An important insight re plasminogen providing context...Below is an excerpt from the "Comments section" of a Seeking Alpha article. In this case someone has included "Fred's Response" (PLI IR). I have included both an excerpt and Fred's full response for anyone not having read this. Fred's full response below the link to the article which I also included. And, the article is definitely worth reading as well. Very good to see others speak out and important to see from PLI IR. Again, insightful and a good overview albeit in a defensive posture but, indirectly.... a well articulated "case for" investing in PLI. --- Excerpt from Fred's response I found particularly insightful.... "Competitors are not pursuing plasminogen as a targeted protein for a very simple reason. In order to extract plasminogen in commercially viable quantities, they would need to disrupt their IVIG process since plasminogen would be extracted from paste 2 3 of the albumin based Cohn fractionation process. Given the large established sales of IVIG, it is completely irrational to think that the large players will contemplate displacing their IVIG worth billions to extract only hundreds of $millions of plasminogen, let alone that this hundreds of $ millions is few years away. We do not have such manufacturing constraint and for us IVIG is a by-product. Our manufacturing capacity is and will continue to be driven and optimized by the numerous clinical applications for plasminogen. Plasminogen is not the first protein to be dismissed by large plasma fractionator to the benefit of other commodity proteins such as IVIG." ---- https://seekingalpha.com/instablog/1107010-edward-vranic-cfa/4942872-prometic-promotion-just-like-biotech --- In Comments section... From IR: answer from Fred ( ir at pli ) It is absolutely mind boggling that any coward hiding being a pseudonym can create such havoc with one report filled with inaccuracies, half-truths and blatant lies. That being said, I will not even dignify this useless rag with a point by point rebuttal. I will however use this opportunity to reiterate some cold hard facts and scientifically demonstrated data backed by world leading authorities in their respective fields. I choose to believe that our shareholders are better than that and deserve a factually complete and accurate response without stepping down to such gutter levels tactics. We believe at ProMetic that great science will always prevail in the end and strongly believe that the data generated so far in both our small molecules and plasma derived therapeutics ongoing and completed trials are compelling enough to demonstrate the benefits of our approach. 1- PPPS process: It has taken us more than 20 years and over 500 million dollars in investments (partnerships and equity) to optimize our proprietary plasma purification process called PPPS. The American Red Cross could have partnered with anyone else in the world including the industry TITANS and decided that it was with ProMetic that they had the best chances to optimize the recovery of valuable therapeutics . The large industry players are limited in the number of proteins they can extract and the yields they can get as a result of the legacy manufacturing process called the Cohn fractionation. A process optimized for the purification of albumin, the most abundant and least valuable of all human proteins. To this day, our yield for albumin is not better than theirs at around 80%. However, ProMetic has clearly stated since the beginning that it would target proteins where it would have a distinct advantage, free from the existing manufacturing constraints and limitations resulting from an alcohol based process such as Cohn. The chromatography used by ProMetic is much gentler on the proteins and avoids denaturing rare and valuable proteins as the process does not require alcohol or harsh chemicals. Our affinity resins (ProMetic smart filters, chemical hooks) are designed to specifically recognize and bind to targeted proteins in a very efficient manner that allows for greater recovery yields. We have not intentions of establishing ProMetic as a large plasma fractionator competing on commodity like proteins. We are working hard to be recognized as a low volume and very high value plasma purification company that can address rare diseases and unmet medical needs through world class technologies. Our process is definitely proprietary with a combination of issued and pending patents and trade secrets establishing a strong barrier to entry to anyone looking for a quick fix or market entry. One of the reasons why it has taken so long and cost so much to optimize our process is related to the facts that we have established a very precise and optimized extraction sequence that allows us to get in a very systematic approach a series of proteins (so far publicly disclosed: Plasminogen, IVIG, AAT, C1-INH, Fibrinogen, Albumin, Inter Alpha 1) and more yet to be disclosed in manner consistent with the low volume high value philosophy. Once approved by the regulatory authorities, it becomes very, very difficult to alter the sequence that has been approved. With plasminogen being in the last stages before final approval, we already know where to find and how to extract at superior yields many other very valuable proteins. Something that cannot be matched by the Cohn fractionation process. One should also keep in mind that the FDA has reviewed our manufacturing process before allowing us to proceed with a clinical trial in humans for our plasminogen therapeutics and could therefore logically conclude that this manufacturing process is for real. It would indeed be of concerns if we were targeting the albumin and IVIG as our core and key targeted markets. In the case of the PPPS process, they are merely what you can call a by-product that we will be able to sell as we proceed to extract much more valuable proteins addressing rare and orphan diseases, and major unmet medical needs. Being valuable by-products, we were certainly not about to throw them down the drain because they are not our targeted primary proteins of interest. We thought that our shareholders would