Welcome to the Protagonist Therapeutics IL-17 Oral Peptide Antagonist Development Candidate Nomination Conference Call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief question-and-answer session. As a reminder, this call is being recorded today, Thursday, November 21, 2024. I will now turn the call over to Dr. Corey Davis of LifeSci Advisors. Please go ahead. Thanks, Shamali. Hello, everyone. Thanks for joining us on our call today. Joining me from Protagonist are Dr. Dinesh Patel, President and CEO, Dr. Newman Yeilding, Chief Scientific Advisor, Dr. Samuel Saks, Clinical Development Advisor, and Dr. Ashok Bhandari, EVP, Chief Drug Discovery and Development Officer, and Asif Ali, CFO. Earlier today, Protagonist issued a press release announcing the formal nomination of an oral peptide IL-17 antagonist development candidate. A copy of this press release is available on the company's website. On slide number two, please note that on today's call, we'll be making forward-looking statements, including statements relating to the safety and efficacy and the therapeutic and commercial potential of our investigational product candidates. For further information relating to risks and uncertainties related to our business, please see the periodic reports we have filed with the SEC. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 21, 2024. Protagonist undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities law. With that, I will now turn the call over to Dinesh Patel. Thank you, Corey. Hi, everybody. We appreciate you all being on this call. I would start by highlighting on slide number three that Protagonist is focused exclusively on the discovery and development of peptide therapeutics. We have an innovative technology platform and very unique expertise and experience with peptides that has now led to two distinct assets that are in late stages of clinical development. Rusfertide is a first-in-class hepcidin mimetic partnered with Takeda Pharmaceuticals and is currently in a phase III study in polycythemia vera, and we look forward to sharing our results in the first quarter of next year. Icotrokinra, or ICO, is a first-in-class and only-in-class oral IL-23 receptor antagonist peptide, where earlier this week, we and our partner, Johnson & Johnson, or J&J, reported successful outcome from two separate phase III studies in psoriasis, confirming its potential as a best-in-class oral targeted therapy for psoriasis. With such multiple validations and a balance sheet that is now stronger than ever before, with cash runway extending at least up to the end of 2028, we can now afford to initiate multiple new oral peptide-based discovery programs in succession and also afford to keep full ownership of these programs for longer time periods, including up to clinical proof of concept and beyond. The specific objective of today's call is to share with you the selection of PN-881, a potential best-in-class oral IL-17 receptor antagonist peptide as a development candidate for the potential treatment of various immune-mediated skin diseases. A common theme with our oral approach, be it ICO or 881, is that we choose to work on biological targets that are strongly validated with blockbuster category of injectable drugs, thereby eliminating the biological rationale risk. Our strong differentiation usually comes from offering a unique oral peptide against such validated targets that will have the potential of being a best-in-class oral paradigm-shifting targeted therapy in those areas. So slide four lays out the general pros and cons of the two broad categories of drugs, namely small molecules and big biologics, which is what the pharmaceutical industry has most commonly worked on ever since its inception 50, 60 years ago. In general, small molecules are less potent but can be administered orally, whereas the antibodies are much more potent but are administered as injectables. With oral peptides, Protagonist is trying to combine the best of both worlds. That is, combining the amazing picomolar potency of antibodies and the convenience of the oral pill characteristics of small molecules in a single peptidic chemical entity. We have already done this successfully with the IL-23 blocker Icotrokinra and would now like to achieve the same with PN-881. On slide five, IL-17 is a clinically and commercially validated pathway with multiple successful parenterally administered drugs currently on the market for several immune-mediated conditions, including psoriasis, psoriatic arthritis, HS, and axial spondyloarthropathies. IL-17 inhibitors and IL-23 inhibitors are the two go-to treatment options for psoriasis and these other derm conditions. And together, they command the vast majority of market share. Fortunately for Protagonist, it has a highly differentiated presence in both of these areas. First, through the IL-23 blocker ICO in partnership with J&J, and now with the IL-17 blocker PN-881, which is fully owned by us. Recent reports estimate that IL-17 therapeutics sales could more than double by 2031 to 9.3 billion for psoriasis alone, and that other derm indications where IL-17 therapeutics are effective could offer an additional $8 billion opportunity. It is very important to stress that currently, there are no approved oral IL-17 antagonists on the market. So with PN-881, our new asset, it is an outcome of our expertise and experience with oral peptides, and it has the potential to be a best-in-class oral IL-17 antagonist. We have achieved the very ambitious target profile by having 881 match or exceed the potency of IL-17 antibody drugs and also by being able to block all three isoforms of IL-17, AA, AF, and FF. And this collectively could lead to optimal and durable efficacy through an oral pill. With this general introduction, now I would like to hand it over to Dr. Newman Yeilding, our full-time Chief Scientific Officer, to go over the IL-17 biology and share more details about the drug properties of PN-881. Newman. Thank you, Dinesh. If you go to slide six, thank you. This simplified schematic provides a high-level mechanistic overview of psoriasis and the successful identification of its key mediators. Over the last two decades, two targets have emerged as the key mediators of psoriasis: IL-23, which polarizes the immune response towards a Th17 phenotype, and then IL-17, which directly activates keratinocytes, resulting in their hyperproliferation and production of additional inflammatory cytokines, and on slide seven, you'll see that multiple injectable agents targeting IL-23 and IL-17 have transformed the care of psoriasis patients. Recent efforts to develop oral agents have largely focused on these same two key pathways targeting the IL-23 receptor or its downstream signaling cascade, in other words, TYK2, or by targeting IL-17. On slide eight, we designed PN-881 to block IL-17. There are two relevant isoforms of IL-17, A and F, shown here. The IL-17 receptor can be activated by either the homodimers IL-17 AA or FF or by the heterodimer AF. PN-881 neutralizes all three dimeric forms of IL-17 of the currently approved products: two, Cosentyx and Taltz, target IL-17A, thereby blocking two of the three dimeric forms, AA and AF, and the third, Bimzelx, targets both IL-17A and F, thereby blocking all three dimeric forms. This distinction turns out to be important, as shown in the BE RADIANT clinical trial, which showed higher levels of PASI 90 and PASI 100 responses at week 16 and 48 with Bimzelx as compared with Cosentyx, so these results demonstrate the additional benefit of blocking all three dimeric forms, and taking these data into account, we focused our efforts on creating a product that targets all three dimeric forms, much like Bimzelx. Moving to slide nine, creating oral inhibitors of IL-17 has proven challenging with many unsuccessful efforts to create small molecules. In our peptide approach in creating PN-881, we focused on peptides with high potency and a broad spectrum of activity for IL-17 isoforms. We selected peptides that were stable in the harsh conditions of the GI tract for oral delivery and with metabolic stability in serum after absorption. Final selection of our development candidate was based on in vivo pharmacology assessments, including in vivo PK and a number of animal models, in vivo PD, tissue distribution characteristics likely to achieve efficacy in dermatologic conditions, as well as efficacy assessments in a rat skin inflammation model. This slide shows the extensive data package supporting progression of PN-881, and we look forward to sharing these data in greater detail at future scientific meetings. For today, we'll focus on the highlighted data, namely the in vitro potency of PN-881 and a preclinical proof of concept study in an IL-23-induced skin inflammation rat model. In slide 10, this describes our in vitro assay and graphically illustrates the potency obtained in our labs for PN-881 in comparison to an oral small molecule analog and several approved IL-17 antibody drugs. PN-881 blocks all three dimeric forms of IL-17, but on this slide, we're showing its blocking activity only against the IL-17 AA homodimer. Shown on the left is an illustration of how we assess potency. HT-1080 fibroblasts stimulated with a combination of IL-17 and TNF alpha produce IL-6, and blocking IL-17 inhibits that IL-6 production. In the graph on the right, the orange curve shows that PN-881 maximally inhibited IL-6 production, which is shown on the Y axis at higher concentrations, which is shown on the X axis, while IL-6 production progressively increases at lower PN-881 concentrations, and these data were used to generate the IC50, or the concentration that inhibited 50% of IL-6 production and the IC90, or 90% inhibition. The blue curve shows Bimzelx in this same assay, showing that PN-881 has generally similar potency while being significantly more potent than Cosentyx, which is shown in the gray line, or what we believe is the DICE molecule, DC-806, or a close analog based on the DICE patent, which is shown in the black line. In slide 11, this is our money slide. It captures the potency profile of PN-881 against all three dimers, namely IL-17 AA, AF, and FF, and compares it to the potency obtained in our labs for the oral small molecule analog and several approved antibody drugs. You can see from these data that PN-881 has very good picomolar levels of potency against AA and double-digit nanomolar levels of potency against the AF and FF isoforms. In general, it compares well against the most potent approved antibody drug, Bimzelx, against all three dimeric forms. PN-881, as you can see, is two orders of magnitude more potent than Cosentyx in blocking IL-17 AA, and Cosentyx does not block the FF dimer. Our target is the best-in-class oral, and compared to the most recent oral IL-17 inhibitor in the clinic, DC-806, PN-881 is three orders of magnitude more potent with a broader spectrum in that it also blocks IL-17 FF. We hope to leverage this high potency to drive high levels of efficacy in the clinic. In slide 12, having summarized the in vitro potency of PN-881, here on slide 12, we're summarizing key in vivo preclinical studies. The pharmacology of 881 was evaluated very extensively in a variety of preclinical models with pharmacokinetics evaluated in mice, rats, dogs, and cynomolgus monkeys. In cynomolgus monkeys, PN-881 achieves high levels of systemic exposure, reaching concentrations in excess of 100 nanograms per milliliter after oral administration of 2.5 mg/ kg. As in vivo proof of concept of a pharmacodynamic effect or proof of activity, we challenged mice with a supraphysiologic dose of IL-17 and showed that oral administration of PN-881 inhibited the production of CXCL1, which is a downstream biomarker of IL-17 activity, thus demonstrating good pharmacodynamic effects. And based on valuable feedback from key opinion leaders and scientific advisors, we also have evaluated PN-881 concentrations in the skin and are glad to share that it achieves good skin penetration in mice and also in mini pigs, which have thicker skin and more akin to human skin. So to summarize these data, PN-881 achieves good systemic exposure, good PD effects, and good tissue distribution. And we look forward to sharing more details about each of these studies at future medical conferences. Moving to slide 13, finally, we evaluated PN-881 pharmacology in the same preclinical model of skin inflammation that we use for Icotrokinra. In this rat model, ear inflammation is induced by repeated intradermal injections of IL-23, which causes inflammation through IL-17 production, and ear thickness is measured over time. In the left panel, the orange line with the steepest increase shows the increase in ear thickness over four days with daily injections of IL-23, which is significantly higher than the black line, which shows the ear thickness changes after daily injections of vehicle, but no IL-23. The other colored lines show that rats dosed twice daily with PN-881 at doses from 160 mg down to 10 mg /kg had reduced ear thickness intermediate compared to IL-23 alone, demonstrating that PN-881 inhibits the inflammation induced by IL-23, and we can look at this in the right panel quantitatively, where we assessed this reduction showing that the change in ear thickness was statistically lower from baseline at day four at doses as low as 10 mg/kg. If you move to slide 14, encouraged by these results, we conducted additional experiments that are shown here, same model, lower doses, that demonstrate that PN-881 ameliorates skin inflammation in this same model at doses as low as 1 mg /kg BID. So the IL-23-induced inflammation in this model is ultimately driven by IL-17, which is potently inhibited by PN-881. Moving to slide 15, based on these very promising discovery in preclinical studies of PN-881, we've nominated this peptide as a development candidate and have initiated IND-enabling work, including manufacturing to support initiation of toxicology and early clinical development studies. I'd like to point out that we have already accelerated our tox program and are skipping the customary 28-day tox and are instead opting to move directly into a three-month tox program. This way, after completion of our phase I SAD/MAD study, we'll be well positioned to begin a 12-week proof of concept dose-ranging trial in patients with moderate to severe psoriasis, and based on the strong precedents from injectable antibody drugs, we believe that the results of this phase II study can be used to effectively gate our decisions about rapid expansion into other IL-17 mediated diseases, including psoriatic arthritis, hidradenitis suppurativa, and spondyloarthropathies, so with that overview of PN-881, I'll now hand it back over to Dinesh for concluding remarks. Thank you, Newman, for that excellent overview on the IL-17 blocker PN-881. Now, let me make a high-view, high-level comment on what's next in our promising pipeline, so clearly, as you can see on this slide number 16, the Protagonist team continues to demonstrate its expertise, experience, and dominance in the field of oral and injectable peptides. In the IL-23 program earlier this week, we shared the successful outcome from two phase III psoriasis studies with Icotrokinra, the only oral IL-23 receptor antagonist. I jokingly refer to this as an overnight success story that was only 10 years in the making. In the first quarter of next year, we look forward to the results from the phase II ulcerative colitis study and also to the initiation of the phase III psoriatic arthritis study by our pharmaceutical partner, J&J. While the phase III cross-trial comparison results already look favorable for ICO, in the second quarter, we anticipate getting preliminary results from the direct head-to-head comparison studies of Icotrokinra versus the oral small molecule TYK2 inhibitor, Sotyktu. Finally, in the second half of 2025, one can expect NDA filing of Icotrokinra for psoriasis. So this decade-long journey with IL-23 blockers