ORYZON at EHA-2022: iadademstat 42-month ALICE data demonstrate robust efficacy in combination with azacitidine in AML
- 81% of evaluable patients achieved an objective response
- Deep responses: 64% are CR/CRi, of which 86% achieved transfusion independence
- Rapid and durable responses: 91% by end of cycle 2, with 64% of CR/CRi lasting more than 6 months
- Iadademstat and azacitidine combination shows a good safety profile
MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, June 10th, 2022 - 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, today presents new positive efficacy data from its ongoing Phase IIa ALICE trial, investigating iadademstat in combination with azacitidine in elderly or unfit patients with acute myeloid leukemia (AML), in a poster at the European Hematology Association annual congress (EHA-2022), being held in Vienna on June 9-12.
The evidence of clinical efficacy continues to be robust and consistent with previously reported data, with an objective response rate (ORR) of 81% (22 of 27 evaluable patients); of these, 64% were complete remissions (14 CR/CRi) and 36% partial remissions (8 PR). The historical ORR in elderly or unfit AML population treated with azacitidine alone is 28%. Eighty-six percent of the CR/CRi patients became transfusion-independent, and 75% of CR tested samples were MDR negative by flow cytometry. Of note, among AML subgroups all evaluable patients with FLT3-ITD (3/3) and 6 of 8 evaluable patients with p53 mutations responded.
Responses are rapid, with 91% of patients responding by end of cycle 2, and durable, with 64% of CR/CRi responses lasting more than 6 months. Three patients remained on study for more than 1 year, 2 patients for more than 2 years and 1 patient for more than 3 years. Six patients are still ongoing in the trial.
Dr. Carlos Buesa, Oryzon’s CEO, said: "These results confirm previous data in supporting a strong synergy between iadademstat and azacitidine in combination. It is highly encouraging that we continue to see high levels of response and extended remissions, alongside good tolerability.”
Dr. Douglas Faller, Oryzon’s Global CMO, stated: “Combinations with iadademstat have the potential to significantly improve patient outcomes as they will increase therapeutic options for AML patients not only in first line, but also in patients who are refractory or intolerant to BCL2 inhibitors. To further investigate the effect in second line, Oryzon is launching FRIDA, a new clinical trial with iadademstat in combination with gilteritinib in FLT3-mutant relapsed/refractory AML patients.”
The combination of iadademstat with azacitidine continues to show a good safety profile, with only two serious adverse events reported as probably related to treatment. The most frequent adverse reaction was platelet reduction, observed in about half of patients (53%), although thrombocytopenia (Grade ≥3) was already present at baseline in a high proportion of patients (58%). Besides the expected hematological impact, in line with the pharmacologic mode of action and previously presented at several ASH and EHA meetings, the combination continues to appear safe and well tolerated by elderly AML patients, with no other significant non-hematological toxicities or other organ-related toxicities observed.
Thirty-six patients (median age 77 years) have been enrolled in the trial and are reported in the poster, with 27 evaluable for efficacy.
Oryzon’s poster at EHA-2022 is entitled “Iadademstat combination with azacitidine shows encouraging safety and efficacy data in elderly and unfit AML patients”. A copy of the poster is available here
For more information about EHA-2022, please visit EHA-2022’s website
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). The company has recently 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). New trials in combination in SCLC and NET are under preparation. In total iadademstat has been dosed so far to more than 100 cancer patients in four clinical trials.
FORWARD-LOOKING STATEMENTS
This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements.