Oryzon Genomics Initiates RESTORE Phase Ib Trial Of Iadademstat In Sickle Cell Disease

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company and recognized leader in epigenetic therapeutics, announced that the first patient has been enrolled in RESTORE, its Phase Ib clinical trial evaluating iadademstat in adults with sickle cell disease (SCD). Conducted across multiple sites in Spain, the open-label study will enroll approximately 40 adult participants to assess the safety, tolerability, and recommended Phase 2 dose (RP2D) of iadademstat, while also examining its potential to induce fetal hemoglobin (HbF) expression, an endpoint the FDA recognizes as clinically meaningful in SCD treatment.

Dr. Ana Limón, Senior Vice President of Clinical Development and Medical Affairs at Oryzon, said: “Iadademstat has demonstrated PoC in preclinical baboon models of SCD. Achieving FPI in RESTORE in a record time is an important milestone as we bring the first oral LSD1 inhibitor into clinical testing for SCD in Europe. Our goal is to deliver to SCD patients a clinical benefit comparable to the one achieved with certain gene therapies through inducing HbF, with the potential advantages of an oral, scalable approach”. 

Iadademstat is an oral, highly selective LSD1 inhibitor currently in clinical development for oncohematology indications. It reactivates fetal hemoglobin expression through epigenetic reprogramming of the hemoglobin switch, a mechanism also targeted by certain FDA-approved gene therapies for SCD. The drug has demonstrated a favorable safety profile in previous first-in-human and combination studies, with nearly 200 patients treated to date, supporting its readiness for evaluation in the RESTORE study.

Dr. Carlos Buesa, Oryzon’s CEO, stated: “SCD represents a major unmet medical need, and we are excited to expand the scope of iadademstat’s clinical development to hematology. This is an important step toward offering new hope and potential treatment options for patients living with this condition. Given the openlabel design of RESTORE, we expect to obtain initial insights within the next few months that will help us better understand iadademstat’s potential in this indication.”

Sickle cell disease, the most prevalent inherited blood disorder in the United States, remains a major unmet medical need with few accessible therapies. By elevating HbF levels, iadademstat aims to reduce vaso-occlusive events, hemolysis, and organ damage—the primary causes of morbidity and reduced survival in SCD. Numerous epidemiological studies have shown that higher HbF concentrations correlate with longer life expectancy, underscoring the therapeutic potential of iadademstat for this patient population.