お知らせ • Jun 12
Oryzon Genomics Presents Updated Clinical Data for Iadademstat in Acute Myeloid Leukemia At European Hematology Association 2026 Annual Congress
Oryzon Genomics presented updated positive clinical data from two clinical trials of its selective LSD1 inhibitor iadademstat in acute myeloid leukemia (AML) at the 2026 European Hematology Association (EHA) Annual Congress. In first line AML (ALICE-2 trial), iadademstat with azacitidine and venetoclax showed high levels of clinical activity, with 100% (18/18) overall response rate (ORR), 89% (16/18) composite complete remission (CRc) and 78% (14/18) complete response (CR), and continued to demonstrate a favorable safety profile. All patients with TP53 or RAS pathway mutations achieved a complete response, showcasing the activity of the iadademstat combination across genomically defined adverse-risk subgroups and its potential in these populations. In FLT3-mutated refractory-relapsed patients (FRIDA trial), iadademstat with gilteritinib continued to show a favorable safety profile and a high CRc rate of 67%. ALICE-2 Phase Ib clinical trial (NCT06357182) investigating iadademstat in combination with azacitidine and venetoclax in newly diagnosed AML reported high rates of activity, with a 100% (18/18) overall response rate (ORR), 89% (16/18) composite complete remission (CRc) rate and 78% (14/18) complete response (CR) rate. CRs occur early, most of them in cycle 1. Efficacy was observed across different genomic risk groups, including TP53 and RAS pathway mutations and patients with complex karyotypes, all considered adverse risk. Patients with TP53-mutated disease (2/2) attained CR and showed a reduction in TP53 variant allele frequency (14% to undetected and 22% to 1%, respectively). All patients with RAS pathway mutations (3/3) achieved CR. After a median follow-up of 8 months, median overall survival (OS) and event-free survival (EFS) were not reached; estimated 12-month OS and EFS were 79% and 71%, respectively. 9 patients successfully transitioned to allogeneic hematopoietic cell transplantation (HCT), with an estimated 12-month OS of 88%. The iadademstat-azacitidine-venetoclax combination continues to show a favorable safety profile. FRIDA Phase Ib clinical trial (NCT05546580) investigating iadademstat in combination with gilteritinib in FLT3-mutated relapsed/refractory AML reported data from the expansion cohort at the selected pharmacological active dose (PAD, 75 ug iadademstat); 23 patients have been enrolled at this dose, with 18 being evaluable for response. High CRc rate of 67% (12/18) in a heavily pre-treated population. Iadademstat plus standard of care (SoC) treatment gilteritinib demonstrated a manageable safety profile, without adding toxicity to the SoC. ALICE-2 (NCT06357182) is a Phase Ib investigator-initiated study sponsored by Oregon Health & Science University (OHSU) in newly diagnosed AML. It is evaluating treatment with iadademstat in combination with azacitidine and venetoclax, the standard of care, in newly diagnosed unfit patients. The study’s primary endpoint is the incidence of dose-limiting toxicities (DLTs). Secondary endpoints include efficacy measurements such as composite complete remission (CRc: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete recovery [CRi]), and overall response rate (ORR: CRc + morphologic leukemia free state [MLFS] + partial remission [PR]). The trial plans to enrol 24 patients to achieve 21 evaluable patients. FRIDA (NCT05546580) is a Phase Ib clinical study sponsored by Oryzon. It is evaluating iadademstat in combination with gilteritinib for the treatment of FLT3-mutant relapsed/refractory AML. The primary endpoints are incidence of treatment emergent adverse events (TEAEs) and determination of the recommended Phase II dose (RP2D). Secondary endpoints include response rates (CR, CRh, CRi, MLFS, CRc), event-free survival (EFS), and overall survival (OS). Iadademstat (ORY-1001) is an oral, highly selective inhibitor of the epigenetic enzyme LSD1, with potent differentiating effect in hematologic cancers. Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L acute myeloid leukemia (AML) patients (ALICE trial). Iadademstat is currently being evaluated in combination with azacitidine and venetoclax in 1L AML in the ALICE-2 trial, an investigator-initiated study (IIS) led by OHSU, and in combination with gilteritinib in the company-sponsored Phase Ib FRIDA trial in relapsed/refractory FLT3-mutant AML, with highly encouraging preliminary safety and efficacy data in both trials reported at EHA-2026: 100% overall response rate (ORR) and 89% composite complete remission rate (CRc), with 78% strict CR in 1L AML, and 67% CRc in R/R Flt3-mut AML. Additional studies in hematologic malignancies include an IIS in myelodysplastic syndrome (MDS) and National Cancer Institute (NCI)-sponsored trials in myeloproliferative neoplasms and 1L AML conducted under the Cooperative Research and Development Agreement (CRADA) between Oryzon and the NCI. Beyond hematological cancers, iadademstat is being evaluated in extensive stage small cell lung cancer (ED-SCLC) in a Phase I/II randomized trial in 1L in combination with immune checkpoint inhibition (ICI) sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center, and an IIS trial in combination with ICI and radiotherapy. Oryzon has also expanded iadademstat into non-oncological hematology indications, with ongoing trials in sickle cell disease and essential thrombocythemia. Iadademstat has orphan drug designation for AML in the US and EU and for SCLC in the US.
