Thanks everybody. Good afternoon. Welcome to day two of the Citizens Life Sciences Conference. My name is John Walbon, Senior Analyst here. Pleased to have Protagonist Therapeutics and CEO and Presid ent, Dine sh Patel. Dinesh, thanks so much for joining us. It's a real pleasure, and thanks for choosing such a wonderful location. It's beautiful. We'll get outside at some point today. Yeah. Protagonist has been, you know, one of the best stories I think it's mid-cap biotech the past several years, and there's a lot behind the success and the stock when you look at it. You know, for people who may not be as familiar, what are you guys working on, and what's kind of the secret to the success? Yeah. I think to kind of set the stage, as you know, we have been focusing on peptide therapeutics and that's a skill set we have been perfecting since 2008, right? As they say, when nobody is watching you, that is the best time to become excellent at something. We started working on peptides when it was not that fashionable. People were barely aware of it, that sort of thing. That has allowed us to create an edge, create our own secret sauce, be the pioneers in the field. Now fast-forward to 2026, what we have is like two late-stage assets, partnered assets that hopefully will get approved this year. The phase III data has been outstanding with both of the assets, and both are partnered assets. It's like the big pharma that is doing the heavy lifting, so to speak. We become beneficiaries of it by virtue of being the discoverers and inventors and participants in the early stages of development. The economics are great, which then kind of almost gives us the financial flexibility, or should I dare to say, financial independence to really support our next wave of R&D pipeline, which is also along the same theme, focused on peptide therapeutics. To break it down in a simple way, obviously, we would want to work in areas where we can address unmet need. A very important component for us also is that we want to address the unmet need with a very strong differentiation, right? If five companies are already addressing that unmet need, I don't want to be the sixth company addressing the same unmet need with the same approach. That is where we have created a distinction. As you know, in a lot of space where the market is dominated by, let's say, the injectable biologics or even the injectable peptides in the obesity space, we are saying we'll come up with oral peptides, and we have been able to do that in the space such as hormones or hormone mimetics. It's like, hey, a small molecule may not be a good way to approach it, but maybe with an injectable peptide like rusfertide, we have the upside in mimetic. I think, it's like excellence in science, really being like the leaders and pioneers in the field of peptide therapeutics. Applying it very judiciously to target certain diseases and indications that are in demand where there is a significant unmet need. I think that has brought us where we are today. The next wave, as you know, we are continuing with the theme in the I&I space, in the anti-obesity space, and also in the Heme space. Yeah. Are you therapeutic area agnostic then when you look at these kind of opportunities? You talk big picture about unmet need, peptide therapeutic as the backbone, but are there areas that make more or less sense? I guess the answer in a way is both, yes and no, in the sense that we don't want to confine ourselves by being restricted to a very specific therapeutic area, right? At the same time, now over the past 15 years or so, we have landed ourselves into the HEM space with rusfertide in a prominent way in the I&I space. With icotrokinra. Then more recently, we just decided we should be in the anti-obesity space as well, and the logic was very simple. It's like, hey, the two prominent drugs that are out there and that are kind of changing the face of the pharmaceutical sector, they are both injectable peptides. One of our expertise is to come up with oral peptides in this kind of situation. We thought it was just very natural for us to participate in that as well. I think it will almost be dictated by where is it that we can create the strongest differentiation to address very significant unmet need. Okay. We got a lot of ground to cover in the time we have today, but I wanna start maybe with rusfertide. Later PDUFA in the year, but a potential approval later this year, December, and for polycythemia vera. Can you talk a little bit about, you know, you know, there's a lot we could say, but, you know, unmet need, you know, the problem that rusfertide could fix, and then also how you think about the commercial opportunity with your partner, Takeda. Yeah. I think there are definitely three components over here. One, by the way, as you may know, we got a priority review about a week and a half ago. Hopefully, if you just do the math on the clock, then the approval might be in the third quarter of this year, right? Because of the priority- Review kind of component. In PV, what we found is like, hey, this is a disease, it's a rare disease, but at the same time, there are about 100,000 patients in the U.S. alone that- that are on treatment, and the actual prevalence number is like 165,000, something like that. These patients, they unfortunately stay with the disease on an average for about 20 years or something. The hallmark of the disease is excessive red blood cell production, so very high hematocrit levels. Yet there is no erythrocytosis specific agent that is out there. As science geeks, we are like, "Hey, what if a mimetic of the natural hormone hepcidin, whose function is to really, you