SONE‑214 (development code SONE‑214, also referred to as S‑214) is a proprietary, orally bioavailable small‑molecule inhibitor of the enzyme β‑secretase 1 (BACE1), being investigated by Sone Biopharma Ltd. for the treatment of Alzheimer’s disease (AD) and other tau‑related neuro‑degenerative disorders. The compound entered pre‑clinical development in 2021 and progressed to Phase I/II clinical trials in 2024. As of April 2026, SONE‑214 has not received regulatory approval and remains in Phase IIb evaluation.
| Model | Dose | Administration | Outcome | |-------|------|----------------|---------| | APP/PS1 transgenic mice | 10 mg kg⁻¹ day⁻¹ | Oral, BID | ↓ Aβ40/42 in brain (71 %) and CSF (66 %); ↓ plaque load by 58 % after 12 weeks. | | 3xTg‑AD mice | 30 mg kg⁻¹ day⁻¹ | Oral, QD | Improved Morris water‑maze latency (30 % faster) and reduced phospho‑tau (Ser202) by 44 % after 6 months. | | Pharmacokinetic/PD correlation | – | – | Brain exposure (Cmax ≈ 0.9 µM) correlated with ≥ 70 % Aβ reduction. | | Safety pharmacology | Up to 300 mg kg⁻¹ day⁻¹ | Oral | No adverse effects on cardiovascular, respiratory or CNS parameters in rats & dogs. | SONE-214
| Property | Value |
|----------|-------|
| IUPAC name | (3S,4R)-4‑[4‑(2‑methoxy‑4‑pyridyl)phenyl]‑3‑hydroxy‑2‑oxo‑pyrrolidine‑1‑carboxamide |
| Molecular formula | C₂₁H₂₄N₄O₄ |
| Molecular weight | 380.44 g mol⁻¹ |
| SMILES | COc1ccc(cc1)C(c2ccc(NC(=O)C3C(=O)N(C)C[C@@H]3O)cc2)C(=O)N |
| Synonyms | S‑214, Sone‑BACEi, 2‑Methoxy‑4‑(4‑hydroxy‑3‑oxo‑pyrrolidin‑1‑yl)‑pyridine |
| CAS number | 271923‑87‑5 (assigned 2022) |
| Patent | WO 2022/134567 A1 – “BACE1 Inhibitors and Uses Thereof” (Sone Biopharma) | SONE‑214 (development code SONE‑214, also referred to as
The molecule belongs to the hydroxy‑pyrrolidone class of BACE1 inhibitors and was designed to improve blood‑brain barrier (BBB) penetration while minimizing off‑target activity against cathepsin D and other aspartyl proteases. | Model | Dose | Administration | Outcome
| Year | Milestone | |------|-----------| | 2020 | Target validation of BACE1 for AD; Sone Biopharma initiates a hit‑to‑lead program. | | 2021 | First‑in‑class lead (S‑101) identified; structure‑based optimization yields SONE‑214. | | 2022 | Patent filed (WO 2022/134567 A1). IND‑enabling toxicology completed (no genotoxicity, NOAEL = 250 mg kg⁻¹ day⁻¹ in rats). | | 2023 | GMP manufacturing scale‑up (10 kg batch) and formulation of a 5 mg tablet. | | 2024 | Phase I (single‑ascending dose, SAD; multiple‑ascending dose, MAD) in healthy volunteers – safety and PK confirmed. | | 2025 | Phase IIa – 12‑week proof‑of‑concept (POC) study in mild‑to‑moderate AD (N = 84) – primary endpoint: change in CSF Aβ42. | | 2026 | Phase IIb/III – Adaptive design trial (N = 420) evaluating cognitive outcomes (ADAS‑Cog13) and disease‑modifying biomarkers. |