Oryzon Genomics has presented at the 67º Congress Annual of the American Society of Hematology (ASH) new clinical data that reinforce the therapeutic potential of iadademstat, its selective LSD1 inhibitor, in the treatment of acute myeloid leukemia (AML). The results cover two ongoing studies that combine the drug with standard treatments in both newly diagnosed patients and those in relapsed or refractory patients.
- The first of the tests, ALICE-2 is a Phase Ib study promoted by Oregon Health & Science University to evaluate the combination of iadademstat with azacitidine and venetoclaxreference therapy for older patients or patients not candidates for intensive chemotherapy. The primary endpoint of the study is incidence of dose-limiting toxicities (DLTs). Secondary endpoints include measures of efficacy such as composite complete remission rate (CCR: complete remission [RC] + CR with partial hematological recovery [RCh] + CR with incomplete recovery [RCi]) and overall response rate (ORR: CRC + morphologic leukemia-free status [MLFS] + partial remission [RP]). In the publication of ASH data from 10 patients are presented. Treatment with iadademstat in combination with azacitidine and venetoclax was safe and well tolerated, with an adverse event (AE) profile similar to that of other combination treatments in the setting of newly diagnosed AML. The dose search to establish the maximum tolerated dose (MTD) is ongoing. The combination showed a very encouraging ORR of 100% and a CRC rate of 90%, with 80% of patients achieving a strict CR. 70% of patients underwent allogeneic hematopoietic transplantation (HT). 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 enrollment of N=21 DMT-evaluable patients.
- The second study, FRIDAsponsored by Oryzon, analyzes iadademstat together with gilteritinib, one of the reference treatments for relapsed or refractory AML with FLT3 mutation. The primary endpoints are the incidence of treatment-emergent adverse events (TEAEs) and determination of the recommended dose for Fase II (RP2D). Secondary endpoints include response rates (CR, CRh, CRi, MLFS, CCR), event-free survival (EFS) and overall survival (OS). The communication presented at ASH reports data from 37 patients, with 4 cohorts evaluated in the dose escalation phase. All doses tested in the escalation phase were safe according to DLT criteria. The study is in the expansion phase at a selected pharmacologically active dose, with a total of 17 patients included in the study at this dose level, as of the data cut-off date for the poster. ASH. This dose continues to be well tolerated according to continuous safety monitoring, and has achieved the deepest responses, which correlate with the PK and PD values. Preliminary activity at the expanding dose shows un 67% CRC (10/15 patients) and 47% CR+CRh (7/15) in 15 patients evaluable for response, which compares favorably with the results of the ADMIRAL trial (CR+CRh 34%), especially in light of contemporary practice, with many patients (47%) treated at this dose in FRIDA after failing venetoclax, a population with a markedly diminished response to gilteritinib monotherapy. Four patients have undergone LT.
“Impressive results” and a roadmap for the future
The CEO of Oryzon, Carlos Buesahighlighted that the results “underscore the potential of iadademstat to provide significant clinical benefit when combined with current standard treatments.” He also noted that the efficacy observed in complex refractory AML populations reinforces the drug’s positioning as a potential “class leader” within combination therapies. The company continues to explore strategic alliances to accelerate its development.
The two studies maintain their active recruitment and provide growing evidence on the usefulness of targeting the LSD1 enzyme, a key epigenetic regulator in the proliferation and differentiation of malignant blood cells. If current trends are confirmed in subsequent clinical phases, iadademstat could establish itself as an important player in the treatment of AML, a disease in which medical needs remain critical.