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.”

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com

About Iadademstat

Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Additional studies in MDS and myeloproliferative neoplasms are ongoing. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. In addition, Oryzon is expanding iadademstat’s clinical development into non-oncological hematology indications, with trials in sickle cell disease (enrolling) and essential thrombocythemia (trial in preparation). Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU.