Oryzon Genomics, S.A. has reported encouraging results from its Phase 1b ALICE-2 clinical trial, with an investigational three-drug combination involving iadademstat achieving a 95% overall response rate in patients with newly diagnosed acute myeloid leukemia (AML). The treatment also produced an 84% composite complete remission rate and a 74% complete remission rate, strengthening the clinical rationale for advancing the selective LSD1 inhibitor into a planned Phase 3 study.
The latest findings come from 19 efficacy-evaluable patients receiving iadademstat alongside azacitidine and venetoclax, including individuals with adverse-risk leukemia who are considered unsuitable for intensive chemotherapy. Oryzon Genomics also reported encouraging results from a separate study involving patients with relapsed or refractory FLT3-mutated AML, expanding the evidence supporting its epigenetic treatment strategy.
The company will present additional findings at the American Society of Hematology Annual Meeting in December, including more mature data from the ALICE-2 study following completion of enrollment. Although the response rates are encouraging, the trials remain early-stage investigations, and larger controlled studies will be required to establish whether adding iadademstat improves survival or other clinical outcomes.
How Oryzon Genomics’ ALICE-2 trial achieved a 95% response rate in newly diagnosed acute myeloid leukemia
The Phase 1b ALICE-2 study is evaluating iadademstat in combination with azacitidine and venetoclax in patients with newly diagnosed acute myeloid leukemia who are not considered suitable candidates for intensive chemotherapy. This population represents a particularly challenging treatment setting because advanced age, underlying medical conditions and unfavorable genetic characteristics can limit treatment options. Although azacitidine and venetoclax have become an important therapeutic combination for certain patients, treatment resistance and disease relapse remain substantial concerns.
At the July 2026 data cutoff, 19 patients were evaluable for efficacy. The investigational triplet achieved a 95% overall response rate, indicating that approximately 18 patients met the study’s criteria for treatment response.
The composite complete remission rate reached 84%, while the stricter complete remission rate was 74%. These measurements are important because overall response includes a broader range of treatment outcomes, whereas complete remission requires patients to meet more demanding criteria involving the disappearance of detectable leukemia and recovery of blood counts.
The results suggest that adding iadademstat to the established azacitidine-venetoclax regimen may produce substantial antileukemic activity. However, the study does not provide randomized evidence showing that the three-drug combination performs better than azacitidine and venetoclax alone.
The treatment demonstrated rapid responses and what the company described as acceptable hematological recovery. These observations are relevant because AML therapies frequently cause prolonged suppression of healthy blood-cell production, potentially increasing the risks of infection, bleeding and treatment interruption.
Oryzon Genomics reported that the combination maintained a manageable safety profile during the early-stage study. Nevertheless, detailed adverse-event information and longer follow-up will be necessary to determine whether the additional drug introduces clinically significant toxicity.
The study population also included a substantial proportion of patients with unfavorable genetic and clinical characteristics. Approximately 82% of enrolled patients were classified as having adverse-risk disease under the European LeukemiaNet 2022 framework.
This is particularly relevant because patients with adverse-risk AML frequently experience lower remission rates and shorter survival than those with more favorable disease characteristics. Encouraging responses in this population could support further investigation, although the small sample size limits conclusions about specific genetic subgroups.
The updated ALICE-2 findings will be presented on December 12, with additional patients and more mature clinical observations expected to provide greater clarity about treatment activity and tolerability.
Why iadademstat’s 84% composite remission rate and early survival findings matter for high-risk leukemia treatment
Beyond the overall response rate, Oryzon Genomics reported encouraging early survival observations from the ALICE-2 study. Following a median follow-up of eight months, the estimated 12-month overall survival rate was 76%, while median overall survival had not yet been reached.
The company also reported estimated 12-month survival rates of 100% among patients classified as intermediate risk and 74% among those with adverse-risk disease. These subgroup findings are notable, but they require cautious interpretation because the patient population is small and follow-up remains relatively limited.
A 12-month survival estimate derived from a cohort with shorter median follow-up is not equivalent to observing every patient for a full year. Survival calculations can incorporate patients with different observation periods, and the estimates may change as additional clinical events occur.
The absence of a reached median overall survival means that the available data were insufficient to establish the time by which half the study population had died. While this can be encouraging during early follow-up, it does not independently demonstrate a survival advantage over existing treatment.
The findings follow earlier ALICE-2 results presented at the European Hematology Association Annual Congress, when investigators reported a 100% overall response rate among 18 evaluable patients. The updated 95% response rate reflects a subsequent analysis with an additional evaluable patient rather than evidence that the treatment’s underlying efficacy has materially deteriorated.
Earlier analyses also demonstrated activity among patients with TP53 mutations, RAS pathway alterations and complex chromosomal abnormalities. These genetic features are frequently associated with poor treatment outcomes, making them important considerations in AML drug development.
However, the number of patients within individual molecular subgroups remains limited. Additional evidence will be necessary to determine whether iadademstat offers a consistent benefit across different genetic forms of leukemia.
Oryzon Genomics Chief Executive Officer Carlos Buesa indicated that the ALICE-2 findings strengthen management’s confidence in the combination’s tolerability, dose selection and potential clinical activity. He also identified the results as an important foundation for the company’s planned ALICE-3 Phase 3 development program.
The proposed study would represent a significant progression from early dose-finding and exploratory efficacy research toward a more definitive evaluation. Its design will be important for establishing whether iadademstat provides additional clinical value when combined with established AML medicines.
The central question is whether the high remission rates translate into longer survival, durable disease control and an acceptable safety profile in a larger patient population. Until those outcomes are established, the early findings remain promising but insufficient to support regulatory approval.
How Oryzon Genomics’ LSD1 inhibitor iadademstat could improve existing acute myeloid leukemia treatment combinations
Iadademstat, also known as ORY-1001, is an orally administered, highly selective inhibitor of lysine-specific demethylase 1, commonly referred to as LSD1. The enzyme participates in epigenetic regulation, influencing how genes are expressed without directly changing the underlying DNA sequence.
Epigenetic abnormalities are involved in several forms of cancer, including acute myeloid leukemia. In some leukemia cells, disrupted gene regulation can interfere with normal cellular maturation, allowing immature malignant cells to accumulate in the bone marrow and bloodstream.
Inhibiting LSD1 is intended to influence these abnormal regulatory pathways and promote cellular differentiation. The therapeutic hypothesis is that restoring aspects of normal cell maturation may complement other treatments that interfere with leukemia cell survival.
Azacitidine is a hypomethylating agent that modifies abnormal epigenetic processes, while venetoclax inhibits the anti-apoptotic protein BCL-2. Combining these mechanisms with LSD1 inhibition could potentially produce complementary effects against leukemia cells.
However, the biological rationale does not guarantee that the three-drug regimen will outperform existing treatment. Combination therapies may also introduce additional toxicities, making careful evaluation of dosing, treatment interruptions and blood-cell recovery essential.
Oryzon Genomics is investigating iadademstat across several hematological malignancies, reflecting its interest in developing LSD1 inhibition as a broader treatment strategy rather than a therapy restricted to newly diagnosed AML.
The company’s Phase 1b FRIDA trial is evaluating iadademstat alongside gilteritinib in patients with relapsed or refractory FLT3-mutated AML. These patients have often received multiple previous treatments and face substantial challenges associated with resistant or recurrent disease.
At the recommended Phase 2 dose, the combination achieved a 67% composite complete remission rate, according to the newly announced topline results. The company also reported an estimated 12-month overall survival rate of 31% in this heavily pretreated population.
The safety profile was described as manageable and broadly comparable to standard treatment expectations. Additional findings will be presented at the American Society of Hematology meeting, helping clarify the clinical characteristics of patients who responded and the durability of their remissions.
