CNS(Vafidemstat)
Appointed renowned Rolando Gutierrez-Esteinou, M.D. as new CMO for CNS
Preparing protocol resubmission to incorporate FDA guidance on Phase III PORTICO-2 trial in aggression in BPD
Ongoing expansion of Phase IIb schizophrenia trial into additional EU countries
Finalizing preparations for new Phase II trial in aggression in autism spectrum disorder as a part of the IPCEI EU Grant in personalized medicine
Oncology, Hematology(Iadademstat)
Seven ongoing oncology trials, with six sponsored by the NCI or top-tier U.S. institutions
Positive data in 1L AML unfit patients presented at ASH with 100% ORR (90% strict CR)
Positive data in R/R FLT3+ AML presented at ASH; 67% CCR at the selected dose under expansion
Initiated enrollment in new Phase Ib trial in small cell lung cancer in combination with ICI and radiotherapy
Continued momentum in Phase Ib sickle cell disease trial with first two cohorts enrolled
New Phase II trial in essential thrombocythemia approved by EMA
MADRID and CAMBRIDGE, Mass., Feb. 27, 2026 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a global leader in epigenetics, today reported financial results for the twelve months ended December 31, 2025 and provided a corporate update on recent developments.
"After securing over $60 million in the first half of 2025, marking a clear financial turnaround for Oryzon, we ended the year with a solid cash position of $33.3 million (€28.4 million)," said Dr. Carlos Buesa, Oryzon's Chief Executive Officer. "This financial strength allows us to sharpen our focus on key regulatory catalysts across both of our programs: oncology and CNS."
"In oncology-hematology, iadademstat continues to receive strong external validation, with seven ongoing trials, six of which are sponsored by the NCI or leading U.S. institutions, including the most recent study sponsored by Yale University," Dr. Buesa added. "In first-line AML, the triple combination has shown a 100% overall response rate to date, with no dose-limiting toxicities, highlighting a highly competitive profile among emerging triplet regimens. The trial continues to enroll rapidly, and we plan to present data from 15-16 patients at the European Hematology Association Annual Congress (EHA) in June. This would represent approximately 75% of the planned enrollment, providing a very meaningful interim assessment of efficacy and safety. Encouraging results are also emerging in MDS and MPN."
"In sickle cell disease, we are advancing iadademstat into what we believe represents a new paradigm for the pharmaceutical industry, medium-priced therapies addressing large patient populations. The first two cohorts of the RESTORE trial have been enrolled, and we expect to report meaningful data later this year."
"In CNS, we have further strengthened our medical and regulatory capabilities with the appointment of renowned CMO Dr. Rolando Gutierrez, who brings extensive experience from the psychiatric field to lead vafidemstat through late-stage development and regulatory interactions, particularly with the U.S. Food and Drug Administration (FDA)," continued Dr. Buesa. "Discussions with the Agency are expected to continue in the coming months, and the Company anticipates a resubmission of the Phase III protocol before year-end, in line with standard regulatory timelines. At the same time, we continue to advance our programs in schizophrenia and ASD."
Fourth Quarter and Recent Highlights
Iadademstat:
Very encouraging preliminary data from the ongoing ALICE-2 Phase Ib clinical trial of iadademstat in combination with venetoclax and azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) were presented at the American Society of Hematology (ASH) Annual Meeting held in December 2025. The iadademstat triplet combination with venetoclax and azacitidine achieved an overall response rate (ORR) of 100% (n=10), with 90% of patients achieving strict complete remission (CR). 70% of patients transitioned to allogeneic hematopoietic stem cell transplantation (HSCT). Median overall survival (OS) was not reached, and 6-month OS was 66%. Treatment with iadademstat in combination with venetoclax and azacitidine was safe and well tolerated, with an adverse event profile similar to other combination treatments in newly diagnosed AML setting. The trial continues to enroll patients at dose level 2 (DL2). This investigator-initiated study (IIS) is led by the Oregon Health & Science University (OHSU) Knight Cancer Institute, and plans to enroll up to 24 patients to attain 21 evaluable patients. The company aims to present a data update at the European Hematology Association (EHA) congress in June 2026.
