Animal-derived pharmaceuticals are the most commonly produced drugs in the biopharmaceutical sector. This type of production is characterized by serious shortcomings and is in dire need of innovation.
Plant-derived pharmaceuticals have the potential to provide this innovation and fundamentally disrupt the biopharmaceutical industry.
ProCellEx, a proprietary system developed by Protalix BioTherapeutics, is poised to significantly advance the production and development of plant-derived pharmaceuticals.
The value of the ProCellEx platform has been demonstrated by the successful development, production, and commercialization of Elelyso for Gaucher disease.
Investors wishing to capitalize on the development of plant-derived pharmaceuticals should consider Protalix BioTherapeutics.
Protalix BioTherapeutics (PLX) and its proprietary ProCellEx platform are poised to fundamentally transform the biopharmaceutical industry. This industry has long been constrained by the limitations associated with animal-derived pharmaceuticals. ProCellEx has the potential to develop and produce plant-derived pharmaceuticals which are safer, more cost-effective, and provide more effective relief to patients. Pharmaceutical companies, investors, and, above all, patients with unmet medical needs are set to greatly benefit from this innovation.
Introduction
In a recent Seeking Alpha article, Protalix BioTherapeutics: A Novel Enzyme Innovator for Orphan Diseases, Dr. Hung V. Tran thoroughly set out Protalix's financial position, ongoing clinical trials, and the market for the company's drugs. Investors wishing to gain an initial understanding of Protalix should consider reading Dr. Tran's article. This article will focus specifically on the potential for the ProCellEx platform to fundamentally transform the biopharmaceutical industry.
This article will delve deeply into the processes which underpin the transformative value of ProCellEx. Much of the research which forms the basis of this article will be obtained from peer-reviewed journal articles and other scientific sources. A sincere effort will be made throughout to avoid overly technical language and esoteric concepts. For a thorough, technical analysis of ProCellEx, investors should consider reading Large-scale production of pharmaceutical proteins in plant cell culture—the Protalix experience, an open-access article in the Plant Biotechnology Journal.
This article will begin by briefly describing Protalix Biotherapeutics. Next, the current state of the biopharmaceutical industry will be explored. It will be demonstrated that this industry is large, growing, and in need of innovation. The most common form of recombinant protein production for biopharmaceuticals derives from animal cells. The shortcomings of animal-derived pharmaceuticals will be discussed. Next, plant-derived pharmaceuticals will be discussed and their advantages when compared to animal-derived pharmaceuticals will be described. Protalix's proprietary ProCellEx system will then be explored. Finally, competition and risks which may hinder the success of ProCellEx will be explored.
Protalix Biotherapeutics
Protalix is a clinical stage biopharmaceutical company which seeks to develop, produce, and commercialize recombinant proteins created through the ProCellEx system. While Protalix has a robust pipeline of drugs in various stages of clinical trials, this article will focus specifically on the potential for the ProCellEx system to revolutionize the biopharmaceutical sector. A specific and detailed description of each drug being developed by Protalix is best left to other articles.
Biopharmaceutical Sector
The biopharmaceutical sector is a subsection of the broader pharmaceutical industry. Biopharmaceuticals are medicinal drugs manufactured through the use of live organisms. Medicinal drugs that are not derived from live organisms are simply pharmaceuticals, and do not qualify as biopharmaceuticals. Biopharmaceuticals include protein-based drugs created from the cells of living organisms such as mammals, bacteria, fungi, and plants.
The market for biopharmaceuticals is growing at a faster rate than any other sector in the pharmaceutical industry. It is estimated that the value of the international biopharmaceutical market was approximately US $200 billion in 2013. The size of this market may reach approximately US $500 billion by the year 2020. The market for therapeutic recombinant proteins in particular, which will be discussed further below, is growing at such a rate that supply is likely to struggle to meet demand.
Recombinant DNA and Protein-Based Drugs
In order to appreciate the need for ProCellEx, it is essential to first understand the demand for safe and effective medicinal drugs derived from the cells of living organisms. By combining multiple strands of DNA, scientists are able to create recombinant DNA. Recombinant DNA is then able to produce recombinant proteins through the use of living cells. The recombinant proteins created through this process are then developed into protein-based drugs to be used in a variety of clinical settings.
Recombinant proteins cannot be created through chemical processes. Accordingly, a biological source such as animal, bacterial, fungal, or plant-based cells is necessary. Mammal-derived cells have become the most common source of recombinant proteins for clinical applications. Bacteria and yeast are respectively the second and third most common biological sources of cells for the creation of recombinant proteins.
