All right. Hey, everyone. Welcome to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior at this cover, Simica Biotech. It is my great pleasure to have the next five-side chat with Protagonist Therapeutics. We have a CEO, Dinesh Patel. Hey, Dinesh.

Well, thank you for inviting us. It's a pleasure to be here.

I have to say protagonists are in a very enviable position in the entire biotech world. You have a significant royalty stream from your great partnership with Pharma, and you have one of the most exciting pipelines based on your Oropeptide platform. Maybe Dinesh, take a moment, right? So, you know, soak it in, and then say, okay, what is the state of art for protagonists at this moment, and what excites you the most for the company?

Yeah, I think, you know, we had our humble beginnings all the way back in 2008. We have come a long way. In a way, we can also claim to be a company with a commercial presence with the approval of IcoTide that is partnered with J&J and with Resfetide partnered with Takeda. The Padufa date is in the third quarter. So that gets us qualified, I guess, in the commercial space, so to speak. But then at the other extreme, we have a very thriving R&D engine, and the genesis of all that is our proprietary peptide technology platform and our expertise. One distinction I would make is like I would like to make a claim that the probability of success at protagonist in its R&D programs is probably significantly higher in comparison to what the industry norms may be for a biotech company. And there are two reasons for making that statement, right? One is that if you looked at our targets, we are working on biological targets and pathways that are already validated largely by injectable antibody drugs. So that kind of takes away some component of the biology risk that is usually associated in new undertakings. And the second is our approach has been validated now with one commercial drug, one under priority review. Hopefully it will get into commercial in Q3 as well, that sort of thing. So those two components de-risk us. And then on top of that, we have a very strong financial position. So it's fair to say that we can fund all of our R&D programs to clinical proof of concept. And so it's pretty clear that, you know, we are not going to dilute away shareholders with equity financing in the foreseeable future. If at all anything, we may be concentrating their positions potentially through share buyback programs. by the end of the year, and assuming Resvertide also gets approved in Q3.

You've been humble. I think you've made quite a few very exciting statements on both commercial and then the pipeline and then the financial, right? So this is basically the key thing for all the biotech at your stage. Okay, so let's maybe zoom in for your most exciting commercial product, which is a partner with J&J. And J&J, in the last earning call, they basically say J&J will be one of the, if not the most kind of exciting, the biggest product they ever had, ever, for J&J. So that puts us think about, you know, 10 billion even are kind of a starting point. So maybe tell us, based on your communication with J&J, it's been a long kind of great partnership. how much you think J&J has really put the effort into this program and then how much you can share with us the relationship with J&J at this point?

Yeah, so, you know, first things first, J&J is an outstanding partner. It's like for a biotech company, partnership with J&J is like a dream come true. And, of course, then the biotech has to deliver, which in case we did with Icotide. But to just offer a perspective, we have been working with J&J since 2013, at least. Our Series B financing, when we were a private company, was led by JJDC, the investment arm of J&J. And it worked out well for them. They have close to 4% ownership of the company, especially since they haven't sold a single share. So it's a win-win. But to their credit, I mean, it took a few years for both parties to Incadil in 2017. But they have constantly been supportive. And, you know, the division of labor typically has been we discover, we do preclinical, We do phase one studies and then we hand it off to them. So I could tie this, the outcome of a joint effort between both companies and getting it approved, it's, in a way, this is just the beginning. It has been approved for psoriasis, but if you look at the history of successful IR23 blockers, right, Skyrizi, Trumfire, Stellara, they are approved in all four indications. psoriasis, psoriatic arthritis, UC, and Crohn's, and as you know, ICO is being studied in phase three studies in the other three indications also, so I think this is a product that is going to get bigger and broader each year, and of course, J&J, their executives, including the CEO, they have been very vocal in their excitement about ICO-type.

