ORYZON Reports Financial Results and Corporate Update for Half-Year Ending June 30, 2025

Between December 2024 and July 2025, Oryzon secured financing totaling €52 M, approx. $61 M (€30.0 M from a capital increase, €7.0 M from commercial bank loans, €13.2 M from the EU-IPCEI grant, and €1.8 M from R&D cash-back incentives)

Company has terminated the Convertible Bonds financing facility with Nice&Green

Clinical trial protocol for vafidemstat's Phase III PORTICO-2 trial in BPD submitted to the FDA

Expansion of ongoing Phase IIb EVOLUTION study with vafidemstat in schizophrenia into other EU countries

New Phase II trial in preparation: vafidemstat to target aggression in Autism Spectrum Disorder

Significant clinical progress achieved in ongoing iadademstat's oncology trials in AML (R/R and 1L), MDS and SCLC

Expanding iadademstat into non-malignant hematological indications, with a first clinical trial in sickle cell disease

MADRID and CAMBRIDGE, Mass., July 30, 2025 (GLOBE NEWSWIRE) -- 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 half-year ended June 30, 2025 and provided a corporate update on recent developments.

Since last December, the company has secured $61 million in funding, including $35.2 million (€30 million) from a successful capital raise completed in April through a straight equity issuance with no warrants attached. Despite challenging market conditions, the offering attracted strong investor demand and was significantly oversubscribed.

"Our successful €30 million capital raise, executed under extraodinarily challenging market conditions, represents a strong vote of confidence in Oryzon's science, clinical pipeline, and long-term value proposition," said Dr Carlos Buesa, Oryzon's Chief Executive Officer. "The proceeds not only reinforce our financial position but also elevate our visibility in the international biotech arena. This funding enables us to advance our clinical programs with renewed momentum and strategic clarity. We are confident that the clinical progress and data to be presented in the coming quarters will further validate the trust placed in us by the investment community."

Dr. Buesa continued, "We are moving closer to becoming a Phase III-stage company, following the submission in June of the Phase III clinical trial protocol for vafidemstat in the treatment of agitation and aggression in Borderline Personality Disorder (BPD) to the FDA. This protocol incorporates all feedback and recommendations received from the agency regarding endpoints. In parallel, additional exploratory data from earlier Phase IIa studies suggest that vafidemstat may also reduce aggression in other patient populations. Building on this, we are now initiating preparations for a new Phase II trial to evaluate vafidemstat in aggression associated with autism spectrum disorder, which will be supported under the recently awarded EU-IPCEI grant. Following the recent financing, we are also expanding the ongoing EVOLUTION trial in schizophrenia, previously conducted exclusively in Spain, into additional European countries. This geographic expansion is designed to accelerate recruitment and further strengthen the robustness of the trial."

"In oncology, we are pleased with the solid progress being made across all ongoing iadademstat clinical trials," said Dr. Buesa. "This includes the company-sponsored FRIDA trial in relapsed/refractory FLT3-mutated AML, as well as the IIS and CRADA studies in first-line AML, MDS, and small cell lung cancer. We anticipate presenting updates and data from some of these programs at the upcoming ASH-2025 conference this December, marking an important opportunity to share our clinical advances with the broader hematology and oncology community."

Dr. Buesa added, "We are extremely excited to expand iadademstat's clinical evaluation into non-malignant hematological indications, beginning with sickle cell disease (SCD). In SCD, LSD1 inhibition plays a central mechanistic role in re-inducing fetal hemoglobin, needed to rescue the disease phenotype. Our preliminary data in nonhuman primate models have been highly encouraging compared to other agents in development". He added,"The SCD market is substantial, as highlighted by Pfizer's experience with voxelotor (Oxbryta®), which received FDA accelerated approval in 2019. Although the drug was later withdrawn in 2024 due to emerging safety concerns, its initial commercial promise underscored the significant unmet medical need and the market potential in this indication."

First Half and Recent Highlights

Vafidemstat:

The clinical trial protocol for the PORTICO-2 Phase III trial with vafidemstat in Borderline Personality Disorder (BPD) was submitted to the U.S. Food & Drug Administration (FDA) for approval in June. The primary and key secondary endpoints of the trial have been defined in collaboration with Oryzon's Clinical Advisory Board (CAB), which comprises leading experts in psychiatric research and clinical trials. PORTICO-2 will use two clinical outcome measures to assess aggression: the STAXI-2 Trait anger scale (a patient-reported outcome) as the primary endpoint, and the Overt Aggression Scale-Modified (OAS-M) (a clinician-rated scale) as a key secondary endpoint. Additional secondary endpoints will assess overall BPD improvement and quality of life. The study will enroll approximately 350 patients, randomized 1:1 to receive vafidemstat or placebo, with a total trial duration of 18 weeks. Subject to FDA's review of the final data, PORTICO-2 has the potential to be one of the two registrational trials required by the FDA for potential approval of vafidemstat in this indication. FDA approval for the study is expected in 2H25.

