Periodic Reporting for period 2 - EDVance (EDV2209 – a Paradigm shift in the treatment of stroke.)
Reporting period: 2023-01-01 to 2024-10-31
More than 13 M people are hit by stroke each year. Subarachnoid Haemorrhage (SAH) is a specific type of stroke, caused by bleeding into the space surrounding the brain. The short-term mortality rate is approximately 50%, and more than 50% of survivors make an incomplete recovery, enduring life-long neurological and cognitive impairment. SAH represents 5% of all strokes but affects people of all ages (with a peak at ~55 years), accounting for 25% of all productive life-years lost to all subtypes of stroke. The socioeconomic burden of SAH almost equals that of ischemic stroke, a condition 20 times more frequent than SAH. Despite the huge burden, healthcare systems, the society, and the economy, current drug therapies have little or no effect, and all attempts to develop new drugs have so far failed. With EDVance project, we will pursue clinical validation of EDV2209 and establish its safety and efficacy in SAH patients. Our aim is to develop a pharmacological treatment for SAH, based on a fundamentally different approach: EDV2209 reduces the upregulation of cerebrovascular contractile receptors that occurs after SAH, reducing vasoconstriction. By ensuring that the blood vessels remain open, brain cells are continuously supplied with oxygen and nutrients, which is vital to reduce tissue damage.
In 2021, prior to the current project, Edvince submitted the Clinical Trial Application for the first-in-man phase I/II clinical trial with EDV2209 in subarachnoid haemorrhage and received the necessary approvals from the Danish Medicines Agency (DKMA) and Ethics Committee. The first batch of investigational medicinal product ((IMP) was also produced and the new IMP batch was released to the site. The site was trained and qualified by our clinical CRO and greenlight was given in March 2022 where the first patient was enrolled in cohort 1 with a single low dose EDV2209. Cohort 1 with 3 patients all on low dose EDV2209 was completed whereafter the first dose conference by the Safety Committee (SC) was held. No adverse events related to the drug were reported. The SC therefore decided to double the dose in cohort 2 and split the planned cohort 2 with 8 patients at the highest single dose into one cohort of 4 patients with a medium single dose and one with 4 patients at the highest single dose. This amendment of the protocol was approved by DKMA and ethics committee. Cohort 2 (3 active, 1 placebo) with the medium single dose was thereafter completed. The SC found no adverse events related to the drug and decided to escalate to the highest dose in cohort 3. Cohort 3 (3 active, 1 placebo) was started where the first patients was recruited. The cohort 3 was subsequently completed with no signs of any safety concerns. The multiple dose group 4 (3 injections over the first 24 hours) was initiated in early 2024 again completed without signs of toxicity. The final multipel dose group 5 was initiated subsequently and was completed February 2025. This means an unfortunate delay according to the original plan. It is important to note that the recruitment of the 4 first cohorts (15 patients) was slower than in cohort 5 (12 patients) due to the fact that the next patients in the first cohorts can first be recruited 7 days after the patient patient has been dosed dosed as well as there was a safety committee approval efter each dose group. Nevertheless, as shown the recruitment in this rare patient population is difficult to predict and hence associated with risks of delays. Edvicne to risk mitigation for this for the Cohort 5 and opened a new clinical site to increase recruitment.
Based on Professor Edvinsson’s pioneering research and breakthrough discoveries, Edvince proposes a transforming new treatment to the benefit of SAH patients and the society. EDV2209 is a small molecule that has convincingly been shown to inhibit the upregulation of contractile receptors, which, in the aftermath of SAH, cause blood vessel constriction and reduced blood supply to the brain (ischemia), causing cell death. The drug thus helps to keep the blood vessels in the brain open, allowing brain cells to receive oxygen and nutrients to prevent brain damage. Preclinical studies in an animal model of SAH have demonstrated that EDV2209 significantly improves functional outcome and reduces inflammatory response after an SAH event. With only 1 drug available for SAH treatment, EDV2209’s high potential to treat this disease has been acknowledged by the regulatory authorities in the EU and USA, who have granted it with Orphan Drug Designation.
The project is aimed at demonstrating the safety of EDV2209 in humans and to show how the drug can reduce brain damage after SAH. The potential is to be the first drug to reduce brain damage and help survivors back to a normal life. After a successful outcome of the clinical trial we will identify a a competent CNS partner with sufficient financial, technical and commercial capacity. Thanks to the significant results we have initiated a significant business development activity. We have therefore a systematic plan onboard to execute the various commercial initiatives. We are also discussing with brokers and investment banks who can assist us in identifying the right partner(s) and secure an attractive license agreement. We explore to extend the orphan drug designation to Japan where SAH is more prevalent than in Europe and the US. We are currently working on new inventions to strengthen our IP protection and increase the commercial potential. To this end we have filed a formulation patent in October 2024 enabling a better stability and potential for a simpler administration. Furthermore, we have another early stage project (outside the scope of this project) based on the same biological rationale and with an intravenous administration to treat broader stroke indications. The project will be continued by financing by private and specilallist investors. We have now started a solid investor relation effort.
The project is aimed at demonstrating the safety of EDV2209 in humans and to show how the drug can reduce brain damage after SAH. The potential is to be the first drug to reduce brain damage and help survivors back to a normal life. After a successful outcome of the clinical trial we will identify a a competent CNS partner with sufficient financial, technical and commercial capacity. Thanks to the significant results we have initiated a significant business development activity. We have therefore a systematic plan onboard to execute the various commercial initiatives. We are also discussing with brokers and investment banks who can assist us in identifying the right partner(s) and secure an attractive license agreement. We explore to extend the orphan drug designation to Japan where SAH is more prevalent than in Europe and the US. We are currently working on new inventions to strengthen our IP protection and increase the commercial potential. To this end we have filed a formulation patent in October 2024 enabling a better stability and potential for a simpler administration. Furthermore, we have another early stage project (outside the scope of this project) based on the same biological rationale and with an intravenous administration to treat broader stroke indications. The project will be continued by financing by private and specilallist investors. We have now started a solid investor relation effort.