Bringing nature into the laboratory

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By Shawn Lawrence

He began his venture into biotech in the mid nineties, following a trip to Rome, Italy. There he met two Jesuit fathers who introduced him to a patent developed by Corodo Galeffi. The patent was a unique abstract from a plant believed to have strong medicinal powers among them a positive effect on patients with Malaria. Already frustrated with the lack of affordable therapy for those with Malaria, Stella set out to use this plant as a means to satisfy this need. On a hunch, he made the acquisition of the patent hoping to bring it to the market. By 1997, he had established Millenia Hope Inc. but with the patent in toe, other complications arose.

Difficulties in harnessing the technology and in trying to decipher why the plant was able to treat malaria were just some of the obstacles he faced. Around a the corner, Avance Pharma Inc., a Canadian pharmaceutical company with a multidisciplinary team of biologists, biochemists, botanists, chemists and bioengineers dedicated to harnessing nature's unparalleled ability to synthesize compounds of pharmaceutical interest was struggling to survive. Despite having a unique technology, Phytomics and a solid scientific team, money was an issue. The Avance team was almost out of options when Stella came knocking. "We started out with $24,000,000 in venture capital but year after year we weren't able to land a contract and it became increasingly hard to manage things," remembers Dr. Bahige Baroudy.

The former Scientific America Top 50 Research Leader for 2003, he knew he had something special on his hands but he needed more time and money to make it come into fruition. "Avance was never a money maker, then Leo comes in and immediately we were able to sign two contracts," said Baroudy.

Following MHI's takeover in February 2006 of Avance Pharma Inc., MHI subsidiary Millenia Hope Biopharma (MH-B) was born. After a seamless transition, the company that used to be Avance Pharma was no longer in the red and Baroudy was appointed president and chief science officer-director of both MHI and MH-B. It was in a way the proverbial turning point for both companies, the perfect marriage between business and science.

Situated in Montreal, Millenia Hope Biopharma today is a biopharmaceutical company focused on the production of ingredients of interest to pharmaceutical, cosmetic and nutraceutical companies. Operating as a subsidiary to MHI, it provides a great deal of support to its parent company in finding comprehensive solutions to the problems of world disease. Its corporate strategy, as it was under Avance, is to become a worldwide leader in the development of plant-based materials to be utilized for the discovery and development of innovative pharmaceutical, cosmetic and nutraceutical products with a plant cell culture-based platform unique to the industry. Phytomics remains MH-B's core technology.

Patented in May 2000, Phytomics is a process that starts with plant material, ideally seeds, which are then germinated and converted through suspension culture to individual cells that allow its production to be scaled up in size. Once suspended culture is achieved, elicitors are used to turn them into secondary metabolites thus elevating their yield. 'Phytomics can be considered 'Green Chemistry'. Since in nature plants can often take years to come to maturity, or to the point where their metabolites can be harvested, the ability to achieve a production run of a specific metabolite in a matter of months and at a highly elevated yield is an important advantage of Phytomics," said Baroudy. "Phytomics also removes the effects of climate, terrain, weather and seasonality on horticultural production, which are limitations for many field grown medicinal plants. Once an ideal cell line has been identified, it can be grown indefinitely and at any scale."

Describing the technology, Baroudy says, "basically, plant materials have been used since the inception of pharmaceuticals, cosmetic ingredients, and, of course nutraceuticals. Phytomics is a process that allows us to extract the wealth of chemo-diversity that resides in plants and deliver and commercialize them on a large scale vast amounts of ingredients for these industries."
The technology has also allowed MBI to create a unique library that is used as the basis of the company's drug discovery and development efforts, something Stella is quite proud of.

"We're very unique in our process. There are other companies that do things that are similar to us, as in working with plant abstracts, but we're looking deeper into the mechanisms that make the extracts work the way they do. And through Phytomics, we've been able to go all the way."

He also believes the Phytomics technology is better than synthetic chemistry and traditional natural product extracts because it addresses all the challenges associated with traditional natural product discovery, that it provides readily available access, high reproducibility and yield. "You can take one seed and create an endless amount of extracts. One seed is perpetual."

