VentiRx Pharmaceuticals, Inc., a biopharmaceutical company has announced the publication of preclinical data demonstrating that VTX-2337, the Company's lead small molecule, is a novel, highly potent and selective TLR8 agonist. VTX-2337 directly activates human myeloid dendritic cells (mDCs), monocytes and natural killer (NK) cells resulting in the production of high levels of mediators known to orchestrate adaptive anti-tumor responses. Data were published in the journal Clinical Cancer Research.
The findings clearly distinguish TLR8 from other human TLRs. TLR8 is expressed on human monocytes, macrophages and mDCs circulating in blood and lymph nodes as well as on dendritic cells that are prevalent throughout the tumor microenvironment. Results demonstrate that the direct activation of mDCs by VTX-2337 results in a uniquely robust production of inflammatory cytokines and chemokines that increase cell mediated immunity and potentially enhance the anticancer effect of standard chemotherapy. Additionally, VTX-2337 has a direct effect on NK cells and augments antibody dependent cellular toxicity (ADCC), which supports the opportunity of combining VTX-2337 with monoclonal antibodies where ADCC contributes to clinical efficacy.
"These preclinical findings underscore the potential of a TLR8 agonist as a promising novel agent for cancer immunotherapy," said Mary L. Disis, M.D., professor of medicine in oncology at the University of Washington and associate dean of translational science at the UW School of Medicine, and co-author of the publication. "This research provides validation for current clinical trials evaluating VTX-2337 in combination with existing cancer treatments."
"VTX-2337 provides unique abilities compared to other TLR agonists in clinical development, most notably a robust and highly selective activation of myeloid dendritic cells and natural killer cells," said Robert Hershberg, M.D., Ph.D., President and Chief Medical Officer of VentiRx. "These preclinical efficacy findings combined with the favorable safety profile of VTX-2337 established in the recently completed Phase 1 trial support the advancement of our broad clinical development program currently underway to evaluate the safety and efficacy of VTX-2337 in combination with standard of care cancer therapies."
VentiRx has advanced VTX-2337 into clinical trials designed to evaluate the compound in multiple oncology indications in combination with a variety of anticancer agents, including chemotherapy and monoclonal antibody therapy. Clinical trials of VTX-2337 currently underway include a combination study with chemotherapy in late stage ovarian cancer and a combination trial with cetuximab in head and neck cancer patients. In addition, a trial of VTX-2337 in combination with chemotherapy in metastatic breast cancer is targeted to begin in mid-2012.