vafidemstat (ORY-2001) / Oryzon - LARVOL DELTA

Oryzon Genomics…announced that the United States Patent and Trademark Office (USPTO) has granted U.S. Patent No. 12,673,044, entitled 'Methods of treating borderline personality disorder' (GlobeNewswire) - "The granted claims cover methods of treating non-aggressive symptoms of borderline personality disorder (BPD) using LSD1 inhibitors, including vafidemstat, complementing Oryzon’s patent portfolio covering the treatment of aggression. The patent is expected to expire in March 2043, including 1,095 days of Patent Term Adjustment (PTA) awarded by the USPTO to compensate for delays during patent prosecution....A Decision to Grant has also recently been issued for a corresponding Canadian patent application in this patent family, with allowed claims covering the use of vafidemstat for the treatment of non-aggressive symptoms of BPD....The non-U.S. patents are expected to remain in force until at least 2040, excluding any potential patent term extensions or equivalent adjustments."

Patent • Borderline Personality Disorder

ORYZON raises €12 million and signs a financing agreement with COFIDES to strengthen its balance sheet and accelerate its clinical programs (Oryzon Press Release) - "The funds raised will be used to: Strengthen the Company's balance sheet to support corporate development initiatives in anticipation of future partnership discussions; Advance the clinical development of iadademstat for the treatment of acute myeloid leukemia; Progress the other ongoing clinical programs in hematology and psychiatry; Cover general and administrative expenses and financial obligations....This commitment will apply to any future capital increase that Oryzon may undertake within six months of the execution of the share subscription agreement. This period may be extended by mutual agreement between the parties."

Financing • Acute Myelogenous Leukemia • Amyotrophic Lateral Sclerosis • CNS Disorders

CL12-ORY-2001: A PHASE 1, OPEN-LABEL STUDY TO ASSESS THE ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION, INCLUDING THE MASS BALANCE, OF A SINGLE ORAL DOSE OF [14C]-VAFIDEMSTAT IN HEALTHY MALE PARTICIPANTS (clinicaltrialsregister.eu) - P1 | N=8 | Not yet recruiting | Sponsor: Oryzon Genomics S.A.

New P1 trial

CL09-ORY-2001: A Clinical trial to evaluate the efficacy of vafidemstat in negative symptoms and cognitive impairment associated with schizophrenia. (EVOLUTION study) (clinicaltrialsregister.eu) - P1/2 | N=239 | Recruiting | Sponsor: Oryzon Genomics S.A. | N=84 ➔ 239

Enrollment change • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Oryzon Genomics…announced that it has received a 'Decision to grant' communication from the Japanese Patent Office for its patent application JP2023-136283, titled 'Methods of treating behavior alterations', related to vafidemstat, Oryzon’s LSD1 inhibitor in clinical development for the treatment of psychiatric disorders (GlobeNewswire) - "The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal - two symptoms associated with several CNS disorders....Once formally granted, this Japanese patent will remain in force until at least 2038, excluding any potential patent term extension, which could provide additional years of protection. Corresponding patents have already been granted or allowed in Europe, Australia, Canada, Hong Kong, Israel, South Korea, Malaysia, the Philippines, and Russia, and additional applications are pending in other countries."

Patent • CNS Disorders • Personality Disorder • Psychiatry

Challenging behaviors in adolescents with intellectual and developmental disabilities: current pharmacological perspectives. (PubMed, Curr Opin Psychiatry) - "Effective care requires holistic evaluation, elimination of iatrogenic contributors, and individualized treatment. Combining behavioral therapies with judicious medication use can improve functioning and safety. Emerging pharmacologic and biologic strategies warrant further investigation in this vulnerable population."

Journal • CNS Disorders • Developmental Disorders • Mood Disorders • Polycystic Ovary Syndrome • Psychiatry

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