Intracerebral Hemorrhage (ICH) remains one of the most devastating forms of stroke, affecting over 350,000 patients annually across the EU, USA, and Japan. It results from the rupture of small cerebral arteries and subsequent blood accumulation within the brain, forming a hematoma that exerts mass effect and triggers secondary injury. Current management is limited to intensive care and monitoring; no approved pharmacological treatment exists. Consequently, 75% of ICH patients either die or suffer from severe lifelong disability.
Previous clinical trials aiming to stop bleeding or protect brain tissue have failed to improve outcomes, and surgical evacuation of deep hematomas remains ineffective. However, the MISTIE III trial has provided valuable insights: while it did not demonstrate benefit for alteplase, it revealed a clear correlation between the extent of hematoma evacuation and functional recovery, validating hematoma volume reduction as a therapeutic target.
Building on these insights, Op2Lysis is developing O2L-001, a first-in-class treatment designed to safely and effectively remove intracerebral hematomas. O2L-001 is derived from the company’s proprietary NANOp2Lysis® platform, a deep-tech system enabling the stabilization of active enzymes through reversible precipitation into solid nanoparticles, followed by encapsulation in tailored carriers for targeted, controlled delivery.
O2L-001 is a locally administered hydrogel formulation containing OptPA, a novel engineered thrombolytic agent with enhanced fibrinolytic activity and an improved safety profile. After minimally invasive catheter injection, the formulation gels at body temperature, ensuring prolonged, localized release within the hematoma.
Key features of O2L-001 include:
• Ease of use: simplified, once-daily local administration
• Efficacy: superior thrombolytic activity in clinically relevant translational models compared to alteplase
• Safety: reduced risk of bleeding and neurotoxicity
The OP2DRAIN project aims to (i) optimize and scale up the manufacturing process for both the drug substance (OptPA) and the drug product (O2L-001); (ii) establish validated analytical methods for product characterization and release; and (iii) produce GMP-like batches for toxicology studies.
A subsequent objective is to conduct preclinical toxicology studies to determine the maximum tolerated dose (MTD) and no-observed-adverse-effect level (NOAEL), supporting the future IMPD/IND submission and authorization for first-in-human clinical trials.
In parallel, the project engages with regulatory authorities (EMA and FDA) to align the development plan with international standards, de-risk the translational pathway, and secure early scientific guidance in preparation for the clinical phase and Series A financing.
