ORYZON receives European Medicines Agency approval to initiate a Phase II study of iadademstat in essential thrombocythemia
Essential thrombocythemia is the most common type of myeloproliferative neoplasm (MPN) and is associated with an increased risk of serious complications such as stroke, heart attack, and pulmonary embolism.
Oryzon Genomics, S.A. (ISIN Code: ES0167733015, Ticker: ORY), a clinical-stage biopharmaceutical company and a global leader in epigenetics, today announced that the European Medicines Agency (EMA) has authorized its Clinical Trial Application (CTA) to initiate a Phase II study of iadademstat, Oryzon’s potent and selective LSD1 inhibitor currently in clinical development in oncology and hematology, for the treatment of essential thrombocythemia (ET).
The study, named IDEAL (IaDademstat treatment for EssentiAL thrombocythemia), is a multicenter, single-arm Phase II study to be conducted in Spain in adult patients with ET who are resistant/intolerant to hydroxyurea. The primary objectives of the study are to evaluate the safety and tolerability of iadademstat and to assess its efficacy in reducing the percentage of adult ET patients with abnormal platelet counts. Secondary objectives include assessing the durable clinical hematologic response (DCHR) rate, confirming the pharmacokinetic and pharmacodynamic profile of iadademstat in ET patients, and evaluating the duration of hematologic remissions (DHRs).
Iadademstat will be administered for up to 24 weeks. An additional 24-week extension phase will be available for patients who are benefiting from treatment and who, in agreement with their physician, elect to continue in the study.
Essential thrombocythemia is the most common type of myeloproliferative neoplasm (MPN) and is associated with an increased risk of serious complications such as stroke, heart attack, and pulmonary embolism. The disease affects approximately 200,000 people in the United States. Current treatment strategies focus primarily on reduction of platelets and ET symptom control, aiming to reduce the risk of thrombo-hemorrhagic complications and prevent progression to post-ET myelofibrosis or secondary acute myeloid leukemia (AML). Despite available therapies, a significant proportion of patients develop resistance or intolerance to first-line treatments such as hydroxyurea, highlighting the need for novel therapeutic approaches.
Inhibition of LSD1 has been shown to block the terminal differentiation of megakaryocytes into platelets, leading to a steady reduction in circulating platelet counts, supporting the use of LSD1 inhibitors in ET. Positive results with another LSD1 inhibitor have been reported in a Phase II trial in high-risk ET patients, further validating this mechanism in the disease.
Dr. Carlos Buesa, Oryzon’s CEO, said, “The initiation of the IDEAL study reinforces our strategy to broaden the clinical utility of iadademstat beyond acute leukemia into additional hematologic indications with significant unmet medical need. Iadademstat is by far the most potent LSD1 inhibitor in clinical development, with more than 100-fold greater potency than any other LSD1 inhibitor currently in development. We believe the mechanistic profile of LSD1 inhibition uniquely positions iadademstat to address the underlying biology of essential thrombocythemia, and we look forward to advancing this important program, with the potential to demonstrate efficacy across the full spectrum of myeloproliferative diseases.”
Dr Ana Limón, Oryzon’s Senior Vice-president of Clinical Development and Global Medical Affairs added, “LSD1 inhibition alters the natural biology of myeloid diseases by reversing differentiation blocks and reducing the prevalence of leukemic stem cells. Early intervention in ET could potentially prevent progression to post-ET myelofibrosis or secondary AML. The IDEAL study will explore this potential of iadademstat, in addition to assessing its dose-dependent effects on platelet counts and thrombotic events in ET patients who are resistant or intolerant to standard-of-care treatment with hydroxyurea.”
Iadademstat is also being actively investigated in multiple oncology clinical trials, including the Phase Ib ALICE-2 study in combination with venetoclax and azacitidine in first-line AML. Highly encouraging preliminary data were presented at the American Society of Hematology (ASH) 2025 annual meeting, showing a 100% overall response rate (ORR) and 90% strict complete remission (CR) rate. Additional studies include the company-sponsored FRIDA trial evaluating iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutated AML, for which preliminary positive data were also presented at ASH-2025, as well as several trials conducted under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute in first line AML, myeloproliferative neoplasms and small cell lung cancer, and investigator-initiated studies in myelodysplastic syndrome and small cell lung cancer. In addition, the company is conducting a clinical trial evaluating iadademstat in sickle cell disease.