Making progress getting-up the PLI learning curve & sharing...in case others may have not seen/ read. It's "must read" article on PLI's plasma protein purification system. Explains the process very well and it's "relative advantage" to current processes and another biotech's different approach to current processes. Suggest not reading this (if not familiar with title of article below) but go right to the article (again by C. Abbott on Seeking Alpha site dated Sept 8-17) using this link.... --- https://seekingalpha.com/article/4105245-2-game-changers-therapeutic-proteins-protalixs-procellex-prometics-ppps --- 2 Game-Changers In Therapeutic Proteins: Protalix's ProCellEx And Prometic's PPPS Sep. 8, 2017 9:41 AM ET | C. C. Abbott Long only, biotech (391 followers) Summary Therapeutic Proteins make up a multi-billion global market. Protalixs ProCellEx and Prometics PPPS are game-changers in this market. This article takes a closer look at both technologies. Between 2011-2016, the FDA has approved 62 therapeutic proteins for a wide variety of therapeutic indications, including: hematology, oncology, musculoskeletal disease, endocrinology, immunology, cardiology/vascular disease, dermatology, infectious disease, ophthalmology, pulmonary/respiratory disease, gastroenterology, genetic disease, nephrology and rheumatology. These approved therapeutic proteins serve to meet unmet medical needs in a very wide spectrum of intended patient populations. Graph 1: U.S. Food and Drug Administration-approved protein therapeutics (20112016) To understand the importance of this relatively new approach to therapy, one needs to understand the wide-ranging roles and functions that proteins play in maintaining a healthy body. Table 1 shows the five basic categories of proteins and their critical roles. Whenever any of these proteins is not in its "right" condition, e.g. deficient, or non-functioning in its normal capacity, a disease will be the ensuing result. Table 1 (Source: Genetics Home Reference) Therefore, it should not be a surprise that the market size for therapeutic proteins is enormous. It was reported that the achieved global sales for therapeutic proteins in 2010 was over $90 B (13.8% of the total global market for pharmaceuticals, approximately $650 B, in the same year). What is surprising then is to find two little-known small companies - Protalix Biotherapeutics (NYSEMKT:PLX) in Israel and Prometic Life Sciences (OTCQX:PFSCF) in Canada - that have therapeutic proteins in their drug pipelines addressing different diseases and indications. Furthermore, what is more important than the individual proteins, is that these two companies have developed their own proprietary technologies, which are superior to what is currently available in their respective fields of therapeutic protein production. The two proprietary technologies enable these two companies to develop their own respective portfolios of therapeutic proteins, and in time will be extremely competitive, if not dominant in the huge global market. Lets have a closer look. Protalixs ProCellEx In the introduction of this article, I mentioned that the FDA has approved 62 therapeutic proteins. The majority of these are in a category called "recombinant therapeutic proteins." Recombinant proteins are proteins produced from the recombinant DNA. They are not the original, naturally occurring proteins found in the body, but are man-made versions for therapeutic use. In simple terms, scientists select and combine specific DNA (which contains genetic codes), and then insert these "designed" DNA into suitable host cells which might be bacteria, yeast, or most often mammalian cells. These host cells then grow ("express") the desired therapeutic proteins. The first approved recombinant therapeutic protein was human insulin, developed by Genentech and Eli Lilly in 1982. Protalixs ProCellEx platform is a proven, alternative way of producing recombinant therapeutic proteins that does not use the traditional bacteria, yeast or mammalian cells. Instead, it uses a plant cell-based expression system. See Figure 1. Figure 1: Protalix's ProCellEx Technology It is a proven technology because Protalix has used it to produce their first FDA approved recombinant protein therapy, the only one approved from plant cells to date. Their lead product, taliglucerase alpha (Elelyso), was approved by the FDA in May 2012 for long-term enzyme replacement therapy (ERT) for patients with a confirmed diagnosis of type 1 Gaucher disease. Protalixs platform has several significant advantages over current technologies. As indicated in the company web site: As opposed to mammalian cells, plant cells tolerate a relatively wide range of culturing conditions and naturally do not carry the risk of infection by human or animal pathogens. This translates into lower capital investment in the set up as well as in ongoing maintenance of the production plant. Plant cells provide a natural barrier to human and animal pathogens and are able to utilize a simple culture medium with no requirement to any animal originated supplements. This may prove to be important advantage from a regulatory perspective. Protalixs ProCellEx platform uses flexible polyethylene disposable bioreactors designed and optimized for plant cell cultures. As opposed to the large stainless steel reactors commonly used for recombinant protein production, the ProCellEx bioreactors are easy to use, entail low initial capital investment, and can be scalable cost-effectively. Additionally, they require relatively low hands-on maintenance between cycles. ProCellEx can potentially express certain proteins that are difficult to express in other systems. Through the ProCellEx system, it is possible in certain cases to develop and commercialize recombinant proteins without infringing upon the method-based patents or other intellectual property rights of third parties. Additionally, the ProCellEx platform has the ability to more rapidly develop clinical material for testing versus other protein platforms. In summary: Protalixs ProCellEx platform enables them to produce recombinant proteins that are safer, more cost efficient, and easier and faster to make, using a proprietary technology. In addition, Protalix is able to improve biologic dynamics (e.g., glycosylation, half-life extension) of a protein when compared to established methods. Glycosylation, in simple terms, is when the body fixes different types of sugar to a protein in order to give it specific biological properties. These modifications are very hard to reproduce (copy) accurately in recombinant proteins. Differences between the recombinant protein and the natural one run the risk of triggering an immune response, i.e. production of antibody when the patient receive the therapy, which in the worst case may be fatal. Therefore, it is very significant that Protalixs recombinant proteins, produced in a plant cell based system, have a more accurate glycosylation pattern (as confirmed by independent studies), and so are less likely to trigger an undesired immune response. This will enhance