know, do the iron homeostasis in the body, right? If we can come up with a more potent, more stable, functional mimetic of hepcidin, that could be a wonderful approach over here, and it has panned out very well. Now, in terms of the opportunity, like I said, large number of patients, and the disease duration is very, very large. If you look at all across the treatment paradigm from the early onset of this disease to the late stages of the disease, whatever treatments are out there, one common thing is uncontrolled hematocrit. Because almost every treatment, whether it's phlebotomy or hydroxyurea or Jakafi, it's almost like a pan approach, right? It affects everything, not just the RBCs. The uncontrolled hematocrit is an unsolved problem that exists all across the pool of patients and the stages of treatment, and that is why with rusfertide, the opportunity is very interesting and very broad. In a way. We remind people that, look, if your current treatment is working, then stay with it. If your current treatment is excessive phlebotomies, which is like just going in circles, then here is a very good remedy. Ultimately, at the end of the day, with each treatment, people do succumb to excessive phlebotomies because, you know, that's ultimately the way of like, okay, let's remove iron out of the body, that kind of thing, or let's remove the red blood cells out of the body. That doesn't work in their favor because you're also removing iron, and you become anemic, and you have the symptoms. Now, our data was just outstanding. It was presented at ASCO as a plenary session, right? for the discussant to say, "Hey, this is practice-changing. Yeah “should be standard of care,” The data spoke for itself. We, I think, are the first company that actually demonstrated symptom control, right? We had all positive patient-reported outcomes were positive for the drug. In terms of partnering the drug, as you know, we were already in phase III on our own when we did the partnership with Takeda. You know, this was a partnership that where both parties were in a position of strength, and we were able to come to terms that were fair to both parties. Well, I'd say for sure. Then also the optionality you had, and I know, you know, I think it was this time last year, like you could opt in or opt out. You're like, "Hey, we really like the idea of opting out." I think now you're officially saying, "We're gonna opt out." Can you talk a little bit about the downstream economics for you guys? Right. As you can imagine, you know, like for any big pharma, the first attempt by them is like, "Hey, let's, why don't you guys just license out the drug to us?" If we opt out, then that is what it would translate to. Of course, at that time, we said, "Now let's do a 50-50 co-development, co-commercialization." That is the situation we are in right now. Now if you look at the economics of opting out, right? We have shared more detail about this since the beginning of the year. The royalty rates are like 14%-29%. For the first $1.5 billion, the weighted average royalty rate is 21%. Whatever is in excess of 1.5, that is 29%. If we opt out, what is the biggest fear we would have? If this becomes a big drug, then, you know, we give up that opportunity. Well, with a 29% royalty cut, I don't think we are leaving that much at the table, no matter how big the drug is. Yep. I think that was a simple math and common sense logic that basically allowed us to conclude that we should be opting out. Again, you know, it's like let the experts do what They are best at doing. Takeda is an amazing partner, if you look at what they did with Entyvio, right? In the IBD space. It exceeded $6 billion-plus in annual sales. We have big faith and trust in them. HEM is a very important disease area for them. Our drug is a very important drug in their pipeline, so they will do full justice to it, and it's going to be a win-win situation. Takeda, great partner and you're in the enviable situation where you actually have an even more premier partner in J&J with that icotrokinra. Tell us about that asset and that partnership. Yeah, I think, maybe can I dare to say that we are able to choose the best commercial partners, right? Yeah. With icotrokinra, as you know, we are partnered with J&J. What attracted us over there was these were the champions of Stelara, Tremfya. Their expertise in IL-23 is very deep-rooted. Now icotrokinra, the phase III data in psoriasis has been fantastic, hopefully that also gets approved this year. The NDA was filed in July of last year, the 12-month math will say sometime in the third quarter of this year. Over there also we have amazing terms, 6%-10% royalty. The 10% kicks in for anything over $4 billion. The weighted average for the first $4 billion is 7.25%. The other thing I would add also is like, you know, the sales milestones, which typically are just aspirational in most deals. The sales milestones of these two drugs combined is $1.2 billion, and we believe all of that is achievable. I think we are in a very good situation where we should be able to check the box on development and sales milestones and also the significant revenues from the royalty structure. Well, J&J, they have Stelara, which has been a phenomenal drug. They know what they're doing, but they also have that coming off patent, so they need this to be successful as well. There's a lot of motivation for them to really, you know, jazz the launch and make sure it goes well. On that front, can you talk about the data that you guys have produced, and then also how disruptive an effective oral drug could be in the psoriasis market? Yeah. icotrokinra, or iCoTIDE rather now, this