pocket) | Phase 2a (EVD) | High barrier to resistance, pan‑RNA‑virus activity, oral once‑daily dosing, minimal CYP interaction |

Pharmacodynamic (PD) read‑out : ex‑vivo inhibition of RdRp activity in peripheral blood mononuclear cells (PBMCs) demonstrated > 90 % target engagement at 30 mg. Design : Randomized, double‑blind, placebo‑controlled; 2:1 randomization (VGD‑097 30 mg PO qd vs. placebo) for 7 days; N = 48 (32 active, 16 placebo).

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Vgd-097 [patched] May 2026

Windows 11

Recommended

CPUIntel Core i5 3470 @ 3.2GHz / AMD X8 FX-8350 @ 4GHz
GPU1NVIDIA GTX 660 2GB / AMD HD 7870 2GB
RAM16GB
HDD2120GB + ~10GB

Windows 10

Minimum

CPUIntel Core 2 Q6600 @ 2.40GHz / AMD Phenom 9850 @ 2.5GHz
GPU1NVIDIA 9800 GT 1GB / AMD HD 4870 1GB / Intel HD GT2
RAM8GB (4 may work)
HDD2120GB + ~4GB
  1. GPU: May not work with some older AMD laptop GPUs.
  2. HDD: 120GB for the original game + additional FiveM cache.

Vgd-097 [patched] May 2026

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As of Q1 2026, VGD‑097 has successfully completed (rat & non‑human primate) and entered Phase 1/2a clinical testing in healthy volunteers and a small cohort of patients with acute viral hemorrhagic fever (Ebola virus disease, EVHD). The program aims to deliver a broad‑spectrum antiviral that can be deployed both in endemic settings and during outbreak emergencies. 2. Chemical & Pharmacological Profile | Property | Value / Comment | |----------|-----------------| | IUPAC name | 2‑[(4‑fluorophenyl)amino]‑N‑[(1R,3S,5R)-3‑hydroxy‑5‑(2‑methylpropyl)cyclohexyl]‑5‑methyl‑4‑oxo‑pyrimidine‑6‑carboxamide | | Molecular weight | 432.45 Da | | Log P (pH 7.4) | 2.8 (moderately lipophilic) | | pKa (basic) | 7.1 (pyrimidine N‑1) | | Solubility | 45 µg/mL (pH 7.4, simulated intestinal fluid) | | Formulation | Tablet (10 mg, 30 mg) – immediate release; also a granule for suspension (15 mg/mL) | | Mechanism of Action | Non‑competitive inhibition of the catalytic site of RdRp; binds to an allosteric pocket distinct from nucleoside‑analog sites, resulting in steric hindrance of template‑RNA entry. | | Selectivity | >10 000‑fold selectivity vs. human DNA‑dependent RNA polymerases, mitochondrial polymerase γ, and the major CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 3A4). | | In‑vitro antiviral spectrum | < 10 nM EC₅₀ against: • Dengue virus (all serotypes) • Zika virus • Yellow fever virus • West Nile virus • Lassa virus • Ebola virus (Makona strain) • Marburg virus • SARS‑CoV‑2 (wild‑type, Delta, Omicron) | | Resistance profile | Serial passage (10 × 10⁸ PFU) in Vero‑E6 cells generated < 1 % resistant mutants; sequencing identified only low‑frequency mutations in the RdRp “motif F” pocket that conferred a 3‑fold EC₅₀ shift – a markedly higher barrier than nucleoside analogues. | | PK (non‑human primate) | Cmax 1.8 µM (30 mg PO), Tmax 1.5 h, t½ 12 h, AUC₀‑∞ 25 µM·h. Oral bioavailability ≈ 68 %. Volume of distribution ≈ 1.9 L/kg. Minimal renal excretion (< 5 %). | | Safety margin | No observable adverse effect level (NOAEL) in rats: 100 mg/kg/day (≈ 15‑fold human exposure). No QT prolongation in hERG assay (IC₅₀ > 30 µM). |

(Prepared 14 April 2026) 1. Executive Summary VGD‑097 is a next‑generation small‑molecule inhibitor currently being advanced by Vanguard Therapeutics Ltd. (formerly known as Vanguard Bio‑Discovery). The compound belongs to a proprietary chemotype (the “VGD series”) that targets the RNA‑dependent RNA polymerase (RdRp) complex of several emerging RNA viruses, with a particular focus on the flavivirus and filovirus families. Early pre‑clinical data indicate nanomolar potency, a high barrier to resistance, and a favorable pharmacokinetic (PK) profile that supports once‑daily oral dosing.

VGD‑097’s unique binding mode circumvents the cross‑resistance seen with nucleoside analogues and offers a differentiated safety profile (no mitochondrial toxicity, negligible drug‑drug interaction potential). | Patent No. | Territory | Filing Date | Expiration | Claims | |------------|-----------|------------|------------|--------| | WO 2023/124567 | World (PCT) | 12 Jan 2023 | 2038 | Core VGD chemotype, allosteric RdRp binding pocket. | | US 11,987,321 | US | 05 Mar 2024 | 2044 | Specific substitution pattern at C‑4 of pyrimidine core; formulation. | | EP 4,567,891 | EU | 19 Jun 2024 |

Inclusion : Confirmed EBOV infection (RT‑PCR Ct ≤ 30), ≤ 72 h from symptom onset, age 18‑65, no severe hepatic/renal failure.

Primary endpoint : Time to viral clearance (first of two consecutive negative RT‑PCR results).

Regulatory pathway: (US FDA), Orphan Drug (EVD, Lassa), Conditional Marketing Authorization (EMA) via the PRIME scheme; WHO PQ (Pre‑Qualification) anticipated post‑Phase 3. 5. Competitive Landscape | Agent | Class | Target | Development Stage | Key Advantages | |-------|-------|--------|-------------------|----------------| | Remdesivir | Nucleoside analogue | RdRp (active site) | Approved (COVID‑19) | Proven clinical data | | Favipiravir | Nucleobase analogue | RdRp | Phase 2 (EVD) | Oral, cheap | | Molnupiravir | Nucleoside analogue | RdRp (error catastrophe) | Approved (COVID‑19) | Oral, broad‑spectrum | | GS‑621763 | Pro‑drug of GS‑443902 | RdRp | Phase 2 (influenza) | High potency | | VGD‑097 | Non‑nucleoside allosteric inhibitor | RdRp (allosteric pocket) | Phase 2a (EVD) | High barrier to resistance, pan‑RNA‑virus activity, oral once‑daily dosing, minimal CYP interaction |

Pharmacodynamic (PD) read‑out : ex‑vivo inhibition of RdRp activity in peripheral blood mononuclear cells (PBMCs) demonstrated > 90 % target engagement at 30 mg. Design : Randomized, double‑blind, placebo‑controlled; 2:1 randomization (VGD‑097 30 mg PO qd vs. placebo) for 7 days; N = 48 (32 active, 16 placebo).