Vivoryon Therapeutics N.V. provided an update on its operations and the clinical development progress of the Company's lead candidate, varoglutamstat (PQ912), a small molecule medicine in development to treat Alzheimer's disease (AD). Varoglutamstat is currently being investigated in two Phase 2 clinical trials in patients living with early and mild AD: the European Phase 2b VIVIAD study and the recently initiated Phase 2a/b VIVA-MIND study in the U.S. In 2020, Vivoryon initiated VIVIAD, a Phase 2b study in Europe designed to investigate the safety, tolerability and efficacy of varoglutamstat compared to placebo over 48 to 96 weeks of treatment in 250 patients suffering from mild cognitive impairment (MCI) and mild AD. Continuously meeting all recruitment objectives despite the ongoing global pandemic, the study is enrolling patients as planned. In the ongoing parallel group dose finding part of the study, the first 90 participants are randomized 1:1:1 between 300 mg varoglutamstat, 600 mg varoglutamstat, and placebo and are twice daily treated for 24 weeks, followed by an interim safety analysis to select the final dose. Patients will then be treated for a minimum of 48 weeks on the selected dose twice daily vs. placebo. A composite Neuropsychological Test Battery (NTB) score will be administered throughout the study in order to assess cognitive efficacy. Additionally, a set of exploratory read-outs including cognitive tests, functional electroencephalogram (EEG), magnetic resonance imaging (MRI) assessments and the analysis of new molecular biomarkers in the cerebrospinal fluid (CSF) will be used to evaluate the compound's effect on disease pathology. Secondary endpoints include long-term safety and tolerability of varoglutamstat and its efficacy on brain activity, cognition and activities of daily living. To avoid delays in recruitment and as a reaction to COVID-19-related patient and staff protection policies implemented at German study sites, Vivoryon is planning to more than double the originally planned number of study centers. Additional sites in Germany and the Netherlands have already been opened and the Company anticipates to initiate up to 10 additional sites in Spain and Poland over the next weeks. Vivoryon is also sponsoring VIVA-MIND, a complementary Phase 2a/b trial in the U.S., which is coordinated by the Alzheimer's Disease Cooperative Study (ADCS) at the University of California San Diego (UCSD) School of Medicine and supported by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH) with a $15 million grant (NIA award number R01AG061146). VIVA-MIND was initiated in September 2021. The study seeks to enroll 180 patients into the Phase 2a adaptive dose-finding part and is ongoing, with one site now approved to screen participants and a group of another eight sites having secured regulatory approval. The initial Phase 2a adaptive dose-finding part will investigate a range of 150 mg to 600 mg twice daily. An interim futility analysis is planned for the first half of 2023. If predefined criteria are fulfilled, the trial will pass a stage-gate into the Phase 2b part, enrolling an additional 234 patients treated at the selected dose for at least 72 weeks, with a total of 414 patients being treated on stable doses of varoglutamstat for 18 months. The primary endpoint for this study is CDR-SB (clinical dementia rating scale - sum of boxes), an established approvable endpoint measuring a combination of cognitive abilities and activities of daily living. Prior to VIVIAD and VIVA-MIND, Vivoryon completed two clinical studies of varoglutamstat. A first-in-human Phase 1 trial conducted in 205 healthy volunteers showed that varoglutamstat was well-tolerated and also provided important information on dose response and target occupancy. The subsequent first-in-patient Phase 2a trial, SAPHIR, enrolled 120 patients suffering from early AD achieved not only the primary objective of obtaining important safety information, but also showed evidence of the disease-modifying activity of varoglutamstat. The study delivered encouraging results after only 12 weeks of treatment, showing evidence of improving not only pathological hallmarks, but also synaptic function and connectivity, cognition, memory and attention in AD patients. The Company based the selection of endpoints for both VIVIAD and VIVA-MIND on the outcome of SAPHIR as well as the regulatory draft guidelines for AD drug development by FDA and EMA introduced in 2018. By combining these two studies, Vivoryon intends to assess if potential cognitive improvements in patients in the European VIVIAD trial will translate into an established clinical endpoint in patients in the U.S. VIVA-MIND trial. Vivoryon is committed to efficiently moving varoglutamstat through clinical development. To ensure sustainable study drug supply for the VIVA-MIND U.S. study, Vivoryon has decided to expand its manufacturing capabilities for production of active pharmaceutical ingredient (API) by initiating a second line of manufacturing with an additional partner. This will increase the total number of manufacturing sites for varoglutamstat to three on two different continents, providing supply for VIVA-MIND beyond the ongoing Phase 2a adaptive dose finding part, as well as for potential future studies in other geographies, with the added benefit of increasing flexibility to react to global challenges such as the ongoing pandemic. To account for the costs associated with these measures, Vivoryon is updating its financial guidance. According to current planning and estimates, the Company now expects a cash reach until mid-2022. A detailed update on anticipated working capital requirements and associated potential financing activities as well as resulting timelines will be given in the context of Vivoryon's regular filings. The commencement of the VIVA-MIND clinical study demonstrates Vivoryon's commitment to the U.S. patients and market. It is Vivoryon's intention to establish a U.S. listing on Nasdaq. To this effect, Vivoryon recently confidentially submitted a draft registration statement on Form F-1 to the U.S. Securities and Exchange Commission for purposes of a potential initial public offering of its common shares in the United States. While the timing of the transaction, if any, is uncertain and will depend on market conditions, among other things, Vivoryon expects the size and other characteristics of the transaction to be such that an approved EU prospectus, in addition to the U.S. registration statement on Form F-1, would not be required.