ORYZON announces first patient dosed in an Investigator-initiated Phase Ib study of iadademstat in extensive stage small cell lung cancer

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a global leader in epigenetics, announced today that the first patient has been dosed in an investigator-initiated Phase Ib dose-finding trial evaluating iadademstat, Oryzon’s potent and selective LSD1 inhibitor, in combination with radiotherapy and an immune checkpoint inhibitor in patients with residual, progressive or recurrent extensive stage small cell lung cancer (ES-SCLC). The study is sponsored and conducted by Yale University.

The allowed claims cover the use of vafidemstat for the treatment of aggression and social withdrawal – two symptoms associated with several CNS disorders. Oryzon is preparing a Phase III trial to evaluate vafidemstat for the treatment of aggression in borderline personality disorder (BPD). The Company is also preparing a Phase II trial in aggression in autism spectrum disorder (ASD) patients, and a Phase II trial is already ongoing in schizophrenia.

The trial (NCT07113691), titled “Iadademstat and Radiation Therapy With Atezolizumab in Extensive Stage Small-cell Lung Cancer (ES-SCLC) Patients With Persistent, Recurrent or Progressive Disease After First Line Systemic Therapy”, is an open-label, non-randomized Phase Ib study that will evaluate the safety, tolerability, and efficacy of iadademstat combined with atezolizumab and stereotactic body radiation therapy (SBRT) followed by maintenance therapy with atezolizumab and iadademstat. The study will enroll patients with residual, progressive or recurrent ES-SCLC who previously received platinum-based chemotherapy with or without immune checkpoint inhibitor therapy. Dr. Anne Chiang at Yale University is serving as Principal Investigator.

Dr. Carlos Buesa, Oryzon’s CEO, stated: “The initiation of this investigator-led study at Yale University represents an important milestone in our efforts to expand the clinical development of iadademstat in small cell lung cancer. Combining LSD1 inhibition with immunotherapy and radiotherapy is a compelling strategy, and we look forward to the insights this trial may provide into the potential role of iadademstat in addressing this aggressive disease with high unmet medical need.”

Dr. Chiang, Principal Investigator of the study, added: “Some SCLC patients have had long-term benefit with immunotherapy, and we hope to learn how to extend benefit to more people. Through this study, we aim to boost the immune response by adding radiation and iadademstat to immunotherapy in SCLC patients. The use of paired biopsies will help us understand key events that are occurring in the tumor and its microenvironment as well.”

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com

About Iadademstat

Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study (IIS) led by OHSU and in combination with gilteritinib in the company-sponsored Phase Ib FRIDA trial in relapsed/refractory FLT3-mutant AML, with highly encouraging preliminary safety and efficacy data recently reported at ASH-2025 for both trials: 100% ORR and 90% strict CR in 1L AML, and 67% CCR (at the dose under expansion) in R/R AML. Additional studies in hemato-oncology include an IIS in MDS, and trials in myeloproliferative neoplasms and 1L AML both sponsored and conducted by the U.S. National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. In addition, Oryzon is expanding iadademstat’s clinical development into non-oncological hematology indications, with trials in sickle cell disease (approved by EMA, enrolling) and essential thrombocythemia (submitted to EMA). Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU.