Periodic Reporting for period 1 - SAVEBRAIN (Proof of principle for a first in class neuroprotective therapy in stroke and other acute neurodegenerative conditions)
Période du rapport: 2018-04-01 au 2019-09-30
Stroke is the leading cause of disability and represents one of the largest unmet medical needs as only one drug is available for treatment. This drug is limited to the acute phase of stroke and dissolves clots that reduce blood flow to the brain. It is, however, only marginally effective, bears a high risk of fatal bleeding and has over 30 contraindications, which is why most stroke patients are not treated with it. We need a stroke drug that is broadly applicable, has few or no contraindications, bears no bleeding risk, reduces brain damage and improves brain function. In the course of my ERC-ADG RadMed I discovered a therapeutic approach that fulfils all of the above criteria and is also commercially innovative and rapidly applicable in the clinic. In the present PoC grant I proposed to repurpose drugs that are already registered but for a different indication than stroke and to enable its commercialization to ensure market entry and patient benefit. All three sub-goals were achieved. We performed an IP and FTO analysis to choose three optimal compounds. By combining them, I also reduce the risk of the frequent failure of single compounds in drug development. All three chosen compounds are strongly neuroprotective on their own; all target the same disease mechanism, yet at different positions and thereby potentiate each other, which increases the chance of therapeutic success in subsequent clinical studies, which are essential for commercialization. We were also able to lower the dose of each compound, which lowers the risk of possible side effects. This allowed us to develop two patent submissions. In preparation of a clinical trial, which for regulatory requirements has to have safety as primary outcome, we extended our small animal validation data by conducting a successful large animal safety study with two of the compounds that were suitable for administration in sheep. Moreover, through plasma biomarkers measured in biobank samples from stroke patients we narrowed down the ideal time-window up to which the drug combination is highly likely to be effective. Following a competitive analysis, our resulting business plan for commercial development will issue exclusive timed patent licences with milestones to a world-wide operating pharmaceutical company capable of conducting a full market entry and distribution.