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 an update on both clinical studies of its lead candidate, varoglutamstat, a small molecule medicine in development for the treatment of Alzheimer’s disease (AD), VIVA-MIND and VIVIAD at the end of March. Furthermore, the Company presents updated safety data from its European Phase 2b study, VIVIAD, at the 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD) in Gothenburg, Sweden.

“We are pleased to report that both of our ongoing studies are progressing steadily, and we continue to broaden the overall data package for varoglutamstat with consistently positive incremental results,” commented Dr. Ulrich Dauer, CEO of Vivoryon. “Varoglutamstat is strongly positioned as a differentiated oral, outpatient small molecule that has the potential to significantly impact the AD treatment landscape and address ongoing unmet need. Designed to modulate all major hallmarks of AD including Abeta aggregation, neuroinflammation and tau pathology, and also enabling improvement of synaptic function, varoglutamstat captures the key features of a novel drug that has already exhibited a favorable safety profile with no signs of ARIA side effects. We are incredibly encouraged by what we have been able to report to date, and we see a unique opportunity for ultimately realizing the promise of a widely accessible treatment option in AD with the realistic potential to reach the millions of patients in need.”

Vivoryon is pursuing a unique and highly differentiated approach to AD treatment, with a meticulously designed clinical development strategy. Grounded in the discovery that the enzyme glutaminyl cyclase (QPCT) catalyzes formation of the neurotoxic Abeta variant N3pE- Abeta, a key driver of AD pathology, Vivoryon is pioneering small molecule-based therapies to block this disease pathway. 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.

“We are extremely encouraged by the exceptionally low discontinuation rates in both of our studies,” added Dr. Michael Schaeffer, CBO of Vivoryon. “Vivoryon is acutely focused on lessening the burden of AD for both patients and their families. As we are addressing an elderly patient population, we know how important it is to design a drug that is convenient. These patients typically have to live with and manage many different health conditions at the same time, which heavily impacts their everyday lives. Many feel overwhelmed by the sheer number of medicines they have to take every day and it is therefore our goal to make taking varoglutamstat as easy and convenient as possible. By investigating options to further optimize the formulation of our tablets, we feel that we have the unique chance to facilitate adherence to the correct dosing in our clinical studies and beyond.

Clinical development of varoglutamstat
Following a meticulously designed clinical development strategy, varoglutamstat was shown to be well-tolerated in both a completed first-in-human Phase 1 study in over 200 participants and the subsequent first-in-patient Phase 2a study, SAPHIR (NCT02389413), which enrolled 120 patients suffering from early AD. Importantly, after only 12 weeks of treatment, this study showed evidence of improving not only pathological hallmarks, but also synaptic function and connectivity, cognition, memory and attention in AD patients, including statistically significant changes from baseline in working memory.

Building on these encouraging results, Vivoryon based the selection of endpoints for both VIVIAD (NCT04498650) and VIVA-MIND (NCT03919162) on the outcome of SAPHIR, as well as on the regulatory draft guidelines for AD drug development introduced by FDA and EMA in 2018. With these two complementary studies, the Company intends to assess if potential cognitive improvements in patients in the European VIVIAD study will translate into an established clinical endpoint in patients in the U.S. VIVA-MIND study.

Vivoryon remains on track to report the final data readout from the VIVIAD study in the first quarter of 2024 and expects to provide the next update on the VIVA-MIND study in the second half of 2023.

Read more about the clinical design and study highlights here.

“As a neurologist confronted with the severe impact this devastating disease has on peoples’ lives on a daily basis, I am very pleased to see the progress being made in Vivoryon’s varoglutamstat studies and the hope that this new treatment might offer to patients,” commented Dr. Howard Feldman, Professor of Neurosciences and Director of the ADCS at UC San Diego, and the VIVA-MIND study director. “While there remains much to be done in terms of research and development for safe and effective disease-modifying therapies that are widely available to patients, I believe that varoglutamstat represents a new approach to reducing the pathological events in AD. The complementary studies, VIVIAD and VIVA-MIND, present a strong clinical path forward for varoglutamstat. It is encouraging to see the VIVA-MIND trial receive its most recent DSMB recommendation for the trial to continue forward based on their most recent safety review of March 13, 2023.”

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.

Vivoryon bleibt auf Kurs, um die finalen Daten der VIVIAD-Studie im ersten Quartal 2024 zu veröffentlichen, und rechnet damit, in der zweiten Jahreshälfte 2023 ein nächstes Update zur VIVA-MIND-Studie geben zu können.

Weitere Informationen zum Studiendesign und den Highlights finden Sie hier.

„Als Neurologe, der tagtäglich mit den schweren Auswirkungen dieser verheerenden Krankheit auf das Leben der Menschen konfrontiert ist, freue ich mich sehr über die Fortschritte, die in den Varoglutamstat-Studien von Vivoryon erzielt werden, und über die Hoffnung, die diese neue Behandlung den Patienten geben könnte“, kommentierte Dr. Howard Feldman, Professor für Neurowissenschaften und Direktor des ADCS an der UC San Diego sowie Leiter der VIVA-MIND-Studie. „Es bleibt zwar noch viel zu tun in der Forschung und Entwicklung sicherer und wirksamer krankheitsmodifizierender Therapien, die den Patienten in großem Maße zur Verfügung stehen, aber ich glaube, dass Varoglutamstat einen neuen Ansatz zur Reduzierung der pathologischen Vorgänge bei Alzheimer darstellt. Die komplementären Studien VIVIAD und VIVA-MIND zeigen einen starken klinischen Fortschritt für Varoglutamstat auf. Es ist ermutigend zu sehen, dass die VIVA-MIND-Studie ihre jüngste DSMB-Empfehlung für die Fortsetzung der Studie auf der Grundlage ihrer jüngsten Sicherheitsüberprüfung vom 13. März 2023 erhalten hat.“

Vivoryon ist ein Biotechnologieunternehmen in der klinischen Phase, das sich auf die Entwicklung innovativer Arzneimittel auf Basis kleiner Moleküle konzentriert.
Angetrieben von unserer Leidenschaft für bahnbrechende Wissenschaft und Innovation streben wir danach, das Leben von Patienten zu verändern, die an schweren Krankheiten leiden. Wir nutzen unsere umfassende Expertise im Verständnis posttranslationaler Modifikationen, um Medikamente zu entwickeln, die die Aktivität und Stabilität von Proteinen modulieren, die im Rahmen von Erkrankungen verändert sind. Neben unserem Lead-Programm Varoglutamstat, das sich in der Phase 2 der klinischen Entwicklung zur Behandlung der Alzheimer-Krankheit befindet, haben wir eine solide Pipeline oral verfügbarer niedermolekularer Inhibitoren für verschiedene Indikationen wie Krebs, entzündliche Erkrankungen und Fibrose aufgebaut.