ORYZON Announces First Patient In in NET, a Collaborative Phase II Basket Study With Iadademstat in R/R Patients With Neuroendocrine Carcinomas

• Collaborative study with Fox Chase Cancer Center
• Trial will assess the safety and efficacy of iadademstat in pulmonary and extrapulmonary NECs
• Part of a broad collaboration with The Cancer Epigenetics Institute (CEI)

MADRID, Spain and BOSTON, Jan. 18, 2023 (GLOBE NEWSWIRE) — 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 the enrollment of the first patient in a Phase II collaborative study with iadademstat in patients with relapsed/refractory high grade neuroendocrine carcinomas (NEC). This trial is 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.

NET (NCT05420636) is an open-label basket study conducted by FCCC as the sponsor, with Dr. Namrata Vijayvergia, MD, Assistant Chief, Gastrointestinal Medical Oncology, member of the Cancer Epigenetics Institute, and Nuclear Dynamics and Cancer program at Fox Chase Cancer Center, as the principal investigator. The trial will assess the safety and efficacy of iadademstat in combination with paclitaxel in patients with relapsed/refractory small cell lung cancer or extrapulmonary high grade NECs.

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 Faller, Oryzon’s Global Chief Medical Officer said: “Relapsed and refractory NECs and Small Cell Lung Cancer carry an unfortunately dismal prognosis and represent a major unmet medical need in oncology. We are very pleased to be collaborating with Dr. Vijayvergia and her colleagues at FCCC, a center of excellence for research in both NECs and in epigenetics, to work towards improving the outlook for patients suffering from these diseases. Achieving First-Patient-In in the study is an important milestone in our plan to utilize our epigenetic therapeutic drug, iadademstat, in combination with selected other agents, as a new approach to the treatment of NECs, with the potential to provide meaningful benefit to these patients.”

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 a recently completed Phase IIa study (ALICE trial) in elder/unfit acute myeloid leukemia (AML) patients sponsored by Oryzon, iadademstat demonstrated robust efficacy in combination with azacitidine, with 81% ORR in the evaluable patients, of which 64% were CR/CRi. Final data were presented as an oral communication at the 64th ASH annual conference (see here for more details). The company is now initiating an FDA-approved Phase Ib trial (FRIDA trial, NCT05546580) of iadademstat in combination with gilteritinib in FLT3-mutant relapsed/refractory AML patients and is preparing a new Phase Ib/II trial (STELLAR trial) of iadademstat 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.

About Oryzon
Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company considered as the European leader in epigenetics. Oryzon has one of the strongest portfolios in the field, with two LSD1 inhibitors, iadademstat and vafidemstat, in Phase II clinical trials, and other pipeline assets directed against other epigenetic targets. 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). In a recently completed Phase IIa trial in elder 1L-AML patients (ALICE trial), iadademstat has shown encouraging safety and efficacy data in combination with azacitidine (see Salamero et al., ASH 2022 oral presentation). The company has obtained approval from the U.S. FDA for its IND for FRIDA, a Phase Ib trial of iadademstat plus gilteritinib in patients with relapsed/refractory AML with FLT3 mutations. 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 being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination in SCLC. Oryzon has also entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers. In total iadademstat has been dosed so far to more than 100 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU.

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