Oryzon cleared to start trial of sickle cell drug in Europe
Phase 1b RESTORE trial to enroll 40 patients in Spain
Oryzon Genomics said it received European Medicines Agency approval to start a Phase 1b clinical trial of iadademstat in people with sickle cell disease (SCD).
The trial — RESTORE (2025-521838-29-00), short for REgulation of Sickling ThrOugh Reprogramming Epigenetics — will enroll 40 SCD patients, ages 18 and older, across clinical sites in Spain.
Iadademstat is an oral medication that selectively inhibits an enzyme called lysine specific demethylase-1 (LSD1). LSD1 works as an epigenetic modulator, meaning it regulates the activity of certain genes by removing methyl groups from histones, the proteins around which DNA is normally wrapped.
The enzyme plays a role in various biological functions, including the behavior of cancer cells. While iadademstat has been tested as a potential treatment for different cancers, this is the first trial where the therapy is being tested for other diseases.
“We are thrilled to be the only LSD1 inhibitor currently into clinical development for SCD,” Ana Limón, PhD, senior vice president of clinical development and medical affairs at Oryzon, said in a company press release. “Targeting LSD1 presents a highly promising therapeutic approach for this disease, which affects approximately 7.7 million people worldwide.”
Therapy aims to boost HbF production
SCD is caused by mutations that lead to the production of an abnormal form of hemoglobin, the protein responsible for transporting oxygen in red blood cells. This defective hemoglobin tends to aggregate within red blood cells, causing them to take on a crescent or sickle shape, which is characteristic of the disease. These misshapen red blood cells are rigid and can block blood vessels, leading to serious complications.
Sickle cell affects the adult form of hemoglobin. An alternative form of the protein known as fetal hemoglobin (HbF) is produced during early fetal development, but production typically stops shortly after birth. A strategy to overcome the defects associated with SCD is to boost the production of HbF. While certain gene therapies have been approved for this purpose, their complexity and high costs often limit access for many patients. This highlights the urgent need for more effective and accessible treatment options.
Previous research has shown that inhibition of LSD1 promotes the production of HbF, laying the foundation for the potential therapeutic benefits of iadademstat for SCD.
“Iadademstat has produced a significant increase in HbF levels in baboons, the only animal model with strong translational relevance to humans, after just a single dose,” Limón said. “Increased HbF levels mitigate — and potentially reverse — the pathological phenotype of the disease, and increases in HbF have already been recognized by the FDA as a clinically meaningful endpoint for the treatment of SCD. The trial has been carefully designed to deliver a rapid and clear signal of biological activity.”
The main goal of the RESTORE trial is to assess the therapy’s safety and tolerability. It also aims to determine the recommended dose that will be tested in a Phase 2 study. Additional goals include assessing the therapy’s ability to turn on HbF production.
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