ORYZON Announces Final Phase IIa ALICE Results with Iadademstat Published in The Lancet Hematology

Oryzon Genomics, a clinical-stage biopharmaceutical firm, has revealed the final outcomes of their Phase IIa ALICE study, which assessed the combination of iadademstat and azacitidine in newly diagnosed and unfit patients with acute myeloid leukemia (AML). These results, published in The Lancet Hematology, highlight the potential of iadademstat, a selective LSD1 inhibitor, in the treatment of hard-to-treat AML forms.

The ALICE study demonstrated significant antileukemic activity with deep responses and an acceptable safety profile, even among patients with high-risk prognostic indicators. The study included 27 patients, 22 of whom (82%) showed an objective response. Among these, 52% achieved either complete remission (CR) or complete remission with incomplete hematological recovery (CRi). For context, comparable trials with azacitidine alone reported considerably lower CR/CRi rates (approximately 28%).

Of particular note was the rapid onset of responses, with 87% occurring by the second assessment. A significant proportion of these responses (36%) were sustained for 12 months or longer. At the one-year database lock, nine patients were still alive, and as of February 2024, five remained alive, with three continuing treatment and maintaining complete remission.

The depth of response was highlighted by a high rate of measurable residual disease (MRD) negativity, observed in 91% of evaluable samples. This MRD negativity is associated with improved survival outcomes, suggesting a durable benefit of the treatment.

Responses were also recorded across various adverse prognostic mutational landscapes. For example, in patients with M5 AML, a form typically resistant to venetoclax and azacitidine, all three patients achieved CR/CRi with complete MRD negativity. Additionally, 63% of patients with TP53 mutations reached CR/CRi, with a median overall survival of 10 months.

Encouraging results were also observed in patients with other poor-prognosis mutations. All seven patients with RAS pathway mutations responded, with a median overall survival of 467 days. Similarly, patients with DNM3TA, NPM1, and RUNX mutations exhibited 100% response rates, primarily achieving CR or CRi.

Building on the successes of the ALICE study, Oryzon is conducting further research through an investigator-initiated study with Oregon Health & Science University (OHSU). This Phase Ib trial aims to evaluate the combination of iadademstat with the standard of care (SoC) treatments, venetoclax and azacitidine, in first-line AML patients.

Additionally, iadademstat is being tested in combination with gilteritinib in the ongoing FRIDA study, a Phase Ib trial targeting relapsed/refractory AML patients with FLT3 mutations in the U.S. Preliminary results from the initial two cohorts (thirteen patients) demonstrated safety and significant antileukemic activity. The study continues to explore optimal dosing in line with the FDA’s new OPTIMUS doctrine, with a third cohort currently recruiting.

Beyond hematological cancers, iadademstat's potential is being explored in other malignancies. Under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI), Oryzon is preparing a trial combining iadademstat with immune checkpoint inhibitors in small cell lung cancer (SCLC).

Oryzon Genomics, established in 2000 and headquartered in Barcelona, Spain, is recognized as a leader in epigenetics and personalized medicine, particularly within oncology and central nervous system (CNS) disorders. The company’s robust clinical portfolio includes two LSD1 inhibitors—vafidemstat for CNS disorders and iadademstat for oncology—among other innovative pipeline assets targeting epigenetic modifications.