ORYZON Announces First Patient In in FRIDA, a Phase Ib Trial With Iadademstat in Relapsed/Refractory FLT3-mutant Acute Myeloid Leukemia Patients

• In combination with gilteritinib
• Primary objectives: to assess safety, tolerability and RP2D
• Secondary objectives: to assess efficacy

MADRID, Spain and BOSTON, March 15, 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 its Phase Ib trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory acute myeloid leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), at the Massachusetts General Hospital in Boston, US.

FRIDA (NCT05546580) is an open-label, multicenter study of iadademstat plus gilteritinib for the treatment of patients with relapsed or refractory AML (R/R AML) with FLT3·mutations. The trial’s primary objectives are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination. Secondary objectives include evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the duration of responses (DoR) and the assessment of measurable residual disease (MRD). The trial’s principal investigator is Amir Fathi, M.D., Associate Professor at Harvard Medical School and Director of the Leukemia Program at Massachusetts General Hospital. FRIDA will be conducted in 10-15 sites in the US. The study will enroll up to approximately 45 patients and if successful, the Company and FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much in need AML population.

Dr. Carlos Buesa, President and CEO of Oryzon, said: “FRIDA’s initiation is a significant corporate milestone for Oryzon, marking a further expansion of our clinical pipeline as we seek to improve the treatment options for patients. Iadademstat has already shown strong efficacy data in AML. We hope this combination will open up new ways to treat these patients and make an important difference to their outlooks.”

Oryzon’s Global Chief Medical Officer, Dr. Douglas Faller, said: “We are pleased to announce the first patient entering into the FRIDA trial. It is our hope that the combination of iadademstat and gilteritinib will safely provide deep and durable responses for patients whose leukemias are driven by FLT3 mutations.”

FRIDA’s scientific rationale is based on iadademstat’s ability to inhibit the lysine specific demethylase 1 (LSD1), thereby triggering a powerful differentiating effect in hematologic cancers, as well as producing an anti-leukemic effect by targeting leukemic stem cells. Furthermore, the combination of iadademstat with gilteritinib demonstrated a very strong synergy in FLT3·mut+ AML preclinical models. This together with the fact that iadademstat has been administered to more than 100 cancer patients (including AML patients) demonstrating a good safety profile, activity and excellent pharmacologic properties supports exploring its combination with FLT3 inhibitors in FLT3·mut+ AML, targeting between 30-40% of AML patients. In a recently finalized Phase IIa study (ALICE trial) in elder/unfit AML patients, iadademstat demonstrated robust efficacy in combination with azacitidine, with 81% ORR in the evaluable patients, of which 64% were CR/CRi. Final data from the ALICE trial were presented as an oral communication at the recent 64th ASH annual conference (see here for more details).

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 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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