ORYZON presents iadademstat ALICE 30-month data at EHA-2021, confirming positive and robust efficacy in combination with azacitidine in AML

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, presented today new positive efficacy data from its ongoing Phase IIa ALICE trial, which is investigating iadademstat in combination with azacitidine in elderly or unfit patients with acute myeloid leukemia (AML). The data were presented at the virtual EHA-2021 Conference, in an e-poster entitled “ALICE MAINTAINS HIGH CLINICAL RESPONSE RATES SUPPORTING THE EFFICACY OF IADADEMSTAT COMBINATION WITH AZACITIDINE IN AML MANAGEMENT”.

Twenty-seven patients (median age 77 years) had been enrolled in the trial up to May 24th and are reported in these data, one of whom did not fulfill the inclusion criteria. Eighteen patients were evaluable for efficacy as per protocol and two more were still in Cycle-1. The evidence of clinical efficacy continues to be robust and consistent with previously reported data, with an objective response rate (ORR) of 83% (15 out of 18 evaluable patients); of these, 67% were complete remissions (10 CR/CRi), and 33% partial remissions (5 PR). Of note, one patient with M5b (monocytic) AML, a traditional hard-to-treat leukemia subgroup and who also had an adverse prognosis, achieved CRi in 29 days. Mean Time to Response (TTR) was only 29 days. 

With historical response rates of 28% in this population when treated with azacitidine alone (19% CR/CRi and 9% PRs), these results support a strong synergy between iadademstat and azacitidine when used in combination. 

The duration of the observed responses is also encouraging, with 60% of the CR/CRi lasting more than 6 months. The current longest remission at the data cut-off date for the EHA-2021 communication was 858 days in a patient that continues transfusion independent and MRD-negative. Four other patients have achieved responses longer than 1 year (3 still ongoing). Those patients with longer treatment periods have also improved or overcome their dependency on blood transfusions, with 50% of the CR/CRi patients already transfusion independent.

Dr. Carlos Buesa, Oryzon’s CEO, said: "We are pleased with these very positive data from the ALICE trial after 30 months of study and with a growing number of patients enrolled, confirming a robust high percentage of responses. We also see these responses maturing in longer times of remission, which extends survival. Considering the different mechanisms of action of proapoptotic BCL2 inhibitors and the pro-differentiating agent iadademstat, we believe that combination approaches with iadademstat will increase therapeutic options for AML patients in first line, as well as for refractory or intolerant patients who have received BCL2 inhibitors as first line.”

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 events continue to be a decrease in the platelet and neutrophil count. Besides the expected hematological impact, in line with the pharmacologic mode of action and previously presented at ASH 2020 and EHA-2020, the combination continues to appear safe and well tolerated by elderly AML patients.

The purpose of the ALICE trial is to inform the broader use of iadademstat in leukemia. ALICE is designed as a single-arm, open-label study of iadademstat in combination with the standard of care treatment azacitidine in newly diagnosed elderly or unfit AML patients and is being carried out in eight Spanish hospitals. The study will recruit up to a maximum of 36 patients. 

A copy of the EHA-2021 poster is available here

For more information about EHA-2021, please visit EHA-2021’s website

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company considered as the European champion in Epigenetics. Oryzon has one of the strongest portfolios in the field. Oryzon’s LSD1 program has rendered two compounds, vafidemstat and iadademstat, in Phase II clinical trials. In addition, Oryzon has ongoing programs for developing inhibitors against other epigenetic targets. Oryzon has a strong technological platform for biomarker identification and performs biomarker and target validation for a variety of malignant and neurological diseases. Oryzon has offices in Spain and the United States. Oryzon is one of the most liquid biotech stocks in Europe with +90 M shares negotiated in 2020 (ORY:SM / ORY.MC / ORYZF US OTC mkt). For more information, visit https://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 first Phase I/IIa clinical trial with iadademstat in refractory and relapsed acute leukemia patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi. 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. Iadademstat has been tested in four clinical trials (two in monotherapy in SCLC and AML, and two in combination, in SCLC and AML) in more than 100 patients. In the combination studies, ALICE (ongoing), a Phase IIa trial in combination with azacitidine in elderly or unfit AML patients, and CLEPSIDRA (finalized), a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients, preliminary efficacy results have been reported.

About Vafidemstat 

Vafidemstat (ORY-2001) is an oral, CNS optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive preliminary clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 months of treatment, and the pilot, small scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS. A Phase IIb trial in borderline personality disorder (PORTICO) has been recently authorized and the company is preparing a Phase IIb trial in schizophrenia patients (EVOLUTION). Vafidemstat is also being explored in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection.

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