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Oryzon Nominates Specific LSD1 Inhibitor as Drug Candidate
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Oryzon Nominates Specific LSD1 Inhibitor as Drug Candidate

Oryzon Nominates Specific LSD1 Inhibitor as Drug Candidate
News

Oryzon Nominates Specific LSD1 Inhibitor as Drug Candidate

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Oryzon announced that it is entering preclinical development with its second drug candidate, a first-in-class specific Lysine Specific Demethylase 1 (LSD1) inhibitor for the treatment of hematological cancers. Our LSD1 inhibitors reduced tumor load especially in acute leukemia models by targeting Leukemia Stem Cells, while normal myeloid progenitor cells were spared.

Lysine specific demethylase 1 (LSD1) is an enzyme that removes methyl groups from lysine 4 of histone H3 proteins that organize the nucleosomes, an epigenetic modification that leads to a repression of transcriptional activity of the target genes. LSD1 has been suggested as a possible target for cancer, viral infections and neurodegenerative disorders.

Oryzon’s LSD1 advanced leads were efficacious in the treatment of Acute Lymphoblastic Leukemia (ALLs), which represents 25% of juvenile leukemia, and in certain types of multiple myeloma and Chronic Lymphocytic leukemia. Independently, Oryzon´s compounds were shown to be efficient in the treatment of acute myeloid leukemia (AML), which represents 40% of all leukemia in humans, and especially in mixed lineage leukemia (MLL), an aggressive form of acute myeloid leukemia. These data that were published recently in CancerCELL by a UK research team, indicate that there is a significant potential therapeutic window for the use of LSD1 inhibitors in the MLL molecular subtype of AMLs.

Oryzon’s drug candidate is an enantiomerically pure, potent and selective compound with a low MW, good pharmacological properties, orally bioavailable, with good PK, safety and selectivity profile. Our candidate is active in vivo at doses of down to 0.05mpk. After successful completion of regulatory toxicology studies, the company expects to move its compound into Clinical Phase I/IIa early next year.

Acute myeloid leukemia (AML), and especially an aggressive form of acute myeloid leukemia called mixed lineage leukemia (MLL), are still being treated today with updated versions of old drugs developed 40 years ago. These intensive chemotherapies and bone marrow transplantation provide a successful therapy in only 50% of the cases. There is consensus among hematologists and oncologists that there’s an urgent need for new drugs. Inhibition of LSD1 is a completely new approach to halt this disease and could help to address this medical need. Other types of leukemia and hematological malignancies could also be treated by targeting LSD1.

Next week, Oryzon will present its LSD1 program in Acute Leukemias at the GTC’s 2nd Epigenetics in Drug Discovery conference in the session Drug Discovery in Epigenetics (May 30-31 at the Hyatt Harborside in Boston, MA).

Carlos Buesa , CEO of Oryzon said: " We have been working really hard the last 4 years in a first in class drug discovery program in LSD1 inhibition producing almost 800 compounds. We believe we have a dominant patent position in the field with 19 patent applications. Now, we and others have identified a subset of hematological cancers in which LSD1 inhibition defines a mechanism of action that looks particularly efficient. We have also verified the high interest amongst hematologists and oncologists for this new approach. We are eager to see the potential of these compounds in the clinic. This is Oryzon’s second compound entering in preclinical development”

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