A Product For Gaucher Disease And A Plant-Cell For Protein Production – Protalix Biotherapeutics Is On The Rise

By Wayne Koberstein, executive editor

SNAPSHOT
Protalix has a unique plant-cell platform for therapeutic protein production and an approved product, Elelyso/Uplyso (taliglucerase alfa), for Gaucher disease. In the company’s pipeline is a chemically modified version of the recombinant alpha-Galactosidase-A protein for Fabry disease (Phase 1/2), an oral glucocerebrosidase (GCD) enzyme replacement therapy for Gaucher disease (Phase 1), an oral anti-TNF (tumor necrosis factor) fusion protein for autoimmune/inflammatory conditions (preclinical), and a human deoxyribonuclease I (DNase I) for cystic fibrosis (preclinical), and other enzyme replacement therapies in early research.

WHAT’S AT STAKE
Be careful when someone claims to be number one; it depends on how you define the field. Just after filing my recent story on Medicago (March 2014), I encountered another plant-technology company, Protalix, that made the fine but significant distinction that I might have otherwise failed to mention: Medicago and others in the plant-based production sector grow whole plants, such as tobacco, in large gardens or greenhouses; Protalix produces proteins in plant cells, grown like other cell media in traditional bioreactors. But it is not just its platform that sets Protalix apart — it’s also the company’s approved plant-cell-produced product and several other candidates in its pipeline.

“In the early days of therapeutic recombinant proteins, manufacturing used bacteria for the simpler proteins, then evolved into using mammalian cells such as Chinese hamster ovary [CHO] cells,” explains David Aviezer, president and CEO. “But we offer a new way to transition from using mammalian cells to using plant cells as the cell source for special therapeutic proteins.”

Aviezer cites a “substantially lower” cost of goods as one advantage of the Protalix platform. “As an example, it is like comparing the cost of having a pet dog or cat to having a flower pot in your living room,” he says. Safety is another factor. “Humans are not affected by any plant viruses so what we have is a built-in biological firewall, preventing any kind of transmission of mammalian-associated infectious viruses or prions.”

Why is it significant that Protalix uses plant cells rather than whole plants? Use of bioreactors versus plant-growing operations keeps the technology in familiar territory for engineers, manufacturing personnel, and perhaps above all, regulators. Equipment, guidelines, procedures, and processes remain essentially the same as they have been for decades in the biotech industry. With typically dry humor, Aviezer says, “We grow carrot cells. And, as we like to say, the only carrots we have in our facility are the carrots in chicken soup. But we have a very well-regulated and controlled system for producing our therapeutic proteins that really can comply with all the regulatory necessities needed for highquality drug production.”

Oral delivery is a somewhat serendipitous outcome of the plant-cell product. Protalix takes advantage of the cellulose base in its oral-delivered drugs as a natural way of keeping them protected from digestion until they reach the small intestine, where the physical jostling opens up pores in the cellulose, releasing the active drug where it can be absorbed intact by the gut. Aviezer refers to the anti-TNF drug as “basically a plant-cell expressed Enbrel [etanercept]” that will go into human studies this year.

Although Aviezer says there is room for other plant-based technologies in drug manufacturing, he clearly believes easy adoption, low cost, safety, effective delivery, and protein refinements will give his company’s platform the competitive edge. After 10 years in the business, having a healthy product on the market and arguably taking a technology lead, Protalix gives its CEO good reason for careful optimism.

Vital Statistics

Employees: 260
Headquarters: Carmiel, Israel

Finances:
Raised $100M in underwritten public offerings

Research Partnership Funding
Pfizer: $98.3M for Elelyso development and commercialization

Other Partners
Fundação Oswaldo Cruz, Ministry of Health, Brazil: Uplyso supply & technology transfer agreement

Teva: R&D with ProCellEx platform

Latest Updates

February 2014: Reported top-line Phase 1 clinical trial results for oral glucocerebrosidase in Gaucher patients.

2013: Continued worldwide approvals of Elelyso / Uplyso.

August 2013: Added three new plant-cell recombinant proteins to the development pipeline.