Gilteritinib Fumarate

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, February 27th, 2025 – Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, today reported financial results for the fourth quarter ended December 31, 2024 and provided a corporate update on recent developments. “The publication of the final dataset from the REIMAGINE study on aggression in autism, ADHD, and borderline personality disorder (BPD) in a prestigious specialized journal has allowed the scientific and investment community to better contextualize and appreciate the relevance of vafidemstat’s results in treating aggression in our Phase IIb PORTICO trial,” said Dr Carlos Buesa, Oryzon’s Chief Executive Officer. “As we mentioned in the previous Note, we received the official minutes from our End-of-Phase II meeting with the FDA, confirming that we can proceed to a Phase III. The FDA also indicated that agitation/aggression in BPD may be an acceptable indication, and agreed that we may use the same aggression scale that showed the strongest signal in Phase II. With this positive feedback, we are continuing the preparations to submit the full Phase III protocol to the FDA within the next 1–2 months. We have also continued patient recruitment in our ongoing EVOLUTION trial in schizophrenia in Spain.” Dr Buesa continued, “In oncology, we continue our efforts to further evaluate iadademstat in first line unfit AML patients through two ongoing trials in combination with azacitidine and venetoclax - one under our CRADA agreement with the NCI and another as an investigator-initiated study (IIS) at Oregon Health & Science University (OHSU). The OHSU-led trial has already enrolled the first two cohorts, representing a significant progress in our oncology program and potentially expanding our clinical development options, if results are positive. Additionally, a new IIS sponsored by the Medical College Wisconsin in combination with azacitidine in patients with myelodysplastic syndrome has started to enroll patients. In June, we presented promising initial data from our FRIDA Phase Ib trial at the EHA Conference, showing that iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML was safe and showed strong antileukemic activity, with encouraging response rates and a faster time to response compared to historical data on gilteritinib alone. With the third cohort enrolled, and as the data matures, we plan to present additional results at ASH in December.” Dr Buesa added, “As the company transitions into a Phase III organization for the first time, we are restructuring our Board of Directors to be more U.S.-centric. The Board will now have three Directors based in the Bay Area, with extensive Nasdaq and industy experience. This will enhance our outreach and strengthen our dialogue with corporate partners and Tier-1 investors. While maintaining strict budgetary discipline and leveraging our Convertible Notes program, we also anticipate additional financial support from the recently approved IPCEI grant from the EU. This funding will be instrumental in advancing our R&D efforts in personalized medicine for CNS and oncology. Meanwhile, the company continues discussions with corporate partners and actively evaluates additional financing opportunities.” Fourth Quarter and Recent Highlights Vafidemstat in large multifactorial CNS indications: Following positive feedback from the end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), Oryzon is advancing in the preparations for Phase III, including the preparation of a full protocol for the PORTICO-2 Phase III trial to submit to the FDA for study approval. The trial will use STAXI-2 Trait anger as a primary efficacy endpoint measure. Secondary endpoints will include both patient-rated and clinician-rated scales to assess agitation/aggression and overall BPD improvement. 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 company expects to obtain FDA’s approval for PORTICO-2 in 1H2025. The final results of the Phase IIa REIMAGINE study, which evaluated the safety and efficacy of vafidemstat on aggression in adult patients with BPD, attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD), have been published online in the clinical psychiatry journal Psychiatry and Clinical Neurosciences. As reported in the publication, the study showed that vafidemstat was safe and well-tolerated and elicited significant and consistent reduction in agitation/aggression in patients with BPD, ADHD, and ASD. REIMAGINE was a proof-of-concept trial that laid the foundation for the subsequent PORTICO Phase IIb clinical trial in BPD. A summary of the final data from REIMAGINE had been previously released at the 2020 European Psychiatry Association (EPA) annual meeting. Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter, with an additional “Decision to grant” communication in its patent family titled “Methods of treating borderline personality disorder”, now in Russia. Oryzon has also received “Decision to grant” communications for corresponding patent applications in Europe and Mexico, and a patent has already been granted in Japan, with patent applications pending in other relevant markets. These patents will not expire until at least 2040, excluding potential patent term extensions that may provide additional protection. Additionally, Oryzon recently secured granted patents in Europe, Australia, Korea, Malaysia, Philippines, and Russia under another patent family that covers the use of vafidemstat for the treatment of aggression and social withdrawal, with patent applications pending in additional countries. These patents will not expire until at least 2038, excluding any potential patent term extension that 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 continue to evaluate the feasibility of a new precision medicine trial in Kabuki Syndrome. The company will decide on a possible submission of an IND for HOPE to the FDA in 2025. 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. 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 first patient has been dosed in the Phase I dose-finding clinical trial of iadademstat in combination with venetoclax and azacitidine in newly diagnosed acute myeloid leukemia (AML), sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI. This Phase I dose-finding study is now actively enrolling patients. Additionally, the Investigator-initiated study (IIS) sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute also evaluating the combination of iadademstat with venetoclax and azacitidine in first line AML continues to enroll patients. The first patient has been dosed in the IIS Phase I dose-finding trial of iadademstat in combination with azacitidine inmyelodysplastic syndrome (MDS), led by the Medical College of Wisconsin (MCW). This Phase I dose-finding study is now actively enrolling patients. 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 Fox Chase Cancer Center. The Phase I/II trial with iadademstat plus immune checkpoint inhibitors in first line SCLC patients with extensive disease under the CRADA agreement with the NCI, already approved by the FDA, is ready to start enrolling patients. 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, with Dr. Charles Rudin from the Memorial Sloan Kettering Cancer Center (MSKCC) as the main PI for the trial, and Dr. Noura Choudhury from University of Chicago as co-PI. 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 1Q2025. 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: Fourth Quarter 2024 Financial Results Research and development (R&D) expenses were $2.1 million and $8.7 million for the quarter and twelve months ended December 31, 2024, compared to $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023. As a result of the completion of the PORTICO clinical trial, the company saves $7.9M with respect to the twelve months ended December 31, 2023. General and administrative expenses were $0.9 and $3.7 million for the quarter and twelve months ended December 31, 2024, compared to $1.2 and $4.2 million for the quarter and twelve months ended December 31, 2023. Net losses were $1.0 and $4.6 million for the quarter and twelve months ended December 31, 2024, compared to $1.4 and 5.0 million for the quarter and twelve months ended December 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 $3.8 million (–$0.06 per share) for the twelve months ended December 31, 2024, compared to a negative net result of $3.7 million (–$0.06 per share) for the twelve months ended December 31, 2023. Cash, cash equivalents, and marketable securities totaled $5.8 million as of December 31, 2024.