Oryzon Genomics, S.A. is advancing its clinical programs in both central nervous system (CNS) disorders and oncology. The company recently presented final data from the Phase IIb PORTICO trial of vafidemstat in Borderline Personality Disorder (BPD) at the 37th European College of Neuropsychopharmacology (ECNP) annual conference in Milan, Italy. Furthermore, following positive feedback from an End-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), Oryzon is moving forward with preparations for the PORTICO-2 Phase III trial of vafidemstat in BPD.
Vafidemstat in Borderline Personality Disorder
The PORTICO trial data presented at ECNP 2024 showed statistically significant improvements in the State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger, a measure of agitation and aggression (p = 0.0071), and in the Borderline Evaluation of Severity (BEST), an overall measure of BPD disease severity (p = 0.0260). The Global Statistical Test (GST) analysis confirmed a global treatment effect favoring vafidemstat, particularly in improving disease severity and agitation/aggression (p = 0.0362). Vafidemstat was safe and well-tolerated.
The FDA indicated that agitation/aggression in BPD may be an acceptable indication for vafidemstat, and agreed that Oryzon may use the same aggression scale that showed the strongest signal in Phase II. The PORTICO-2 Phase III trial is expected to enroll 350 patients, randomized 1:1 to vafidemstat or placebo, with a trial duration of 18 weeks. The company anticipates obtaining FDA approval for PORTICO-2 by the end of Q1 2025.
Intellectual Property Expansion
Oryzon has been granted European patent EP3661510B1, titled “Methods of treating behavior alterations,” covering the use of vafidemstat for the treatment of aggression and social withdrawal. Corresponding patents have also been granted in South Korea, with “intention to grant” communications received in Australia and Malaysia. These patents will not expire until at least 2038. Additionally, Oryzon has received “intention to grant” communications in Europe and Mexico for another key patent family related to vafidemstat titled “Methods of treating borderline personality disorder,” with a corresponding patent granted in Japan. These patents will not expire until at least 2040.
Iadademstat in Oncology
The first cohort has been dosed in an Investigator-initiated Phase Ib study of iadademstat with venetoclax and azacitidine in first-line AML, conducted by Oregon Health & Science University (OHSU). This trial represents a significant advancement in Oryzon's oncology program. Iadademstat will also be evaluated in combination with venetoclax and azacitidine in first-line AML patients in a trial under the Cooperative Research and Development Agreement (CRADA) signed with the National Cancer Institute (NCI) in the United States. This trial is expected to start enrolling patients in 4Q2024 and plans to enroll 45 patients.
Other Clinical Developments
The EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia continues to enroll participants in Spain. This study aims to assess the efficacy of vafidemstat, with a primary focus on improving negative symptoms. The company is also evaluating the feasibility of a new precision medicine trial in Kabuki Syndrome and will decide on a possible submission of an IND for HOPE to the FDA in 2025.
The FRIDA Phase Ib trial, evaluating iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, continues to enroll patients. The company continues to explore the minimal dose with clinical activity. A 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. 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 is now ready to start enrolling patients.
Financial Highlights
Research and development (R&D) expenses were $1.9 million for the quarter ended September 30, 2024, compared to $3.8 million for the quarter ended September 30, 2023. Cash, cash equivalents, and marketable securities totaled $8.4 million as of September 30, 2024.
