- Both VIVIAD and VIVA-MIND progressing at 600mg twice daily with oral administration following two independent positive DSMB decisions
- Varoglutamstat demonstrates very encouraging safety data with no evidence of drug-related ARIAs at therapeutic dose of 600mg twice daily, a dose demonstrated to result in nearly 90% target occupancy
- On track to report final VIVIAD Phase 2b readout in Q1/2024
- Commenced preparations for open label extension study to provide long-term treatment option to patients after completion of treatment under VIVIAD or VIVA-MIND
- Company to participate at upcoming
Jefferies London Healthcare Conference taking placeNovember 14-16, 2023
“The breadth and significance of data collected thus far from varoglutamstat’s clinical development program further expands our understanding of early AD pathology and treatment. With independent DSMB dose decisions for both of our ongoing Phase 2 studies across multiple geographies and different titration regimens, varoglutamstat, has been cleared from a safety and tolerability standpoint to proceed with the highest investigated dose of 600mg twice daily. By evaluating varoglutamstat in two parallel clinical studies with varying efficacy endpoints, we can meaningfully support our regulatory strategies and provide a clear picture of the cognitive changes potentially resulting from treatment on study. Utilizing a stepwise methodology for clinical development, we have been able to create a statistically robust trial setting in VIVIAD with the intent of VIVA-MIND designed to confirm the findings of VIVIAD,” said
Varoglutamstat Clinical Program
The clinical development program of varoglutamstat in early AD is based on a strong scientific rationale rooted in Vivoryon‘s research and discovery activities in conjunction with support from leading academic partners and scientific organizations worldwide. 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 additional positive impact on tau pathology. Preclinical data supports the N3pE-Abeta hypothesis with the following key highlights:
- Pyroglutamate-modified Abeta (N3pE-Abeta) is a trigger of toxicity and disease pathology in AD and there is a strong rationale for targeting N3pE-Abeta to create a tailored AD therapy.
- Experimental data show that N3pE-Abeta has very different physio-chemical properties compared to other Abeta variants, including its potential to form highly toxic oligomers and fibrils together with non-modified Abeta variants.
- Strong preclinical evidence supports the hypothesis that reducing N3pE-Abeta formation by inhibiting the enzyme QPCT, has the potential to change the course of progression of AD.
Varoglutamstat is a differentiated investigational small-molecule medicine in development to treat early AD. As an orally administered treatment which can conveniently be taken at home, varoglutamstat holds significant advantages in ease of use by patients. Importantly, in line with its mode of action, safety data to-date indicate that varoglutamstat could potentially come without comparable risks of brain swelling and bleeding (ARIA) seen with amyloid lowering mAbs. It is currently being investigated in two large Phase 2 studies, VIVIAD (NCT04498650) in
VIVIAD
VIVIAD (NCT04498650) is a state-of-the-art Phase 2b study being conducted in
- The objective of the Cogstate 3-item scale (Identification, Detection, One Back) as the primary endpoint is to confirm the positive findings on working memory and attention observed in the SAPHIR study.
- The CBB (3-item scale plus One Card Learning), which is the first secondary endpoint, is marketed as Cognigram and has approval as a medical device by the
U.S. Food & Drug Administration (FDA) and multiple other regulatory authorities to assess cognition in early AD patients. - The full Cogstate NTB (8-item scale) enables an assessment of outcome on various cognitive domains.
- Th A-IADL-Q is a fully validated and sensitive scale to measure the impairment of daily function in patients with early AD.
- The EEG captures change in large scale neuronal and synaptic activity. Theta power has been selected as a key secondary endpoint because it is well correlated to working memory and has been shown to increase (worsen) in AD.
Formal testing for significance will begin with the Cogstate NTB 3-item scale and continue until the first endpoint does not show a p value of <=0.05. Furthermore, there will be additional exploratory analysis for domains such as working, executive and episodic memory and language via the
The end of the active treatment phase in VIVIAD is estimated to occur by year end 2023, which is then followed by a period of safety follow up visits and rigorous data and statistical analysis. Vivoryon remains on track to share final topline data in the first quarter of 2024 and the full dataset at a subsequent medical meeting.
VIVA-MIND
VIVA-MIND (NCT03919162) is an ongoing Phase 2 study for varoglutamstat being conducted in the
- In
July 2023 , the Company announced that the first cohort of the study was fully randomized as planned and is now recruiting participants into the second cohort with 21 sites open across theU.S. The primary endpoint of the study is evaluating Clinical Dementia Rating scale Sum of Boxes (CDR-SB) over a 72-week treatment period. In addition to evaluating safety, key secondary efficacy endpoints includeABC score, quantitative EEG-relative theta wave power, FAQ (Functional Activities Questionaire) Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13) and Neuropsychiatric Inventory. - While the Cogstate NTB applied in VIVIAD and the CDR-SB used in VIVA-MIND are distinct and very different scales with each having a specific strength, there has been a positive correlation established between both scales.1
- Recently, Vivoryon shared a positive DSMB dose decision recommending that the highest dose of varoglutamstat 600mg twice daily (BID) be selected for the remainder of the trial, based on a quarterly safety review and subsequent analysis of treatment-emergent adverse events of special interest (AESI) pertaining to skin and subcutaneous tissue disorders and hepatobiliary disorders, as well as target occupancy and plasma pharmacokinetic (PK) data.
- With VIVA-MIND, the Company has confirmed the feasibility of an up-titration protocol to the final dose of 600mg BID which is accelerated compared to the ongoing VIVIAD Phase 2b study.
VIVALONG
In
- The launch of VIVALONG is contingent on the outcome of VIVIAD.
- Pending VIVIAD results, Vivoryon plans to assess the long-term treatment of varoglutamstat including positron emission tomography (PET) imaging and other key safety and efficacy endpoints.
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1 Maruff et al.; BMC Pharmacology and Toxicology 2013
About
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. www.vivoryon.com
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