Oryzon nominates LSD1 inhibitor as preclinical candidate for Treatment of Acute Leukemia

ORYZON is proceeding in preclinical development with its second drug candidate, a first-in-class specific Lysine Specific Demethylase 1 (LSD1) inhibitor for the treatment of Acute leukemia and other hematological cancers 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.

Acute myeloid leukemia (AML) are still being treated today with updated versions of old drugs developed 40 years ago. These intensive chemotherapies and bone marrow transplantation provide successful therapy in only 50% of the cases. There is strong 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.

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 a 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, we expects to move quickly the compound into Clinical Phase I/IIa early next year.

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). Other pharmaceutical companies as Novartis, Genentech, Pfizer or GSK among others will participate.

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. Now, we and other scientists 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 oncologist for this new approach. We are really eager to see the potential of these compounds in the clinic.