Good day and welcome to Q3 Investor Summit Virtual. We appreciate your participation in today's virtual Good day and welcome to Q3 Investor Summit Virtual. We appreciate your participation in today's virtual event. Up next, we are pleased to introduce Protalix BioTherapeutics Incorporated. If you'd like to ask a question during the webcast, you may drop them in the 'Chat Box' button on the left side of your screen. Please type your question into the box and click 'Send' to submit it. At this time, it is my pleasure to hand over the session to Eyal Rubin, SVP and CFO at Protalix BioTherapeutics Incorporated, who will lead the presentation. Sir, the floor is yours. Thank you. Thank you very much, and thank you, everybody, for joining today's presentation. So, my name is Eyal Rubin, and I'm actually will be leaving Protalix in the next couple of weeks, as it was announced. Obviously, I'm proud with the company, and I think that it's a very interesting story that I'd like to convey to our audience today. Obviously, the company is listed on NYSE American. It's a publicly traded company. Hence, please take a moment and read the disclaimer on your screens. Obviously, all the information that will be shared is only publicly available, and there's nothing which is materially not publicly available to all the investors. Let's speak about Protalix. Protalix is not a new company. Protalix is a 30-year-old company based on a very unique technology of expressing complex human protein through plant cell in suspension. All other companies express complex human protein through mammalian cells. We are doing it through plant cells. There are various advantages and disadvantages. I think that the main and the major ones, obviously, are the initial setup of the plant can cost up to a third compared to mammalian cell plants. The ease of manufacturing, we're manufacturing at room temperature. There's no risk of viral contamination. We all remember COVID seems to be like a distant memory, but it was only 4-5 years ago when COVID hit and the world got shut down. While other companies expressing complex human protein through mammalian cells had to change their processing and manufacturing processes, going to closed loops and clean rooms, we kept the manufacturing at regular rooms, open loops. And the reason being because plant diseases or human diseases cannot be transformed to plants and vice versa, at least until that's going to be changed. So it's very easy, easily scale up, scale down. We're manufacturing at room temperature, as I mentioned, taking polyethylene bioreactors, put them in a long line, connecting one to the other, and that's it. Protalix has two approved drugs. The first drug is Elelyso for the treatment of Fabry. I'm going to speak about it in a second. The second one is Elfabrio for the treatment of, I'm sorry, Elelyso for the treatment of Gaucher, Elfabrio for the treatment of Fabry. Both drugs are licensed. We're not selling ourselves. We're selling through Pfizer, the first drug, Elelyso for the treatment of Gaucher. And through Chiesi, a private Italian company, we're selling Elfabrio for the treatment of Fabry. In addition, the company has a couple of early-stage pipeline assets. The most advanced one is the PRX-115 for the treatment of uncontrolled severe gout, a very interesting asset that I would like to take the time and elaborate during this presentation. Here you can see the snapshot of the pipeline, two approved drugs. By the way, it's very unique to a small biotech company, a mid-cap company, to have two approved drugs by the FDA, by the EMA, drugs that they are selling in the market. I think that it's only an evidence of the capabilities, knowledge, and expertise of the team to bring two drugs to the market, which we are proud of. Speaking about our commercial portfolio, so Elelyso for the treatment of Gaucher was approved in May of 2012. It's not a new drug. It's a 13-year-old drug in the market. Obviously, we will. will. I'll speak a little about the reasons as to why this drug is not that known in the market. As I mentioned, we have licensed this drug to Pfizer in 2009 already, even before the end of the phase III trial. Unfortunately, and again, I'm not here to criticize Pfizer, but in reality, despite the great clinical success of bringing this first drug to the market, a first plant cell complex human protein expressed drug to the market, it was not such a big commercial success, to say the least. Out of a $1.5 billion market, Pfizer is selling something like $50 million. At first, we were entitled to get 40% royalties, which was a very rich agreement. Unfortunately, 40% of zero stays a zero. We had to sell the royalties. And right now, we are selling to Pfizer, basically at cost plus. It's very nice. It's interesting. But nevertheless, that's not where the future of the company lies. We are also selling to Brazil. We are selling to a wholly owned arm of the Brazilian Ministry of Health, Bio-Manguinhos/Fiocruz. In general, we are selling both streams, something about $11 million-$12 million to Pfizer annually and $11 million-$12 million to Brazil, $22 million-$24 million. It's very nice. It keeps the plant up and running. Don't forget, it's a biological plant. My apology. It can shut down. You can simply hire and fire people every other day. And these stable, steady streams are basically giving us the comfort that we can hold this line basically operative. In terms of this drug, the manufacturing agreement with Pfizer expires in October 2030. I hope that by then we'll be able to renegotiate with Pfizer, maybe get the drug back. Again, it's not going to be us because we don't have commercial footprint and we have no intention to risk a company and open up commercial operations in the United States and outside the United States, but I hope that Pfizer, I hope that they're not going to let this drug die. We'll be able to negotiate and maybe bring a partner that will be