iadademstat (ORY-1001) / Oryzon - LARVOL DELTA

Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML (clinicaltrials.gov) - P1 | N=45 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

Iadademstat Combination with Azacitidine Is a Safe and Effective Treatment in First Line Acute Myeloid Leukemia. Final Results of the Alice Trial (ASH 2022) - P2 | "Azacitidine (aza) plus venetoclax has shown an OS of 14.7 months (mo) and a complete remission or complete remission with incomplete hematological recovery (CR/CRi) rate of 66% (VIALE-A trial). The combination of iada with aza produces robust, rapid and durable responses in previously untreated unfit AML patients, including those with high-risk features, with a manageable toxicity profile. Further research with iada in combination with SoC treatments for AML is warranted."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia • FLT3 • TP53

Oryzon Genomics…announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. patent application No. US 18/554,241, entitled 'Combinations of LSD1 inhibitors for treating myeloid cancers' (Oryzon Press Release) - "The allowed claims cover combinations of iadademstat, or certain other LSD1 inhibitors, with gilteritinib and their use for the treatment of myeloid cancers, including acute myeloid leukemia (AML). Once granted, the U.S. patent is expected to expire in 2042, excluding any potential patent term adjustment or patent term extension. A corresponding patent has recently also been granted in Taiwan, with additional patent applications pending in other jurisdictions."

Patent • Acute Myelogenous Leukemia

Iadademstat is currently being evaluated in seven ongoing oncology clinical trials, including the Phase Ib FRIDA study in combination with gilteritinib in FLT3-mutated relapsed/refractory AML and the Phase Ib ALICE-2 study in combination with venetoclax and azacitidine in first-line AML (Oryzon Press Release) - "Additional, more mature data from both studies are expected to be presented by year-end."

P1 data • Acute Myelogenous Leukemia

Pharmacological inhibition of LSD1 suppresses the CD155/TIGIT immune checkpoint axis and enhances NK cell-mediated cytotoxicity in colorectal cancer. (PubMed, Bioorg Chem) - "Importantly, pharmacological inhibition of LSD1 with two small-molecule inhibitors, CC-90011 and ORY-1001, markedly decreased CD155 expression and membrane abundance in multiple CRC cell lines. Collectively, these findings reveal that pharmacological inhibition of LSD1 attenuates CRC immune escape, at least in part, by epigenetically suppressing the CD155/TIGIT axis. This study provides a rationale for exploiting LSD1 inhibitors as immunomodulatory agents to enhance antitumor immunity in CRC."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • IFNG • PVR • TIGIT • TNFA

FRIDA: Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+) (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Oryzon Genomics S.A. | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2025 ➔ Dec 2026

Enrollment closed • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3

The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer. (PubMed, J Mol Med (Berl)) - "Clinically, small-molecule inhibitors targeting KDM1A, such as Tranylcypromine (TCP) and Iadademstat, could enhance the efficacy of ICIs by reversing the immunosuppressive microenvironment, especially in mismatch repair proficient (pMMR) CRC. Future studies should further elucidate the molecular networks of KDM1A regulating immunogenicity and explore the synergistic mechanisms of its inhibitors with other epigenetic drugs or immunotherapies in order to provide new strategies for overcoming CRC resistance to immunotherapies."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • CTNNB1

A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs) (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis

ORYZON reports financial results and corporate update for half year ended June 30th, 2026 (Oryzon Press Release) - "'We expect to present final data from ALICE-2 and FRIDA by year-end.'...'we remain on track to engage with the FDA on the design of a potentially registrational study in first-line AML, with the objective of initiating the trial in 2027.'"

New trial • P1 data • Acute Myelogenous Leukemia

ORYZON raises €12 million and signs a financing agreement with COFIDES to strengthen its balance sheet and accelerate its clinical programs (Oryzon Press Release) - "The funds raised will be used to: Strengthen the Company's balance sheet to support corporate development initiatives in anticipation of future partnership discussions; Advance the clinical development of iadademstat for the treatment of acute myeloid leukemia; Progress the other ongoing clinical programs in hematology and psychiatry; Cover general and administrative expenses and financial obligations....This commitment will apply to any future capital increase that Oryzon may undertake within six months of the execution of the share subscription agreement. This period may be extended by mutual agreement between the parties."

Financing • Acute Myelogenous Leukemia • Amyotrophic Lateral Sclerosis • CNS Disorders

ALICE: Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: OHSU Knight Cancer Institute | Trial completion date: May 2026 ➔ May 2028 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ABL1

UPDATED SAFETY AND EFFICACY RESULTS OF A PHASE IB INVESTIGATION OF THE LSD1 INHIBITOR IADADEMSTAT (ORY-1001) IN COMBINATION WITH AZACITIDINE AND VENETOCLAX IN NEWLY DIAGNOSED AML (EHA 2026) - P1 | "Swimmer plot depicting response and survival outcomes of patients treated on protocol through February 2026. Arrows indicate patients remaining on protocol defined therapy."

