vafidemstat (ORY-2001) / Oryzon - LARVOL DELTA

Systematic evaluation of effects and side effects of vafidemstat, a histone-modifying candidate therapeutic agent for psychiatric disorders, in a wildtype rodent model (Neuroscience 2025) - "In summary, this study provides basic information on the transcriptomic and behavioral effects of vafidemstat, suggesting it stabilizes the transcriptome rather than inducing differential expression in one direction. Our results indicate that this compound produces minimal neuropsychiatric side effects, yet has the potential for physical and sensory side effects, highlighting not only the promise of vafidemstat as a therapeutic drug for neuropsychiatric disorders but also the necessity of careful monitoring when administering it to patients."

Adverse events • Epigenetic controller • Preclinical • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia • KMT2C

Vafidemstat: a lysine-specific demethylase 1A inhibitor that shows promise for treating neuropsychiatric disorders. (PubMed, Epigenet Rep) - "This article reviews available preclinical and clinical data on the use of vafidemstat in the treatment of these disorders. Vafidemstat appears to be a potential new and safe drug for the treatment of these disorders."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • Borderline Personality Disorder • CNS Disorders • Genetic Disorders • Mental Retardation • Mood Disorders • Personality Disorder • Psychiatry • KDM1A

Oryzon Genomics…is pleased to announce the strategic collaboration with Dr. Iman Barilero, PharmD, PhD, as Senior Advisor for Regulatory Affairs to support the advancement of its Phase III clinical program with vafidemstat in Borderline Personality Disorder (BPD). (Oryzon Press Release)

Commercial • New P3 trial • Borderline Personality Disorder

ORYZON Receives Feedback From the FDA in Response to the Submitted Phase III Protocol in Borderline Personality Disorder (GlobeNewswire) - "The FDA’s guidance covers different elements such as the selection of study endpoints and certain non-clinical considerations. Oryzon will incorporate these insights and resubmit the revised Phase III protocol. The company underlines that such iterative interactions are common in regulatory dialogue."

Clinical protocol • FDA event • New P3 trial • Borderline Personality Disorder

ORYZON strengthens patent portfolio for…vafidemstat with new Decisions to Grant (Oryzon Press Release) - "Oryzon has also received a Decision to Grant from the European Patent Office for its patent application EP24205125.8, titled 'Vafidemstat for treating behavior alterations'. The allowed claims cover the use of vafidemstat for the treatment of aggressiveness and social withdrawal associated with CNS diseases....Once formally granted, this European patent will remain in force until at least 2038, not including any potential patent term extensions."

Patent • Alzheimer's Disease • Autism Spectrum Disorder • Borderline Personality Disorder • Schizophrenia

ORYZON continues to strengthen its patent portfolio for vafidemstat (Oryzon Press Release) - "Oryzon Genomics, S.A...announced that it has received 'Decision to grant' communications from the Canadian Intellectual Property Office and the Israel Patent Office for its patent applications CA3071804 and IL272092, titled 'Methods of treating behavior alterations', related to vafidemstat, Oryzon’s LSD1 inhibitor in clinical development for the treatment of psychiatric disorders...The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal – two symptoms associated with several CNS disorders...The company is also planning to conduct a Phase II trial in aggression in Austism Spectrum Disorder (ASD) patients, and a Phase II trial is already ongoing in schizophrenia...These patents are expected to remain in force until at least 2040, not including any potential patent term extensions."

New P2 trial • Patent • CNS Disorders • Personality Disorder • Schizophrenia

ORYZON announces submission of Phase III protocol to FDA to initiate PORTICO-2 trial of vafidemstat in Borderline Personality Disorder (BPD) patients (Oryzon Press Release) - "Oryzon Genomics, S.A...announced...that it has submitted the clinical trial protocol for its Phase III PORTICO-2 trial to the U.S. Food and Drug Administration (FDA) to initiate a registrational trial to evaluate vafidemstat in patients with Borderline Personality Disorder (BPD). The PORTICO-2 trial builds upon the encouraging results observed in the previous PORTICO Phase IIb study, where vafidemstat demonstrated significant and clinically meaningful reductions in secondary endpoints measuring aggression and overall BPD improvement...PORTICO-2 will employ two clinical outcome measures for aggression: the STAXI-2 Trait Anger scale (patient-reported) as the primary endpoint, and the Overt Aggression Scale-Modified (OAS-M) (clinicianrated) as key secondary endpoint. Additional secondary endpoints will evaluate broader clinical improvements in BPD symptomatology and quality of life."

