Aphios has established a unique library of diverse marine microorganisms and marine molecule fractions from normal to extremophilic environments for the rapid discovery and development of novel therapeutics, with a focus on anti-infectives.

The Marine Environment

The marine environment represents an enormous and under-explored resource for human therapeutics because of its genetic and chemical biodiversity. This environment is also extremely diverse due to the variety of marine habitats, depending on numerous differences in natural salinities, temperatures, and pressures. Aphios’ unique library was established from marine environments and organisms:

• Marine invertebrates – bryozoans, sponges, corals, and tunicates
• Marine vertebrates – shark and fish
• Hydrothermal vents and hypersaline ponds
• Deep-sea sediments via submersibles
• Shallow mangrove swamps and other near-shore locations
• Tropical and temperate oceans

Marine Microorganisms

In collaboration with Woods Hole Oceanographic Institution, Woods Hole, MA with an unmanned Deep Submergence Vehicle named Alvin, these marine organisms and ecosystems were sampled from US territorial waters.

From these resources and other collections, marine microorganisms were isolated and consist of 70% Gram-negatives; 10% Gram-positives, excluding actinomycetes; 10% actinomycetes; and 10% yeast and fungi. 10% of the collection consists of obligate halophilic bacteria.

The microorganisms are characterized by the following techniques:

• Conventional microbiology, including cell morphology, colony morphology, color, Gram stain, motility, and substrate utilization
• Fatty acid methyl ester (FAME) profiles, including an in-house, expanded MIDI database for marine microorganisms
• DNA fingerprinting by the random amplification of polymorphic DNA (RAPD) technique, utilizing polymerase chain reaction (PCR) for identification and redundancy minimization
• Molecular taxonomy, via DNA sequencing of the 16 genes for similarity rank and blast comparisons with ribosomal sequence databases for certain hit marine microorganisms

Marine Fermentation

Aphios has developed proprietary fermentation techniques that mimic the natural saline marine environment in order to enhance isolation of bioactive compounds and allow large-scale manufacture of new anti-infective drugs.

The microorganisms (bacteria, actinomycetes, yeasts, and fungi) are first fermented in at least four different media designed to maximize the diversity of secondary metabolites being generated.

Biodiversity is further enhanced by selectively extracting secondary metabolites with our proprietary supercritical fluid fractionation CXF and microbial cell disruption CFD technologies.

Marine Research Collaborators

The research leading to this unique marine microorganism library, saline fermentation and fractionation technologies were partially funded by an Advanced Technology Program grant from the National Institute of Standards and Technology, Department of Commerce.

Portions of this research were conducted in collaboration with:

• Bristol-Myers Squibb, Wallingford, CT (high throughput screening)
• Instituto BioMar, Leon, Spain (marine microorganisms fractionation and anti-HIV screening)
• The Gillette Company, Boston, MA (anti-gingivitis screening)
• Woods Hole Oceanographic Institution, Woods Hole, MA (marine organisms and sample collection)
• Massachusetts Institute of Technology, Cambridge, MA (saline fermentation technology)
• Scripps Institution of Oceanography, La Jolla, CA (molecular taxonomy and marine chemistry)

Marine Therapeutics Research and Development

We sourced one of our lead therapeutic products in development from a marine organism, Bugula neritina from which Aphios utilizes its CXP manufacturing technology to isolate Bryostatin 1, a potent protein kinase C (PKC) inhibitor. Bryostatin 1 was recently postulated to be produced by a bacterial symbiont of the bryozoan.

Bryostatin 1 is the active pharmaceutical ingredient of APH-0812 being evaluated Aphios and Spanish collaborators for HIV latency and APH-1104 being developed with an SBIR grant from the National Institute on Aging for Alzheimer’s Disease.

Bryostatin 1 has undergone several Phase I and Phase II clinical trials against melanomas, lymphomas and renal cancers by the National Cancer Institute in the United States and by the Cancer Research Campaign in Great Britain.

Aphios utilizes this unique library of marine molecules, its supercritical fluids CXF fractionation technology and biological targets to discover and develop novel therapeutics with a focus on anti-infectives. To date, our research program has generated several anti-HIV and anti-influenza leads and has a marine anti-plaque lead (APP-214) in development.