Vgd-097 |link| -

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

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). | vgd-097

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 | Inclusion : Confirmed EBOV infection (RT‑PCR Ct ≤