ORYZON reports financial results and corporate update for quarter ended September 30, 2025

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, today reported financial results for the nine months ended September 30, 2025 and provided a corporate update on recent developments.

“We have secured over $60 million in the first half of 2025, marking a significant turnaround for Oryzon,” said Dr. Carlos Buesa, Oryzon’s Chief Executive Officer. “These proceeds enable us to advance our clinical programs with a renewed strategic focus on CNS, particularly in our studies in BPD, schizophrenia, and ASD.”

“Following the FDA’s feedback, the Company has strengthened its clinical, strategic, and regulatory teams by incorporating highly experienced professionals with deep expertise in late-stage clinical development and FDA-EMA interactions,” continued Dr. Buesa. “As part of our strategic plan to become a CNS-focused company and to further strengthen our balance sheet, we are exploring potential partnerships for our promising oncology-hematology asset iadademstat. We continue to enhance its value through ongoing collaborations and the generation of new clinical evidence under our CRADA agreement with the NCI, which requires only a minimal financial commitment from the Company.”

“The impressive data in first-line AML from the triple combination of venetoclax, azacitidine, and iadademstat — showing no dose-limiting toxicities and a 100% overall response rate — clearly illustrates the success of this strategy,” Dr. Buesa added. “We expect that additional promising results in MDS and other studies will continue to demonstrate the clinical relevance of iadademstat across different hematologic malignancies. We believe that the data to be presented at ASH, together with forthcoming results in SCD, will further support our efforts to identify the right partner to ensure that this drug ultimately reaches patients.”

Third Quarter and Recent Highlights

Vafidemstat:

• Following submission of the clinical trial protocol for the PORTICO-2 Phase III trial with vafidemstat in Borderline Personality Disorder (BPD) to the U.S. Food & Drug Administration (FDA) for approval in June, the Company received written feedback from the FDA in October. 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.
• As part of our strategic preparations to advance our late-stage pipeline and to enhance dialogue with the FDA and EMA, the Company has strengthened its clinical, strategic, and regulatory teams by incorporating highly experienced professionals as Senior Advisors: Dr. Iman Barilero, who brings extensive CNS experience from her nine-year tenure as Global Head of Regulatory Affairs at Lundbeck and will be acting as a Chief Regulatory Officer; Dr. Christopher Breder, MD PhD, a veteran drug developer who also spent several years of his career as a Medical Officer at the FDA; and Dr. Raymond Sanchez, former CMO of Cerevel Therapeutics. The Company plans to incorporate additional experts to further reinforce its development capabilities.
• These appointments follow the recent incorporation of distinguished clinical and academic experts into our Clinical Advisory Board (CAB), including Dr. Alan Schatzberg (Chair of the Department of Psychiatry and Behavioral Sciences at Stanford University from 1991 to 2010 and current Director of the Stanford Mood Disorders Center), Dr. Eric Hollander (Professor of Psychiatry and Behavioral Sciences at the Albert Einstein College of Medicine and Director of the Autism and Obsessive-Compulsive Spectrum Program), Dr. Emil Coccaro (Professor of Psychiatry at The Ohio State University College of Medicine and former Chair of Psychiatry & Behavioral Neuroscience at The University of Chicago (2004-2016)), and Dr. Sarah Fineberg (Assistant Professor of Psychiatry at Yale University).
• Oryzon is preparing a new Phase II trial to evaluate vafidemstat for the treatment of aggression in patients with autism spectrum disorder (ASD). This trial, named HOPE-2, plans to include, inter alia, genetically-defined ASD subpopulations, such as individuals with Phelan-McDermid syndrome (PMS), and will initially be conducted in Spain as part of the activities supported by the recently granted Med4Cure IPCEI EU initiative. In parallel with its clinical development efforts in ASD and PMS, Oryzon is collaborating as a sponsor of the first-ever PMS Burden of Illness study, led by CureShank, a research advocacy organization founded by families of individuals affected by PMS. This study, recently launched, aims to characterize the direct and indirect burden of PMS to patients, caregivers, and the US healthcare system.
• The EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia continues to enroll participants. This study aims to assess the efficacy of vafidemstat, with a primary focus on improving negative symptoms. As secondary endpoints, the trial will evaluate vafidemstat’s efficacy in improving cognitive impairment and positive symptoms in schizophrenia. Initially conducted only in Spain, the trial is now being expanded to additional EU countries.
• Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter, with an additional “Decision to grant” communication from the European patent office. The allowed claims cover the use of vafidemstat for the treatment of aggressiveness and social withdrawal associated with CNS diseases, including claims specifically aimed at the treatment of aggressiveness associated with BPD, ASD, Alzheimer’s disease and other conditions, as well as claims directed to treating social withdrawal associated with diseases such as schizophrenia or ASD. Once formally granted, this patent will remain in force until at least 2038, not including any potential patent term extension. Additional patents in this family have already been granted or allowed in Europe, Australia, Canada, Hong Kong, Israel, South Korea, Malaysia, the Philippines, and Russia, with applications pending in other countries.

