ORYZON enters cooperative research and development agreement (CRADA) with U.S. National Cancer Institute to develop iadademstat in different cancers

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. Under this CRADA, Oryzon and the NCI will collaborate on potential further clinical development of Oryzon’s clinical stage LSD1 inhibitor, iadademstat, in different types of solid and hematological cancers.

This research and development agreement with the NCI is a strong validation of iadademstat, the most potent and selective LSD1 inhibitor currently in clinical development, and will also allow Oryzon to significantly expand its clinical development program for this compound. In particular, it will allow us to work with some of the world’s leading oncology researchers to further expand iadademstat’s therapeutic potential and will also dramatically expand Oryzon’s ability to conduct clinical trials in a wide number of indications, and in combination with other novel or established therapies such as immuno-oncology and molecularly-targeted agents.

Iadademstat is an orally active, highly potent and selective inhibitor of the epigenetic enzyme Lysine specific demethylase 1 (LSD1, also known as KDM1A). LSD1 overexpression has been shown to correlate with more aggressive forms of cancer and/or worse prognosis in multiple cancer types. Oryzon is currently developing iadademstat for the treatment of acute myeloid leukemia (AML) and some solid tumors such as small cell lung cancer (SCLC) and neuroendocrine tumors (NETs), with more than 100 cancer patients treated with iadademstat in four Phase I/II clinical trials conducted so far. 

Clinical trial results have demonstrated robust and consistent clinical activity of iadademstat in AML and SCLC. In a still ongoing Phase IIa trial (ALICE trial) in elderly 1L AML patients, iadademstat in combination with azacitidine has shown an objective response rate (ORR) of 81%, of which 64% were complete remissions (CR/CRi), as reported in the European Hematology Association (EHA) 2022 conference held last June. We plan to present final data for the ALICE trial at the upcoming American Society of Hematology (ASH) 2022 conference, which will be held in December in New Orleans. We are now starting a new trial in AML, which will evaluate iadademstat in combination with gilteritinib in FLT3-mutant relapsed/refractory AML patients (the FRIDA trial); the IND for this trial has already been approved by the U.S. Food and Drug Administration (FDA) and we plan to initiate patient recruitment very soon. AML patients are currently underserved with existing drugs; the five-year survival rate for patients diagnosed with AML is approximately 29%, and approximately 75% of patients are either refractory or relapse. FLT3 is the most common mutation in AML (30-40%).

Beyond hematology, Oryzon is developing iadademstat in SCLC and plans to initiate a new Phase Ib/II trial in combination with immune checkpoint inhibitors (ICI) in patients with 1L metastatic SCLC (the STELLAR trial). Iadademstat has shown a strong synergism with ICIs in preclinical models. In addition, iadademstat will be evaluated in a basket Phase II trial in combination with other agents in refractory-relapsed patients with SCLC and extrapulmonary high-grade NETs, which will be conducted as a collaborative clinical study led by a prestigious U.S. institution.

Iadademstat has received orphan drug designation from the FDA and the European Medicines Agency (EMA) for the treatment of AML and from the FDA for the treatment of SCLC