Although the FRIDA results are encouraging, they cannot establish that adding iadademstat improves outcomes compared with gilteritinib alone. Randomized evidence would be necessary to determine the incremental benefit of the investigational combination.
The company is also evaluating iadademstat in accelerated- or blast-phase myeloproliferative neoplasms, a group of blood disorders that can progress toward aggressive leukemia-like disease.
Preliminary findings from a Phase 2 study combining iadademstat with ASTX727 indicated that 50% of treated patients achieved an acute leukemia response classified as partial. The company reported no dose-limiting toxicities in the early dose-escalation analysis. These findings remain preliminary, and the study is continuing to evaluate higher iadademstat doses before selecting a recommended Phase 2 regimen for its randomized component.
The additional programs suggest that LSD1 inhibition could have applications across several blood cancer settings. Nevertheless, each disease population will require independent assessment of safety, efficacy and appropriate treatment combinations.
What Oryzon Genomics’ planned ALICE-3 Phase 3 trial means for future leukemia treatment development
Oryzon Genomics is preparing to advance iadademstat into a planned Phase 3 ALICE-3 study targeting newly diagnosed acute myeloid leukemia. The program is expected to build on the encouraging remission and safety observations generated through the ALICE-2 trial.
The transition toward Phase 3 would represent a major clinical milestone because larger comparative studies are necessary to establish whether iadademstat provides a meaningful therapeutic benefit beyond the existing azacitidine-venetoclax regimen. Important considerations will include patient eligibility, genetic risk classification, dose selection, safety monitoring and the selection of endpoints capable of supporting regulatory evaluation.
Overall survival is particularly important in AML because early remission does not always translate into durable disease control. Patients may experience relapse despite initially responding, making longer follow-up essential for evaluating the true benefit of treatment.
The company has indicated that updated ALICE-2 results following completion of enrollment will help guide its next development stage. These findings could provide additional information about response consistency, hematological recovery and the durability of clinical benefit.
Iadademstat has received orphan drug designation for acute myeloid leukemia in the United States and European Union. Such designations may provide development incentives for therapies targeting qualifying rare diseases, but they do not constitute marketing approval or confirmation of clinical efficacy.
The broader hematology program also includes research in myelodysplastic syndromes and additional studies supported through collaborations involving the U.S. National Cancer Institute. These investigations could help researchers understand whether LSD1 inhibition provides benefits across related disorders involving abnormal blood-cell development.
Oryzon Genomics is simultaneously pursuing iadademstat research in other oncology settings, including small cell lung cancer. However, evidence generated in AML cannot automatically be applied to solid tumors because disease biology, drug combinations and treatment responses may differ substantially.
For patients with acute myeloid leukemia, the strongest potential benefit would be a treatment that increases durable remission rates while maintaining an acceptable safety profile. The new ALICE-2 findings provide an encouraging signal, particularly in a population containing many patients with adverse-risk disease.
The 95% overall response rate, 84% composite complete remission rate and 74% complete remission rate support continued investigation, but they should not be interpreted as cure rates. Likewise, the 76% estimated 12-month survival rate remains an early observation requiring confirmation through longer follow-up.
The separate FRIDA findings broaden the evidence supporting iadademstat in relapsed or refractory leukemia, while the myeloproliferative neoplasm results offer another potential direction for research.
The American Society of Hematology presentations will provide a more comprehensive assessment of the company’s hematology pipeline. Additional patient data, mature survival analyses and treatment-related safety findings will help determine whether the investigational combinations warrant further advancement. Oryzon Genomics’ central development challenge is now to demonstrate that the promising clinical activity observed in relatively small trials can be reproduced in larger, appropriately controlled studies.
If subsequent trials confirm meaningful improvements in survival and durable disease control, iadademstat could eventually become an important addition to combination treatment strategies for acute myeloid leukemia. Until then, the drug remains investigational, and its potential role in clinical practice will depend on further evidence and regulatory assessment.
