Clinical Trials
Oryzon has two compounds in clinical development, iadademstat (also known as ORY-1001), a selective LSD1 inhibitor for oncology and hematology indications, and vafidemstat (also known as ORY-2001), a CNS optimized LSD1 inhibitor for neurological and psychiatric disorders.
In oncology, Oryzon has completed a Phase I clinical trial with iadademstat in patients with relapsed/refractory (R/R) acute leukemia, a Phase IIa trial (the CLEPSIDRA study) evaluating iadademstat in combination with platinum-etoposide in patients with relapsed small cell lung cancer (SCLC), and a Phase IIa trial (the ALICE study) assessing the safety, tolerability, dose finding and efficacy of iadademstat in combination with azacitidine in newly diagnosed patients with Acute Myeloid Leukemia (AML) who were not eligible for intensive chemotherapy. Positive final data from the ALICE study were presented at the American Society of Hematology (ASH) 2022 conference and have been published in The Lancet Hematology.
Oryzon is currently conducting a Phase Ib trial (the FRIDA study) evaluating iadademstat in combination with gilteritinib in patients with R/R AML with FLT3 mutations. In parallel, Oryzon is expanding the clinical development of iadademstat in first-line unfit AML through an investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU), in which iadademstat is being evaluated in combination with the standard-of-care regimen venetoclax plus azacitidine. IISs are clinical trials that are conducted and sponsored under the responsibility of independent non-Oryzon sponsors, such as academic institutions or individual investigators, who must ensure that the studies are conducted and managed in accordance with all applicable laws and regulations. IISs can contribute towards expanding the scientific understanding of Oryzon's products and their potential therapeutic applications. Encouraging preliminary efficacy and safety data from the FRIDA and OHSU studies were presented at ASH-2025. Additional IIS trials in other malignancies are ongoing.
In addition, under a Cooperative Research and Development Agreement (CRADA) between Oryzon and the U.S. National Institutes of Health (NIH), the National Cancer Institute (NCI) is sponsoring several clinical trials with iadademstat, including a randomized Phase I/II trial in first-line extensive disease SCLC evaluating iadademstat in combination with immune checkpoint inhibitors.
In Hematology, Oryzon is conducting a Phase Ib trial (the RESTORE trial) evaluating iadademstat in adults with sickle cell disease (SCD).
With vafidemstat, Oryzon completed a Phase I clinical trial in healthy volunteers, and Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders: Autism Spectrum Disorder (ADS), Borderline Personality Disorder (BPD) and adult Attention Deficit Hyperactivity Disorder (the REIMAGINE study), and in aggressive/agitated patients with moderate or severe Alzheimer’s disease (the REIMAGINE-AD study), with positive clinical results reported in both trials. Additional completed Phase IIa clinical trials with vafidemstat include the ETHERAL and ETHERAL-US studies in patients with mild to moderate Alzheimer’s disease, in which a significant reduction of an inflammatory biomarker was observed after 6 months of treatment; the pilot SATEEN study in patients with relapse-remitting and secondary progressive multiple sclerosis; and the ESCAPE study, a Phase II trial in severely ill COVID-19 patients that assessed the potential of vafidemstat to prevent acute respiratory distress syndrome (ARDS), one of the most severe complications of the viral infection.
Following completion of the global, randomized, double blind Phase IIb PORTICO trial in BPD, vafidemstat is advancing as a Phase III-ready asset for the treatment of agitation/aggression in BPD, with a Phase III trial in preparation. In parallel, vafidemstat is being evaluated in a Phase IIb trial in negative symptoms of schizophrenia (the EVOLUTION trial). A clinical trial to evaluate vafidemstat as a treatment of aggression in autistic conditions like Phelan-McDermid syndrome is currently in preparation.
Both of Oryzon’s investigational compounds target the Lysine-specific demethylase LSD1, a key epigenetic enzyme involved in the regulation of histone methylation and chromatin remodeling. Through inhibition of LSD1, these compounds regulate important genes involved in the control of cellular differentiation, survival and proliferation.
Oryzon’s compounds are investigational medicines and have not yet been approved for use outside of clinical trials. Regulatory approval by authorities such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) at the end of their clinical development is required before these medicines can be made available to patients.
Oryzon’s current priority is to advance its clinical development programs and generate the data required to support regulatory review and potential approval of these medicaments. Below is a summary of ongoing and completed clinical trials for iadademstat and vafidemstat.