has also provided us at Protagonist with very unique insights in the field of oral peptides that we are now successfully applying to multiple new programs, starting with PN-881. With 881, as Newman summarized, we have the potential for a best-in-class oral agent, and we anticipate initiating phase I clinical studies with this peptide in the fourth quarter of next year. Besides 881, we believe we are on track to announce an oral peptide agonist against a validated target in the obesity space in the second quarter of next year, and an oral hepcidin pathway-related ferroportin blocker in the fourth quarter of next year. Finally, while not an oral peptide, Rusfertide, a first-in-class once-weekly subcutaneous injectable hepcidin mimetic, is also an equally valuable asset in our pipeline that was partnered with Takeda earlier this year. The partnership is indeed going very strong, and we look forward to reporting the phase III VERIFY Polycythemia vera study results in the first quarter of next year, and assuming a positive outcome, an NDA filing by the end of 2025. So clearly, it is going to be a very, very busy 2025 for Protagonist, full of new and highly significant disclosures. And in a way, we have none other to thank than our outstanding team of highly talented and dedicated pool of about 120 employees. We are also ever so thankful to our pharma partners, our vendors, consultants, and advisors, and the investigators, and all the human volunteers who have participated in our clinical studies. So with this overview now, I would like to thank you all again for your participation on this call today and hand it back over to the operator. Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing these star keys. One moment, please, while we poll for a question. Our first question comes from the line of Brian Cheng with JP Morgan. Please proceed with your question. Hey, guys. Thanks for taking our questions this afternoon. Lots to digest, not just today, this week. And really congrats on the progress. Got a couple of questions from us. I guess one is, given the similarity to Bimzelx, how do you think about the differentiation of its clinical profile ultimately compared to Bimzelx? And as you kind of think through the potential risk of suicidal ideation that you see on a Bimzelx label, do you think your drug can improve on that specific risk? And then we have a follow-up. Thank you. Thanks, Brian. Much appreciated. If I got your question about the differentiation, right, I think just the focus on trying to be the best oral targeted therapy has been serving us very well. And we are going to be boring and repetitive in a very profound manner by just continuing with that slogan. So that was our approach with Icotrokinra, and that is also going to be our approach with PN-881. In terms of the ideation component that you see, and maybe Sam Saks will comment a bit more, but in talking to the KOLs, and this is the KOL feedback, it's like if at all anything, that's an overreaction, and there is almost nothing to it. Yeah. It's too early to predict, obviously, what a label would look like for this new agent and to what extent FDA will think about class effects of IL-17 inhibitors versus us being a unique oral agent. But as Dinesh said, and I would reinforce, the unique differentiation here is to be oral. And we actually think in some of the disease areas where IL-17 is effective in injectable form, there's actually less oral alternatives available than in psoriasis. And the marketing research that has been done by our partner in the context of IL-23 blocker Icotrokinra clearly suggests just a strong preference for an oral pill in the derm community. And this is something that is reinforced in our conversations with the KOLs as well. And then just maybe one last one is, as you work through your upcoming work with IL-17, and I mean, you just had a great experience with J&J, right? Do you think that you will ultimately need a partner to take this all the way to the finish line? What's your latest thinking on partnership on this specific asset? Yeah. As you know, Brian, we have always been open to all different possibilities that will be in the best interest of our stakeholders. But the beauty over here is we don't have to do anything in desperation. We have a great cash runway all the way, at least through 2028. And that doesn't even count the new potential milestones that we could be earning from both partnerships. So we can assure you and others that we'll be open to the idea of doing the right thing at the right time, but there is no desperation or urgency. Thank you. Our next question comes from the line of Roger Song with Jefferies. Please proceed with your question. Great. Add my congratulations to our second good news within a week. And thank you for taking the question. A couple of questions from us. Maybe the first one relates to the PK profile. I'm not sure if I missed that. So can you just elaborate on the potential PK profile in terms of the once daily or others? Then maybe a little bit descriptive around the CMAX and AUC will be very helpful. Thank you. Yeah. No, I think it's a great question, Roger. What I would say is that, I mean, we did do a little glimpse of what we see in cyno. That is very encouraging concentrations over 100 nanograms per mL at doses as low as 2.5 mg /kg, which kind of