able to take over and maybe expand the market a little. Talking about the second drug and again, talking about the value and where really the value lies, so I personally believe, and we all believe in management and the board, obviously, looking at the Elfabrio, the drug for Fabry, it's a totally different story. While Gaucher is a very steady market, even shrinking a little, talking about approximately $1.5 billion, $1.4 billion in the past, I don't know, something like 7-8 years. Fabry is a rapidly growing market. Last year, sales were $2.2 billion. By the end of the decade, it's expected to reach $3.2 billion. It's a lysosomal storage disease where the body basically accumulates a substrate called Gb3 due to a lack of an enzyme. We are replacing the enzyme by injecting it to the body through an IV. The partner, as I mentioned, we've partnered with Chiesi. They got the global rights to commercialize Elfabrio. It's a very interesting agreement that we have with them, very rich one. We are entitled to get 15%-35% for royalties on sales conducted outside the U.S. and 15%-40% on royalties on sales conducted within the U.S., 15%-40% in the U.S., 15%-35% outside the U.S. And on top of it, we're entitled to get $100 million, potentially commercial and regulatory, as they hit the various commercial thresholds or milestones targets. Obviously, we're entitled to get milestones. The numbers are redacted. Obviously, I'm not going to share with you, but I can certainly say that let's make on the back of the envelope a calculation. If the market by 2030 is going to be $3.2 billion, we believe, and we have every reason to believe that the Chiesi are poised to capture anywhere between 15%-20% of the market. If we make the math, 3.2, 20%, we're talking about $640 million in sales to Chiesi at these levels. And again, the numbers are redacted. But I can tell you that based on our calculation, we're entitled to get anywhere between $100 million-$120 million in net royalties to Protalix. Not including, by the way, the milestones. The milestones at these levels will be hundreds of millions of dollars if they get there. So basically, this is the reason that we believe. And again, I know that one of the things that are confusing the market. Chiesi is a private Italian company, one of the last six family-owned businesses in Italy. And they don't disclose their numbers. They don't share their numbers. I think that looking at the market reactions quarter- by- quarter, and we've said it out loud publicly time after time during our earnings calls, but I'll have to reiterate. I think that what's missing in the market is basically the understanding of the mechanism, the mechanics of our agreement with Chiesi. The way that most royalties agreements work is once the licensee sells it in the market, obviously turns back, turns around, and pays the relevant royalties amount rate to the licensor. In our case with Chiesi, this is not how the agreement works. The mechanics in our agreement case is that as soon as we sell the inventory to Chiesi, it means once the vial, the DP, the drug product, the finished product is being transferred to Chiesi, to their warehouse, we're entitled to get our money. We record the revenue. And hence, obviously, this is where the sales are conducted. I think that what the market really doesn't get, and I think that's where maybe the disconnection is, that the fact that, for instance, in the first quarter, we didn't have sales to Chiesi, this is not indicative in any way to what happens in their sales or their penetration to the market. They're selling every day that passes by. They're acquiring more and more patients, both in the U.S. and ex-U.S. We know their numbers on a monthly basis, obviously. I know it's very difficult to tell an investor, "Trust me. I know what I'm talking about." So I'm not asking you to trust me blindfolded. But at the end of the day, given the fact that it is a private company, they don't disclose the numbers. I can tell you that based on what we see behind the scenes in terms of number of patients, what we see in terms of their projections for purchasing from Protalix, purchasing the inventory from Protalix, we are pleased and even very pleased with their performance in the market. Again, don't forget that ahead of the launch in 2023, Chiesi purchased significant amounts of inventory. In 2024, they even increased the amounts of inventory, and as any other commercial company, they are managing their inventory. Right now, if they don't put orders in a certain quarter, it doesn't mean in any way that they're not selling in the market. They're continuing and acquiring more and more patients and market share. We say it here in the presentation. And again, I think that we believe that Chiesi, based on their teams, the very robust medical and commercial plan that they've put, including pediatric study, pregnant women study, multi-center study, the confirmatory studies that they are running right now in Europe, they are putting their money where their mouth is. And we believe, based on what we see, that they are poised to capture 15%-20% of the market, which by the end of the decade will basically entitle Protalix to anywhere between $100 million-$120 million in sales. I was asked here on the chat, "What about the once every four weeks?" So all other competitors, the ERTs I'm talking, both Fabrazyme and Replagal, if we're looking about the competitive landscape, it's IVs, it's infusions. Every other week means once every two weeks, there's an infusion. This is also the approved dosing regimen that was approved to Elfabrio, to Protalix, and I'm putting aside a second, the Galafold by Amicus. This is an oral formulation. It's a totally different story, but looking at the ERTs, it's once every two weeks. It's true that we have submitted to the EMA late last year to approve an additional dosing regimen once a month. This is being reviewed by the agency, by the EMA