Our Science

At Vivoryon, we are passionate about creating small molecule medicines to improve the lives of all those who are affected by severe diseases. We build on our in-depth expertise in understanding post-translational modifications and pathologic pathways to develop medicines that modulate the activity and stability of proteins which are altered in disease settings. Our lead candidate, varoglutamstat is currently in Phase 2 clinical studies to treat Alzheimer’s disease.

Targeting QPCT/L in Alzheimer’s disease

Around 50 million people worldwide suffer from dementia. Alzheimer’s disease is the most common form of dementia and contributes to about 60-70% of cases, meaning that around ~30 million people are suffering from Alzheimer’s disease (AD) worldwide, with the number expected to double by 20501. The disease, characterized by the major hallmarks Abeta aggregation, neuroinflammation and tau pathology, as well as by synaptic dysfunction, is a heavy burden on patients, families, caregivers and the public healthcare systems around the globe. While a number of novel approaches are currently being developed in search of effective, disease-modifying therapies, there is currently cure available and most drugs on the market address the symptoms of the disease only.

Our scientific founders have discovered that the enzymes glutaminyl cyclase (QPCL) and glutaminyl cyclase-like protein (QPCTL) play an important role in AD, identifying QPCT-mediated formation of a neurotoxic Abeta variant, N3pE amyloid (pGlu-Abeta) as an important driver of AD pathology2,3. QPCT is expressed predominantly in the brain‘s learning and memory centers and catalyzes formation of neurotoxic N3pE amyloid by cyclization of N-terminal glutamate on Abeta2. This toxic N3pE amyloid correlates cognitive (MMSE) status in AD patients and is not found in healthy individuals4. Recent reports have confirmed that increased activity of QPCT is associated with AD pathology in patients5.

At Vivoryon, we are developing small molecule inhibitors to prevent N3pE amyloid formation, rather than aiming to clear existing Abeta plaques6,7. In addition to blocking formation of this toxic Abeta species, these inhibitors also act through a second mechanism of action, targeting QPCTL, which inhibits neuroinflammation by modulating CCL2 activity. CCL2 is also a promoter of the tau pathology and increased levels of QPCTL and high pE-CCL2 levels correlate strongly with low cognitive (MMSE) scores in AD patients8.

Beyond our lead program, varoglutamstat, which is in Phase 2 clinical development to treat Alzheimer‘s disease and has been shown to improve working memory in a completed Phase 2a study, we have established a solid pipeline of orally available small molecule inhibitors for various indications including cancer, inflammatory diseases and fibrosis. See our Pipeline here

  • 2 – Schilling et al., Nat. Med., 2008
  • 3 – Grochowska et al., EMBO, 2017
  • 4 – Morawski et al., JAD, 2014
  • 5 – Gunn et al. J.Neurochem, 2021
  • 6 – Buchholz et al., J. Med. Chem, 2006
  • 7 – Nussbaum et al., Nature, 2012
  • 8 – Hartlage‐Rübsamen et al., Acta Neuropathol, 2015