Welcome to Ohm OncologyDeveloping solutions for blood and solid tumor cancers
A major challenge in chemotherapy is the emergence of drug resistance – in other words “the Ohm of Oncology”!
Ohm Oncology is a drug development company committed to treating drug resistant neoplasms and cancers with novel multi-mechanism compounds.
engagement of multiple disease targets is the best way to achieve disease modifying therapy with JAK and BET pathways being the key targets.
target and refractory diseases
In many cancers and neoplasms, the signaling networks responsible for disease contain redundant pathways allowing resistance to emerge from therapy targeting a single pathway. An example of this is myelofibrosis (MF) treatment with Jakafi. MF is associated with scarring of the bone marrow, which leads to anemia, recurrent infections and other consequences of bone marrow failure. MF is an orphan indication affecting about 18,000 patients in the US with a median survival of 3.5-5.5 years. Patients die due to marrow failure or transformation of their disease into leukemia.
The majority of MF patients contain a JAK2-activating mutation in their blood cells, which leads to bone marrow scarring, enlargement of the spleen and liver, and constitutional symptoms. Jakafi (ruxolitinib) is the only approved therapy for MF. Ruxolitinib targets the JAK/STAT signaling pathway, and in particular, JAK2, which controls normal blood cell production.
Many patients initially benefit from Jakafi therapy but about 50% of patients fail or become intolerant to Jakafi within 2 years and about 75% by 4 years, and the disease continues to worsen. Transfusion dependency is not improved on Jakafi and side effects and splenomegaly (enlarged spleen) return rapidly after Jakafi discontinuation with an estimated survival of only 14 months. About 20% of patients with MF die following transformation to acute leukemia and Jakafi does not alter the incidence of leukemic transformation.
The medicinal chemistry expertise at Ohm includes kinase targeting and developing pharmacophores capable of engaging multiple targets. For myelofibrosis, a second validated target is BET inhibition. BET inhibition may block proliferation of inflammatory bone marrow cells and can synergize with JAK inhibition. Combinations of BET/BRD4 and JAK2 inhibitors result in synergistic inhibition of the growth of ruxolitinib-resistant tumor cells, providing the rationale to create a single molecule with dual BET/BRD4 and JAK2 inhibition.
Ohm medicinal chemists successfully developed poly-pharmacophores that inhibit both BET and JAK kinases with excellent in vitro and in vivo efficacy. Our top candidate dual-inhibitor, OHM-581, was identified during a medicinal chemistry program that synthesized and characterized about 150 analogs.
Ram S. Upadhayaya
Michael J. Weickert
Where we are
2405 Robert Browning St.
Austin, TX 78723
P : +1-408-218-9330