September 1, 2009 (Vol. 29, No. 15)
Australian Firm Seeks to Unlock Plants’ Secrets with EcoLogic Platform
Since 2000, EcoBiotics has been quietly combing the rainforests of Queensland, Australia, for new pharmaceutical compounds. Now with two anticancer candidates in the late stages of preclinical testing, the company is expanding to the U.S. and Europe. Under the guidance of Steve Delco, CEO, EcoBiotics is seeking academic and pharmaceutical partnerships for its natural products. “For this next commercialization stage, we need to develop strategic research relationships for discovery and take the compounds into the clinic,” says Delco.
The researchers at EcoBiotics take a more encompassing approach to exploring the Australian rainforests than do companies who search for new compounds in South America’s rainforests. EcoBiotics’ cofounders, Victoria Gordon, Ph.D., and Paul Reddell, Ph.D., are chemical and forest ecologists who live and work at the company’s headquarters near Cairns in the Daintree Rainforest of northeastern Australia. Their research team experiences firsthand the seasonal variation in plants, insect assaults, and invasions of microorganisms.
In contrast, researchers at other drug companies generally visit rainforests for a few weeks, collect plant materials, and take them back to laboratories to analyze them for new chemicals, according to Delco. The holistic approach at EcoBiotics “is like watching a movie instead of looking at snapshots,” he adds.
Plants evolve amazingly complex and dynamic chemical systems to survive. For example, when attacked by pathogenic microbes, plants use pattern recognition receptors to identify their assailants and produce specific antibiotics to defend themselves. “Attract-or-repel interactions create novel chemicals,” says Delco, as plants respond to injury, climate change, or invaders in a limited space.
The Queensland Government protects its rainforest treasures, which are inscribed on the United Nations’ World Heritage list, by limiting access to them. Dr. Gordon, who chaired the philanthropic Australian Rainforest Foundation, negotiated formal collection rights for EcoBiotics’ scientists to all of Queensland’s diverse range of rainforest ecosystems. EcoBiotics is the only company to receive these rights, Delco says, and it collects all samples in compliance with the United Nations Convention on Biodiversity. Intellectual property rights are assured and wholly owned by EcoBiotics under the agreement.
Tropical rainforests have long been thought to offer an ideal place to discover new drugs. Bioactive chemicals in plants are designed by nature to work within biological systems and have inherent properties that make them highly amenable as drugs. Unlocking the chemical secrets of such complex ecosystems, however, has been problematic. EcoBiotics’ discovery platform, called EcoLogic™, addresses this problem by using knowledge of chemical ecology, physiology, phenology, species distribution, and signaling pathways in rainforest plants to identify particular types of chemistry and bioactivity with potential commercial value, Delco explains.
The observation that rainforest marsupials spit out seeds after eating the fruit of a certain plant led to the company’s lead compound, EBC-46. Scientists at EcoBiotics learned that the unpalatable seeds contain an inflammatory agent that made the animals’ tongues swell. They isolated the active ingredient, a diterpene ester, which belongs to a new class of chemicals.
EBC-46 shows anticancer properties against basal and squamous cell carcinomas, melanoma, and head and neck tumors, Delco reports. The active ingredient in EBC-46 is easily purified from a ubiquitous plant species that can be quickly grown on plantations. The company is developing a GMP process to insure commercial quantities of the drug for future investigations.
EBC-46 is a protein kinase C regulator that initiates apoptosis of tumor cells and causes a local inflammatory reaction that recruits the body’s neutrophils to attack the tumor. When injected into incurable soft tissue sarcoids, nasopharangeal cancers, and oral malignant melanomas in horses, dogs, and sheep, EBC-46 destroyed the tumors and healing was evident in about two weeks, Delco reports. The positive animal results “don’t guarantee that EBC-46 will work in people,” he adds, “but it’s promising.” EcoBiotics plans to file an investigational new drug application for EBC-46 within a year.
EBC-23 is a novel spiroketal in early preclinical development for the treatment of prostate and breast cancers. EBC-23 was extracted from a rainforest flowering plant, but now is made synthetically, allowing for commercial scale-up.
Other compounds derived from plants in the company’s pipeline slow the uptake of glucose, fight off bacterial and fungal infections, prevent inflammation, or protect against neurodegenerative damage. EcoBiotics also develops natural products for ingredients in veterinary nutraceuticals and cosmetics.
Delco is working to set up discovery programs with pharmaceutical firms and academic institutions to identify and screen more rainforest compounds. The general consensus is that the rainforest is a powerful source of antibiotics and other drugs, but the compounds need to be isolated and tested. Delco also wants to license EBC-46 for clinical development.
Pharmaceutical researchers have “banged their heads against the wall trying to find new drugs in their libraries through combinatorial chemistry and genomics,” says Delco. These methods, however, have produced few new drugs, and they cannot compete with millions of years of evolution in plants. Rainforest plants hold a vast untapped chemical reservoir of potential products. However, “we have to unlock their chemical secrets, and at EcoBiotics we have found the key to do this,” Delco says.