-- Strong cash position at year-end 2025: $33.3 million (EUR28.4 million)
CNS Oncology -- Hematology
(Vafidemstat) (Iadademstat)
-- Appointed renowned Rolando Gutierrez-Esteinou, M.D. -- Seven ongoing oncology trials, with six sponsored by
as new CMO for CNS the NCI or top-tier U.S. institutions
-- Preparing protocol resubmission to incorporate FDA -- Positive data in 1L AML unfit patients presented at
guidance on Phase III PORTICO-2 trial in aggression ASH with 100% ORR (90% strict CR)
in BPD -- Positive data in R/R FLT3+ AML presented at ASH; 67%
-- Ongoing expansion of Phase IIb schizophrenia trial CCR at the selected dose under expansion
into additional EU countries -- Initiated enrollment in new Phase Ib trial in small
-- Finalizing preparations for new Phase II trial in cell lung cancer in combination with ICI and
aggression in autism spectrum disorder as a part of radiotherapy
the IPCEI EU Grant in personalized medicine -- 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 (EUR28.4 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 31, 2025, compared to $2.1 and $8.7 million for the quarter and twelve months ended December 31, 2024.
General and administrative expenses were $1.7 and $5.6 million for the quarter and twelve months ended December 31, 2025, compared to $0.9 and $3.7 million for the quarter and twelve months ended December 31, 2024.
Net losses were $2.1 and $6.7 million for the quarter and twelve months ended December 31, 2025, compared to net losses of $1.1 and $4.6 million for the quarter and twelve months ended December 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 $3.1 million (--$0.04 per share) for the twelve months ended December 31, 2025, compared to a negative net result of $3.7 million (--$0.06 per share) for the twelve months ended December 31, 2024.
Cash, cash equivalents, and marketable securities totaled $33.3 million as of December 31, 2025.
ORYZON GENOMICS, S.A.
BALANCE SHEET DATA (AUDITED)(1)
(Amounts in thousands US $)
December December
31st, 2025 31st, 2024
----------- -----------
Cash and cash equivalents 33,316 5,837
Marketable securities 0 0
Total Assets 169,816 114,119
----------- -----------
Deferred revenue 0 0
----------- -----------
Total Stockholders' equity 138,473 91,602
----------- -----------
ORYZON GENOMICS, S.A.
STATEMENTS OF OPERATIONS (AUDITED)(1)
(US $, amounts in thousands except per share data)
Three Months Ended Twelve Months Ended
December 31st December 31st
---------------------- ----------------------
2025 2024 2025 2024
---------- ---------- ---------- ----------
Collaboration Revenue 0 0 0 0
Operating expenses:
Research and Development 5,171 2,116 14,805 8,682
General and
administrative 1,701 866 5,594 3,698
---------- ---------- ---------- ----------
Total operating expenses 6,872 2,982 20,399 12,380
---------- ---------- ---------- ----------
Loss from Operations -6,872 -2,982 -20,399 -12,380
---------- ---------- ---------- ----------
Other income, net 4,804 1,927 13,689 7,785
Net Loss -2,068 -1,055 -6,710 -4,595
========== ========== ========== ==========
Net Financial & Tax 484 -302 3,648 878
Net Result -1,584 -1,357 -3,062 -3,717
========== ========== ========== ==========
Loss per share allocable to common
stockholders:
Basic -0.02 -0.02 -0.04 -0.06
---------- ---------- ---------- ----------
Weighted average Shares
outstanding
Basic 77,513,039 64,370,778 74,365,269 62,847,943
---------- ---------- ---------- ----------
(1Spanish GAAP)
* Exchange Euro/Dollar
(1.1750 for 2025 and
1.0389 in 2024)
About Oryzon
Founded in 2000 and headquartered in Barcelona, Spain, Oryzon (ISIN: ES0167733015) is a clinical-stage biopharmaceutical company and a European leader in epigenetics, with a strong focus on personalized medicine for central nervous system $(CNS)$ disorders and oncology. Oryzon's team comprises highly experienced pharmaceutical professionals based in Barcelona, Boston, and New Jersey. The Company has an advanced clinical portfolio built around two LSD1 inhibitors: vafidemstat, its lead CNS program, which is Phase III--ready; and iadademstat, its oncology/hematology program, with several ongoing Phase I and II studies and outstanding preliminary results in first-line acute myeloid leukemia, including a 100% overall response rate (ORR) presented at ASH 2025. In addition, Oryzon is advancing a broader epigenetics pipeline targeting other mechanisms, including HDAC6, for which a clinical candidate, ORY-4001, has been nominated for potential development in Charcot--Marie--Tooth disease (CMT) and amyotrophic lateral sclerosis (ALS). The Company also operates a robust platform for biomarker identification and target validation across a range of malignant and neurological diseases. For more information, visit www.oryzon.com
About Iadademstat
Iadademstat (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 azacitidine and venetoclax in 1L AML in an investigator-initiated study (IIS) led by OHSU and in combination with gilteritinib in the company-sponsored Phase Ib FRIDA trial in relapsed/refractory FLT3-mutant AML, with highly encouraging preliminary safety and efficacy data recently reported at ASH-2025 for both trials: 100% ORR and 90% strict CR in 1L AML, and 67% CCR (at the dose under expansion) in R/R AML. Additional studies in hemato-oncology include an IIS in MDS, and trials in myeloproliferative neoplasms and 1L AML both sponsored and conducted by the U.S. National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI. 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 two trials in ED-SCLC: a Phase I/II randomized trial in 1L in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center, and an IIS trial in 1L/2L in combination with ICI and radiotherapy. In addition, Oryzon has expanded iadademstat's clinical development into non-oncological hematology indications, with trials in sickle cell disease (approved by EMA, enrolling) and essential thrombocythemia (approved by EMA). 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. Following completion of the global, randomized, double blind Phase IIb PORTICO trial in Borderline Personality Disorder (BPD), with final data presented at ECNP-2024, vafidemstat is advancing as a Phase III-ready asset for agitation/aggression in BPD (PhIII in preparation). 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, as well as in neurodevelopmental syndromes, and is preparing a clinical trial in aggression in autistic conditions like Phelan-McDermid syndrome.
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 etorrell@oryzon.com svonderweid@lifesciadvisors. mcordera@atrevia.com com
(END) Dow Jones Newswires
February 27, 2026 12:29 ET (17:29 GMT)