Another aspect of the technologies benefits is that it produces pure samples, which is integral for testing. In all, the technology has lead to the collection of more than 2,200 plant species, obtained from 40% of known plant families. It has equipped the library with more than 160,000 purified fractions from 560 different plant species meaning there are still many more fractions to be found. As it stands, it is the largest library of its kind worldwide and according to Stella, it is Millenia Hope Biopharma's biggest strength.

"That library is unique in that it can feed every one of the pharmaceutical companies out there. Each one them can develop a particular niche with us for this reason. There are more than enough extracts, the information is there they just need to come to us. Our goal is to do just that, to use our library as a pipeline for those companies."

The focus for the majority of the fractions is on parasitic diseases, particularly AIDS. According to Baroudy, the extracts have been shown to contain antiviral (HIV), antimicrobial and anticancer activities. But the concept of fighting Maria still remains as crucial as it was on the day Stella created MHI. In fact the first product spawned by the library is MMH(TM) Malarex/MMH(TM) 18, a fraction that came from the original plant patent that Stella acquired in Italy. The drug has become MHI's and MH-B's flagship product, an all-natural anti-malarial treatment that is already saving lives in 18 different countries in Africa. Though still in clinical stages, Malarex has been found to kill the Malaria parasite at any stage of development. In all, the majority of patients suffering from Malaria treated with Malarex have been found to have their symptoms subside within three to five days and the parasite itself gone from the blood within a week.

"We've applied for Health Canada licensing approval for the product. Hopefully one day we'll have enough data to satisfy their requirements," says Stella.
Encouraging signs have also been witnessed in MH-B's work with AIDS research. While most current clinical CCR5 Antagonists are Nitrogen containing, toxic and often unsuccessful, MH-B's CCR5 Antagonists don't contain Nitrogen, are not toxic and to date, 210 fractions from 26 plant species are confirmed active on CCR5.

Another major breakthrough for MH-B came in its nutraceutical/cosmetic research, specifically the cell culture production of Feverfew, a plant whose extracts are used in the cosmetic industry. Using advanced plant cell culture, MH-B was able to develop a process that produced parthenolide-free Feverfew extracts, or a Feverfew extract that did not produce allergic reactions making it appealing to cosmetic companies as an option for hand creams, perfumes and body lotions. Because of this breakthrough, MH-B signed several R&D contracts in 2006 with L'Oreal and Pierre Fabre Medicament, a French pharmaceutical company, and followed those deals up in 2007 by signing a contract with Sederma. The deals collectively have gone a long way in funding further plant extract research, adding to a climate of multiple market opportunities for MH-B.

The end idea according to Stella is that MH-B will receive fees for the use of the fractions, milestone payments during development of a drug candidate and royalty payments once a drug is developed and mass-produced.

"We're not arrogant, we don't believe we can take all our drugs all the way to Phase IV. But what we are interested in is getting as many as we can to the big pharmaceutical companies, to part with some of our children to allow these companies to put more drugs on the market. Eventually we can aspire to reach Phase IV, but now is not the time yet," he says.
He adds that he intends to out-license the first drug, take the money from those royalties and apply it to the second drug, where he will partner it into Phase I test. "We'll follow the same process with the following drug and the drug that comes after until we can afford to take one drug all the way. Fortunately we still have lots more in the pipeline. We've got compounds for cholesterol, diabetes, all from plant extracts. And it's all thanks to the library."

Both Baroudy and Stella say they already know which plant abstract may hold the key to going all the way but intend to keep that information under wraps in the meantime.

Overall, both men are satisfied with MH-B's progress in the last year and are encouraged by the company's future prospects.

"It's been a hard fight to get our plant extracts accepted," says Stella. "But I think more and more people are convinced of their potency and of the significance of our technology. We have something no one else does, that library, and we're getting hits and generating interest. The future for the company is bright, and really in terms of our pipeline, the sky's the limit."