Clinical • Combination therapy • IO biomarker • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Immunology • Neutropenia • Septic Shock • Thrombocytopenia • BCL2 • GFI1

SAFETY AND EFFICACY OF IADADEMSTAT PLUS GILTERITINIB IN THE FRIDA EXPANSION COHORT OF FLT3‑MUTATED RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2026) - P1 | "Preclinical studies show that iada is synergistic with gilteritinib in FLT3mut AML cells, including models resistant to venetoclax, azacitidine, or other FLT3is...Methods Adult pts with ≤ 2 prior lines of therapy (including quizartinib or gilteritinib if not refractory) received iada PO at doses of 50 to 150 μg, on a 5 days ON-2 days OFF (5+2) schedule for 3 or 4 wks in 28-day cycles with gilteritinib 120 mg/day PO in the escalation phase...Additional data will be presented at the conference. Summary/Conclusion In a heavily pre-treated and refractory FLT3mut AML population, iadademstat+gilteritinib demonstrated a favorable safety profile and high CCR (67%), supporting further clinical development of this combination."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • FLT3

ALICE-2 Phase Ib clinical trial (NCT06357182) investigating iadademstat in combination with azacitidine and venetoclax in newly diagnosed AML (Oryzon Press Release) - "'As enrollment continues, we anticipate reporting final data by year-end and advancing toward a potential registrational study in first-line AML by 2027'...High rates of activity, with a 100% (18/18) overall response rate (ORR), 89% (16/18) composite complete remission (CRc) rate and 78% (14/18) complete response (CR) rate; CRs occur early, most of them in cycle 1; Efficacy was observed across different genomic risk groups, including TP53 and RAS pathway mutations and patients with complex karyotypes, all considered adverse risk; Patients with TP53-mutated disease (2/2) attained CR and showed a reduction in TP53 variant allele frequency (14% to undetected and 22% to 1%, respectively); All patients with RAS pathway mutations (3/3) achieved CR; After a median follow-up of 8 months, median overall survival (OS) and event-free survival (EFS) were not reached; estimated 12-month OS and EFS were 79% and 71%, respectively..."

New trial • P1 data • P53mut • Acute Myelogenous Leukemia

FRIDA Phase Ib clinical trial (NCT05546580) investigating iadademstat in combination with gilteritinib in FLT3‑mutated relapsed/refractory AML (Oryzon Press Release) - "The poster reports data from the expansion cohort at the selected pharmacological active dose (PAD, 75 ug iadademstat); 23 patients have been enrolled at this dose, with 18 being evaluable for response; High CRc rate of 67% (12/18) in a heavily pre-treated population; Iadademstat plus standard of care (SoC) treatment gilteritinib demonstrated a manageable safety profile, without adding toxicity to the SoC."

P1 data • Acute Myelogenous Leukemia

ORYZON initiates patient enrollment in IDEAL Phase II trial of iadademstat in essential thrombocythemia (Oryzon Press Release) - "IDEAL (IaDademstat treatment for EssentiAL thrombocythemia) is a multicenter, single-arm Phase II study being conducted in Spain in adult patients with ET who are resistant or intolerant to hydroxyurea. The study is designed to evaluate the safety, tolerability and clinical activity of iadademstat, including its efficacy in reducing the percentage of adult ET patients with abnormal platelet counts. Iadademstat will be administered for up to 24 weeks, with an additional 24-week extension period available for those benefiting from treatment."

Enrollment open • Essential Thrombocythemia

A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs) (clinicaltrials.gov) - P2 | N=62 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis

Title: Safety and Efficacy of Iadademstat Plus Gilteritinib in the FRIDA Expansion Cohort of FLT3‑Mutated Relapsed/Refractory Acute Myeloid Leukemia (GlobeNewswire) - "ORYZON to present updated positive clinical data...at EHA 2026....Updated data from a heavily pre-treated relapsed or refractory FLT3mut AML population in the FRIDA trial (NCT05546580) evaluating iadademstat plus standard of care treatment gilteritinib demonstrated a favorable safety profile and a CRc rate of 67% (n=12/18). Additional data will be presented at the conference."

