ORYZON presents data for iadademstat combinations in AML at the American Society of Hematology (ASH) 67th Annual Meeting

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and global leader in epigenetics, today reported updated data from clinical studies investigating iadademstat, the Company’s selective LSD1 inhibitor for onco-hematology indications. The results, recently presented at the 67th American Society of Hematology (ASH) Annual Meeting, highlight encouraging efficacy and safety findings from two ongoing studies evaluating iadademstat in combination with standard-of-care regimens in patients with acute myeloid leukemia (AML).

ALICE-2 (NCT06357182), a Phase Ib investigator-initiated study sponsored by Oregon Health & Science University (OHSU) in newly diagnosed AML, evaluates treatment with iadademstat in combination with azacitidine and venetoclax, the standard of care in this setting for older or 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 (CCR: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete recovery [CRi]), and overall response rate (ORR: CCR + morphologic leukemia free state [MLFS] + partial remission [PR]). Data for 10 patients are reported in the ASH publication. Treatment with iadademstat in combination with azacitidine and venetoclax was safe and well tolerated, with an AE profile similar to other combination treatments in newly diagnosed AML setting. Dose-finding for maximum tolerated dose (MTD) determination is ongoing. The combination treatment resulted in a highly encouraging ORR of 100% and a CCR rate of 90%, with 80% of patients attaining a strict CR. 70% of patients transitioned to allogeneic hematopoietic stem cell transplantation (HSCT). Median overall survival (OS) was not reached, and 6-month OS was 66%. The trial continues to enroll patients at dose level 2 (DL2), with a planned accrual of N=21 MTD-evaluable patients.

FRIDA (NCT05546580), a Phase Ib clinical study sponsored by Oryzon, was designed to investigate 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, CCR), event-free survival (EFS), and overall survival (OS). The ASH communication reports data for 37 patients, with 4 dose level cohorts evaluated in the escalation phase. All doses tested in the escalation phase were safe per DLT criteria. The study is in the expansion phase at one selected pharmacologically active dose , with a total of 17 patients enrolled in the study at this dose level per the ASH poster data cut-off. This dose continues to be well tolerated based on continuous safety monitoring, and has achieved the deepest responses which correlate with the target PK and PD values. Preliminary activity at the dose under expansion shows a 67% CCR (10/15 patients) and a 47% CR+CRh (7/15) in 15 patients evaluable for response, which favorably compares with the results of the ADMIRAL trial (CR+CRh 34%), particularly in light of contemporary practice with many patients (47%) treated at this dose after failing venetoclax, a population with markedly decreased response to gilteritinib monotherapy. Four patients have undergone HSCT.

“These impressive preliminary results in first-line AML underscore the potential of iadademstat to deliver meaningful clinical benefit when combined with standard-of-care therapies and to offer patients renewed hope for a truly curative approach,” said Dr. Carlos Buesa, Chief Executive Officer of Oryzon. “The strong outcomes also observed in relapsed/refractory patients across difficult-to-treat AML subsets further highlight that iadademstat-based combinations can achieve robust efficacy while maintaining a manageable safety profile. This demonstration of clinical relevance at ASH reinforces iadademstat’s potential as a best-in-class combination agent and provides a clear path for future clinical development. We continue to explore strategic partnerships to fully unlock the value of iadademstat as a promising oncology–hematology asset.”