Iadademstat:

• The iadademstat triplet combination with venetoclax and azacitidine achieved an overall response rate (ORR) of 100% (n=8) in a Phase I dose finding clinical trial in patients with newly diagnosed acute myeloid leukemia (AML). The study, which continues active patient enrollment, has been accepted for presentation at the upcoming American Society of Hematology (ASH) Annual Meeting (December 6–9, 2025, Orlando, Florida, USA). As reported in the ASH abstract, 88% of patients achieved complete remission (CR) and 12.5% achieved morphologic leukemia-free state (MLFS). After a median follow-up of nine months, the estimated six-month overall survival (OS) rate was 88%, and no dose-limiting toxicities were observed. This investigator-initiated study (IIS) is led by the Oregon Health & Science University (OHSU) Knight Cancer Institute.
• A second study in the same clinical setting, sponsored by the National Cancer Institute (NCI) and conducted under our Cooperative Research and Development Agreement (CRADA) with the NCI, continues to actively recruit patients and is expected to provide additional data to further substantiate the promising early results in first line AML.
• The iadademstat combination with gilteritinib achieved a 67% overall response rate (8/12 patients) and a 58% complete response rate (CR + CRh + CRi; 7/12 patients) among the 12 evaluable patients treated at the dose currently under expansion in the open-label, multicenter Phase Ib FRIDA clinical trial in patients with relapsed or refractory (R/R) AML harboring a FLT3 mutation (FLT3mut+). The activity observed at this dose was superior to both historical and real-world data reported for gilteritinib monotherapy. Three patients have proceeded to hematopoietic stem cell transplantation (HSCT). The study, which continues to enroll patients, has been accepted for presentation at ASH-2025. The study is being conducted in the United States and will enroll up to approximately 45 patients. As reported in the ASH abstract, 34 patients had been enrolled at the data cut-off for abstract submission, with four dose level cohorts evaluated in the escalation phase. The combination was tolerable at the tested doses, and the study has progressed to the expansion phase at one selected pharmacologically active dose. Updated data will be presented at the congress.
• A new randomized Phase II study of iadademstat in combination with ASTX727 (oral decitabine + cedazuridine) in patients with accelerated/blast phase (AP/BP) myeloproliferative neoplasms (MPNs), sponsored by the NCI under the CRADA with Oryzon, has recently started to enroll patients. The study has a dose escalation phase to identify the Recommended Phase 2 Dose (RP2D) of iadademstat + ASTX727, followed by a randomized phase which will investigate the efficacy of iadademstat + ASTX727 compared to ASTX727 monotherapy. A Trial-in-progress (TIP) abstract has been accepted for presentation at ASH-2025.
• Enrollment has continued in the IIS Phase I dose-finding trial of iadademstat in combination with azacitidine in myelodysplastic syndrome (MDS), led by the Medical College of Wisconsin (MCW), and in the Phase I/II trial of iadademstat plus immune checkpoint inhibitors in patients with extensive-stage small cell lung cancer (SCLC) who have initially received standard of care chemotherapy and immunotherapy, conducted and sponsored by the NCI under the CRADA with Oryzon.
• Beyond oncology, Oryzon has expanded clinical evaluation of iadademstat into non-malignant hematological disorders, with a first trial in sickle cell disease (SCD). This multicenter, open-label Phase Ib trial, named RESTORE (REgulation of Sickling ThrOugh Reprogramming Epigenetics), will evaluate the safety and tolerability of iadademstat in adult patients with SCD, and determine its Recommended Phase 2 dose (RP2D), as well as to evaluate iadademstat’s effect on inducing fetal hemoglobin (HbF) expression. Increases in HbF have already been recognized by the FDA as a clinically meaningful endpoint for the treatment of SCD. The trial, recently approved by the European Medicines Agency (EMA), has started to enroll patients. The study is conducted across several sites in Spain and aims to enroll approximately 40 adult patients.
• A new trial, which will evaluate iadademstat in essential thrombocythemia (ET), is currently in preparation, with Clinical Trial Application (CTA, the EU equivalent to an IND) submission to EMA planned for Q425.
• Oryzon has strengthened its patent portfolio for iadademstat during this quarter, with “Decision to grant” communications from the European and Australian Patent Offices for patent applications entitled “Combinations of iadademstat for cancer therapy”. The allowed claims protect the use of iadademstat in combination with PD1 or PD-L1 inhibitors for the treatment of cancer, including small cell lung cancer (SCLC). Once formally granted, the patents will remain in force until at least 2040, excluding potential patent term extensions. A corresponding patent has already been granted in Russia, with applications pending in the United States, Japan, China, and other territories.

Earlier stage programs:

• ORY-4001, Oryzon’s highly selective histone deacetylase 6 (HDAC6) inhibitor nominated as a clinical candidate for the treatment of certain neurological diseases such as Charcot-Marie-Tooth disease (CMT), Amyotrophic Lateral Sclerosis (ALS) and others, continues to progress through IND enabling studies to prepare it for clinical studies.

Financial Update: Third quarter 2025 Financial Results

Research and development (R&D) expenses were $3.9 million and $9.6 million for the quarter and nine months ended September 30, 2025, compared to $1.9 and $7.1 million for the quarter and nine months ended September 30, 2024.

General and administrative expenses were $1.2 and $3.9 million for the quarter and nine months ended September 30, 2025, compared to $0.9 and $3.1 million for the quarter and nine months ended September 30, 2024.

Net losses were $1.2 and $4.6 million for the quarter and nine months ended September 30, 2025, compared to net losses of $1.1 and $3.8 million for the quarter and nine months ended September 30, 2024. The result is as expected, given the biotechnology business model where companies in the development phase typically have a long-term maturation period for products and do not have recurrent income.

Negative net result was $1.5 million (–$0.02 per share) for the nine months ended September 30, 2025, compared to a negative net result of $2.5 million (–$0.04 per share) for the nine months ended September 30, 2024.

Cash, cash equivalents, and marketable securities totaled $40.4 million as of September 30, 2025.