is the first and only oral IL-23 antagonist. As you know, this is a mechanism that has been the source of multi-billion-dollar franchises, right? Skyrizi from AbbVie, Stelara and Tremfya from J&J, that sort of thing. The market opportunity is huge. The market research done by J&J itself is suggesting that for iCo being the first oral, there are two different types of opportunities. One is the existing market that is dominated by injectables, and their survey has suggested that 75%-90% of the patients who are currently on injectables, they would be willing to switch to an oral if a good option was available. The iCo data, I mean, it is a great option, r ight? Biologics like efficacy, the safety is like in the clinical studies, the results are described as placebo-like safety. How often in our careers do we get a chance to describe a drug safety? Yeah in that kind of a language? The drug usually doesn't work if it does. Yeah, that's right. Yeah. The other component. Of course, as you know, it's a very convenient once daily oral pill. For this kind of indications, right, psoriasis, psoriatic arthritis, ulcerative colitis, Crohn's, I mean, these are lifelong chronic indications, so convenience becomes a very important component. There is nothing more convenient than a once daily oral pill. Now, there is another market. It's like, what their marketing research is also suggesting is that more than half of the I&I patients that are actually eligible for targeted therapy, they are currently not choosing anything. Interesting. For two reasons. One is they don't like injections, and the other is they don't like the choices that are in oral. Like what do you have in an oral? A JAK inhibitor, S1P modulator. A TYK2 inhibitor, things like that. As you know, there are liabilities and concerns with all of those things in terms of the safety thing, right? This could be the drug that could be creating a new market share of its own on top of grabbing some of the existing market share of the injectables. In terms of like, hey, whether this is gonna be at peak sales, a $5 billion dollar drug or a 20 or a 30 billion dollar drug, we are like, you know, do your own models. What we have provided is like, a guidance on like what is our royalty-based revenue cut at certain peak sales. For example, at $10 billion, our cut is $900 million, roughly speaking. Which is a good amount. Yeah. Well, we were just mentioning before we came on that the Skyrizi estimates are like $20 billion, and it's not. I'm watching TV every night, and I see a Skyrizi commercial pretty much every break there is. These are gonna be massive drugs. How do we think about- Maybe after six months you will see the TV ads for iCo. Yeah. We have psoriasis, but then, you know, we trickle down all these other indications. How do we think about when you talk about that's, you know, not psoriasis you're just talking about? Do you think the same dynamics in all these other indications as well? Yeah. Because once again, it's the combination of biologics like efficacy, amazing safety. I cannot emphasize the safety component enough. It's for all these indications, safety is of prime importance, right? These are not acute life-threatening indications. This is something where you are taking the treatment for the rest of your life. You might as well choose something that is proven to be very safe as a mechanism. That becomes very important. If you look at our data, right, psoriasis, we have knocked it out of the park. So far, that is 100% translation success from psoriasis to psoriatic arthritis. Our phase II UC data is off the charts. 30% clinical remission, that is as good as it gets. in the field. There is a scientific reason behind it. We are targeting IL-23, the receptor, whereas the antibodies are targeting the ligand. We chose the receptor because it overexpressed in the GI tissue compartment of IBD patients. Even preclinically, what we observed was like, hey, the minimal dose for efficacy that was required in the colitis models, which are reflective of IBD, let's say, that was an order of magnitude lower compared to the efficacy, minimal efficacy dose that was required to take care of the skin inflammation models. Maybe, I mean, if you really want to look at the glass as half full or almost full, it's like maybe the best is yet to come. Psoriasis is just a preview of like how good the drug is, and maybe the real score will be in the IBD conditions. Interesting. Now you have two drugs on the verge of approval discovered in-house. We have validation of your peptide expertise, and now we have, you know, what's next. You guys have done a great job of backfilling the pipeline now with a bunch of assets, you know, getting into the clinic. Right. Can we talk about PN-881 first? 'Cause then we can stay in the I&I thread here for a little bit. Talk a little bit about PN-881 and then the rationale for that candidate. Yeah. You know, what we noticed is like, just as IL-23 is a dominant player in some of the DERM and IBD conditions, IL-17 blockers like Bimzelx and Cosentyx are dominant players in the DERM space, and including HS and spondyloarthritis, right? That was very attractive. With Bimzelx, what we also observed is like, hey, if you have activity both against the A and F isoforms, that could lead to better superiority in terms of the clinical responses. Right from the get-go then we said, "These are all injectables. Let's try to create the best oral with activity both against the A and F isoforms." That is what PN-881 is. It's almost like trying to go for a repeat performance, like what we did with icotrokinra. Now can we do it in the IL-17 space and try to come up