Clinical protocol • New P3 trial • Borderline Personality Disorder

ORYZON Reports Financial Results and Corporate Update for Quarter Ended March 31, 2025 (GlobeNewswire) - "We are evaluating the feasibility of new precision medicine trials in autistic conditions like Fragile X syndrome or Phelan McDermid Syndrome, among others. The company will decide on a possible submission of an IND for these trials to the EMA, AEMPS or FDA in 2025."

IND • New trial • Genetic Disorders

ORYZON Reports Financial Results and Corporate Update for Quarter Ended March 31, 2025 (GlobeNewswire) - "Oryzon is finalizing the preparations for Phase III in BPD, including the preparation of a full protocol for the PORTICO-2 Phase III trial to submit to the FDA for study approval....The company continues with its plan to submit the PORTICO-2 protocol for FDA approval in 1H2025; The EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia continues to enroll participants....The project is partially funded by the Spanish Ministry of Science and Innovation and is being conducted at multiple hospitals across Spain."

New P3 trial • Trial status • Borderline Personality Disorder • Schizophrenia

ORYZON Raises €30 Million in Capital Increase (Oryzon Press Release) - "Oryzon Genomics, S.A...announced today the successful completion of a €30 million capital increase through the issuance of 12,765,958 new shares, priced at €2.35 per share....The funds raised will be used to: Advance the clinical development of vafidemstat for the treatment of aggression in CNS disorders such as Borderline Personality Disorder (BPD) and Autism Spectrum Disorder (ASD); Expand ongoing clinical programs in oncology and hematology; Support CMC activities and preparations for Phase IIb-III trials, as well as other regulatory initiatives; Strengthen the company's balance sheet to support future partnership or M&A negotiations; Cover general administrative expenses and financial obligations; Enhance legal and audit readiness for a potential dual listing on Nasdaq."

Financing • Autism Spectrum Disorder • Borderline Personality Disorder • CNS Disorders • Oncology

ORYZON continues to strengthen its patent portfolio for vafidemstat (Oryzon Press Release) - "Oryzon Genomics...announced today that the European Patent Office has issued a 'Decision to grant' communication for its European patent application EP20712563.4 relating to vafidemstat. The patent, titled 'Methods of treating Attention Deficit Hyperactivity Disorder using KDM1A inhibitors such as the compound vafidemstat', covers the use Oryzon’s LSD1 inhibitor, vafidemstat, currently in clinical development for psychiatric disorders....Once formally granted, this European patent will remain in force until at least 2040, excluding any potential patent term extension. ...Oryzon also announced that it has received a 'Decision to grant' from the Japanese Patent Office for its patent application JP2022-514201, titled 'Methods of treating autism spectrum disorder'....This Japanese patent, once issued, will also remain in force until at least 2040, not including potential term extension."

Patent • ADHD (Impulsive Aggression) • Autism Spectrum Disorder

Phenotype and psychometric characterization of Phelan-McDermid syndrome patients: pioneering towards personalized medicine. (PubMed, Front Psychiatry) - "No correlation was detected between deletion size and the BPI and RBQ scores. This analysis presents new data on the best potential endpoints, for a future clinical study exploring vafidemstat actionability for SHANK3-associated psychiatric disorders, constituting a good example of how Precision Medicine may open new avenues to understand and treat Central Nervous System (CNS) disorders, pioneering individual management in PMS."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Psychiatry

Oryzon Announces Publication of Study on Phelan-McDermid Syndrome (PMS) Patients, a Form of Autism, Paving the Way for a Novel Personalized Medicine Approach with Vafidemstat (GlobeNewswire) - "Oryzon Genomics, S.A...announced today that the final results of an observational clinical study aimed at psychometrically characterizing individuals with Phelan-McDermid syndrome (PMS) carrying deletions or pathogenic variants in SHANK3 have been published online in the journal Frontiers in Psychiatry...In this pilot study, we clinically characterized the profile of 30 subjects, all diagnosed of molecularly confirmed PMS, by applying different psychometric scales, including Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, ADOS-2, the Battelle developmental inventory screening test and the Behavior Problems Inventory (BPI). As reported in the publication, unsupervised hierarchical clustering of the collected psychometric data identified three groups of patients, with different cognitive, aggression and behavioral profile scores."