at an allometric scaling is equivalent to 50 mg daily dose in humans. So that is all super exciting. And roughly speaking, things are certainly guiding towards a once daily. But as you know, the real determination comes at the end of the day after you see the phase I clinical data in humans. Newman, would you like to add anything? I think you summarized it nicely. We're very impressed with the systemic levels of this particular peptide that we're seeing in animal models. We're very encouraged by the half-life that we're seeing. As Dinesh said, we think that that does open up the possibility, but until we see the once daily dosing, but until we see the data in humans, we don't want to overpromise and underdeliver. Got it. Yeah. Thank you. And then given today is the DC and then IL-17A, and then are you continuing to work on additional compounds as you know more about the property for oral peptide IL-17? Potentially, you can nominate additional DC before you move into the phase I. Thank you. As my wife would say, "Gee, we are barely enjoying the birth of our first child, and my mother-in-law is already inquiring about a second one." But jokes aside, right now, our high priority is on 881, obviously. But look, I mean, it's just very prudent for Big Pharma, as well as for Protagonist, to always have a plan B, always have a backup compound, and that has served us well. So yeah, that's a part and parcel of what we do behind the scenes. Sorry, Sam, go ahead. I was going to say, as we told you in the past, this was a bake-off between various choices that we had to elect this molecule. So we had choices, and that gives us the ability to have a backup molecule. Actually, that's a great point. I mean, in all honesty, for the last four months or so, we had been doing a very stringent compare and contrast of three potential candidates, and this is the winner by all measures. Got it. Yeah. We are enjoying multi-children family. So maybe just last one. In terms of the cash runway right now into 2028, can you just give some color how much the current and how many current operational plans are already embedded in this cash runway, and how much is related to the IL-17? Thank you. That's it. Again, a great question, and I'll pass it on to our CFO, Asif. Yeah. Hi, Roger. Thanks for the question. Yeah. I think all I can tell you is we've told you we've got four years of cash on hand. We've not disclosed our assumptions. But as Dinesh pointed out, if you look fully into our corporate deck, you'll see there is a vast magnitude of potential inflows that's not factored in. So I think while we're not disclosing the assumptions, it gives us the confidence of addressing needs as they arise, capital allocations. Yeah. And maybe what we can disclose in a qualitative sense, that certainly for PN-881, we have baked in all the preclinical three-month tox and clinical studies up to clinical POC. Correct. Got it. Thank you. Congrats again. Thanks, Roger. Sorry, we missed out on your conference, but now you know why. No worries. Good news. Thank you. Our next question comes from the line of Kripa Devarakonda with Truist Securities. Please proceed with your question. Hey, guys. Thank you so much for taking my question, and congrats once again for this week's success. I hope you guys made some time to celebrate. So the IL-17 has primarily approved in derm and rheum indications, and it looks like that's the planned direction for 881 as well. So I was wondering how you think this fits in with ICO opportunity, especially given you just saw really good positive data in psoriasis. Is there any way you can carve out a population where an oral IL-17 could become a preferred option based on what you know about the market? I mean, one of the things we learned from ACR that was held a few days ago is also that IL-23s are becoming not just injectables, but in general, targeting IL-23 is becoming more popular in psoriasis space. So I was wondering how you're thinking about the whole space. And then I have a follow-up question, maybe more about the platform. You talked about three molecules that were in the bake-off before you picked one. If you can talk about any lessons learned through the process of developing the last few oral drugs that helped you zone in on these three, that would be great. Thank you. Yeah. Maybe I'll ask the second question first. And yeah, it's definitely the very kind of close and tight bake-off amongst the three candidates. It really encourages us to take a deeper dive into extensive preclinical studies. I'm sure you must have noticed we did the mini pigs study evaluating skin concentrations in the mini pigs based on the directions we got from some of the psoriasis KOLs and things like that. But in terms of the lessons learned and that kind of thing. So that is something we have been slowly, steadily accumulating over the past 14 years. And with each new program, certainly there are new challenges, but definitely there are more efficiencies that get created in the new program versus the previous one. That much, we can certainly say with certainty. And as I mentioned before, I mean, there are two things. One is, of course, the core technology platform into which, by the way, we have started adding new tools as well. And of course, no surprise, AI is definitely another component that we are adding in our