A dedicated Key Opinion Leader (KOL) webinar with the participation of Dr. Michael Ropacki, Oryzon's CMO for CNS, and Oryzon's CAB members was held on July 9 to discuss the PORTICO-2 study design, the substantial unmet medical need in BPD, and the role of aggression as a clinical target. A replay of this event is available at the company's website, here.

Oryzon has announced plans to evaluate vafidemstat for the treatment of aggression in patients with autism spectrum disorder (ASD) in a new Phase II trial. This trial, named HOPE-2, plans to include, inter alia, genetically-defined ASD subpopulations, such as individuals with Phelan-McDermid syndrome, and will initially be conducted in Spain as part of the activities supported by the recently granted Med4Cure IPCEI EU initiative.

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. Based on insights gained from the PORTICO trial, a reassessment of the number of patients needed to obtain a clinically meaningful impact has been conducted, and as a result, the trial is being re-sized to a total number of 84 patients. Initially conducted only in Spain, the trial is now being expanded to include additional EU countries.

Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter, with additional "Decision to grant" communications from the Canadian and Israel patent offices for patent applications titled "Methods of treating behavior alterations". The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal. Once issued, these patents will not expire until at least 2038, excluding any potential patent term extension. Corresponding patents have already been granted or allowed in Europe, Australia, Hong Kong, South Korea, Malaysia, the Philippines, and Russia, and additional applications are pending in other countries.

Iadademstat:

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 patients with newly diagnosed AML have continued to actively enroll patients. One trial is sponsored by the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI, while the other is an Investigator-initiated study (IIS) sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute.

In addition, 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), has also continued to actively enroll patients.

The Phase I/II trial with iadademstat plus immune checkpoint inhibitors (ICI) in first line small cell lung cancer (SCLC) patients with extensive disease, conducted under the CRADA that Oryzon has in place with the NCI, started to enroll patients in April 2025. The trial 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 30 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.

Beyond oncology, Oryzon has announced plans to evaluate iadademstat in non-malignant hematological disorders, such as sickle cell disease (SCD) and essential thrombocythemia (ET). A clinical trial application (CTA) - the EU equivalent to an IND - for a new Phase Ib trial with iadademstat in SCD has been submitted to the European Medicines Agency (EMA). This trial, named RESTORE (REgulation of Sickling ThrOugh Reprogramming Epigenetics), aims to enroll 40 patients. The primary objectives will be to evaluate the safety and tolerability of iadademstat in adult patients with SCD, and to determine its Recommended Phase 2 dose (RP2D). Secondary objectives include assessing iadademstat's activity in inducing fetal hemoglobin, among others. CTA approval is expected in September. A second trial, which will evaluate iadademstat in ET, is currently in preparation, with CTA submission to EMA planned for 2H25.

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 half 2025 Financial Results

Research and development (R&D) expenses were $3.0 million and $5.8 million for the quarter and six months ended June 30, 2025, compared to $2.3 and $4.9 million for the quarter and six months ended June 30, 2024.

General and administrative expenses were $1.4 and $2.7 million for the quarter and six months ended June 30, 2025, compared to $1.2 and $2.1 million for the quarter and six months ended June 30, 2024.

Net losses were $1.7 and $3.4 million for the quarter and six months ended June 30, 2025, compared to $1.5 and 2.6 million for the quarter and six months ended June 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 $1.9 million (–$0.03 per share) for the six months ended June 30, 2025, compared to a negative net result of $1.1 million (–$0.02 per share) for the six months ended June 30, 2024.

Cash, cash equivalents, and marketable securities totaled $36.5 million as of June 30, 2025.

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 July 2025, the company received the full disbursement of the Important Project of Common European Interest (IPCEI) grant, totaling €13.2 million (approximately $15 million USD), for its VANDAM project.

Given the Company's current treasury needs, the financing agreement between Nice & Green and the Company was terminated in July through a payment of €4.7 million. As a result, Oryzon received 1,340,083 of its own shares, increasing its treasury stock to a total of 2,374,666 shares.

ORYZON GENOMICS, S.A.

BALANCE SHEET DATA (UNAUDITED)1

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June 30th, 2025

 

June 30th, 2024