Oryzon was co-founded by Tamara Maes in 2000. Initially focused on personal genomics and drug discovery, Oryzon has several assets in clinical development, including Vafidemstat and Iadademstat. The company, publicly listed since 2015, is based in Spain and employs around 50 people at its headquarters in Barcelona.
Oryzon’s therapeutic strategy targets LSD1, a protein expressed ubiquitously and involved in multiple biological processes. She explained that LSD1 knockouts in early embryos were lethal, while tissue-specific knockouts revealed roles in various biological processes. In cancer, LSD1 knockouts affect growth and cell phenotypes, and the protein also plays a significant role in neurobiology.
The presentation highlighted the different types of LSD1 inhibitors, categorised into five types. Type 1 inhibitors target the catalytic centre and could be either covalent FAD binders or reversible binders. Type 2 inhibitors have a transient interaction with the FAD cofactor, while type 3 inhibitors are allosteric. Type 4 inhibitors focus on specific protein-protein interactions, and type 5 inhibitors are degraders (PROTACs).
Maes discussed Vafidemstat, a type 1 LSD1 inhibitor optimised for human CNS diseases. It shows high potency in biochemical and cell assays, has no off-target effects in central nervous, cardiovascular, or respiratory systems, and is penetrates the blood-brain barrier. In animal models, Vafidemstat improves memory, reduces aggression, and enhances sociability without impacting haematology
In clinical trials, Vafidemstat is safe, well-tolerated, and effective in reducing aggression and improving sociability in patients with borderline personality disorder, schizophrenia, autism, and ADHD. The compound shows no risk for drug-drug interactions and has comparable safety profiles between placebo and Vafidemstat.
Maes concluded by discussing the potential of LSD1 inhibition in personalised medicine for CNS diseases and other genetically driven indications. She emphasised the need to characterise patient populations and design clinical trials based on mechanistic evidence.