Observational data • Genetic Disorders

Oryzon defines Phase III Trial endpoints for Agitation and Aggression in BPD with input from new Clinical Advisory Board (Oryzon Press Release) - "Oryzon Genomics...today announced that it has established the primary and key secondary endpoints for its planned Phase III clinical trial evaluating vafidemstat in Borderline Personality Disorder (BPD). This milestone was reached in collaboration with Oryzon’s newly formed Clinical Advisory Board (CAB), composed of leading experts in psychiatry research and clinical trials for psychiatric disorders....Oryzon remains committed to progressing vafidemstat as a potential first-in-class treatment for agitation and aggression in BPD. Following the FDA’s feedback on the PORTICO trial results, Oryzon plans to submit the Phase III protocol in the first half of 2025, with trial initiation expected soon after, pending regulatory approval and securing the necessary funding."

FDA event • Trial status • Borderline Personality Disorder

Fourth Quarter and Recent Highlights (Oryzon Press Release) - "Preparations for PORTICO-2 Phase III trial with vafidemstat in agitation/aggression in Borderline Personality Disorder ongoing...Subject to FDA’s review of the final data, the PORTICO-2 Phase III study has the potential to be one of the two registrational trials required by the FDA...The company expects to obtain FDA’s approval for PORTICO-2 in 1H2025....We continue to evaluate the feasibility of a new precision medicine trial in Kabuki Syndrome. The company will decide on a possible submission of an IND for HOPE to the FDA in 2025."

IND • New P3 trial • Borderline Personality Disorder • CNS Disorders

ORYZON Announces Journal Publication of Final Phase IIa REIMAGINE Results with Vafidemstat in Psychiatry and Clinical Neurosciences (GlobeNewswire) - P2a | N=32 | REIMAGINE (2018-002140-88) | Sponsor: Oryzon Genomics S.A. | "Oryzon Genomics, S.A...announced today that the final results of the Phase IIa REIMAGINE study, which evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD), were published online in Psychiatry and Clinical Neurosciences...In the trial, participants received 1.2 mg/day of vafidemstat for 8 weeks. As reported in the publication, the study showed that vafidemstat was safe and well-tolerated and elicited significant and consistent reduction in agitation/aggression in patients with BPD, ADHD, and ASD. Vafidemstat also produced a significant improvement in nonaggressive features and overall disease indicators in these populations."

P2a data • ADHD (Impulsive Aggression) • Autism Spectrum Disorder • Borderline Personality Disorder • CNS Disorders

REIMAGINE: A central nervous system basket trial showing safety and efficacy of vafidemstat on aggression in different psychiatric disorders. (PubMed, Psychiatry Clin Neurosci) - "In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • Borderline Personality Disorder • CNS Disorders • Mental Retardation • Mood Disorders • Personality Disorder • Psychiatry

Topline Results : a double-blind, randomized placebo-controlled, adaptive phase IIb trial to assess vafidemstat's efficacy in treating borderline personality disorder (ECNP 2024) - P2 | "Though the primary endpoints measuring overall BPD disease severity and agitation/aggression were not statistically significant, secondary measures of agitation/aggression (i.e., STAXI-2) and overall disease (i.e., BEST) achieved nominal statistical significance and clinically meaningful reductions as defined as a >25% symptom reduction compared to placebo. All primary and secondary efficacy measures statistically favored vafidemstat over placebo, and the GST was also consistent with a global treatment effect favoring vafidemstat. Treatment with vafidemstat was safe and well-tolerated."

Clinical • P2b data • Borderline Personality Disorder • CNS Disorders • Depression • Personality Disorder • Psychiatry • Suicidal Ideation

Topline Results : PORTICO a double-blind, randomized placebo-controlled, adaptive phase IIb trial to assess vafidemstat's efficacy in treating borderline personality disorder (ECNP 2024) - P2 | "Vafidemstat is a promising potential epigenetic therapy for BPD, a disease with no approved therapy and high unmet medical need."

Clinical • P2b data • Borderline Personality Disorder • CNS Disorders • Depression • Mood Disorders • Personality Disorder • Psychiatry • KDM1A

ORYZON receives “Decision to grant” for two important patents for vafidemstat in Japan (Oryzon Press Release) - "Oryzon Genomics...announced today that it has received 'Decision to grant' communications from the Japanese Patent Office (JPO) for two Japanese patent applications related to vafidemstat, Oryzon’s LSD1 inhibitor in clinical development for the treatment of psychiatric disorders like BPD and schizophrenia. These two patent applications are JP2021-556616 entitled 'Methods of treating borderline personality disorder' and JP2021-556629 entitled 'Methods of treating attention-deficit hyperactivity disorder using KDM1A inhibitors such as the compound vafidemstat'....Both patents, once granted, will not expire until at least 2040..."

