Vivoryon Therapeutics highlights progress of lead candidate varoglutamstat in Alzheimer’s disease

The Phase 2 trials of the N3pE-Amyloid-targeting small molecule continue to show encouraging safety data

Dr. Ulrich Dauer, CEO von Vivoryon Therapeutics N.V.

Dr. Ulrich Dauer, CEO of Vivoryon Therapeutics N.V.

“The growing evidence supporting varoglutamstat as a potential novel medicine to treat Alzheimer’s disease with a favorable safety profile is incredibly encouraging, particularly as we think about its positioning within the broader treatment landscape.“

Dr. Ulrich Dauer, CEO of Vivoryon Therapeutics N.V.

IZB alumnus Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, provided a clinical development update highlighting the progress of its unique N3pE-amyloid-targeting small molecule varoglutamstat in Alzheimer’s disease (AD) in mid-July. The update included data presented at the Alzheimer’s Association International Conference (AAIC), held July 16-20, 2023, in Amsterdam, the Netherlands. The Company is also providing updates from the ongoing clinical Phase 2 studies VIVIAD in Europe and VIVA-MIND in the U.S.

“In light of the renewed momentum within the Alzheimer’s disease drug development space with the first full approval of a potentially disease-modifying medication, I am particularly encouraged by the opportunity to be testing varoglutamstat within our Phase 2 Proof-of-Concept trial,” commented Dr. Howard Feldman, Professor of Neurosciences and Director of the ADCS at UC San Diego School of Medicine, and the VIVA-MIND study director. “As a small molecule alternative that can conveniently be taken at home and potentially without comparable risks of brain swelling and bleeding seen with amyloid lowering monoclonal antibodies, varoglutamstat may hold significant advantages in safety and ease of use by patients.”

“As varoglutamstat continues to progress through clinical development, we are very pleased to report that VIVIAD’s independent Data Safety Monitoring Board has determined that the VIVIAD study can continue without modifications and no additional meetings will be required until the meeting scheduled at study completion,” added Dr. Ulrich Dauer, CEO of Vivoryon. “This is the first time varoglutamstat long-term safety data from patients suffering from Alzheimer’s disease with a treatment duration of more than a year and up to two years have been reviewed independently. Our path forward both from a clinical and regulatory perspective is promising and we see the outcomes of this meeting as an important point of validation for our approach. The growing evidence supporting varoglutamstat as a potential novel medicine to treat Alzheimer’s disease with a favorable safety profile is incredibly encouraging, particularly as we think about its positioning within the broader treatment landscape. We look forward to reporting on the final data, which we expect to read out in the first quarter of 2024. In tandem, given the excellent progress of VIVIAD, we have decided to initiate preparations for an open label extension study, which, following positive VIVIAD study outcome, could provide a long-term therapeutic option to patients who have been treated under VIVIAD or VIVA-MIND protocols.”

Varoglutamstat Clinical Program:
Varoglutamstat is a differentiated investigational small-molecule medicine in development to treat Alzheimer’s disease. It is currently being investigated in two large Phase 2 studies, VIVIAD (NCT04498650) in Europe and VIVA-MIND (NCT03919162) in the U.S., where it continues to show evidence of a favorable safety profile at the therapeutic dose of 600 mg twice daily (BID), a dose demonstrated to result in a target occupancy of nearly 90%.

Varoglutamstat is designed to prevent N3pE- Abeta formation, rather than aiming to clear existing plaques, making it an intervention upstream of other approaches such as monoclonal antibodies (mAbs). Through a second mode of action, varoglutamstat also modulates neuroinflammation via the CCL2 pathway, which, in turn, has an impact on tau pathology.

VIVIAD (NCT04498650) is a state-of-the-art Phase 2b study being conducted in Europe and designed to evaluate the safety, tolerability, and efficacy of varoglutamstat in 259 (final number of randomized participants) subjects with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD).

Data from AAIC 2023: P1-18 / P1-904 Poster #82642 – “VIVIAD, a Phase 2b Study Investigating Varoglutamstat in Patients with MCI or Mild AD: Analysis of Baseline Cognition Data.” These data demonstrate that Vivoryon’s strategy of recruiting individuals with evidence of baseline deficits on the WAIS-IV Coding test, a well-known measure of cognitive function, successfully enriches study cohorts with respect to deficits in attention and working memory, enabling reliable assessment of potential cognitive improvement after treatment.

Safety Results: Data from all 259 randomized patients showed no clinical signs of ARIA at the cutoff date of June 14, 2023. 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, while retaining a similar level of target inhibition at the dosing in both studies.

After carefully reviewing the updated safety data, the independent Data Safety Monitoring Board (DSMB) decided in its recent meeting on June 22, 2023, that the study should continue as planned and that no additional DSMB meeting will be required until study completion.

The study is on track for the final data readout in Q1/2024.

VIVA-MIND (NCT03919162) is a complementary Phase 2 study for varoglutamstat conducted in the U.S. which seeks to enroll 180 patients with early AD into the Phase 2a adaptive dose finding portion and enroll a further 234 patients in the Phase 2b portion of the study.

Study Updates: The first cohort was fully randomized into the study as planned and the study is now recruiting participants into the second cohort, with 19 sites open across the U.S.

In its June 12, 2023, meeting, the study’s independent DSMB recommended to continue the study without modification, supporting the rationale for accelerated uptitration to 600 mg BID dosing.

The Company anticipates a decision on final trial size following the data readout of the VIVIAD study.

Vivoryon intends to provide a study update in Q4/2023.

Read more about the clinical design and study highlights here.

Vivoryon is a clinical stage biotechnology company focused on developing innovative small molecule-based medicines
Driven by our passion for ground-breaking science and innovation, we strive to change the lives of patients in need suffering from severe diseases. We leverage our in-depth expertise in understanding post-translational modifications to develop medicines that modulate the activity and stability of proteins which are altered in disease settings. Beyond our lead program, varoglutamstat, which is in Phase 2 clinical development to treat Alzheimer’s disease, we have established a solid pipeline of orally available small molecule inhibitors for various indications including cancer, inflammatory diseases and fibrosis.