Oryzon Receives EMA Approval for First LSD1 Inhibitor Trial in Sickle Cell Disease
Key Insights
Oryzon Genomics (search) received European Medicines Agency (search) approval to initiate the RESTORE Phase Ib trial of iadademstat in sickle cell disease (search), marking the first clinical investigation of an LSD1 (search) inhibitor in this indication.
The study will enroll 40 adult patients across multiple Spanish sites to evaluate safety, tolerability, and the drug's ability to induce fetal hemoglobin (search) production.
Preclinical data showed iadademstat significantly increased fetal hemoglobin (search) levels in baboons after a single dose, targeting a clinically meaningful endpoint recognized by the FDA.
Oryzon Genomics (search) has received European Medicines Agency (search) (EMA) approval to initiate a Phase Ib clinical trial of iadademstat in sickle cell disease (search) (SCD), representing the first investigation of a lysine-specific demethylase 1 (LSD1 (search)) inhibitor in this indication. The Clinical Trial Application approval marks a significant expansion of the epigenetic drug's development beyond oncology applications.
Novel Therapeutic Approach for Sickle Cell Disease
The Phase Ib study, named RESTORE (REgulation of Sickling ThrOugh Reprogramming Epigenetics), will be conducted at multiple sites in Spain and aims to enroll 40 adult patients with SCD. The trial's primary objectives include evaluating the safety and tolerability of iadademstat and establishing its Recommended Phase 2 dose (RP2D). Secondary objectives focus on assessing iadademstat's activity to induce fetal hemoglobin (search) (HbF).
"We are thrilled to be the only LSD1 (search) inhibitor currently into clinical development for SCD," said Dr. Ana Limón, Senior Vice-president of Clinical Development and Medical Affairs at Oryzon. "Targeting LSD1 presents a highly promising therapeutic approach for this disease, which affects approximately 7.7 million people worldwide as per 2025 estimates."
Promising Preclinical Evidence
Iadademstat demonstrated significant efficacy in preclinical studies, producing a substantial increase in HbF levels in baboons after just a single dose. This animal model represents the only system with strong translational relevance to humans for SCD research. The induction of fetal hemoglobin (search) is particularly significant as increased HbF levels can mitigate and potentially reverse the pathological phenotype of the disease.
The FDA has already recognized increases in HbF as a clinically meaningful endpoint for SCD treatment, providing regulatory validation for this therapeutic approach. Dr. Limón noted that "the trial has been carefully designed to deliver a rapid and clear signal of biological activity."
Addressing Significant Unmet Medical Need
SCD is a chronic, inherited blood disorder caused by a mutation in the β-globin gene, leading to the production of hemoglobin S (HbS) instead of normal hemoglobin A. Under low oxygen conditions, HbS polymerizes, causing red blood cells to assume a sickle shape and become rigid and fragile. This results in microvascular occlusion, hemolysis, and chronic inflammation.
The clinical manifestations include vaso-occlusion and hemolytic anemia, leading to vaso-occlusive crises, acute and progressive organ damage, reduced quality of life, and premature mortality. SCD represents the most common inherited blood disorder in the United States and constitutes a significant unmet medical need with limited therapeutic options currently available.
Market Opportunity and Commercial Potential
According to multiple market research reports, the SCD treatment market is expected to grow substantially from approximately USD 3 billion in 2025 to around USD 8 billion by 2032. While gene therapies that reinduce HbF have received FDA approval, their widespread use is constrained by technical complexity and very high costs, limiting access for much of the global patient population.
The commercial potential for effective SCD treatments was demonstrated by Oxbryta, a once-approved oral therapy that reached annual sales of USD 328 million in a relatively short period before being withdrawn from the market. This underscores both the strong commercial opportunity and the urgent need for effective, scalable, and accessible treatments for SCD.
Expanding Clinical Portfolio
Iadademstat (ORY-1001) is a small oral molecule that acts as a highly selective inhibitor of the epigenetic enzyme LSD1 (search). Beyond the new SCD indication, the drug remains under active investigation in multiple oncology clinical trials, including the company-sponsored FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3 (search)-mutated acute myeloid leukemia (search) (AML).
The compound is also being evaluated in several trials conducted under a Cooperative Research and Development Agreement with the U.S. National Cancer Institute (search), including combinations with venetoclax and azacitidine in first-line AML, and with immune checkpoint inhibitors in small cell lung cancer (search). Iadademstat has received orphan drug designation for small cell lung cancer in the U.S. and for AML in both the U.S. and EU.