Medicinal drugs created from recombinant proteins have become an essential part of modern medicine. Recombinant insulin used to address diabetes and antibodies used to fight cancer are just two examples of the beneficial nature of recombinant proteins. Other medicines created through the use of recombinant proteins address anemia, hepatitis, and cardiovascular ailments.
Mammal-Derived Pharmaceuticals
The process of creating mammal-derived pharmaceuticals begins when the recombinant DNA is transferred to a mammalian cell. Next, the cells which are deemed suitable are transferred to cultivation vessels where they are used to produce cloned cells. Finally, the recombinant proteins are produced from the cloned cells which exhibit the proper characteristics. Commonly, cells from Chinese hamster ovaries are used to create recombinant proteins which are used in clinical purposes.
Shortcomings Associated with Animal-Derived Recombinant Proteins
There are several shortcomings associated with the production of recombinant proteins from animal cells. The first major drawback associated with using animal cells is the high cost of production. The second shortcoming is the risk that animal cells will become contaminated by pathogens such as viruses. Finally, it is difficult to rapidly scale up production of animal cells in order to meet increased market demand. In short, recombinant proteins from animal cells are characterized by high production costs, potential for contamination, and difficulty in increasing production.
Animal-Derived Recombinant Protein ProductionSource: Boston.com
Examples of Setbacks Faced by Mammal-Derived Recombinant Protein Production
A notable example helps to illustrate one of the major shortcomings associated with the production of recombinant proteins from animal cells. In 2009, a biotechnology company called Genzyme was forced to shut down production of Fabrazyme and Cerezyme due to the contamination of chinese hamster ovary cells with Vesivirus 2117. The FDA and the media both took notice of this incident which threatened Genzyme with millions of dollars in lost revenue. Genzyme and its parent company Sanofi later faced litigation due to the shortage of drugs caused by the rationing following the viral contamination.
Cleaning ContaminationSource: Boston.com
Need For Innovation
The discussion above demonstrates that there is a clear need for innovation in the biopharmaceutical sector. A group of researchers published a report in Nature Reviews Genetics which determined that there is a need for a new system which enables the mass production of safe and effective recombinant proteins for clinical purposes. This new system must be cost-effective and address the shortcomings associated with animal cell-based production of recombinant proteins. The following discussion will demonstrate that plant-derived pharmaceuticals and, in particular, the ProCellEx system can satisfy the need for innovation.
Shortcomings Associated with Recombinant Protein Production From Bacteria and Yeast
Earlier in this article, it was mentioned that bacteria and yeast cells are respectively the second and third most commonly used forms of biological cells for the production of recombinant proteins with therapeutic benefits. Therefore, it is worth inquiring into whether bacteria and yeast can satisfy the need for innovation in the biopharmaceutical sector.
Unfortunately, bacteria and yeast cells have their own shortcomings which limit their capability of replacing animal cells for the production of therapeutic recombinant proteins. Bacterial cells cannot be developed into complex forms of proteins and have high production costs. Additionally, bacterial cells face contamination risks similar to those faced by animal cells. Yeast cells secrete protein inefficiently and are characterized by low production yields. In sum, the need for innovation in the biopharmaceutical sector likely cannot be addressed by increasing the usage of bacteria and yeast cells.
Plant-Derived Pharmaceuticals
Plant-derived pharmaceuticals are a relatively recent innovation. In the early 1980s the first plant cells were used to create recombinant proteins. An initial obstacle which prevented the widespread proliferation of plant-derived pharmaceuticals was a lack of knowledge about genes suitable for plant cells. Advances in genomics have led to the discovery of a large number of new genes which can be used to produce plant-derived pharmaceuticals. Companies are currently attempting to produce plant-derived pharmaceuticals in order to treat a wide range of medical issues such as ebola, HIV, malaria, and fabry disease.
Transgenic DevelopmentSource: Protalix
Superiority of Plant Cells as a Source for Recombinant Proteins
A comparison of plant and animal cells as sources for recombinant therapeutic proteins demonstrates that plant cells are superior in a number of ways. A major advantage of using plant cells is that plant cells can be mass produced in a relatively inexpensive manner. Similarly, production of recombinant proteins from plant cells can be rapidly scaled up to meet patient needs. Animal cells, on the other hand, are more expensive and require a significant amount of time to grow. Furthermore, it is much more difficult and time intensive to scale up production of recombinant proteins through animal cells.
When compared to animal cells, plant cells have the advantage of being able to undergo modification after recombinant DNA translation. This allows plant cells to be used to create a greater variety of therapeutic recombinant proteins than animals cells. Additionally, plant cells are able produce complex forms of recombinant proteins with less manual assistance than animals cells. Unlike animal cells, plant cells do not face the risk of contamination from human pathogens such as viruses.