Positive preliminary results were also reported at ASH-2025 from the ongoing open-label, multicenter Phase Ib FRIDA clinical trial of iadademstat in combination with gilteritinib in patients with relapsed or refractory (R/R) AML harboring a FLT3 mutation (FLT3mut+). The ASH communication reported data for 37 patients, with 4 dose level cohorts evaluated in the escalation phase. All doses tested in the escalation phase were safe per DLT criteria. At the time of the data cut-off, the study was in the expansion phase at one selected pharmacologically active dose, with a total of 17 patients enrolled at that dose level. Preliminary activity at the dose under expansion showed a 67% composite CR rate (CCR, 10/15 patients) and a 47% CR+CRh (7/15) in 15 patients evaluable for response, which favorably compares with the results of the ADMIRAL trial (CR+CRh 34%), particularly in light of contemporary practice with many patients (47%) treated at this dose after failing venetoclax, a population with markedly decreased response to gilteritinib monotherapy. Four patients had undergone HSCT. The trial is now fully enrolled and the company intends to submit updated data for presentation at EHA-2026.
A new Phase Ib trial of iadademstat in combination with an immune checkpoint inhibitor and radiotherapy in extensive-stage small cell lung cancer (ES-SCLC) has recently started to enroll patients. The study, which is sponsored and conducted by Yale University, is an open-label, non-randomized Phase Ib study that will evaluate the safety, tolerability, and efficacy of iadademstat combined with atezolizumab and stereotactic body radiation therapy (SBRT) followed by maintenance therapy with atezolizumab and iadademstat in patients with residual, progressive or recurrent ES-SCLC who previously received platinum-based chemotherapy with or without immune checkpoint inhibitor therapy.
Enrollment has also actively continued in the additional ongoing iadademstat trials, conducted under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) in first line AML, myeloproliferative neoplasms and small cell lung cancer, and as an investigator-initiated study in myelodysplastic syndrome.
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), and investigate 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 is actively enrolling patients, with the first two cohorts already enrolled. The study is conducted across several sites in Spain and aims to enroll approximately 40 adult patients.
Oryzon plans to initiate a clinical trial to evaluate iadademstat in essential thrombocythemia (ET) following recent approval by the European Medicines Agency (EMA). The study, named IDEAL (IaDademstat treatment for EssentiAL thrombocythemia), is a multicenter, single-arm Phase II study to be conducted in Spain in adult patients with ET who are resistant/intolerant to hydroxyurea. The primary objectives of the study are to evaluate the safety and tolerability of iadademstat and to assess its efficacy in reducing the percentage of adult ET patients with abnormal platelet counts. Secondary objectives include assessing the durable clinical hematologic response (DCHR) rate, confirming the pharmacokinetic and pharmacodynamic profile of iadademstat in ET patients, and evaluating the duration of hematologic remissions (DHRs).
Oryzon has recently strengthened its IP protection for iadademstat, with a "Decision to grant" communication from the Japanese Patent Office for its patent application entitled "Combinations of iadademstat for cancer therapy", relating to its use in combination with PD1 or PD-L1 inhibitors. Once formally granted, this patent will remain in force until at least 2040, excluding potential patent term extensions. Corresponding patents have already been granted or allowed in Europe, Australia, and Russia, and additional patent applications are pending in other countries.
Vafidemstat:
Oryzon continues to advance the Phase III PORTICO-2 trial with vafidemstat in aggression in Borderline Personality Disorder (BPD) following written feedback from the U.S. FDA, which included guidance on study endpoints and certain non-clinical considerations. In preparation for protocol resubmission and in alignment with the Agency's recommendations, the Company is undertaking a range of activities, including qualitative research to generate additional evidence on the content validity and appropriateness of clinical outcome measures proposed as endpoints.
To further enhance its clinical strategy and execution, Oryzon has appointed Rolando Gutierrez-Esteinou, M.D., as Chief Medical Officer for CNS programs. Dr. Gutierrez-Esteinou is a Harvard-trained psychiatrist and experienced clinical development executive with more than 20 years of leadership in neuroscience and psychiatry drug development, including oversight of late-stage clinical trials and global development strategy. Most recently serving as Chief Medical Officer at Atai Life Sciences, he brings extensive expertise in advancing innovative CNS therapies through pivotal studies, reinforcing the Company's medical leadership as it progresses vafidemstat towards Phase III clinical development.
Oryzon is finalizing preparations for 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 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 under the Med4Cure IPCEI EU initiative.
Enrollment continues in the EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia. 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 IP protection for vafidemstat, with an additional "Decision to grant" communication from the Japanese Patent Office. The allowed claims cover the use of vafidemstat for the treatment of aggressiveness and social withdrawal. Once formally granted, this patent will remain in force until at least 2038, excluding any potential patent term extension, which could provide additional years of protection. 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.
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 for clinical trials.
Financial Update: Fourth quarter 2025 Financial Results
Research and development (R&D) expenses were $5.2 million and $14.8 million for the quarter and twelve months ended December ...