as we speak. We anticipate and believe that by mid to late October, we will have the CHMP opinion, and based on this opinion, obviously, we will see where it leads. If approved, by the way, in each one of the continents separately, because we're dealing with the FDA on one hand, we're dealing with the EMA on the other hand. But in each continent that this will get approved, we strongly believe that this is a very, very strong card. And Chiesi will be able to acquire anywhere between 25 to a third of this market. Don't forget, in terms of patient quality of life and ease of treatment and most of the other factors, obviously, everybody prefers to be treated once a month rather than once every two weeks. Can I provide the mix of milestone payments between regulatory and sales? It's mostly sales. The only regulatory milestones that are left is basically the once every four weeks in each one of the continents separately. By the way, the agreement with Chiesi deals with each one of the continents separately, ex-U.S. and U.S. Thresholds are different, milestones are different, targets are different, and obviously, numbers are different. So other than the once every four weeks, regulatory milestone, all other milestones that I was referring to are commercial milestones whenever we hit or actually Chiesi hits a certain sales threshold. Really, I don't think that I have to elaborate too much about Chiesi, but looking two years back in January of 2023, the company bought Amryt for $1.48 billion in cash. No debt, no equity was involved. Simply, they put the money on the table. They are built on three different legs, I will call it, streams: Rare, Air, and Care. The air is respiratory. The care is all the branded generics, which was the basis for their business in the European market and right now outside the European market, obviously. And rare is obviously the rare disease where we fall. Our drug is Elfabrio and very highly important. We hear it from Giacomo Chiesi, obviously the grandson of, and he runs the Rare Disease business. He heads it, and we hear loud and clear that for them, it is a priority, so based on the research agreement that we have with them, I reiterate, and again, I don't think that sales or quarterly sales to Chiesi are indicative in any way of their performance in the market, and we believe that by the end of the decade, this will worth it. Protalix, anywhere between $100 million-$120 million in sales, and on top of it, obviously, the milestones that we're entitled to get. In terms of the development portfolio, again, I'm not going to tell you fairy tales about the very early stage, the ones that are not in clinics yet, the ones that are still on the drawing board. But we, I believe, again, and management believes that we have a very interesting asset called PRX-115 for the treatment of gout. Gout, for those of you who don't know, is not a rare disease, by the way. Something like 14 million-15 million people in the U.S. suffer from gout, of which, according to, again, I'm talking about publications, 5% considered to have refractory or chronic gout. We're talking about big, big numbers. There's only one approved drug currently in the market called KRYSTEXXA, ex-Horizon was bought by Amgen for many, many, many billions of dollars. And what we believe, again, and based on the same technology, I didn't dive into the technology of Elfabrio, but the reason that we believed and we submitted an additional dosing regimen is that we have PEGylated our enzyme. The only PEGylated enzyme for Fabry is our enzyme. By PEGylate, it means that we added a PEG, a very small PEG, 2 kDa PEG that basically wraps the enzyme and obviously lowers the infusion-related reactions, the TEs, the STs. The body doesn't detect something was infused into the body. It doesn't attack it. It doesn't attack it. Obviously, it stays longer in circulation. Evidently, if you look at the half-life or half-life for Elfabrio, the drug for Fabry is 78.9 hours compared to up to two hours in the case of our competitors. We've done the same thing with a little bigger PEG, 3.42 kDa PEG. We've wrapped the enzyme in a way that basically it covers completely the enzyme. We've conducted a phase I trial, 64 patients, eight cohorts, a single ascending dose. I know I'm not trying to sell you fairy tales. It's not a phase III asset yet. But based on the very, very interesting results from the phase I, looking at what we got from a single dose, we believe that based on these results, we will be able to infuse anywhere between once in six to once in eight weeks. Obviously, protocol is not public yet. I'm not going to share with you, obviously, not the number of patients and the arms and what we're going to be testing there and what the endpoints are going to be. But at the end of the day, please understand that we will not try to compete with KRYSTEXXA. KRYSTEXXA sales last year were $1.2 billion. We're not going to try to compete with them on the same dosing regimen. There's another company, Sobi, Selecta. They also submitted, and they have announced that their PDUFA date is going to be June 2026. They have submitted once a month. Their immunomodulator is different than the methotrexate that KRYSTEXXA is using. So please understand that we're not going to try to compete, obviously, on the same dosing regimens and frequencies. It makes no sense at this point, so obviously, if approved, and that's what we heard. I came from the U.S. last week. We all participated at the H.C. Wainwright conference. We met famous and very respected investors and VCs, and we heard from most of them that they strongly believe that we will be able to mimic what we have shown improved in the phase I in our phase II. This is a very, very, very interesting asset for them and for the market. I think that that's a significant value driver. By the way, I see that there are many, many questions on the chat. I'll try to address all of them in the next couple