In RP1, significant progress was made in optimizing the upstream and downstream production processes to be easily scalable, meet regulatory requirements and support planned (pre-) clinical activities.
We completed the optimization of the downstream production process, increasing the original yield fivefold, higher purity of TBSV.pLip. better physo-chemical characteristic of the final product, faster operational timelines, and a scalable production workflow suitable for GMP manufacturing. A batch intended for toxicology studies in a GMP-like environment has been produced, ensuring compliance with the standards required for preclinical testing. In parallel, the facility layout and procedures were redesigned to align with GMP regulations and to further improve process performance. Key actions completed include: recruitment of a Qualified Person and a QA Manager; execution of a gap assessment for full Quality Management System (QMS) implementation, including main QMS procedures, with 12 SOPs already implemented.
On technical side, progress continued in the execution and refinement of the toxicology program, including an in vitro phase and an in vivo one. The in vitro phase has been fully completed, while the animal phase is on goind. We are applying for Scientific Advice with AEMPS (Spain), proposing to conduct the toxicology program in a single animal species.
The toxicology study design includes a Part A, an initial in vitro phase aimed at evaluating the effects of the particles on PBMCs from healthy donors and THP 1 cells, focusing on cell viability and on the induction of pro inflammatory cytokines. The results demonstrated the absence of toxic and inflammatory effects, confirming the actual safety profile of the product. Part B involves the in vivo toxicology study., which has been submitted for scientific advice, for approval to perfom the study in a single animal species, in accordance with the 3Rs principle and regulatory expectations.
During this period, we defined a clear regulatory strategy for the clinical development of our product, and the Phase 1 clinical trial design has been completed. All preparatory activities for study initiation have been finalized, including the definition of the study protocol, identification of key stakeholders, scientific advice with AEMPS, and an audit of the selected clinical site.
