ORYZON announces FDA approval of IND for FRIDA, a Phase Ib trial with iadademstat in R/R AML FLT3mut+ patients

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical needs, announced today that it has received notification from the U.S. Food and Drug Administration (FDA) that its Investigational New Drug application (IND) for iadademstat is now approved to initiate a Phase Ib clinical trial in patients with relapsed/refractory Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+).

FRIDA 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 has as its primary objectives 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. FRIDA will be conducted in 10-15 sites in the US. The study will accrue 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: “FDA’s clearance to start FRIDA is a relevant corporate milestone for Oryzon and the patients we hope to serve. It also represents our new development strategy for iadademstat in hemato-oncology and solid tumors, which is going to gravitate mostly in US clinical activities and where FRIDA is the first step.”

Dr. Ana Limon, Senior VP of Clinical Development and Global Medical Affairs of Oryzon said: “Epigenetics is emerging as one of the underlying roots of leukemia and other cancers. LSD1 is a key target in this space. Iadademstat, a uniquely potent and selective LSD1 inhibitor, has already shown a safe profile and high and prolonged responses in AML patients in combination with azacitidine. Iadademstat’s excellent pharmacologic properties and synergy with Flt3 inhibitors make this study a very solid proposition for the treatment of this relapsed/refractory patient population. At Oryzon, we are thrilled to pioneer this momentum in creating next-generation medicines.”

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 still ongoing, fully recruited, Phase IIa study in elder/unfit AML patients, iadademstat demonstrated robust efficacy in combination with azacitidine with 78% ORR in the evaluable patients, of which 62% were CR/CRi (data presented at ASH2021; 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 an ongoing 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 2021 poster). 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, 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). In total iadademstat has been dosed to more than 100 cancer patients in four clinical trials.