ORYZON reports financial results and corporate update for quarter ended March 31, 2024

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, May 6^th, 2024 – Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with a strong unmet medical need, today reported financial results for the quarter ended March 31, 2024 and provided a corporate update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon continued with a strong path in its clinical programs in the first quarter. In CNS, following presentation in January of topline data from our Phase IIb PORTICO trial evaluating vafidemstat as a treatment for Borderline Personality Disorder (BPD), we are finalizing the full data set analysis. The company is preparing the request of an End-of-Phase II meeting with the FDA to discuss the design of a Phase III. Our Phase IIb trial with vafidemstat in schizophrenia, EVOLUTION, has also continued to enroll patients. Importantly, we have received from the European Patent Office (EPO) an “intention to grant” communication for Oryzon’s European patent application covering the use of vafidemstat for the treatment of aggression and social withdraw. We have also received a notice of allowance for this patent in Korea. These patents will significantly strengthen our IP position, extending the commercial life for our drug.”

Dr Buesa continued: “In oncology, our iadademstat program has continued to make good progress. In the FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, the second cohort is completed, and the third cohort is currently recruiting. The company’s assessment on the initial preliminary data looks very promising when compared to gilteritinib alone in historical data. We will report some preliminary data at the EHA Conference next June in Madrid. In addition, we are expanding iadademstat’s clinical development through additional clinical trials under our CRADA with the NCI and also through investigator-initiated studies. Iadademstat’s randomized Phase II trial under CRADA in 1L-ED SCLC in combination with ICIs received FDA IND approval recently and will provide critical data on this disease. We expect this trial and the IIS trial in first-line AML in combination with venetoclax and azacitidine to start enrolling in the next 2-3 months.”

Dr Buesa added: “While we have experienced a clear advance in our clinical pipeline, on the financial side, the company has continued its budgetary discipline in an adverse market for public companies. This, and the combination of non-dilutive funds (private and public grants and loans from commercial Spanish banks) with the withdrawal of €10 million from our €45 million Convertible Bond program allow us to extend the runway until 2025 and to focus now on the next conversations with the FDA and EMA and our clinical execution.”

First Quarter and Recent Highlights

Vafidemstat in large multifactorial CNS indications:

• Following presentation of topline data from the Phase IIb PORTICO trial in January, the company is currently completing the full data analysis and plans to provide a full data presentation at a psychiatric conference later this year, as well as in a peer-reviewed journal publication. Once the full analysis is completed, Oryzon intends to request an end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA) to discuss plans for a registrational Phase III study for the treatment of BPD.
• ORYZON secures another important patent for its lead CNS asset, vafidemstat in the EU. The European Patent Office (EPO) has issued an “intention to grant” communication for Oryzon’s European patent application EP18748921.6 entitled “Methods of treating behavior alterations”. A corresponding intention to grant communication has also been recently received in Korea. The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal.
• The EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia continues to enroll patients. This Phase IIb study aims to evaluate the efficacy of vafidemstat on negative symptoms and cognitive impairment in patients with schizophrenia. This project is partially financed with public funds from the Spanish Ministry of Science and Innovation and is being carried out in various Spanish hospitals.

Vafidemstat in monogenic CNS indications:

• We continue the preparations of a new precision medicine trial in Kabuki Syndrome (KS). The company is in a dialogue with the regulatory agencies to refine the final design of this trial and expects to submit an IND for HOPE to the FDA in 2024.

Iadademstat in oncology:

• 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. The first two cohorts have been completed (thirteen patients), and the combination was safe and showed strong antileukemic activity. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity, and a third cohort has been started and is recruiting. 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. Secondary objectives include the evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the Duration of Responses (DoR), and the assessment of Measurable Residual Disease (MRD). 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 is further expanding the clinical development of iadademstat in AML through an Investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This trial is a Phase Ib dose-finding study to evaluate iadademstat in combination with venetoclax and azacitidine in first-line AML patients, and is expected to begin enrolling patients in 2Q2024.
• The collaborative Phase II basket trial of iadademstat in combination with paclitaxel in platinum R/R small cell lung cancer (SCLC) and extrapulmonary high-grade neuroendocrine tumors (NET trial) continues to enroll patients. This trial is being conducted in the U.S. under a collaborative clinical research agreement with the FCCC, under which the FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug, and technical expertise.
• The FDA has recently approved the Investigational New Drug (IND) application to initiate a Phase I/II trial with iadademstat plus immune checkpoint inhibitors in first line SCLC patients with extensive disease. This will be the first iadademstat’s trial under the Cooperative Research and Development Agreement (CRADA) signed with the National Cancer Institute (NCI) in the United States. The trial is entitled “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” and will be conducted and sponsored by the NCI, part of the National Institutes of Health, with Dr. Noura Choudhury from the Memorial Sloan Kettering Cancer Center (MSKCC) as the main PI for the trial. A number of prestigious cancer centers in the US, including the MSKCC, the JHU Sidney Kimmel Comprehensive Cancer Center and many others will participate. The trial plans to enroll 45-50 patients and is expected to start enrolling patients in Q2 2024.
• The STELLAR trial, a randomized, multicenter Phase II study of iadademstat plus a checkpoint inhibitor in first-line extensive-stage SCLC, will be informed and refined from the findings of the CRADA-MSKCC trial in the same space and with the same design that is expected to start in 2Q2024, as mentioned above. The company believes that STELLAR could potentially support an application for accelerated approval.

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 2024 Financial Results

Research and development (R&D) expenses were $2.6 million for the quarter ended March 31, 2024, compared to $4.4 million for the quarter ended March 31, 2023. As a result of the completion of the PORTICO clinical trial, the company saves $1.8M with respect to the first quarter of 2023.

General and administrative expenses were $0.9 million for the quarter ended March 31, 2024, compared to $1.2 million for the quarter ended March 31, 2023.

Net losses were $1.1 for the quarter ended March 31, 2024, respectively, compared to $1.4 million for the quarter ended March 31, 2023. 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 $1.2 million (–$0.02 per share) for the first quarter ended March 31, 2024, compared to a negative net result of $1.8 million (–$0.03 per share) for the first quarter ended March 31, 2023.

Cash, cash equivalents, and marketable securities totaled $11.6 million as of March 31, 2024, compared with $13.5 million as of Dec 31, 2023.