P1 data • Acute Myelogenous Leukemia

Title: Updated Safety and Efficacy Results of a Phase Ib Investigation of the LSD1 Inhibitor Iadademstat (ORY-1001) in Combination with Azacitidine and Venetoclax in Newly Diagnosed AML (GlobeNewswire) - "ORYZON to present updated positive clinical data...at EHA 2026....As of the February 2026 data cutoff, the triplet combination of iadademstat, azacitidine and venetoclax evaluated in the ALICE-2 trial (NCT06357182) continues to demonstrate favorable safety and high response rates. Among evaluable patients (n=14/15) the overall response rate (ORR) was 100% with a complete response (CR) rate of 79% (n=11/14) and a composite complete remission (CRc: CR+CRh+CRi) rate of 93% (n=13/14). After a median follow-up of 6 months, the estimated 12-month OS rate was 74%. Updated data with additional patients and more mature responses will be presented at the meeting."

P1 data • Acute Myelogenous Leukemia

Human Ductal Carcinoma In Situ: Role of Spatial Niches in Invasive and Metastatic Progression (ASBrS 2026) - "Transcriptional drivers were functionally validated using Lysine-Specific Demethylase 1(LSD1) inhibitors (ORY-1001 and bomedemstat) in HER2+ DCIS cell lines and xenograft models (BCM 3613, BCM 3963). Spatial niches enriched with FOXA1-driven, stem-like luminal hormone-responsive cells play a key role in the underlying invasive and metastatic potential of DCIS, particularly in HER2+ subtypes. These niches are characterized by distinct ligand-receptor signaling (e.g., CEACAM6–EGFR) and epigenetic regulation. Targeting transcriptional regulators of stemness, like FOXA1, along with their microenvironmental signals, offers a promising strategy to prevent progression in high-risk DCIS."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CEACAM6 • EGFR • FOXA1 • HER-2

Synergistic growth-inhibitory efficacy of LSD1 and BCL-XL inhibitors in JAK2+ AML/MPN cells (AACR 2025) - "We explored the synergy between the LSD1i Iadademstat (Selleckchem), and BCL-2/BCL-XL inhibitor, Navitoclax, or the platelet-sparing BCL-XL degrader, DT2216 (Dialectic Therapeutics). In summary, JAK2+-mutant post-MPN AML cell lines and isogenic Ruxolitinib-resistant lines showed sensitivity to BCL-XL inhibitors and a synergistic increased sensitivity to these compounds when combined with low dose LSD1 inhibitor, Iadademstat. Mechanisms behind the synergy are being studied and will be reported.Summary of Glo Titer Assays and Annexin 5 Flow Cytometry Data with mean Synergy ScoresGlo Titer AssayNavitoclaxDT2216LSD1iLSD1i+NavitoclaxLSD1i+DT2216Hel ParentalIC501.3±0.2µM2±0.8µMNot Reached6.5±3 nM0.25±0.08 µMHel RRIC500.5±0.3µM1.8±0.7µMNot Reached6±3nM0.3±0.15 µMSet 2 ParentalIC500.4±0.4µM2.5±1 µMNot Reached6.5±02.5nM2±1.3 µMSet 2..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • BAX • BCL2 • BCL2L1 • JAK2

Updated data from iadademstat’s clinical trials in acute myeloid leukemia to be presented at EHA-2026 in June (The Manila Times)

Clinical data • Acute Myelogenous Leukemia

Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged acute myeloid leukemia (AACR 2026) - "In this study, we performed a combination drug screen using an epigenetic compound library in KMT2A-r AML cells to identify synergistic agents that could potentiate menin inhibitor activity.MV4-11 cells were treated with DSP-5336 (menin inhibitor) to optimize assay performance (Z′ > 0.5)...Follow-up studies used ORY-1001 (LSD1 inhibitor) and SNDX-5613 (menin inhibitor) across dose ranges...Ongoing in vivo studies aim to further elucidate the underlying mechanisms and therapeutic potential of this combination. Ultimately, this work may guide the development of innovative combination treatment strategies for KMT2A-r AML patients."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AFDN • ITGAM • KMT2A • PTPRC

Minimal-length CAG repeats in AR define a hyperactive AR-LSD1 axis driving metabolic reprogramming in prostate cancer (AACR 2026) - "Minimal-length CAG repeats in AR establish a hyperactive AR-LSD1 chromatin axis that drives transcriptional and metabolic reprogramming, leading to prostate cancer progression. These findings link inherited germline AR polymorphism to epigenetic-metabolic remodeling and identify LSD1 inhibition as a promising therapeutic strategy for aggressive and racially disparate PCa subtypes harboring minimal-length CAG repeats."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • FOXA1

LSD1-ESM1 regulates extravillous trophoblast function through metabolic reprogramming in recurrent spontaneous abortion. (PubMed, J Assist Reprod Genet) - "This study reveals a role of epigenetic-metabolic coupling in the pathogenesis of pregnancy loss. It identifies a potential molecular target and mechanistic basis for the diagnosis and treatment of RSA."

Journal • Metabolic Disorders • ESM1 • KDM1A