In short, plant cells are superior for the production of recombinant proteins because of lower costs, easier scale-up of production, and lower risk of contamination.
Mammal vs PlantSource: Protalix
Successful Examples of Plant-Derived Pharmaceuticals
There are numerous recent examples of plant-derived pharmaceuticals which have displayed beneficial therapeutic properties. Antibodies derived from tobacco plants have successfully been used to address the ebola outbreak which affected several West African nations in 2014. Plant-based immunoadhesin has been demonstrated to be effective in preventing the Middle East Respiratory Syndrome virus from infecting lung cells. Finally, as will be discussed in more depth later in this article, Protalix's Elelyso for Gaucher disease is a successful example of a plant-derived pharmaceutical which has received FDA approval.
Regulation of Plant-Derived Pharmaceuticals
Like regular pharmaceuticals, biopharmaceuticals are regulated by the FDA in the United States. The United States Department of Agriculture (USDA) could also play a role in ensuring that plant cells which have undergone genetic transformation do not threaten native plants and agriculture. The FDA approval of Protalix's Elelyso for Gaucher disease should substantially diminish concerns that regulation will prevent plant-derived pharmaceuticals from reaching the market.
ProCellEx Platform
The ProCellEx platform provides a system to produce therapeutic recombinant proteins through the use of plant cells.
Process OverviewSource: Protalix
Several aspects of the ProCellEx platform make it more cost-effective than other methods used to create recombinant proteins. This platform can be set up quickly and inexpensively when compared to the systems required to produce animal cell recombinant proteins. ProCellEx uses "flexible polyethylene disposable bioreactors designed and optimized for plant cell cultures". These disposable bioreactors require significantly less capital investment than the steel reactors which are typically used. Furthermore, ProCellEx is characterized by lower maintenance costs when compared to other systems. Finally, the ProCellEx platform can operate at room temperature while animal cell-based production must occur at a strictly controlled temperature.
ProCellEx is also characterized by increased safety when compared to other methods of creating recombinant proteins. The plant cells used in the process are not at risk of viral contamination.
It is possible that the recombinant proteins produced through the ProCellEx platform will experience greater regulatory success than animal-derived recombinant proteins because plant cells are not susceptible to human and animal pathogens.
Elelyso (taliglucerase alfa)
The first plant-derived pharmaceutical to ever receive approval from the FDA for human treatment was Protalix's Elelyso in May, 2012. Elelyso was developed to treat Gaucher disease and was fast-tracked by the FDA. Elelyso is made through the ProCellEx system using plant-cells from carrots. Beyond providing therapeutic relief to Gaucher patients, Elelyso validates the ProCellEx platform as an effective mechanism for the production of plant-derived pharmaceuticals.
Potential Competition
Several companies are attempting to develop, produce, and commercialize plant-derived pharmaceuticals. Competition between these companies and Protalix to capture portions of the biopharmaceutical sector is a possibility. It is worth restating, however, that Protalix is the first company to have a plant-derived pharmaceutical approved by the FDA. Furthermore, Protalix's strong and advanced pipeline should inspire a degree of confidence that Protalix can bring more drugs to the market. Above all, the ProCellEx system is intrinsically valuable and, as will be demonstrated, has significant advantages over competitors.
Superiority of ProCellEx Over Competitors
The technologies that other companies have developed to create recombinant therapeutic proteins from plant cells simply do not match up to ProCellEx. Unlike the ProCellEx system, other major technologies used to create plant-derived recombinant proteins use metal or glass containers which are more expensive and have high maintenance costs. Furthermore, other technologies face more difficulty increasing production than ProCellEx. Finally, other technologies have significant difficulties controlling aeration of their cell cultures.
Risks Facing ProCellEx
A major risk faced by any development biopharmaceutical company is the potential failure to attract sufficient investment. Protalix has so far been successful in collaborating with larger entities, signing agreements with Pfizer and Fundação Oswaldo Cruz. It is also possible that the drugs developed through the ProCellEx system may fail to meet primary endpoints at any stage in their clinical trials. Protalix's robust pipeline and the commercial success of Elelyso, however, should provide significant optimism to investors.
Conclusion
The biopharmaceutical sector is large, growing, and requires innovation in order to address the shortcomings associated with animal-derived pharmaceuticals. Research into the alternative approaches that can be used to create recombinant therapeutic proteins demonstrates that plant cells are highly promising. The biopharmaceutical sector requires an innovative system which is cost-effective, safe, and capable of rapidly increasing production in order to respond to market demands. ProCellEx meets these criteria and is poised to upend the biopharmaceutical sector. Protalix is in a strong position to move ProCellEx forward and create fundamental changes in the biopharmaceutical sector.
Disclosure: I am/we are long PLX.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
