Oryzon Genomics SA

A non-interventional study published in Frontiers in Psychiatry Psychometric profile characterization of 30 subjects with Phelan-McDermid Syndrome (PMS), defining three distinct subsets Study provides clinical scales and thresholds for patient selection in future clinical trials, based on aggressiveness, cognition, and behavioral traits Conducted in collaboration with the Medical and Molecular Genetics Institute (INGEMM) and the Research Institute La Paz Hospital (IdiPaz) in Madrid MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, March 5th, 2025 - Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, 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. The purpose of this study was to gather data that could serve as a foundation for a future precision psychiatry clinical trial involving vafidemstat for this patient population. Agitation and aggression are key components of PMS, and vafidemstat has demonstrated efficacy in reducing agitation and aggression in a basket trial involving patients with Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and Borderline Personality Disorder (BPD). This characterization paves the way for addressing these symptoms in a subset of PMS patients, further expanding the potential application of vafidemstat in reducing aggression in this specific patient population. Dr. Jordi Xaus, Oryzon’s CSO, stated, “The publication of these results in this prestigious clinical psychiatry journal marks a critical first step toward establishing vafidemstat as a novel personalized medicine therapy for relevant psychiatric indications. In recent years, a range of monogenic rare neurodevelopmental disorders linked to alterations in the epigenetic machinery and other key neuronal genes have been identified as potential targets for precision medicine. The use of LSD1 inhibitors has been shown to partially or fully rescue the complex phenotypes caused by these genetic mutations. Vafidemstat is currently the only LSD1 inhibitor in clinical development in CNS and represents a promising opportunity for these patients.” Dr. Julian Nevado, first author of the study and Head of Structural and Functional Genomics at INGEMM said “There is currently no treatment approved specifically for Phelan-McDermid syndrome. This study is a proof of concept that highlights the importance of patient stratification in PMS. Selecting PMS patients for a clinical trial based on their distinctive clinical and genetic characteristics will be essential in the era of personalized precision medicine.” 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. Statistically significant differences in deletion sizes were detected comparing the three clusters (corrected by gender), and the size of the deletion appears to be correlated with some of the assayed scores. A link to access the online publication can be found here. Oryzon is developing vafidemstat in prevalent multifactorial psychiatric indications like BPD, with a Phase III trial in preparation, or schizophrenia, with the ongoing EVOLUTION Phase IIb trial, but is also committed to exploring the potential of vafidemstat in rare monogenic psychiatric and neurodevelopmental disorders such as PMS or Kabuki Syndrome. In the Phase IIb PORTICO trial in BPD, vafidemstat demonstrated nominal statistical significance in reducing agitation and aggression, also a relevant feature of some PMS patients and a significant caregiver burden that often results in sedation or institutionalization of these PMS patients. This published study provides relevant data for patient inclusion in a future clinical study exploring vafidemstat actionability for SHANK3-associated psychiatric disorders, including PMS, 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.

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, March 3rd, 2025 - Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, 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. The CAB’s insights have been instrumental in ensuring that the Phase III protocol aligns with FDA expectations and incorporates well-validated, widely recognized assessment scales to measure agitation and aggression in BPD patients. This development follows the successful completion of the Phase IIb PORTICO trial, which received positive feedback from the FDA, and positions Oryzon to submit the Phase III protocol for regulatory review in the first half of 2025. “We are honored to collaborate with such a distinguished panel of experts as we advance vafidemstat into Phase III development,” said Dr. Carlos Buesa, Chief Executive Officer of Oryzon. “Their expertise in psychiatric disorders and clinical trial methodology strengthens our program and ensures that we are well-prepared for the next regulatory interactions. Addressing aggression and agitation in BPD remains an urgent medical need, and we are committed to delivering innovative solutions for these patients.” Oryzon’s Clinical Advisory Board Members: Oryzon’s CAB includes internationally recognized leaders in psychiatry and clinical trial research: “These are the right experts to help us shape a Phase III program that is both scientifically rigorous and clinically meaningful,” added Dr. Buesa. “It is particularly reassuring that their expert medical opinion and years of practice recognize aggression as one of the most debilitating aspects of many psychiatric disorders, and particularly in borderline personality disorder. Their contributions have been instrumental in defining the primary and secondary endpoints, that will generate robust data for regulatory submissions.” Next Steps in Vafidemstat’s Development 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. Beyond BPD, vafidemstat is being evaluated in a Phase IIb trial for the treatment of negative symptoms in schizophrenia (EVOLUTION trial) and is part of Oryzon’s broader CNS precision medicine approach. The company is also exploring additional applications in genetically defined subpopulations and neurodevelopmental disorders. For more information about the experience of the CAB members, please visit the CAB section in our website, here.

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, February 28th, 2025 - Oryzon Genomics S.A., a clinical-stage biopharmaceutical company focused on epigenetics for the development of therapies for diseases with significant unmet medical needs, today announced the results of voting at the Extraordinary General Shareholders' Meeting held today in Madrid. A total of 24,030,812 of the Company's issued and outstanding ordinary shares (representing 36.5312% of the share capital) were at the Meeting, either in person or represented by proxy. The Company's shareholders approved all of the resolutions listed below, proposed by the Board of Directors at the Company's Extraordinary General Meeting, with favorable votes ranging from 94% to 97%. Appointment and re-election of directors.Re-election of Mr. Carlos Buesa as executive director. Re-election of Mr. Manuel López-Figueroa as independent director. Appointment of Mr. Konstantinos Alataris as independent director. Appointment of Mr. Luis Sánchez Quintana as independent director. Appointment of Ms. Montserrat Vendrell as independent director. Appointment of Mr. Pierre Beaurang as independent director. Approval of the issuance of convertible bonds, excluding the pre-emptive subscription right, under the investment agreement entered into with Nice & Green, S.A., on November 20, 2023. Authorization to the Board of Directors to increase the share capital under the terms of Article 297.1.b) of the Spanish Companies Act. Delegation for the exclusion of pre-emptive subscription rights in accordance with the provisions of Article 506 of the Spanish Companies Act. Delegation to the Board of Directors of the power to issue fixed income securities, preferred participations or instruments of a similar nature (including promissory notes or warrants) convertible and/or exchangeable into shares of the Company. Establishment of criteria for the determination of the bases and modalities of the conversion and/or exchange and attribution to the Board of Directors of the powers to increase the capital by the necessary amount, as well as to exclude the preemptive subscription rights of the shareholders and holders of convertible securities. Authorization to the Board of Directors for the acquisition of own shares, directly or, as the case may be, through companies dependent on the Company. Delegation of powers for the formalization, correction, registration, interpretation, development and execution of the resolutions adopted by the General Shareholders' Meeting. Re-election of Mr. Carlos Buesa as executive director. Re-election of Mr. Manuel López-Figueroa as independent director. Appointment of Mr. Konstantinos Alataris as independent director. Appointment of Mr. Luis Sánchez Quintana as independent director. Appointment of Ms. Montserrat Vendrell as independent director. Appointment of Mr. Pierre Beaurang as independent director. The complete details of the resolutions that have been approved in their entirety and the results of the votes by separate items will be available on the Company's website in the near future.