with an oral that is a best in class, only in class as far as activity both against A and F isoforms is concerned. Right? The drug, as you know, is currently in phase I studies. By the middle of the year, we should have the data that we need to make a decision. I think in Q3, that is what we are guiding. Sometime in Q3, we will be able to tell the world what are our plans with PN-881. Are we going forward or not? That kind of thing. Would that just be a safety gating issue or PK exposure? Or like what would- PK exposure is where the focus is because. Got it. ... the, as you know, the antibodies have already taught us like what level of target inhibition one would need. Then based on the potency of the drugs, then we can do the math and say, "Hey, these are the drug levels you need to achieve to, in theory, kind of block this amount of target. So you- That's the math we are going with. Now, one of the other thing I would add is like our peptide is almost 100x smaller in size compared to the antibodies. In theory, it could give us an advantage by virtue of having better tissue and skin penetration. ... which will become important for these conditions, and especially the arthritic, kind of conditions, right? Just to be clear, for our math of drug levels, we are not factoring in that potential advantage at all. We are being very conservative. We want to hit certain drug levels. If we hit those drug levels, it will be a go. Even though a healthy volunteer study will be able to do some triangulation on potential, you know, efficacy implications. Based on the drug levels. Yeah. Because as you know, there are no PD readouts, PD markers. Yeah With the healthy volunteers. Yeah. enough to warrant moving forward. Correct. Correct. You mentioned anti-obesity, and I'm just gonna make sure I get my numbers right 'cause I'm learning these candidates as well. PN-477, PN-458, you got a triple agonist and then a GLP GIP. Talk to us about kind of your strategy in obesity when you say, "We don't wanna have like the fifth or sixth drug coming to market." What makes these assets different? The biggest distinction would be that we have, we are oral, and we have oral polyagonists. In obesity, the way we look at it is like this is an opportunity of unprecedented scale and level for our sector. We may just be scraping the surface, and especially if you blend it with the affiliated comorbidities and the impact of those drugs on that. I mean, this, these are the drugs that are going to be treating billions of patients. We have never been able to say that there is a drug for billions of patients. This. I think our entry point, if you couple it with the differentiation that we are going after, then it's very timely. We are the only oral triple, right? In talking to the KOLs, it became apparent that, hey, you know, there may be a need for some patients for some periods of time to have a weekly sub-Q, so we are developing both. What we are saying is, like we don't have a crystal ball, but we know that this is going to be something very huge and useful. We are covering all the bases. As you know, fortunately, we have the financial flexibility. to support all our aspirations and all that. Yeah, we are developing an oral triple as well as a subQ triple. The subQ triple will go into phase I study by the middle of the year. The other advantage is in phase I study itself, you are gonna know whether your drug. Yep is working or not, right? Clinical POC will come pretty soon. Well, I thought we could get to everything, but we still even have the oral hepcidin mimetic, you got an oral amylin, and another early stage candidate as well. You guys are doing- Mile 4. Yeah. ... MYL4. The beauty is we can fund all of thes e things up to clinical POC. I mean, if it is just a numbers game, we could fund phase III studies also, but we are not gonna do that. We are big believers of pharma partnerships for bigger indications. We may participate more financially in the clinical development cost and all that kind of thing. At the end of the day, we need, we believe in the expertise of pharma. We will join hands with them on bigger indications. For something like an oral hepcidin for rare indication. that we can take it to the finish line on our own, things like that. We touched on these during the conversation, but just to remind us, in the last minute where investor focus should be in 2026 with Protagonist. All along the spectrum. I mean, if you think about it, right, in the month of May, in theory, we could be announcing opting out of the Takeda deal. In Q3, hopefully, there could be approval of both the drugs. In Q3, we will also tell the street what is our verdict on 881. We are not gonna show the data, so they will just have to trust our judgment and our expertise, but we believe we are pretty well-regarded and very sincere and serious folks. By the end of the year, we'll have data from the subQ triple, and the oral will be behind by a quarter or two. You know, if it works in one, it has to work in the other, that kind of thing, right? Yeah, there will be a flurry of events and sequences. Well, it's been a fe- Without any threat for going out and raising money and diluting shareholders. Now your balance sheet is very, very strong. It's been an incredible couple of years and a lot going on this year, a bunch of value inflection points. Next year, we're gonna have even more data coming from the pipeline. Dinesh, congrats on the progress, and we're looking forward to tracking it moving forward. Tha nks again for coming. Thank you so much for all your support. Really appreciate it. Let's hope we can continue the dialogue. Absolutely. Yeah. Thank you.