Michal Yahav, Head of CMC at Clexio Biosciences, introduced the OLAR platform, a novel gastric retention drug delivery system designed for continuous release of drugs in the gastrointestinal tract. The platform aimed to improve the bioavailability and pharmacokinetics of small molecule drugs with narrow absorption windows or short half-lives by providing sustained release for up to 24 hours.
Clexio Biosciences, a small biotech company, is focused on neurological and psychiatric conditions. The company had a team of 45, including MDs and PhDs, and four clinical-stage programmes. The most advanced programme, CLE-100, targeted major depressive disorder and was about to start an additional phase two study in the US. Other programmes included CLE-400 for neuropathic itch and CLE-500 and CLE-600, drug-device combinations for nasal administration.
The OLAR platform was an orally administered, non-invasive device that unfolded in the stomach after swallowing, enabling prolonged gastric retention and continuous drug release to enhance absorption and reduce plasma fluctuations. The platform was designed to be swallowed as a folded configuration inside a capsule, which unfolded into a triangular shape in the stomach, too large to pass the pylorus. The inner formulation gradually released the drug, and once fully dissolved, the platform disassembled into small parts for natural excretion.
The OLAR platform offered several innovative features, including gastric retention, mechanical strength to withstand stomach forces, and a timer mechanism controlled by tablet formulation dissolution. The platform parts were produced using hot melt extrusion and moulding, while tablets were prepared via standard pharmaceutical methods. The OLAR could convert immediate-release tablets into extended continuous release profiles, enabling better control of drug plasma levels, reduced peak concentration (Cmax), and sustained drug exposure (AUC).
In phase one studies, the OLAR platform demonstrated significant pharmacokinetic advantages compared to standard Sinemet IR. Imaging and retention studies confirmed OLAR's gastric retention for at least 8 hours, proper unfolding within 10 minutes, gradual tablet erosion, and disassembly with passage into the colon by 24 hours. The platform was being tested in Parkinson's disease patients for nocturnal symptom management, with ongoing clinical studies. The OLAR platform supported a plug-and-play approach, enabling partners to combine their tablet formulations with OLAR for improved drug performance.