This could be their largest drug ever, and very rightfully so yeah you know we came back from AAD I have to say J&J made the biggest splash they can ever made for Aquatai and then a unicorn sign there that's right it is a unicorn right it's a bigger unicorn okay so maybe just ask us some pointed question everyone going to look at the script and we've been tracking this I think you know so far it's not reflected in the third Party, QVL, or Symfony yet, but J&J is vocal about how many prescriptions they are already prescribed, I think 1,500 or something. How should we think about those numbers reconciled with the database we have seen? That's number one question. Number two is how protagonists will start to report in those royalty or the sales as the quarters come?

Yeah, I think both are very relevant and excellent questions. And what I would say is, like, right now these are the early days, so you can anticipate at least an order of magnitude discrepancy between what you will pick up from IQV and symphonies of the world versus what the real data may be. But let me give you a granular example. If you recall, IcoTide was launched or approved on St. Patrick's Day, March 17th, And then J&J had their earnings call on April 14th, right, where they said, oh, more than 1,500 scripts have been written, filled, and from more than 1,000 prescribers. But two, three days later, when we looked at the symphony number, that was like 58. So that's a 25-fold difference. So I don't want to get too granular with these numbers, but, you know, J&J most likely should be working its way through specialty hubs and that sort of thing. Right now, it's the stage of establishing the presence and the market and that kind of thing. So that will continue, but, of course, J&J will report the updates during their quarterly earnings. and eventually at some stage, whether it's for Q2 or Q3, time will tell, but we will have to start reporting a separate revenue line from the royalty income generation, right? And most likely what we'll be doing is we will report based on whatever earn-out is going to be for a particular quarter from J&J, right? And usually it takes like one and a half, two months for the actual money to come into the bank, so to speak.

Yeah, yeah. So basically, the rev rack will, along with the J&J, because usually J&J typically is the first reporting for the pharma side. And then after that, when you report, you will recognize that revenue, but the money is going to come in a month or a month and a half afterwards. And then, oh, that's exciting. By the way, we took a look at the consensus number for J&J, for the equitite, as well as the protagonist for the royalty. I think the street is still undervalued, you know, particularly for the long-term, you know, the peak or the high, you know, growth. I think still way undervalued the revenue J&J can make if they think it's the biggest product. Unless they think J&J's biggest product is only like $3-5 billion, so this is not the case. And then also protagonists as well.

Yeah, and we are very patient, you know. The data will speak for itself, whether it's scientific data or financial data. eventually it all settles down but you may recall Roger actually I think it was three earnings call ago that J&J and you know typically pharma will be conservative by nature but over here they did mention that their own forecast and this is like three quarters ago I think for ICO for 2027 was 1.4 billion which is twice of what the consensus analyst estimate was around 700 million and this is before the drug was approved so.

Yep yep that's right I remember J&J call I even count the question that they got asked about the Gakotai last quarter among the pharma side maybe 80% of the question is ready to Gakotai which is very humble too.

Yeah and and and in their own words I I think recently they were asked about what is most underestimated in their pipeline, in the J&J pipeline. And ICO was one of the three products that was mentioned in that context. Because see, ICO is incredibly proven and safe mechanism, right, IO23. And for chronic indications treatment, safety comes first. It's all about safety, safety. so we have that in the bag and these are early days and things are just going to ramp up and also the oral component it's like J&J has done extensive market research right so they are like oh they believe that potentially more than 70% of the patients could switch from injectable to oral if a good option was available We believe ICO is a great option. And then about half of the I&I population that is actually eligible for targeted therapy is sitting on the sidelines because they don't like the current options of injectables or whatever options are available in the oral. So they truly have an opportunity to create a new market out of ICO type.

Totally. By the way, no, Sarasas is just the first indication. But I think the label looks squeaky clean in terms of safety.

No need for TB screening? Can you believe that? That's about as good as it gets. Yeah, that's right.

