HDAC6

Issued 12,765,958 new sharesPriced at €2.35 per share, representing a 15.44% discount on the 5-day VWAPStrong investor demand, with the offering significantly oversubscribed€15 million anchored by a leading US institutional investorProceeds to fund clinical development and corporate initiatives MADRID and CAMBRIDGE, Mass., April 24, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, 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. This pricing reflects a 15.44% discount to the 5-day volume-weighted average price (VWAP) of €2.779 per share prior to April 22, 2025, and a 19.38% discount to the April 22 closing price of €2.915. The offering, which was structured as straight equity with no warrants attached, attracted strong demand and was significantly oversubscribed. A US-based institutional investor anchored the round with a €15 million order, with the remaining demand filled by investors across the US, Europe, and Spain. The capital increase was capped at €30 million by the company’s Board of Directors. Maxim (U.S.), All-Invest (EU/UK), and Singular Bank (Spain) acted as bookrunners. Banco Sabadell, S.A. acted as the Settlement and Technical Pre-financing Agent for the Capital Increase, while Gómez-Acebo & Pombo Abogados, S.L.P. (Spanish law) and Gibson, Dunn & Crutcher LLP (U.S. law) served as legal advisors to the Company, and Loeb & Loeb LLP acted as U.S. legal counsel to Maxim Group LLC. 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 hematologySupport CMC activities and preparations for Phase IIb-III trials, as well as other regulatory initiativesStrengthen the company's balance sheet to support future partnership or M&A negotiationsCover general administrative expenses and financial obligationsEnhance legal and audit readiness for a potential dual listing on Nasdaq Dr. Carlos Buesa, CEO of Oryzon, commented: “This financing marks a key milestone that enables us to continue progressing our clinical programs with vafidemstat in aggression-related CNS disorders and to further develop our oncology and hematology pipeline. It also reinforces our financial position, supporting strategic conversations with investors and potential partners.” About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. 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 (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About IadademstatIadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a collaborative Phase II trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. Oryzon is further expanding the clinical development of iadademstat through additional investigator-initiated studies. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. 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 aggressiveness 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, see Ferrer et al, Psychiatry & Clin Neurosci, 2025, doi.org/10.1111/pcn.13800) 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 was 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 was also 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 patients. Vafidemstat is currently advancing as a Phase III-ready asset in Borderline Personality disorder (BPD) following completion of the global, randomized, double blind Phase IIb PORTICO trial (final data presented at ECNP-2024). Following receipt of the minutes from the End-of-Phase II meeting with the FDA to discuss PORTICO’s results, the company announced plans to move forward with a Phase III PORTICO-2 trial in agitation/aggression in BPD (FDA submission planned in 1H2025). Vafidemstat is also being investigated in a double-blind, randomized, placebo-controlled Phase IIb trial in negative symptoms of schizophrenia (EVOLUTION trial, recruitment ongoing). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is evaluating a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration.. Spain Oryzon IR & Media, Europe & US Patricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com

RIDGE is Largest Natural History Study Conducted with More Than 175 Participants Enrolled to Date with Arrhythmogenic Right Ventricular Cardiomyopathy Due to Mutations in the PKP2 Gene Patients Experience High Burden of Arrhythmias and Severe Disease Progression Despite Standard-of-Care Treatments Large Majority of PKP2-associated ARVC Patients Appear Eligible for TN-401 Gene Therapy Based on Low Rates of Preexisting Immunity to AAV9 Antibodies SAN DIEGO, April 24, 2025 (GLOBE NEWSWIRE) -- Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today announced interim data from its ongoing RIDGE (NCT06311708) natural history and seroprevalence study of adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the Plakophilin 2 (PKP2) gene will be presented at the Heart Rhythm Society’s annual Heart Rhythm meeting taking place in San Diego, CA from April 24-27, 2025. RIDGE is the largest non-interventional natural history and seroprevalence study of adults with PKP2-associated ARVC to date and was designed to collect and assess participants’ clinical characteristics and medical history, as well as to test for preexisting neutralizing antibodies to AAV9. PKP2 gene mutations result in insufficient levels of critical proteins needed to maintain the structural integrity and cell-to-cell signaling of heart muscle cells. Tenaya is developing TN-401 gene therapy as a potential treatment for PKP2-associated ARVC (also known as arrhythmogenic cardiomyopathy, or ACM). TN-401 gene replacement therapy is designed to deliver a functional PKP2 gene into heart muscle cells using an adeno associated virus serotype 9 (AAV9) capsid. “Interim data from the RIDGE observational study bring into focus what we’ve long understood about PKP2-associated ARVC – the current treatment approaches such as ablation or prescribed medications are insufficient to address the high burden of arrhythmias or alter the progression of disease, placing patients at