of minutes. Let me just run through and finish. Looking at the growth strategy, again, Protalix, after almost two years of a clinical strategic process that we have gone through, Protalix had decided to basically use its core competencies and strengths, means basing our drugs on one hand on the ProCellEx, a platform that we express our complex human protein, and at the same time, not be closed and not just to focus on this, and if we find assets in the rare renal disease space, we will be open also to work on those. I don't believe that we're going to open up a gene therapy or a cell therapy trial tomorrow. We have zero added value there of zero understanding. Obviously, we'll focus on places and areas that we think that we have a competitive advantage. Talking about rare renal diseases, ADPKD, Alport, FSGS, those are the type of diseases that we will be looking at internally and obviously collaborating with external parties. I will really finish with this slide, and I'll try to address the questions on the chat. The company is well capitalized. At present, I think that then we've announced that we have approximately $34 million as of the end of the second quarter. We have zero debt. We have repaid our debt in September of last year. We have no warrants at this point. All the warrants that were outstanding from the pipe that we have executed in 2020 had expired. Very small amounts were converted or exercised, and the rest had expired. We believe that based on the income that we have from the three streams, Pfizer, Brazil, and Chiesi, and based on the expenses, we are funded for the day-to-day operations, and I have to be very careful here because we are being asked time after time, "Will you be going and raising for this or for that?" Or maybe you'll be raising to accelerate the phase II. Again, the day-to-day operations, the company is well funded. Don't forget that if we want to cut the times and save time going into the phase III, again, assuming that we will see good signs in the phase II, it's a double blind, whatever, but again, you can tell and you can have a feeling we will need to expand the manufacturing plant in a way that we'll be able to support three drugs. Right now, we're manufacturing two drugs in our facility. All of these expenses, again, depends on how broad and how fast we want to go with the phase II. And the same for our appetite for R&D expenses on the early stage. This whole thing will really dictate if the company will raise money or not. But at this point, as I've mentioned, the company is funded for its ongoing operations. This is the team. I'm not going to elaborate because you have the presentation online. You don't need me to flip through the names. Now, I'll try to take the remaining three and a half minutes. Has the four-week dosing submitted to the FDA? If not, when do we plan to? Again, we're a publicly traded company. In case we wanted to share, we would have shared. This is obviously all the correspondence with agencies is subject to confidentiality. We're not able to share it. We will once it will be outside. Could the platform be used to help other companies with life cycle management by developing more effective versions? The answer is no. If you want to do life cycle management, the LCM using our platform, it's taking it all the way back to the drawing board. It's obviously safety and take it through the entire process. You can't take a drug that's manufactured through mammalian cells or whatever. Right now, it's small molecules. We want to go to ERT and use our platform. It doesn't work this way. I see here some other questions. Okay. So I think that I also addressed the question about contract manufacturing for Pompe and others. It's not a contract manufacturing platform. You have to take it all the way back. Which company do you plan to partner with on Elfabrio in the future? It is partnered already with Pfizer. If we'll be able to buy it back, the options are, but I think it's going to be irresponsible to share just names, but the usual suspects obviously are the ones that we're going to be trying to use. Any plan to expand the Fabry outside the U.S. and EU? It's not only in the U.S. and EU. It's ex-U.S. It's basically U.S. and ex-U.S. So it covers, I think, the universe in general. So talking about the catalyst in the next 12- 18 months, we're talking about basically the once every four weeks decision by the CHMP in the next couple of weeks. We're talking about mid to late October. And obviously, the phase II that we have started on PRX-115, where the first patient is going to be sometime in November, I guess, in the next couple of weeks, you're going to have the protocol on ClinicalTrials.gov, a very robust, highly powered to efficacy. And we believe that if successful and if the data is going to be there, the agency will consider this trial as one of the pivotal trials in a way that we will have to run just one other pivotal trial and not more than this. So we're basically talking about two catalysts. The first one in the next couple of weeks. The second one is the beginning of H2 or maybe late H1 2027 when the top-line results of this trial, the phase II trial of gout, which is a very interesting asset, is going to be out there. What else do we have? So basically, those are the key takeaways and what you should feel free to barge in and send me emails. You have our website, so you can also send questions using the website. That's it, I guess. Thank you, Mr. Eyal. So I think this is the end of the presentations. Thank you, everyone, for joining here, and have a wonderful day. Thank you. Thank you, everybody, for listening to today's presentation. Have a good day. Take care. That concludes Protalix BioTherapeutics Incorporated's presentation. You may now disconnect. For details on upcoming presentations, please refer to the conference agenda. Thank you for your participation, and we look forward to welcoming you to the next session.