Phase I/II clinical trial targeting solid cancer

The company’s leading anti-cancer drug candidate, APS001F is recombinant anaerobic bacteria B. longum modified to express cytosine deaminase (CD) gene, which results in 2overexpression of the CD enzyme. B. longum is a major component of normal human intestinal flora; they can be detected in a wide variety of mammalian species. When APS001F is administered intravenously to tumor-bearing mice, the bacteria localize and grow specifically in the tumors, but not in normal tissues. When flucytosine (5-FC, a fluorinated analog of cytosine that is approved for use as an anti-fungal agent) is administered in the presence of APS001F, the CD enzyme converts the cytosine residue of 5-FC to uracil, producing Fluorouracil (5-FU), an established cancer chemotherapeutic agent.5-FC is inherently less toxic than 5-FU. Thus, by selectively targeting tumor tissues, APS001F facilitates the local conversion of 5-FC to 5-FU in the tumor environment, resulting in tumor-specific exposure to 5-FU while minimizing the exposure of normal tissues. It is anticipated that higher intra-tumoral 5-FU concentrations will be achieved with APS001F than with systemic administration of 5-FU because APS001F-mediated 5-FU delivery to the tumor will not be limited by systemic toxicity. In the experiments using tumor-bearing mice and rats, it has been demonstrated that APS001F rapidly disappeared from normal tissues while at the same time colonizing tumor tissue and proliferating at the site. Following administration of 5-FC, high concentrations of 5-FU were detected in tumor tissue (more than 10,000 ng/g tumor tissue), while very low levels of 5-FU were detected in the normal tissues, approximately a 1000-fold difference. This is a significant improvement over the tumor vs. normal tissue ratios observed for other agents designed to improve intra-tumoral 5-FU concentration in comparison to normal tissues.

The Phase I/II trial of APS001F is currently ongoing in US. This is the first-in-human dose escalation study designed to explore APS001F in patient with advanced and/or metastatic solid tumors whose disease is no longer considered responsive to available treatments. The trial is to evaluate safety, tolerability and efficacy of the study agent.