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The field of epigenetics is rapidly advancing, with new therapies being developed to address a variety of mental health disorders. Epigenetics is the study of changes in gene expression that are not caused by changes in the DNA sequence itself. Instead, these changes are caused by chemical modifications to the DNA or to the proteins that package the DNA.
One promising area of research in epigenetics is the use of LSD1 inhibitors to treat mental health disorders. LSD1 inhibitors are drugs that target an enzyme called lysine-specific demethylase 1 (LSD1), which plays a crucial role in regulating gene expression. By inhibiting LSD1, these drugs can alter the way that genes are expressed, potentially leading to therapeutic benefits for a variety of mental health disorders.
The Role of Oryzon Genomics in Epigenetic Therapies
Oryzon Genomics is a clinical-stage biopharmaceutical company that is leveraging epigenetics to develop innovative therapies for diseases with unmet medical needs. The company's focus is on developing therapies for CNS disorders and oncology using LSD1 inhibitors.
Oryzon's lead drug candidate is vafidemstat (ORY-2001), an oral, CNS-optimized LSD1 inhibitor. Vafidemstat has shown promising results in preclinical studies and has been tested in a variety of clinical trials for different indications.
The PORTICO Trial for Borderline Personality Disorder
One of the ongoing clinical trials for vafidemstat is the PORTICO trial, a Phase IIb trial to evaluate the efficacy and safety of vafidemstat in adult patients with Borderline Personality Disorder (BPD).
The trial is being conducted at multiple centers and is double-blind, randomized, and placebo-controlled. The primary objectives of the trial are to reduce agitation and aggression and to produce an overall improvement in BPD severity.
The trial plans to recruit 188 patients, and the initial blinded safety data from the first 167 randomized patients has been positive. From the blinded data, there were no treatment-related serious adverse events or deaths. An aggregated number of 306 adverse events, affecting 98 patients treated either with vafidemstat or placebo were reported, most of them were mild (216) or moderate (78), with only 12 reported as severe, in 9 patients, leading to 6 treatment discontinuations or patient withdrawals.
Following the blinded portion of the Data Monitoring Committee (DMC), the independent DMC members reviewed the unblinded safety data and provided the recommendation to continue the trial without modifications until full enrollment, which is planned for early Q3 2023.
The REIMAGINE Trials for Aggressiveness and Alzheimer's Disease
In addition to the PORTICO trial, Oryzon has also conducted two Phase IIa clinical trials with vafidemstat in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe Alzheimer's Disease (AD) (REIMAGINE-AD).
Positive clinical results were reported in both trials, with significant reductions in aggressiveness and agitation observed in the REIMAGINE-AD trial. In addition, vafidemstat reduced the inflammatory biomarker YKL40 in patients with Mild to Moderate AD in the ETHERAL trial.
The ESCAPE Trial for Severe COVID-19
Oryzon has also tested vafidemstat in a Phase II trial in severe COVID-19 patients (ESCAPE) to assess the drug's ability to prevent Acute Respiratory Distress Syndrome (ARDS), one of the most severe complications of the viral infection. The drug showed significant anti-inflammatory effects in severe COVID-19 patients.
Other Potential Applications of Vafidemstat
Vafidemstat has also shown promise in preclinical models of multiple sclerosis (MS), where it exhibits fast, strong, and durable efficacy. Oryzon has conducted a pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has been observed.
The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes, including Kabuki Syndrome.
The Future of Epigenetic Therapies for Mental Health Disorders
The development of epigenetic therapies for mental health disorders represents an exciting new area of research. LSD1 inhibitors like vafidemstat have shown promise in preclinical and clinical trials for a variety of disorders, including BPD, aggressiveness, AD, multiple sclerosis, and COVID-19.
As research in epigenetics continues to advance, it is likely that more innovative therapies will be developed to address the complex underlying causes of mental health disorders. Oryzon Genomics is at the forefront of this research, and its efforts to develop effective epigenetic therapies offer hope for patients with unmet medical needs.
Conclusion
The field of epigenetics is rapidly advancing, with new therapies being developed to address a variety of mental health disorders. Oryzon Genomics is a clinical-stage biopharmaceutical company that is leveraging epigenetics to develop innovative therapies for diseases with unmet medical needs. Its lead drug candidate, vafidemstat, is an oral, CNS-optimized LSD1 inhibitor that has shown promise in preclinical and clinical trials for a variety of disorders.
The ongoing PORTICO trial for BPD has shown positive blinded safety data from the first 167 randomized patients, and other trials have reported positive clinical results as well. As research in epigenetics continues to advance, it is likely that more innovative therapies will be developed to address the complex underlying causes of mental health disorders.