ORYZON announces FDA clearance of IND to initiate a collaborative Phase II basket study with iadademstat in R/R patients with Neuroendocrine carcinomas (NECs)

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the FDA has approved the Investigational New Drug (IND) application to initiate a Phase II collaborative study with iadademstat in patients with relapsed/refractory high grade neuroendocrine carcinomas (NEC). This trial will be conducted under a collaborative clinical research agreement entered between Oryzon and the Fox Chase Cancer Center (FCCC), under which FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug and technical expertise.

The first collaborative Phase II trial will be an open-label basket study to be conducted by FCCC as sponsor, with Dr. Namrata Vijayvergia, MD, Associate Professor and member of the Cancer Epigenetics Institute at Fox Chase Cancer Center, as the principal investigator.

Neuroendocrine neoplasms are rare and heterogeneous cancers arising from neuroendocrine cells, representing 0.5% of all newly diagnosed malignancies, with a prevalence of 100,000 cases in the US. 22- 27% of NETs are pulmonary (i.e., small cell lung cancer, SCLC), and the remainder are extrapulmonary, with gastrointestinal tract as the most common presentation followed by genito-urinary tumors. Some of these cancers are poorly differentiated NECs, which are very aggressive. Patients often rapidly develop progressive disease after first line cytotoxic chemotherapy and lack clearly efficacious second line treatment options. Response rates for NECs and SCLC in second line are generally less than 5% and 20%, respectively, and survival is measured in months.

Dr Douglas V. Faller, Oryzon’s Global Chief Medical Officer said: “Relapsed and refractory NECs and Small Cell Lung Cancer carry a dismal prognosis and represent a major unmet medical need in oncology. We are very pleased to initiate this collaboration with Dr. Vijayvergia and her colleagues at FCCC, a center of excellence for research in both NECs and epigenetics, to work towards improving the outlook for patients suffering from these diseases. NECs have been shown to be dependent upon LSD1 for their growth and the survival of the tumor stem cells. We believe that our epigenetic therapeutic drug, iadademstat, in combination with selected other agents which have shown activity in these malignancies, represents a new approach to the treatment of NECs, with the potential to provide meaningful benefit to these patients.”

Dr. Namrata Vijayvergia, Principal investigator of the study at FCCC, said: “NECs are difficult to diagnose and treat because these types of carcinomas behave differently depending on where they grow in the body. There are very few treatment options for these patients and even fewer trials, which makes this effort even more important. The approval of iadademstat for research studies represents a new paradigm and option for patients. I am excited about the collaboration between the Cancer Epigenetics Institute at Fox Chase Cancer Center, led by Dr. Johnathan Whetstine, and with Oryzon in this important scientific endeavor.”

Iadademstat is an orally active, highly potent and selective inhibitor of the epigenetic enzyme LSD1, currently under clinical development for the treatment of hematologic cancers and certain solid tumors. In an ongoing and fully-accrued Phase IIa trial (ALICE trial) in elderly 1L acute myeloid leukemia (AML) patients, iadademstat has shown encouraging safety and efficacy data in combination with azacitidine. The company is now starting a Phase Ib trial (FRIDA trial, IND approved) in combination with gilteritinib in FLT3 mutant relapsed/refractory AML patients and is preparing a new Phase Ib/II trial (STELLAR trial) in combination with immune checkpoint inhibitors in SCLC. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU.