ORYZON Reports First Patient Dosed in NCI-Sponsored Trial of Iadademstat, Venetoclax, and Azacitidine for AML

On January 13, 2025, Oryzon Genomics, S.A., a company at the forefront of epigenetic-based biopharmaceutical developments, disclosed that it has commenced a Phase I clinical trial involving its novel compound, iadademstat. This trial, conducted as part of a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), a division of the National Institutes of Health, involves testing iadademstat in combination with two other drugs—venetoclax and azacitidine—for treating patients newly diagnosed with acute myeloid leukemia (AML).

The study, officially titled "Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML" (NCT06514261), focuses on assessing the safety, tolerability, and optimal dosage of iadademstat. The trial is designed to include 45 treatment-naïve AML patients and also aims to gather preliminary data on the effectiveness of this drug combination. Under the leadership of Dr. Natalie Galanina from the University of Pittsburgh Cancer Institute, this trial marks a significant step in exploring advanced treatment options for AML.

The enthusiasm for this trial is evident in the remarks of Dr. Carlos Buesa, CEO of Oryzon, who highlighted the potential of iadademstat when used with azacitidine. Previous studies, such as the ALICE trial, have yielded promising results, demonstrating strong anti-leukemic effects and a favorable safety profile, even in high-risk patients who typically do not respond well to existing treatments like venetoclax and azacitidine.

Beyond this trial, iadademstat is being tested in combination with venetoclax and azacitidine at Oregon Health & Science University (OHSU) Knight Cancer Institute, targeting newly diagnosed AML patients. Additionally, there is a company-sponsored Phase Ib study evaluating iadademstat with gilteritinib in patients with relapsed or refractory AML who have a FMS-like tyrosine kinase mutation (FLT3mut+).

Oryzon Genomics, founded in 2000 in Barcelona, Spain, has established itself as a leader in the field of epigenetics. The company is renowned for its commitment to personalized medicine, particularly in central nervous system disorders and oncology. Oryzon’s clinical portfolio includes two advanced LSD1 inhibitors: vafidemstat, which is ready for Phase III trials in CNS disorders, and iadademstat, which is in Phase II trials for oncology applications. The company is also investing in other pipeline assets, such as ORY-4001, which targets HDAC-6 for potential use in conditions like Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis.

Iadademstat (ORY-1001), a selective LSD1 inhibitor in oral form, has shown considerable promise in various clinical trials. In earlier studies involving patients with relapsed or refractory AML, the drug demonstrated both safety and early indications of anti-leukemic activity. Its potential has been further supported by Phase IIa trial results, which showed robust clinical activity when combined with azacitidine in elderly patients with first-line AML.

In addition to its potential in hematologic cancers, LSD1 inhibition by iadademstat is being explored as a therapeutic strategy for certain solid tumors, including small cell lung cancer (SCLC), neuroendocrine tumors, and medulloblastomas. The drug is currently part of several collaborative trials, including ones at Fox Chase Cancer Center and Memorial Sloan Kettering Cancer Center. Moreover, iadademstat has received orphan drug designation in the United States for SCLC, and for AML in both the US and EU, underscoring its potential impact in treating these challenging diseases.

Oryzon Genomics continues to advance the clinical development of iadademstat, leveraging its strong scientific foundation and collaborative partnerships to potentially offer new hope for patients with limited treatment options.