Patent • Attention Deficit Hyperactivity Disorder • Borderline Personality Disorder • Personality Disorder

ORYZON announces presentation of final data from PORTICO, vafidemstat’s global Phase IIb trial in Borderline Personality Disorder, at the 37th ECNP annual conference (Oryzon Press Release) - "Oryzon Genomics, S.A...today announced that it will present final data from its Phase IIb PORTICO trial, which investigated the efficacy of vafidemstat in the treatment of Borderline Personality Disorder (BPD), as an oral presentation at the 37th European College of Neuropsychopharmacology (ECNP) annual conference, to be held on September 21-23, 2024 in Milan, Italy...The trial had two primary endpoints: reduction of agitation and aggression and overall disease improvement in BPD severity. The trial also included two secondary endpoints also exploring the reduction of agitation and aggression and overall disease improvement in BPD severity by different scales."

P2b data • Borderline Personality Disorder • CNS Disorders • Personality Disorder

Jefferies gives the keys that will boost Oryzon's share price and gives it a potential of 32% [Google translation] (Yahoo Finance) - "The Jefferies analyst highlights that the combined Net Present Value (NPV) of approximately €2 per share for vafidemstat largely supports Oryzon's current share price. This suggests that iadademstat's $1 billion-plus sales potential in oncology indications, with a cumulative NPV of approximately €1.5 per share, 'is essentially a free option for investors.'....Additionally, initial phase Ib/II data for Iadademstat + Xospata in mFLT3 rel/ref acute myeloid leukemia are expected in the second and fourth quarters of 2024."

P1/2 data • Sales projection • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology

ORYZON secures another important patent for its lead CNS asset, vafidemstat (Oryzon Press Release) - "Oryzon Genomics...announced today that the European Patent Office (EPO) has issued an 'intention to grant' communication for Oryzon’s European patent application EP18748921.6 entitled 'Methods of treating behavior alterations' related to vafidemstat, Oryzon’s LSD1 inhibitor in clinical development for the treatment of psychiatric disorders like borderline personality disorder and schizophrenia. The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal. The intention to grant is a formal communication from the EPO in which it indicates that the patent application has reached the status where it is allowed for issuance as a patent. The patent, once granted, will not expire until at least 2038, excluding any potential patent term extensions that may provide additional protection."

Patent • Borderline Personality Disorder • Schizophrenia

Transcriptomic dysregulation and autistic-like behaviors in Kmt2c haploinsufficient mice rescued by an LSD1 inhibitor. (PubMed, Mol Psychiatry) - "Intriguingly, the administration of vafidemstat was shown to alter the vast majority of DEGs in the direction to normalize the transcriptomic abnormalities in the mutant mice (94.3 and 82.5% of the significant upregulated and downregulated DEGs, respectively, P < 2.2 × 10-16, binomial test), which could be the molecular mechanism underlying the behavioral rescuing. In summary, our study expands the repertoire of ASD models with high etiological and face validity, elucidates the cell-type resolved molecular alterations due to Kmt2c haploinsufficiency, and demonstrates the efficacy of an LSD1 inhibitor that might be generalizable to multiple categories of psychiatric disorders along with a better understanding of its presumed mechanisms of action."

Journal • Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Mental Retardation • Psychiatry • KMT2C

ORYZON to Provide Corporate Progress Updates at Several Events in February-March (GlobeNewswire) - "Oryzon will attend the 2024 Epigenetic Mechanisms and Cancer Treatment conference, organized by Keystone Symposia, which will be held on February 4-7 at the Eldorado Hotel & Spa in Santa Fe, NM (USA). Dr. Tamara Maes, Chairman of Oryzon’s Scientific Advisory Board, will give a presentation...on February 7....Oryzon has been invited to participate at the Bio-Neuroscience conference, which will be held at the Rosarium in Amsterdam (The Netherlands) on February 14-15, where the company will provide a corporate update on its CNS program."

Clinical • CNS Disorders • Hematological Malignancies • Oncology • Solid Tumor