ORYZON reports financial results and corporate update for quarter ended March 31, 2025

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, May 12^th, 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 first quarter ended March 31, 2025 and provided a corporate update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer said “The company has completed a successful €30 million capital increase structured as straight equity with no warrants attached. Despite the very adverse market conditions, the financing attracted strong demand and was upsized from the original planned €25 million and ended significantly oversubscribed. A US-based institutional investor anchored the round with a €15 million order. The capital increase was capped at €30 million by the company’s BoD.”

Dr. Buesa continued “We are finalizing preparations for the upcoming Phase III of vafidemstat for the treatment of agitation and aggression in Borderline Personality Disorder (BPD). In collaboration with our recently formed Clinical Advisory Board, comprising leading U.S. psychiatry experts, we have designed a Phase III clinical trial protocol that we believe aligns with FDA expectations. As a continuation of our End-of-Phase 2 (EoP2) dialogue with the FDA, we have received additional requests for complementary information, which we are currently addressing. We expect to submit both the PORTICO-2 protocol and the additional information to the FDA in the first half of 2025”. “We have also continued patient recruitment in our ongoing EVOLUTION trial in schizophrenia in Spain. The observational clinical study in Phelan-McDermid syndrome (PMS), a form of autism, published in Frontiers in Psychiatry is a first step towards a personalized medicine approach to explore vafidemstat actionability in SHANK3-associated psychiatric disorders, including PMS, where agitation and aggression are key components of the disease.”

Dr Buesa continued, “In oncology, we are thrilled that the trial evaluating iadademstat in combination with atezolizumab or durvalumab in small cell lung cancer (SCLC), sponsored by the NCI under our CRADA agreement, has begun recruiting patients. The biology underlying the synergy between iadademstat and immune checkpoint inhibitors (ICIs) is highly compelling. Recent retrospective analyses of multiple Phase III ICI trials in SCLC have shown that patients with the lowest LSD1 expression achieved the best outcomes.”

Dr Buesa continued, “We are also very excited with the IIS trial of iadademstat in combination with azacitidine in myelodysplastic syndrome, a disease with significant unmet medical need, led by the Medical College of Wisconsin. The trial has continued to actively enroll patients during this quarter, completing the first cohort with no safety concerns and encouraging efficacy signals.”

Dr Buesa added, “We have secured €13.26 million through the non-refundable Med4Cure IPCEI grant from the EU. Combined with the recent €30 million fund raising, the company has now secured approximately $50 million, despite challenging market conditions. These two financings, along with other additional inflows, place the company in a solid cash position to focus on execution and advance our R&D programs in personalized medicine for CNS and oncology.”

First Quarter and Recent Highlights

Vafidemstat in large multifactorial CNS indications:

• 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 primary and key secondary endpoints for this trial have been defined 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 trial will use STAXI-2 Trait anger as a primary efficacy endpoint measure, with secondary endpoints including clinician-rated and patient-rated scales to assess agitation/aggression and overall BPD improvement. The company continues with its plan to submit the PORTICO-2 protocol for FDA approval in 1H2025. The estimated total sample size for PORTICO-2 is 350 patients (randomized 1:1 vafidemstat or control), with a trial duration of 18 weeks in total. 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 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 Frontiers in Psychiatry journal. 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. The purpose of this study was to gather data that could serve as a foundation for a future precision psychiatry clinical trial with vafidemstat in PMS.
• Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter, with additional “Decision to grant” communications from the European and Japanese patent offices for patent applications titled “Methods of treating Attention Deficit Hyperactivity Disorder using KDM1A inhibitors such as the compound vafidemstat” and “Methods of treating autism spectrum disorder”, respectively. Once issued, these patents will not expire until at least 2040, excluding any potential patent term extension. These patents complement Oryzon’s patent portfolio for vafidemstat in CNS, which 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, while the second patent family relates to the treatment of borderline personality disorder, with allowed or granted patents so far in Europe, Japan, Mexico, Russia, Singapore and South Africa. The patents in these two patent families will remain in force until at least 2038 and 2040, respectively, excluding any potential patent term extensions, which may provide additional years of protection.
• 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 explore vafidemstat’s efficacy in improving cognitive impairment and positive symptoms in schizophrenia. The project is partially funded by the Spanish Ministry of Science and Innovation and is being conducted at multiple hospitals across Spain.

Vafidemstat in monogenic CNS indications:

• 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.

Iadademstat in oncology:

• The Phase I/II trial with iadademstat plus immune checkpoint inhibitors (ICI) in first line SCLC patients with extensive disease, conducted under the Cooperative Research and Development Agreement (CRADA) that Oryzon has in place with the National Cancer Institute (NCI), started to enroll patients in April 2025. The trial, titled “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer”, will evaluate the safety, tolerability, dose finding and efficacy of iadademstat in combination with an ICI, either atezolizumab or durvalumab, in patients with extensive-stage SCLC who have initially received standard of care chemotherapy and immunotherapy. This study is conducted and sponsored by the NCI, with Dr. Charles Rudin from the Memorial Sloan Kettering Cancer Center (MSKCC) as the main PI for the trial. More than 20 sites accross the U.S. participate in the trial, including renowned institutions such as MSKCC, Johns Hopkins, City of Hope, University of Chicago, and many others. The trial plans to enroll 45-50 patients.
• FRIDA, an open-label, multicenter Phase Ib clinical trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), continues to enroll patients. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity. The primary objectives of the trial are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination, while the secondary objectives focus on assessing treatment efficacy. The study is being conducted in the U.S. and will accrue up to approximately 45 patients. If successful, Oryzon and the FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much-in-need AML population. The company plans to present the next data update from this trial at ASH-2025.
• The two Phase I dose-finding clinical trials evaluating iadademstat in combination with venetoclax and azacitidine in newly diagnosed AML, one sponsored by the NCI under the CRADA signed between Oryzon and the NCI andand the other as an Investigator-initiated study (IIS) sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute, have both continued to actively enroll patients.
• In addition, the IIS Phase I dose-finding trial of iadademstat in combination with azacitidine inmyelodysplastic syndrome (MDS), led by the Medical College of Wisconsin (MCW), has also continued to actively enroll patients during this quarter and completed the first cohort.

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: First quarter 2025 Financial Results

Research and development (R&D) expenses were $2.6 million for the first quarter ended March 31, 2025, in line with the investment made during the first quarter of 2024.

General and administrative expenses were $1.2 million for the first quarter ended March 31, 2025, compared to $0.9 million for the first quarter ended March 31, 2024 .

Net losses were $1.6 for the first quarter ended March 31, 2025, compared to $1.1 million for the first quarter ended March 31, 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 $1.8 million (–$0.03 per share) for the first quarter ended March 31, 2025, compared to a negative net result of $1.2 million (–$0.02 per share) for the first quarter ended March 31, 2024.

In April 2025, the company raised a capital increase of €30 million, as straight equity with no warranties attached, which will be used to fund clinical development and corporate initiatives. Despite the very adverse market conditions, the financing attracted strong demand and was upsized from the original planned €25 million and ended 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.

In May 2025, the Spanish provisional resolution proposal for Med4Cure, the first Important Project of Common European Interest (IPCEI) in the health sector in Europe was published, awarding Oryzon a non-refundable grant of 13.26 million € (approximately 15 million USD) for its VANDAM project. This amount corresponds to 64% of the total accepted budget (20.68 million €) for the VANDAM Project. Following the publication of the provisional resolution, the final resolution is expected in the next few weeks, with the grant to be disbursed in a single installment shortly thereafter.