Oryzon announces journal publication of final Phase IIa ALICE results with iadademstat in The Lancet Hematology

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 that the final results of the Phase IIa ALICE study evaluating iadademstat in combination with azacitidine in unfit patients with newly diagnosed acute myeloid leukemia (AML) were published online in The Lancet Hematology. A summary of the final data from this study had been previously released in an oral presentation at the 2022 American Society for Hematology (ASH) annual meeting, where it was selected as one of the 25 most relevant communications in AML. 

This notable publication is a continuation of Oryzon’s previous pioneering research featured in the Journal of Clinical Oncology (First-in-Human study in AML with iadademstat) and Cancer Cell (Characterization of iadademstat as a potent and selective LSD1 inhibitor), cementing the company’s position at the forefront of epigenetics in oncology and LSD1 innovation. 

Dr. Carlos Buesa, Oryzon’s CEO, stated, “We are thrilled to publish these groundbreaking results in one of the most prestigious journals in clinical oncology. Our study demonstrates that targeting LSD1 is a completely novel anti-leukemic mechanism of action in AML, potentially offering a new therapeutic approach, especially for patients with hard-to-treat forms of the disease such as myelomonocytic leukemias, DNMTs mutations, or TP53 mutations. These patients currently respond poorly to available treatments and may benefit from the innovative treatment option of iadademstat. We want to reiterate our gratitude to the patients, their families and the researchers involved in this study.”

Summary of the main results reported in the publication

• The combination of iadademstat with azacitidine induced a high proportion of responses, with 22 (82%) of 27 patients in the efficacy analysis set having an objective response. Notably, 52% of patients had either a complete remission (CR) or complete remission with incomplete hematological recovery (CRi) in the ALICE trial. For comparison, the percentage of patients who experienced a CR/CRi in the intention-to-treat azacitidine populations was 28% in the acute myeloid leukaemia-001 trial, 28% in the VIALE A trial, and 27% in the Monarch trial. 
• Most of the responses occurred rapidly (87% by the second assessment) and 36% lasted 12 months or longer. At database lock (1 year after the last patient was enrolled), nine patients were alive and as of February, 2024, five patients remain alive, with three continuing treatment (and in complete remission) under compassionate use after four years.
• The CR/CRi responses in ALICE were generally deep, as determined by the high rate of measurable residual disease (MRD) negativity (91% in the evaluable samples), which is associated with improved survival. 
• Remarkably, responses were seen across the entire adverse prognostic mutational landscape. Of note are the responses in specific subgroups: 
  • Three patients with M5 AML (a population primary refractory to venetoclax and azacitidine) had CR/CRi with iadademstat plus azacitidine, with 100% measurable residual disease negativity. 
  • In patients with AML with TP53 mutations in combination with a complex karyotype or high variant allele frequency, or both, CR/CRi was reached in 63%, with a duration of response of 7.9 months and a median overall survival of 10 months. 
  • Responses in leukemias harboring other poorer-prognosis mutations were also encouraging. All seven patients harboring a mutation or mutations in the RAS pathway responded, with a median overall survival of 467 days. Patients harboring mutations in DNM3TA (n=7), NPM1 (n=4), and RUNX (n=3) had 100% response rates, mostly CR or CRi.

A temporary link to access the publication for free can be found in The Lancet Hematology.

As a continuation of ALICE, Oryzon is further expanding the clinical development of iadademstat in 1L unfit AML through an Investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This trial is a Phase Ib dose-finding study to evaluate iadademstat in combination with the SoC, venetoclax and azacitidine, in first-line AML patients and is expected to begin enrolling patients in the coming weeks. 

Iadademstat is currently being evaluated also in combination with gilteritinib in relapsed/refractory AML patients harboring a FLT3 mutation in the FRIDA study, an open-label, multicenter Phase Ib trial being conducted in the US and which plans to accrue up to approximately 45 patients. The first two cohorts have been completed (thirteen patients), and the combination was safe and showed strong antileukemic activity. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity, and a third cohort has been started and is recruiting. Preliminary results from this trial will be presented at the upcoming European Hematology Association (EHA) 2024 congress in June.

In addition, in neuroendocrine tumors, in the context of the CRADA agreement between Oryzon and the NIH, the NCI is sponsoring a randomized Phase I/II trial in 1L extensive disease small cell lung cancer combining iadademstat with immune checkpoint inhibitors. The IND for this trial was recently approved by the FDA