Vivoryon Therapeutics N.V. announced detailed results of the completed parallel group, dose-finding part of its European Phase 2b study VIVIAD (NCT04498650). The data were presented at the Alzheimer's Association International Conference (AAIC) in San Diego in a poster presentation by Dr. Michael Schaeffer, Vivoryon's CBO. The presentation titled "VIVIAD, A Phase 2b Study Investigating Varoglutamstat in Patients with MCI and Mild AD: Dose Selection and Preliminary Safety Results" (poster P1-403, abstract 69290) included data that led to the independent Data Safety Monitoring Board's (DSMB) decision to select the highest dose investigated in the study (600 mg twice daily (BID)) as the final dose to be administered in the second part of the study.

All data remain blinded outside the DSMB. The safety data showed that varoglutamstat was well tolerated with only 14% of overall reported adverse events (AEs) considered to be potentially related to study treatment. All of the AEs were gastrointestinal, general, or related to the nervous system or skin.

Only four patients (2.2%) experienced serious AEs (SAEs) and only two patients (1.1%) discontinued the study. Both the total number of SAEs and the discontinuation rate were considerably lower than the respective numbers at the 800 mg BID varoglutamstat dose in Vivoryon's completed Phase 2a SAPHIR study (NCT02389413; 15% SAEs, 33% discontinuation), while retaining a similar level of target inhibition. A total of 110 (60.8%) patients reported treatment emergent adverse events (TEAEs), the majority of which (66%) was rated as not related to study treatment, with 20% not assessable.

Overall, most AEs were defined as mild (67%) or moderate (31%). The DSMB decision on the selected dose moving forward was based on data at the cut-off date, May 17, 2022. At data cut-off, 181 patients, 91 of which had completed the 24 weeks visit, had been randomized into the study at 600 mg, 300 mg or placebo.

Notably, no clinical signs of on-target toxicity, such as amyloid-related imaging abnormalities (ARIA), a side effect frequently reported for antibody-based AD treatment approaches, were observed. The safety results to date further substantiate the potential of varoglutamstat as a monotherapy and as an interesting component of combination therapies, including with anti-Abeta antibodies. Vivoryon is currently investigating this approach in preclinical studies, one of which will also be presented at AAIC on July 31, 2022 (poster P1-457, abstract 69050, see https://bit.ly/3JglkN9).

VIVIAD is actively enrolling patients at 22 study centers in five European countries and will continue to evaluate its primary and secondary outcome measures, which include multiple cognitive, safety and biomarker endpoints. Vivoryon remains on target to report final data for the study in the second half of 2023.