VentiRx Pharmaceuticals has announced preclinical data demonstrating that VTX-2337, the company’s lead small molecule, is a novel, highly potent and selective TLR8 agonist.
The results demonstrated that VTX-2337 directly activates human myeloid dendritic cells (mDCs), monocytes and natural killer (NK) cells. The activation mDCs results in the production of high levels of mediators known to orchestrate adaptive anti-tumour responses. The production of inflammatory cytokines and chemokines will increase cell mediated immunity and potentially enhance the anticancer effect of standard chemotherapy.
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VTX-2337 shows 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. The study findings distinguish TLR8 from other human TLRs, the company said.
TLR8 is expressed on human monocytes, macrophages and mDCs circulating in blood and lymph nodes and even on dendritic cells that are prevalent throughout the tumour microenvironment.
VentiRx president and chief medical officer Robert Hershberg said VTX-2337 provides unique abilities over other TLR agonists in clinical development, notably selective activation of mDCs and natural killer cells. "These preclinical efficacy findings combined with the favourable safety profile of VTX-2337 established in the recently completed Phase I trial support the advancement of our broad clinical development programme," he added.
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The company has advanced VTX-2337 into clinical trials designed to evaluate the compound in multiple oncology indications in combination with a variety of anti-cancer agents. A combination study with chemotherapy in late stage ovarian cancer and a combination trial with cetuximab in head and neck cancer patients are clinical trials of VTX-2337 currently underway. The company will also begin a trial of VTX-2337 in combination with chemotherapy in metastatic breast cancer in mid-2012.
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