increased risk for life-threatening ventricular tachycardias,” said Hugh Calkins, M.D., Catherine Ellen Poindexter Professor of Cardiology and Director, Johns Hopkins Hospital ARVD Program and an investigator for the RIDGE study. “I am encouraged by the potential of disease-modifying treatment approaches, such as TN-401 gene therapy, which is intended to alter the course of disease by delivering a functional PKP2 gene to the heart.” The RIDGE study has enrolled more than 175 patients at approximately 20 clinical sites in the U.S., UK, France, Germany, Italy and Sweden. As of the February 2025 cut off, clinical data from 144 adults with PKP2-associated ARVC were analyzed. Key findings being shared at Heart Rhythm 2025 include: Adults with PKP2-associated ARVC experience a high burden of arrhythmias despite treatments with standard of care medications including beta blockers and anti-arrhythmic medications such as flecainide, as well as surgical interventions such as ablation and implantable cardioverter-defibrillator (ICD) placement. 83 percent (95 of 115) of participants with available Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, a threshold linked with increased risk of life-threatening ventricular arrhythmias. 49 percent (56 of 115) of participants for whom Holter monitoring data was available had a history of ventricular tachycardia Current treatments appeared to do little to halt or prevent progressive structural changes to the heart that occur as a result of PKP2 mutations. Study participants show evidence of progressive structural changes that occur as a result of PKP2 mutations, in which the instability and disintegration of cellular structures in the desmosome results in fibrofatty scar tissue 60 percent of patients with MRI data available showed disease progression, as indicated by measures of right and left ventricular function, and heart tissue health Electrocardiogram results affirmed that a majority of patients had T-wave inversions (an indicator of ventricular strain or myocardial injury). Both QRS prolongation, which can indicate a delay in electrical conduction, and terminal active duration (TAD) were not present in a majority of participants, potentially indicating that changes in fibrofatty replacement and conduction system develop more slowly than arrhythmia symptoms. 93 percent of patients show AAV9 neutralizing antibody titers ≤1:40 A large majority of participants in the RIDGE study meet key eligibility criteria for participation in Tenaya’s ongoing Phase 1b RIDGE-1 clinical trial of TN-401 gene therapy 83 percent (95 of 115) of participants with available Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, a threshold linked with increased risk of life-threatening ventricular arrhythmias. 49 percent (56 of 115) of participants for whom Holter monitoring data was available had a history of ventricular tachycardia 60 percent of patients with MRI data available showed disease progression, as indicated by measures of right and left ventricular function, and heart tissue health Enrollment is also underway in Tenaya’s Phase 1b clinical trial, known as RIDGE™-1, to assess the safety, tolerability and activity of a one-time dose of TN-401. Tenaya plans to report safety and biopsy data from the first cohort of RIDGE-1 patients in the second half of 2025. “The RIDGE natural history study provides a rich source of data detailing the disease characteristics and burden for adults with ARVC. We extend our heartfelt gratitude to the patients and investigators involved in this important study. Their continued support has been instrumental in achieving the progress we've made thus far,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “As the largest collection of prospective and retrospective patient demographic and medical history data, RIDGE is expected to serve as a control arm to assess activity and efficacy of the interventional TN-401 study in determining meaningful clinical and surrogate endpoints for measuring gene therapy’s efficacy in the PKP2-associated ARVC indication, as well as serving as an important means of engaging with patients and clinical sites as we enroll our Phase 1b trial of TN-401.” The interim data from RIDGE will be presented at Heart Rhythm 2025 on April 26, 2025 by Dr. Calkins during the Basic Translational Science session in a poster titled “Determining Eligibility for RIDGE™-1, a Phase 1b Interventional Study to Evaluate Safety and Efficacy of TN-401 Gene Therapy in Adults with Plakophilin-2 (PKP2)-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Interim Results of an Observational Study to Assess Seroprevalence to Adeno-Associated Virus Serotype 9 (AAV9)”. About PKP2-Associated ARVCPlakophilin-2 (PKP2) mutations are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC, also known as arrhythmogenic cardiomyopathy or ACM), estimated to represent approximately 40 percent of the overall ARVC population. The prevalence of PKP2-associated ARVC is estimated at more than 70,000 people in the U.S. alone. In PKP2-associated ARVC, mutations of the PKP2 gene results in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in irregular heart rhythms. ARVC symptoms include arrhythmias, palpitations, lightheadedness, dizziness and fainting. It is typically diagnosed before age 40, and sudden cardiac arrest due to life-threatening ventricular arrhythmias is frequently the first manifestation of disease. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease. About TN-401 Gene Therapy and the RIDGE-1 Clinical TrialTN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC due to mutations in the PKP2 gene. AAV9 was selected as the vector for delivery of Tenaya’s PKP2 gene therapy based on its extensive clinical and commercial safety record and demonstrated ability to target heart muscle cells. In preclinical studies, Tenaya has shown that a single dose of TN-401 restored healthy levels of PKP2 protein, normalized heart rhythms, improved right and left ventricular size and function and extended survival. TN-401 has received Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration. Tenaya is conducting the RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. The RIDGE-1 Phase 1b clinical trial is a multi-center, open-label, dose escalation study being conducted in the U.S. and UK. RIDGE-1 will assess the safety, tolerability and preliminary clinical efficacy of a one-time intravenous infusion of TN-401. RIDGE-1 will seek to enroll up to fifteen adults who have been diagnosed with PKP2-associated ARVC, have an implantable cardioverter defibrillator (ICD) and are at increased risk for arrhythmias as determined by PVC count during screening. To learn more about gene therapy for ARVC and participation in the RIDGE-1 study, please visit ARVCstudies.com or ClinicalTrials.gov (NCT06228924). About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Tenaya employs a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of genetic medicines aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. Tenaya’s pipeline includes TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), TN-301, a small molecule HDAC6 inhibitor intended for heart failure with preserved ejection fraction (HFpEF), and multiple early-stage programs in preclinical development. For more information, visit www.tenayatherapeutics.com. Forward Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “potential,” “expected,” “plans, “will,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of, and expectations regarding TN-401; expectation’s regarding the RIDGE data in support of determining meaningful clinical and surrogate endpoints for measuring gene therapy’s efficacy in the PKP2-associated ARVC indication; the planned timing to report initial data from RIDGE-1 and RIDGE; and statements made by Tenaya’s Chief Medical Officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; actions and decisions of regulatory agencies; the timing and progress of RIDGE-1; availability of RIDGE-1 and RIDGE data at the referenced time; the potential for any RIDGE-1 clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.Tenaya ContactsMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsPrecision AQ annemarie.fields@precisionaq.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com

New “Decision to grant” communications in Europe and JapanMADRID and CAMBRIDGE, Mass., April 21, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, 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. A “Decision to grant” is a formal communication from a Patent Office indicating that the patent application has met all requirements for issuance as a patent. Once formally granted, this European patent will remain in force until at least 2040, excluding any potential patent term extension. A counterpart patent has already been granted in Japan, and additional applications are pending in other countries. 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 will be the first granted patent in this patent family, with applications pending in other countries. This Japanese patent, once issued, will also remain in force until at least 2040, not including potential term extension. “These new patent allowances in Europe and Japan complement the ample portfolio we’ve already secured for vafidemstat,” said Neus Virgili, Oryzon’s Chief IP Officer. “They further strengthen our global IP position and support the compound’s commercial potential across multiple CNS indications and our competitive position.” Oryzon’s patent porfolio for vafidemstat in CNS also includes two additional patent families:. One covers the treatment of aggression and social withdrawal, with patents already granted or allowed in Europe, Australia, Hong Kong, Korea, Malaysia, the Philippines, and Russia, and patent applications pending in other countries. These patents will remain in force until at least 2038, excluding any potential patent term extensions, which may provide additional years of protection.The second patent family relates to the treatment of borderline personality disorder, with allowed or granted patents in Europe, Japan, Mexico, Russia, Singapore and South Africa, and patent applications pending in additional countries. These patents will remain in force until at least 2040, excluding any potential patent term extensions, which may provide additional years of protection. About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. 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 (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. 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 aggressiveness 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, see Ferrer et al, Psychiatry & Clin Neurosci, 2025, doi.org/10.1111/pcn.13800) 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 was 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 was also 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 patients. Vafidemstat is currently advancing as a Phase III-ready asset in Borderline Personality disorder (BPD) following completion of the global, randomized, double blind Phase IIb PORTICO trial (final data presented at ECNP-2024). Following receipt of the minutes from the End-of-Phase II meeting with the FDA to discuss PORTICO’s results, the company announced plans to move forward with a Phase III PORTICO-2 trial in agitation/aggression in BPD (FDA submission planned in 1H2025). Vafidemstat is also being investigated in a double-blind, randomized, placebo-controlled Phase IIb trial in negative symptoms of schizophrenia (EVOLUTION trial, recruitment ongoing). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is evaluating a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration.. Spain Oryzon IR & Media, Europe & USPatricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com