And then we saw a special panel at the AED this year, and then they literally talk about the TB testing and then why they still need to get there. And then a lot of physicians do think it's very onerous to have that monitoring requirement. Okay, good. So I remember, you know, Dinesh, we used to spend majority of the time talking about Echotide, but I want to move on from here. I want to talk about your pipeline.

That's right. There is a limit to basking in the glory of achievements from the past, right?

Let's look forward to the future. Yeah, let's look forward. So before we talk about your pipeline, for sure, but I don't want to lose sight of the ResverTide because it is getting priority review. I went there, the plenary session last year, I asked Cole, and then, you know, a lot of the assignment there. So how you think about this op-out decision and then, you know, what does that mean to your protagonist, you think, for Resphotide?

Yeah, no, I think, look, it's a very interesting situation. I mean, the Resphotide phase three data, we couldn't have asked for better data and especially scoring on the secondary endpoints of symptom improvements. And as you know, at EHA now, we are presenting four different posters, So we'll encourage the interested parties to pay attention to that as well. But with Rusphatide, I mean, we have priority review. The PDUFA date is in Q3, so everything is lined up. And now for us, it was a question of, you know, until recently it was a 50-50 co-development, co-commercialization partnership. But, of course, right from the get-go, even when we inked the partnership in January of 2024, Takeda was always interested in an outright license. So a provision was made wherein they are like, you will have the option of opting out at some junction, and we will make that component very attractive. And they were right. So net-net we decided to opt out. But let me offer some granularity around that. So by opting out, what we are achieving is a $400 million as opt-out fee in total, and then an extra $25 million in the FDA approval kind of milestone. So it's a scenario of a total of $425 million. If we still opted in, what it meant in a way was like I am investing an extra $425 million in resveratide. And if I opted out, I'm taking that money and saying, well, I have invested enough in resveratide. Now let Takeda take charge, and we could be investing that money into our pipeline of the future. So that is what we have done. The other way to look at it is like, you know, I mean, this is going to be a new drug launch. And initially, if it was a 50-50 profit loss thing, I mean, for the first quarter or two, whether we are participating in loss or breaking even, whatever, that kind of thing. So we are devoid of all that drama. Now our earnings are just based on 14% to 29% cut of the revenue, right? And then let's say after a few years, this becomes like a big product. Then at that time, are we going to regret that we opted out? The answer is absolutely not. Because as you know, we have 29% royalty cut for things that are over 1.5 billion, right? And this is 29% of net revenues. So it's significantly higher numbers in terms of net profits and that kind of stuff. So I think it's a win-win situation for both parties. Takeda is very attentive to this drug. This is one of the three major drugs in their pipeline, and they are an incredibly talented company. They were the ones who brought NTVO to the IBD community, and NTVO is one of the safest drugs. So this is a company that very much knows what they are doing. So we are in good hands. Rasputide is in great hands with Takeda. Absolutely.

And I think the number definitely validate this deal or the option is very attractive, right? 29% royalty, you don't spend a penny. I think that's probably the highest royalty rate I have been modeling.

Yeah, it's a good arrangement. Okay, good. We do want to spend the rest of the time on your pipeline.

You have a lot, right? So based on the platform, you have IOS 17, you have the obesity franchise leading by the triple G, and then you do have the oral hepcidin, and then you announce a couple new targets. So maybe spend more on the IOS 17 because this is a more near term, right? So you will make a decision if how you want to move into the phase two, mid-year, this year, or third quarter in the coming months. And then what are the key profile or what are the targets you want? looking at before you move into phase two, and how should we think about the phase two strategy from here?

