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EXCLUSIVE LIFE SCIENCE FEATURE leaders LIFESCIENCELEADER.COM MARCH 2014 32 The Novelties Of VLPs Medicago's CEO Andy Sheldon expounds on the characteristics and potential ad- vantages of the "viral-like particles" (VLPs) produced by the company's tobacco-based vaccine technology: "VLPs confer all the great benefi ts of a live virus in a vaccine, but they are not live, they do not have any genetic material, and therefore they have better safety aspects. The virus-like particle for infl uenza is very similar in size to the naturally occurring infl uenza particles. We have seen now, through our clinical trials on H1 and H5 fl u vaccines, that we have the opportunity for some cross reactivity, and thus cross pro- tection. In other words, the VLP structure may confer a better immunity than exist- ing technologies by protecting against more strains, as well as elucidating both of the pathways needed to induce cell-medi- ated immunity. And we're working hard to demonstrate that. A simple example would be in the elderly, who often lack the anti- bodies but resist infl uenza because they have cell-mediated immunity, or T-cell re- sponses. So we believe we may have some huge advantages in the marketplace with a more effi cacious product, all due to the structure of the virus-like particle." Regulators might be expected to take a longer look at such a different means of manufacturing. Sheldon expresses no qualms, however. "When we work through clinical trials, the rules are the same. We must be able to demonstrate safety and efficacy and purity of product, exactly as with cell-culture, egg-based, or any other vaccine types." Sheldon says the main distinction between Medicago vaccines and all others is in the upstream production phase — it uses biomass generation of plant tissue — but he says downstream purification technologies are standard. Still, anticipating some additional regu- latory hurdles with a new technology, the company compensated by attending to its quality and documentation sys- tems from the beginning. "We were even ahead of where we needed to be as a biotech company, and over time we'll work as closely as possible with the regu- latory agencies." PLANTS OVER THE HORIZON Even at best, the company faces a long road to its ultimate goal: expanding its technology beyond vaccines to gener- ate scaffolds for therapeutic antibodies, most likely to improve on existing mAbs (monoclonal antibodies). The expan- sion is not commercially driven, accord- ing to Sheldon; instead, the company's deepening investigation into its own technology revealed a broader potential. " When we first started to produce these virus-like particles, we had no way of knowing the plants would pro- duce these complex antigen structures, where you have an antigen sticking out from the lipid layer, looking just like a virus. People have been making VLPs, for example, in insect cells, where you need to add various proteins to hold the particle together. Lo and behold, the plant expresses the same proteins in its plasma membrane. Now we know we may be able to use these particles as chimerics — the stem sticking out from the lipid layer could be something other than a viral antigen. We'll see where the science takes us, but we may find some rather interesting solutions to very com- plex problems." Among the possible areas of applica- tion for Medicago's platform are cancer immunotherapy and HIV vaccination. "Although we have actually produced a virus-like particle for HIV, we've never taken it anywhere," says Sheldon. "It is blue sky, but nonetheless, it's a real blue sky." Because Medicago is building a new, plant-based technology, it finds itself in a leadership position, compared to com- panies in the same space that lack a product focus. (One company, Protalix Biotherapeutics — using plant cells rather than growing plants to produce proteins — has a hormone-replacement product on the market.) If Medicago succeeds in validating its leading role among the plant-growers in vaccine and protein production, Sheldon would cred- it its "adaptability" for putting it ahead of the pack. Fair to say, when you're pioneering a way to make medicines from tobacco, adaptation is your game —by definition. L on a winning ascent, and our technol- ogy will be disruptive — and yes, it could change the way people think." Medicago's story recalls how biotech first got started: mainly as a manufactur- ing alternative, only then with E. coli or yeast cells. "We've got this plant in front of us, a living system, and it can make very complex molecules. And it's quite likely we'll find out over time that we're able to do things existing technologies cannot do." It would not be surprising if Medicago meets with some pushback from tradi- tional as well as other innovative vac- cine makers as the company gains more visibility. Some companies are develop- ing vaccines based on DNA technologies or other platforms that might or might not be compatible with VLPs, and long- established doctrine favors live, animal- based vaccines for invoking a strong immune response. But so far in the clinical trials for its pandemic flu candidates, Medicago's approach appears to produce potent immune stimulation and immunologi- cal memory, according to the company. "We are doing a lot of extra work to demonstrate what we've always believed — we can make better vaccines with this technology than existing technol- ogy, with a strong parallel between us and live viruses." MEDICAGO APPLIES INNOVATION AT THE PLANT LEVEL By W. Koberstein 0 3 1 4 _ F e a t u r e _ M e d i c a g o _ F . i n d d 5 0314_Feature_Medicago_F.indd 5 2 / 1 9 / 2 0 1 4 2 : 2 7 : 3 9 P M 2/19/2014 2:27:39 PM