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, announces the publication of a scientific paper in the peer-reviewed international scientific journal, ACS Pharmacology & Translational Science. The article reports a comprehensive comparison of iadademstat, the first LSD1 inhibitor to be developed in the clinic, with most of the LSD1 inhibitors in development.
The manuscript, entitled "Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology”, compares iadademstat with four LSD1 inhibitors in clinical development in oncology and with five commonly used compounds used in the academia as tool LSD1 inhibitors. Results show that iadademstat is consistently the most active compound across diverse cancer cell lines, that its capability to bind the target is superior, specially at low concentrations, and that the disruption of the transcriptional complexes implicated in the oncogenic programs is more efficacious in the case of iadademstat.
Dr. Jordi Xaus, Oryzon’s CSO, commented: “This set of head-to-head controlled comparisons have shown that iadademstat is clearly the most potent and selective LSD1 inhibitor among all tested clinical molecules. This correlates with the need for lower doses in the clinic, which greatly reduces the potential for idiosyncratic toxicity. A relevant result in this study is that at lower concentrations iadademstat is, by far, the most efficacious in binding LSD1. This may have clinical relevance in solid, dense and poorly vascularized tumors, where the access of drugs to tumoral cells is often an issue”.
The paper has been published in the journal ACS Pharmacology & Translational Science as part of the special issue Epigenetics 2022 and is already accessible on-line. The paper can be accessed here: https://pubs.acs.org/doi/abs/10.1021/acsptsci.1c00223
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 www.oryzon.com
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.
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