Yeah, so with the oral IOS-17 approach, we have the advantage that this is a pathway that has been proven and established by amazing antibody injectable drugs like Bimzelex and Cosentix, right? So based on that, the performance of those antibodies, we have a good understanding of, hey, what is the level of inhibition of the target that one would want to achieve to drive it down to good efficacy levels. So in our phase one studies, it's a pretty comprehensive phase one study. We have more than 100 healthy volunteers in the study, but we are studying all aspects of our drug. But the idea is to develop a full understanding of the drug levels and the best forms of oral delivery at the end of phase one study, which will be in Q3. And then our benchmark is, you know, drug levels, exposure levels, especially the trough levels at 24 hours, because ideally we want a, you know, once a day pill kind of thing. and the benchmark is going to be the EC50s, EC90 levels of the drug. That's what will guide us. In terms of what we would announce is we will announce a decision of go or no go after reviewing the phase one results. And if it's a go, then there are two scenarios. It's like one could be where we may say, oh, we will do a quick single-dose or the high-dose proof-of-concept study. Or we may say we are doing a comprehensive phase two study, planning for success, so that at the end of the phase two study, we get a very good idea of the dosing regimen that we can take directly into a phase three study. So I would say stay tuned.

You know, third quarter is not that far away. I think that's very helpful because you've been saying, you've been guiding, you may not give us the phase one data right away as you disclose the next update, but you also say, you know, how you design phase two may signal what kind of profile you're seeing. And so maybe just the level of disclosure we're going to see, you know, regarding the IOS 17, would you give us the signal on the phase two strategy there when you do that, or it's just a simple go-no-go decision at that point?

Yeah, I think there will be enough that we will share so that the folks like you and others will at least get a good understanding of what we, protagonists, are thinking of our phase one data.

All right, so we're still tuned. I know you're still kind of, you know, kind of finalizing it. Just to give you a sense, you know, what we try to look at, and then we want to get enough comfort or confidence that you will, you know, to move into the phase two. And then in terms of the benchmark, we have the, you know, biologic side and A and A and F, and then also we know small molecule in the earlier stage, and then seems to have some hiccup. So what is your benchmark in terms of the, I think you mentioned that C-12 and exposure and then the QD and then the EC50 and 90. So any specifics you're looking for compared to the other approach?

I would say it's all of the above. But see, one thing that's in our favor also is, like, ours is an oral peptide with activity both against A and F isoforms. And the small molecules generally have struggled in terms of activity against the F isoform. And Bimzelex has made it very clear that it's very desirable to have activity against the FF isoform also. And peptides in general are going to bring more specificity and potency against the biological target, right? That's a big plus in comparison to the small molecules in general. So I think we are well set. We, like I said, our phase one is going to be very data-rich. That's how it has been designed. And there will be a lot of learnings from that, which will influence how we go about our phase two study.

Great. And then just the last question about the R17 is, I understand you can decide either to do a proof concept or do a full-blown dose-ranging for phase two. How should we think about the indication and then the overall clinical strategy by frequency and then the patient population?

Yeah, I think so. You know, with IL-17 blockers, you are going to go for indications such as psoriasis and HS and spondyloarthritis, that kind of thing. And I think for every drug, psoriasis has been the first indication that has been evaluated and very rightfully so. So the way we are looking at it is like if we go into a phase two study, of course it will be a placebo-controlled study, things like that. But I think even by looking at the blinded data, one could start guessing about the potential performance of the drug, that sort of thing. But the sequence is going to be, let's do the phase two psoriasis study first, and if that looks promising, then we will be very aggressive in pursuing other indications very, very quickly. And fortunately, you know, we are not a company that has to announce positive phase two results and then go out and raise money. We can just say we are good and we go aggressively with the other indications without wasting any time.

Okay. All right. I don't know about the other side of how they think, but I like it from a research perspective. Okay, good. So maybe let's move on to the obesity franchise. It seems you picked the winner because when I saw the radar phase three, top line data, I think, oh, yeah, that seems to be a very promising. Not saying they would take the entire market, but at least the profile looks very strong. So you have your triple G. Maybe tell us how you design the program, how you compare to rather true Thai disease drug, and then what's the clinical strategy from there?

