Technology

Necrotic foci are common anatomic and histologic features of human solid tumors. The necrotic areas of solid tumors are generally anaerobic or hypoxic as compared with the normal tissues. The decreased vascular perfusion around tumor areas makes delivery of chemotherapeutic agents challenging. In addi図1tion, the treatment of solid tumors by conventional systemic administration of anticancer agents suffers from obvious drawback. For instance, large doses of such agents are necessary so as to achieve adequate exposure at the tumor site, which might result in serious side effects.

In an aim to improve drug delivery efficiency, Anaeropharma has been developing in situ Delivery and Production System or i-DPS by modifying a non-pathogenic anaerobic bacteria, B. longum, which localizes and proliferates in the anaerobic environment, to produce anticancer proteins, enzymes or other pharmacologically active molecules selectively at tumor site.

B. longum is non-pathogenic obligate anaerobe derived from human intestinal gut flora, which can be colonized only at low-oxygen microenvironment such as hypoxic regions of solid tumor, or lesions of ischemia. Moreover, B. longum is sensitive to antibiotics, according to our previous research, which allows us to effectively eliminate B. longum when needed or at the end of the treatment. Additionally, preclinical studies for our most advanced project, APS001F, provide solid evidence for safety profile of recombinant B. longum to be utilized for i-DPS therapy. Altogether, B. longum, as the host cell for i-DPS, is a promising carrier for drug delivery.

i-DPS is designed to deliver engineered B. longum which expresses active molecules selectively to hypoxic disease sites. Therefore, the technology which enables B. longum to continuously produce therapeutic molecules inside disease sites without nonspecifically attacking healthy tissues to minimize side effects. Currently we are developing cytokine-producing recombinant B. longum (TNFα-i-DPS and IFNγ-i-DPS) for cancer therapy, single chain fragment antibody (scFv) of immune checkpoint molecule producing B. longum (CTLA4 scFv-i-DPS) for cancer immunotherapy, and FGF2-i-DPS for ischemia treatment. Furthermore, we are continuously obtaining substantial betterments in our know-how to achieve simultaneous production of dual active molecules in one recombinant B. longum strain to mimic regional combination therapy. Our leading project on the dual expression of anti-PD-1 and anti-CTLA4 scFv-i-DPS is under preclinical development.

Our goal is to create more effective and safer therapies based on our core platform technology, i-DPS. The technology has the potential for broad applications in oncology and as well as other hypoxic lesions-related diseases.