ORYZON at ASH-2021: iadademstat 36-month ALICE data demonstrate 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, 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), at the 63rd American Society of Hematology Annual Conference, ASH-2021.

The evidence of clinical efficacy continues to be robust and consistent with previously reported data, with an objective response rate (ORR) of 78% (21 of 27 evaluable patients); of these, 62% were complete remissions (13 CR/CRi) and 38% partial remissions (8 PR). The historical ORR in elderly or unfit AML population treated with azacitidine alone is 28%.

Of note, among AML subgroups all patients with M5b AML (2/2) and all patients with TP53-mutant AML (3/3) achieved CR/CRi. The median Time to Response continued to be fast, in 2 cycles (55 days). 

The duration of observed responses is very encouraging, with 77% of the CR/CRi lasting more than 6 months. The longest remission at the data cut-off date for ASH-2021 was over 1,000 days, and is still ongoing, with the patient remaining transfusion independent and MRD-negative. 

Dr. Carlos Buesa, Oryzon’s CEO, said: "These results support a strong synergy between iadademstat and azacitidine when used in combination. We have completed enrollment and continue to see high levels of response and extended remissions, alongside good tolerability. Combinations with iadademstat will increase therapeutic options for AML patients not only in first line, but also in patients who are refractory or intolerant to BCL2 inhibitors.”

The recommended iadademstat dose for future studies in combination with azacitidine has been determined as 90 ug/m2/d, which produced a higher exposure and a higher and more consistent LSD1 target engagement (TE) than 60 ug/m2/d. Preliminary data suggests that there is a direct correlation between quality of clinical response and iadademstat exposure/TE. The 90 ug/m2/d dose more consistently achieved the exposure and TE observed in CR/CRi patients as compared to the lower dose, without increasing the severity of adverse reactions (ARs). In patients whoreceived iadademstat at 90 ug/m2/d, 80% of responses were CR/CRi.

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 AR was platelet reduction, observed in almost half of patients (44%), although thrombocytopenia (Grade ≥3) was already present at baseline in a high proportion of patients (61%). Besides the expected hematological impact, in line with the pharmacologic mode of action and previously presented at ASH-2020 and EHA-2021, 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. ALICE is fully recruited, and patients will be followed for an additional 12 months.

More information in the PR attached