So I think in the obesity space, I mean, there are two extremes or two ways to look at it. One is like the two major approved drugs, Vagovie and Zubbound, I mean, they are injectable peptides, although Vagovie is now available as an oral as well. But what got our attention is like, hey, these are injectable peptides. Our expertise is oral peptides, so we have to be in this area. But obviously, the area is very crowded, and in a way, one could say, hey, you guys are latecomers. which we may be. So we really, right from the get-go, had very, very strong emphasis on the differentiation part, right? So we wouldn't work just on an oral GLP. In fact, what we did is we went to the KOLs and basically said, what is on your wish list? It's like, what would be a dream come true kind of scenario for you? And everybody mentioned oral GGG as the first choice. And the second ask was, can you work around amylin, come up with an oral amylin, polyagonist, that sort of thing. So we focused on the oral GGG. But right from the get-go, we also decided that this is going to be a portfolio play in its own right. So we are working on multiple different targets in the obesity space. And see, the scope and opportunity is just so huge over here. And then especially if you blend in the co-morbidities angle, then the scope becomes even bigger than ever before. So I think our approach of, like, working on multiple kind of modalities and different kind of targets coming up with multiple assets, It's going to be very, very useful down the road and very attractive. The other beautiful thing over here, and I cannot emphasize this enough, in phase one itself, by enrolling healthy volunteers with a higher BMI, there is a good chance that you will start picking up on the clinical proof of concept, right? Whether your drug is achieving weight loss or not. that you will start getting preliminary signals about it. So we believe it's a very exciting chapter in the history of protagonists. And you are absolutely right. We believe that the injectable triple G retatratide from Eli Lilly is going to be an outstanding drug. Their recent data is just fantastic. and our advantage will be, you know, we will be both sub-Q as well as oral. That was another thing we decided based on the KOL feedbacks. It was like, hey, for some patients, for some portions of time, a sub-Q may be desirable. And I'm like, I'm not even going to entertain this debate of oral versus sub-Q. Let's do both. It's easy enough to do both. And there is a very specific advantage of having the same drug substance, both as a sub-Q as well as oral, right? If you look at in the field of anti-infectives, that has proven to be very successful and effective. The final thing is ours is sort of an oral GGG with some differentiation from retatutride, at least at a theoretical level. And, again, this was based on consultation with the KOLs. So if you look at the GLP-GIP-GCG ratio in ratatatide, the GLP-GIP relative potency is different from what they have in terzapatide, their dual GLP-GIP. So what we decided to do was engineer the terzapatide like GLP-GIP dual potency and add the GCG kind of potency on top of it. So that's the other differentiation we have. And, of course, this is all towards the desire of, like, maximizing weight loss, curbing the muscle mass loss, and hopefully also curbing the, you know, nausea and vomiting kind of side effects. But time will tell. We have planned for perfection, but the real findings are in a clinical setting.

Okay.

Awesome. Awesome.

Last minute, in terms of the, I know you are still early on your pipeline development, and then how should we think about the spending and R&D or G&A guidance, and how should we think about the partnership strategy given the success of your lead program before and then also the early pipeline? Last quick question is the share buyback. You've been talking about this, and when should the investor expect you to give us some more clarity?

Yeah, so we have multiple things in our pipeline, and I mean this in a positive way. We are not prioritizing anything. We are pursuing everything because these are highly dearest targets. We have the financial bandwidth to pursue all of that. I tell people think of protagonists as if there are three companies under one roof, right? There is the royalty company, there is the I&I company, there is the metabolic company, that is the Heme Company, that sort of thing. And in terms of share buybacks, you know, we are looking forward to Rasputai's approval in Q3. And I think if that happens then cumulatively we'll be in a position of amazing strength and by the end of the year we should be in a position to announce a share buyback program. And ideally we would hope this is not like a one-time gig but rather a perennial activity depending on the revenue stream that continues from our two commercial drugs. And of course we'll fund our R&D on our own dime and we'll be capable of doing that up to clinical POC at least.

Excellent. Alright. Thank you Dinesh and thank you everyone.

Thank you my friend.