Outsourcing Pharma sat down with Michael Schaeffer, chief business officer at Vivoryon, to discuss the company’s small-molecule Alzheimer’s treatment and how it is striving to stand out in a crowded field.
OSP: What is your role at Vivoryon and what does the company focus on?
I am Michael Schaeffer, CBO of Vivoryon. In my role, I am responsible for the clinical development of Vivoryon’s lead candidate varoglutamstat in Alzheimer’s disease as well as for business development. We are a clinical-stage company focused on developing innovative small molecule-based medicines to modulate the activity and stability of proteins that 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.
OSP: Could you tell us about Vivoryon’s small molecule candidate - varoglutamstat?
With varoglutamstat, Vivoryon is pioneering small molecule-based therapies to block a key Alzheimer’s disease pathway. Varoglutamstat is a small molecule inhibitor of the glutaminyl cyclase enzymes (QPCT and QPCTL). QPCT catalyzes the formation of the neurotoxic Abeta variant N3pE- Abeta, a key driver of AD pathology. 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). In addition, and through its inhibition of QPCTL varoglutamstat modulates neuroinflammation via the CCL2 pathway, which, in turn, has an impact on tau pathology.
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, 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 is currently investigating varoglutamstat in two clinical Phase 2 studies in Europe (VIVIAD) and the U.S. (VIVA-MIND). Vivoryon has received Fast Track designation for varoglutamstat in early AD by the FDA and anticipates final data readout of VIVIAD in Q1/2024 and intends to provide a study update on VIVA-MIND in Q4/2023.
OSP: How would you describe the current state of the Alzheimer’s disease field? And could you tell us about the recent approval of Leqembi and the impact it could have in treating the condition?
After almost 20 years without any significant progress in the field, the recent approval of Leqembi and the positive data reported recently for donanemab are a very encouraging signal for all patients, their families, and caregivers and it is an important step for all of us working in this industry. While both drugs have shown efficacy in clinical studies, they do come with limitations like required infrastructure and potential risk of ARIAs.
Therefore, it is likely that a number of new approaches such as ours will emerge and help shape the landscape of future AD treatments. Similar to the developments in oncology, where a lot of different individualized approaches and combination therapies are being used to treat patients effectively, it can be expected that the AD field will evolve in a similar direction.
OSP: How is Vivoryon making its mark in the space?
While most of the companies developing AD medications are still focused on antibody-based medicines, Vivoryon is pursuing a unique and highly differentiated approach with a meticulously designed clinical development strategy. Grounded in the discovery that the enzyme glutaminyl cyclase (QPCT) catalyzes the formation of the neurotoxic Abeta variant N3pE-Abeta, a key driver of AD pathology, we are pioneering small molecule-based therapies to block this disease pathway. Varoglutamstat has already shown statistically significant improvements in working memory, a cognitive ability that is eventually heavily weakened in AD patients. Through its dual mode of action, varoglutamstat modulates all three important pathological hallmarks of the disease.
In terms of differentiation, we believe that our own approach addresses two key limitations of lecanemab, donanemab (and other Abeta-targeting antibodies):
Firstly, as a small molecule, varoglutamstat is being developed as a pill to be taken orally at home, while therapeutic antibodies have to be injected and therefore need a specialized infrastructure, i.e., infusion centers.
Secondly, Abeta-targeting antibodies have been associated with severe side effects. These are swelling and bleeding in the brain, so-called Amyloid Related Imaging Abnormalities (ARIA). Therefore, patients need to be closely monitored, especially in the first months of treatment by so-called magnetic resonance imaging (MRI). This, again, requires specific infrastructure and cannot be done at home or at any physician’s practice. In contrast, varoglutamstat has already shown substantial clinical evidence of a favorable safety profile with no ARIAs reported in any of our studies to date.
OSP: Where do you envisage Vivoryon being in 5 years? What progress would you like to see?
Within the next 5 years, we are laser-focused on easing the burden of all those affected by the devastating reality of Alzheimer’s disease, patients, families, caregivers, and physicians, by filling the gap of a safe and effective therapy that is broadly accessible to all those in need.
Our data to date is extremely encouraging and we anticipate final data readout of our European study VIVIAD in Q1/2024. This will be a very important milestone, providing the basis for interactions with the regulatory authorities to shape varoglutamstat’s final stages of clinical development. Beyond its potential as a monotherapy, we have also generated promising preclinical data underscoring the potential of varoglutamstat in combination with other agents, such as anti-Abeta antibodies, increasing our confidence in becoming part of the therapeutic landscape in AD.
