OUR PIPELINE - SMALL MOLECULE INHIBITORS
OncoViRx is developing therapeutics to target specific mechanisms of oncogenesis. Specifically, the company is primarily focusing on compounds for inhibition of c-MYC, and NF-KB, and secondarily Notch1.
Based on the high-throughput screening of compounds from the U.S. Cancer Institute’s Developmental Therapeutics Program, 40 small molecule drug candidates were identified and several were advanced into a pilot animal study with promising results.
The initial focus of screening was to identify compounds with activity against virus-mediated lymphomas. However, the leading compounds demonstrated activity against virus positive and negative cells, in both lymphomas and leukemias, and demonstrated superior activity vs. vincristine (a drug commonly used in first-line combination therapy).
Two of these compounds, which are in the same drug class, have been selected for analog development by the Winkler Laboratory. To date, several early Winkler developed analogs have shown promising results in vitro. Within the next 12 months, our plan is to develop a number of additional analogs, complete in vitro screening, and then advance the most promising candidates into a pilot in vivo study. We anticipate initial clinical development of our lead compound will be in several sub-types of relapsed/refractory non-Hodgkin’s lymphoma and/or acute myeloid leukemia. Our goal is to develop novel treatments that are efficacious, have reduced short and long term side effect profiles, and are cost effective.
c-Myc and NF-KB
Both c-MYC and NF-KB signaling pathways broadly affect cellular functions, including cell proliferation and cell death, and have been implicated in a range of blood cancers.
Specific to c-MYC, a mutated version is found in many cancers, which causes c-MYC to be constitutively (persistently) expressed. This leads to the unregulated expression of many genes, some of which are involved in cell proliferation, and results in the formation of cancer. C-MYC is therefore viewed as a promising target for anti-cancer drugs.
As for NF-KB, it is a protein complex that controls transcription of DNA, cytokine production, and cell survival. NF-KB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-KB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-KB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.
Notch is a signaling pathway, which is critical in cell differentiation and tissue development. As such, the deregulation of notch signaling has been implicated in the development of many cancers. Furthermore, studies have shown that induced Notch1 expression is related to a subset of T-cell lymphomas. The manipulation of this signaling activity has the exciting potential for the management of cancers affected by this mechanism.