both the safety and efficacy of their proteins, when compared to currently established therapies. So far, Protalix's trial results for their drug candidates confirm this, showing superior safety and efficacy profiles. As mentioned earlier, Protalix has already had their first lead product (Elelyso) approved by the FDA in 2012. The next 3 drug candidates are produced using the same platform, and thus share all the same market and clinical advantages. PRX-102 for Fabry Disease, is now in two pivotal studies started in 2016, which should be completed in 2018. PRX-110, a candidate for Cystic Fibrosis (CF), showed in its phase 2 study superior safety and efficacy over the established treatment. It should be noted that many current CF treatments can only treat patients with specific mutations, while PRX-110 is able to treat all CF patients regardless of their mutation. OPRX-106, in on-going phase 2 studies, is for the treatment of inflammatory diseases such as Ulcerative Colitis, Crohns Disease, psoriasis and others. Prometics PPPS Unlike Protalix, Prometics therapeutic proteins are naturally occurred human plasma proteins. Their proprietary platform PPPS (plasma protein purification system), shown in Figure 2, is a superior way of extracting plasma proteins than the current available technology, giving higher yield, and allowing the isolation of high-value proteins which are lost using traditional methods (i.e. traditional methods are unable to isolate these proteins). Figure 2: Prometic's PPPS Process This is how the company describes their technology: PPPS is a multi-product sequential purification process originally developed in collaboration with the American Red Cross. It employs powerful affinity separation materials in a multi-step process to extract and purify commercially valuable plasma proteins in high yields. It allows for a highly efficient extraction and purification of multiple high-value therapeutic proteins from a single human plasma sample at unprecedented activity levels using Prometics Mimetic Ligand adsorbent technology in order to develop best in class biotherapeutic products. At the heart of our PPPS purification process is an application of our core Mimetic Ligand bioseparation technologies which are used in a variety of applications from the production and purification of biopharmaceuticals, to the capture and removal of biocontaminants or extraction and recovery of valuable proteins from various sources. This affinity chromatography technique uses an adsorbent comprised of a porous support matrix to which the ligand is attached. The attachment or bonding is performed so that the immobilized ligand is still able to interact with the protein in a specific and reversible manner. The ligand is normally bound by the protein at a specific site often within a fold of the protein. Simply put, Prometic has developed a gentler, more specific, more efficient way of extracting therapeutic proteins, using which the company has now been able to build a portfolio of therapeutic plasma proteins for various indications. Furthermore, this technology is proprietary to Prometic, establishing a barrier of entry for possible competitors. As I mentioned in my previous articles on Prometic, they have submitted their first BLA (biologic licence application) in April 2017, for the plasma protein, Ryplazim (plasminogen), for the treatment of congenital plasminogen deficiency, and has recently (August 29) received a Rare Pediatric Disease Designation for this indication. The company is expecting to receive approval in 2017-Q4, or early 2018. It is important to note that Prometics plasma proteins, unlike recombinant proteins, are naturally occurring proteins. In other words, these proteins are not the products of any chemical, biological or genetic modification, which should means a quicker regulatory process. In the pivotal trial, plasminogen obtained from PPPS when administered to the patients with congenital deficiency, was shown to have 100% response rate in both primary and secondary end points (the correct, therapeutic level of plasminogen in plasma; and healing of lesions with no recurrence). Similar to Protalix, Prometic has several proteins which target different diseases, that are in various stages of the approval process (including IVIG, AAT, C1-INH & fibrinogen). Finally, besides the relatively small indication of congenital plasminogen deficiency, plasminogen has been shown to be extremely efficacious in indications that have huge potential markets, such as acute plasminogen deficiency (due to trauma, surgery, etc.), severe burns, wound healing etc. Discussion Protalix and Prometic have each built themselves a better mouse trap in their respective areas of therapeutic proteins: proteins which already have huge global sales, and which will continue to be a growing market. Protalix stated that their three drug candidates are targeting over $8B annual sale in their indications, with PRX-102 for Fabry Diseases at $1.2B; PRX-110 for Cystic Fibrosis >$2.4B; OPRX-106 for inflammatory diseases >$5B. Prometics plasma proteins are also potentially very competitive in the area of plasma proteins, covering both orphan diseases and major indications (see Table 2). Table 2 (Source: Prometic web site) Both these companies are deeply discounted by the market for reasons other than their underlying science. In Protalixs case, an inaccurate report by a market analyst might have negatively influenced investors, who were not able to understand the trial results for themselves, but instead relied too heavily on the market reaction for their investment decision. In my opinion, Jesse Donovans subsequent SA article has correctly and completely rebutted this inaccurate report. In Prometics case, the deep discount has more to do with a negative sentiment towards financing through secondary offerings, than from actual progress made in clinical and regulatory paths over the years. As I already commented in one of my earlier articles on Prometic, they have managed to do the nearly impossible, which is to build a full and advanced drug pipeline without any significant partnership with big pharma. Both companies have indicated that they have enough cash in hand to finance their operations, Protalix until 2019, Prometic through 2018. Investment thesis Investors who have done their DD and are patient to withstand the short-term volatility should consider both these companies for a long position. Because of the strength and market advantages of their underlying proprietary technologies, combined with currently being very under-valued, both these companies have considerable room for stock appreciation in the long run. Risks in both these companies are common ones for the sector, including the regulatory risk; the risk that future trial results not as positive as expected; and that the financial risk that secondary offering cannot be completely ruled out in the medium term. Disclosure: I am/we are long PFSCF, 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. Editor's Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.