Oryzon Genomics, S.A. announced Last Patient Last Visit in its ongoing Phase IIb PORTICO trial, investigating vafidemstat's efficacy in Borderline personality Disorder (BPD). PORTICO (EudraCT No.: 2020-003469-20, ClinicalTrials.gov Identifier NCT04932291) is a global double-blind, randomized, placebo-controlled, adaptive 14-week Phase IIb trial evaluating the efficacy and safety of vafidemstat in a BPD population. The trial has two primary endpoints: reduction of agitation and aggression and overall disease improvement in BPD severity.

Last March, a pre-specified Interim Analysis qualified PORTICO as non-futile and recommended that the trial should continue as it is without increasing the number of patients to be recruited. The independent Data Monitoring Committee (DMC) has met routinely and reviewed unblinded safety data throughout the PORTICO trial. The last analysis corresponded to the initial 198 randomized patients (data cut-off, August 2023) and the DMC recommended continuing the trial without modifications until full enrollment (data recently presented at ECNP 2023).

Current safety data of PORTICO are aligned with previous vafidemstat trials and continue to support that vafidemstat is safe and well-tolerated. Topline results are expected in first quarter 2024, followed by a full data presentation at a psychiatric conference and in a peer-reviewed journal publication. Oryzon's team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston and San Diego.

Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects.

In animal studies vafidemstat not only restores memory but reduces the exacerbated agitation of SAMP8 mice, a model for accelerated aging and Alzheimer's disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both.

Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has also been observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patient. Currently, vafidemstat is in two Phase IIb trials in borderline personality disorder (PORTICO) and in schizophrenia patients (EVOLUTION).

The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is preparing a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. Up to 10% of those affected die by suicide.