appreciate our business acumen of generating for example $150 million of IVIG sales while processing plasma for rare and valuable proteins. If you want to accuse us of being prudent and savvy managers, by all means, guilty as charged. The beauty of our process and one of the obvious reasons to anyone who has done more than 5 minutes of research, in good faith that is, is that we always start from whole plasma and not a waste fraction or waste stream of the Cohn process. Therefore, we generate tremendous yield advantages on some specific proteins because the starting quantity from whole plasma is so much larger than what is left in a waste fraction. Just as a quick example, there is approximately 1,2 gr of AAT per liter of plasma. The Cohn fractionation process has left 0.4 gr in paste IV of the process and recovers approximately 0.22gr or 18%. PPPS recovers the equivalent of 0.66gr per liter and why? Because we start form the 1.2 gr per liter with our process and not the o.4gr left in the waste fraction. Our process is optimized to extract the maximum but from the starting liter of plasma and not waste fractions. That same principle applies to other proteins. Some of you may wonder about the differences in certain presentations regarding the claimed yield advantages that may vary sometime. One should keep in mind that some data were presented as recovery yields straight out of plasma while others were presented as finished product yields following downstream process purification steps. However, there is one constant variable that remains from all the presented numbers, the yield advantages cannot be denied. They have been validated at bench scale as with commercial scales with a linearity that is unequivocal. Plasma purification is a business of scaleAbsolutely if you are focused on commodities and legacy products where every drops counts. The industry averages $500 US of revenues generated per liter of plasma processed. PPPS will do a minimum of twice that amount with plasminogen alone, its most advanced plasma derived therapeutic products. Other proteins will come and add revenues that the others simply cant match. IVIG and other commodities will also simply add to the top and bottom lines as by products processed while recovering other extremely valuable proteins. 2- Plasma supply: ProMetic has one fully operational plasma collection (sourced plasma) center in Winnipeg and will open more centers has disclosed during the AGM where a detailed plan and layout of future centers was clearly explained. Furthermore, ProMetic has contractual agreements in place where it is accessing additional sourced plasma on a contractual basis. 3- Plasminogen as a plasma derived therapeutic Lets again set the record straight as to what was said on numerous occasions regarding the plasminogen expected market. Competitors are not pursuing plasminogen as a targeted protein for a very simple reason. In order to extract plasminogen in commercially viable quantities, they would need to disrupt their IVIG process since plasminogen would be extracted from paste 2 3 of the albumin based Cohn fractionation process. Given the large established sales of IVIG, it is completely irrational to think that the large players will contemplate displacing their IVIG worth billions to extract only hundreds of $millions of plasminogen, let alone that this hundreds of $ millions is few years away. We do not have such manufacturing constraint and for us IVIG is a by-product. Our manufacturing capacity is and will continue to be driven and optimized by the numerous clinical applications for plasminogen. Plasminogen is not the first protein to be dismissed by large plasma fractionator to the benefit of other commodity proteins such as IVIG. One just needs to look at C1-INH, where a company called LEV Pharma demonstrated its efficacy between 2004 and 2008 before being sold to Viropharma which in turns was sold to Shire for $4.2 billion in 2013. One also needs to keep in mind that C1-INH addresses a market of approximately 6000 patients world-wide. But then again, I imagine that Shire blindly proceeded to pay $4.2 billion for a product targeting only 6000 patients because it was not pursued by larger plasma fractionators. Plasminogen has been partnered with Hematech Therapeutics in 2012 where Hematech secured 50 % of the profits related to the congenital deficiency only while all other indications remained 100% with ProMetic. The company entered into this agreement in 2012 when it was for all purposes technically insolvent. The total consideration was however no only $10M in upfront cash and milestones money, it was also for the commitment by Hematech to build a $150M facility based on the PPPS process. Much needed capacity that ProMetic did not have at the time and a situation that has since been resolved through the Laval and Winnipeg capacity. This brings us to the revenues that can be expected to be generated from such existing capacities. When we say that existing capacity has the potential to generate $400-$500 million in annual revenues, this is based on the sales of Plasminogen, IVIG and other proteins we expect to have commercially approved by 2020. The plasminogen congenital deficiency sales would amount to approximately $150 - $200 million in revenues at peak sales while additional plasminogen indications would add potentially another $100 million from said additional indications and for the already existing manufacturing and operational capacity. Please feel free to apply the discount of your choice but you would still get a multiple worthy on its own of a much higher share price simply based on the net present value of any of these proteins. Given the fact that human proteins have a faster regulatory approval pathway with a risk profile almost completely eliminated from the start as regulatory authorities do not deny that a human made protein will actually do what they were created to do, I think we can all agree that the risk profiles for said proteins are fairly low. With plasminogen on the verge of having its BLA filed and IVIG already in phase 3 clinical trial, a fairly large percentage of the expected sales from existing capacity is already pretty much secured. Additional indications and proteins will come and be added to the mix and we will continue to monitor and evaluate manufacturing capacity as needed and when needed. Our plasminogen extraction process is protected by numerous patents. Whilst practically any junior scientists, even one very skeptical analyst that shall remain nameless, would be able to extract some plasminogen at bench scale, the true question remains whether or not one can isolate and purify it at commercial scale and produce it as a stable and approvable drug and all the whilst extracting 12 other valuable proteins. ProMetic has the intellectual property to prove it. Others dont, simple as that and end of story. We are gladly discovering that the plasminogen total market size is much more than originally anticipated. Not only are we seeing more patients in recognized industry databases suffering from recognized clinical manifestations associated with the congenital deficiency, we are also discovering that this protein is associated in many acquired deficiencies where certain trauma causes a temporary deficiency that can result in serious medical complications, in some cases leading to death. It is a well-recognized fact in medical literature that plasminogen should be given to patients. Since it is not available and wont be until ProMetic actually brings it to hospitals, physicians will use fresh frozen plasma as a substitute. We believe that physicians would prefer using only plasminogen if available and are convinced that once approved, the product will grow rapidly in market penetration. 4- PBI-4050 ProMetic has developed a portfolio of compelling small molecules drug candidates. Amongst which, its lead product PBI-4050, has been in development for the past 8 years. PBI-4050 has been tested by some of the most reputable world renowned scientists in their respective fields of expertise. All preclinical models, with a large number of them performed externally to ProMetic, have all returned solid data unanimously demonstrating first in class efficacy in some of the most difficult preclinical models. Again, we have acted in a prudent and responsible manner by doing smaller proof of concept trials that would show that the demonstrated efficacy in preclinical models would and indeed did translate to human patients. We believe it was the right approach and so far, all the data generated is confirming our approach. We can now confidently move to the next level with placebo controlled studies. We have generated so far nothing but solid clinical data with our lead compound. In some cases even beyond our own expectations. As an example, one should look at the way we have presented data for the metabolic and type 2 diabetes clinical trial. This disclosure was done in the context of comparing apples to apples. The company explained and disclosed the reduction of HbA1c for all patients, and highlighted the fact that it had enrolled patients with a baseline level of HbA1c much lower than the usual clinical trials to assess the risk of inducing hypoglycemia. This was a success in that very few cases of asymptomatic cases were observed. When comparing whether the reduction of HbA1c is clinically relevant, one has to look at data with patients enrolled with similar baseline. Most studies enroll patients with a baseline of >7.5% , even > 8%. In this context, the reduction of HbA1c compares favourably with commercially approved and available agents. That we believe in our product ability to become a significant drug to treat serious fibrotic diseases should not come as a surprise to anyone who has followed us for the last few years. To doubt that world authorities would be negligent to the point of associating their names to our product without having first conducted some serious and thorough due diligence is indicative of obvious malicious, fraudulent and self-serving intents. Strangely enough, these world class thoughts leaders have come to the same conclusion regarding PBI-4050, it is compelling enough that it deserves their time and attention. Dr Raymond Harris, President of the American Society of nephrology, chief of nephrology of Vanderbilt University has put his name behind PBI-4050 data (not hiding behind a computer and a pseudonym) Dr Jocelyn Dupuis, world expert in Pulmonary hypertension at the Montreal Heart Association has put his name on PBI-4050 data (not hiding behind a pseudonym and a computer) Dr Peter Senior, world expert in diabetes at the University of Alberta has put his name on PBI-4050 clinical data in metabolic syndrome patients (not hiding.) Dr Moran and Dr Hakim, both amongst most reputable nephrologists in the USA, are both putting their name behind the program, and are proud shareholders And we could go on and on Sorry for this ridiculously long email and response. When it comes to our reputation, scientific integrity and the well-being of thousands of patients, we are and will continue to take such matters very seriously. We are available to further discuss, we are reachable, we do not hide behind a computer using false pseudonyms, like cowards with obvious and ridiculously one sided self-serving interests like some do. We are here, driven, successful and unshakeable in our quest to deliver innovative medical solutions to thousands of patients in dire needs. Our determination is as strong as the integrity of all our employees, Board members and collaborators. Lets make one thing very, very clear: Anyone thinking that they will be able to bring us down by simply printing lies hiding behind a computer will find out the hard way that ProMetic is not only here to stay, but also is the real thing. Best regards, Frederic Frdric Dumais, B. Comm., LLB. Directeur principal, Communications et relations avec les investisseurs Senior Director, Communications and Investor Relations ProMetic Sciences de la Vie inc. ProMetic Life Sciences Inc. 440 boul. Armand-Frappier, bureau (suite) 300 Laval, Qubec, Canada H7V 4B4 Tel. : 450-781-0115 Fax : 450-781-4477 Mobile : 514-261-4735 f.dumais@prometic.com https://www.prometic.com