toolbox as a new tool. So we would like to stay at the cutting edge, but the best way to demonstrate that is to come up with real oral peptides and nominating them as development candidates. Now, getting to this kind of tug-of-war between IL-17 versus IL-23, as I mentioned in my prepared remarks, I think for Protagonist, it's like we have a presence in both areas. So that's our huge advantage. Of course, with I CO we have a partial ownership, but a very, very significant one. And of course, that's the most advanced asset. Whereas with 881, it is humble beginnings, but it is fully owned by us. And the antibody drugs are already doing the homework for us in a way in terms of which class of drugs is going to get what type of market share and prominence in different disease indications. So for example, HS and spondyloarthritis will belong to oral IL-17 antagonist or IL-17 antagonist in general, whereas IBD might be contraindicated, and that could belong dominantly to the IL-23 blockers. And psoriasis and psoriatic arthritis, time will tell. Maybe it's a coin flip. Yeah. Great. Thank you so much. Didn't you add anything? I just add one thing. So these are going to be the two dominant pathways in psoriasis for the foreseeable future. We've tried to understand how do dermatologists differentiate between the two. And one key differentiator is IL-17 has a more rapid onset of action. So if you have a patient who needs a rapid onset of action, then IL-17 is probably going to be preferred. IL-23s tend to be less frequently administered. So there are a number of things that distinguish the two in terms of the subcutaneous products. We'll have to. Yeah. We might be in a totally different territory with the oral component. So time will tell. Yeah. I would just remind you that J&J is going to be making all the commercial decisions for the IL-23 receptor inhibitor. So how they choose to commercialize that and move that forward, that's going to be all them. And as Dinesh said, this is the kind of market where ultimately, if we're successful after we've added value, we've proven concept generation, then we would seek large pharmas to help sell here because this requires DTC advertising, heavy marketing lift, all that sort of thing. If someone is going to go up against J&J, it's likely not going to be us, and that person's likely going to determine what that commercial strategy is and how to do it versus not only UCB, but J&J and everyone else in the combined space, including AbbVie, I guess I should say. Yeah. By the way, I mean, in summary, it's like the beauty is we have presence in both, a very distinct presence with the best oral targeted therapy in each category. And it's already evident that there are some areas of overlap, but at the same time, there are some areas of non-overlap. So I think net net, it's all very good for Protagonist. Great. Thank you. Thank you so much. Thank you. Our next question comes from the line of Tara Bancroft with TD Cowen. Please proceed with your question. This is Ken Okafor on for Tara Bancroft. I have a question here about dosing. I was wondering what kind of food effect do you anticipate with 881, and do you expect patients will need to avoid eating before and after taking 881, similar to what they had to do with 2113? It's a great question, and we will just have to see what we learn in the actual clinical studies. But the observation is a very good one because if you think about oral peptides in general, including the experience more recently with oral obesity agents, it kind of loosely points towards, "Hey, take the drug once daily with an empty stomach for 30 minutes," something like that. But time will tell. But again, it's not a showstopper, right? I mean, it's one of the easiest recipes to follow. Take your drug with an empty stomach and don't eat anything for 30 minutes. If you look at the EADV data that J&J just recently published, an IL-23 receptor inhibitor, patient satisfaction is great. So that method of administration that Dinesh just outlined is very well received by patients because it's at the bedside, as he said. You take it on the rising before you go anywhere else, and by the time you're ready to have your breakfast, you're okay, and there are no weird nuances like you have to lie flat in bed or anything like that, right? So it's simple. Okay. Thank you. Thank you. Our next question comes from the line of Julian Harrison with BTIG. Please proceed with your question. Hi. Congratulations on all the recent progress, including the first phase III data set of a Protagonist molecule earlier this week. First, I'm curious what in this upcoming phase I trial you are most interested in to tell you whether or not you're on the right track? And sorry if I missed it. On half-life, is your base case twice-a-day dosing for 881? In general, things are loosely pointing towards once daily. Actually, more than loosely, it's strongly pointing towards once-daily dosing. But as you very well know, the real finding will be when we conduct the phase I studies in healthy volunteers. That is what will enable us to sharpen our dosing regimen. It was the target product profile for the discovery group. The once daily. Yeah. Yes. Excellent. Thanks. That's very helpful. And then oral preference in psoriasis and psoriatic arthritis seems pretty well characterized already. I'm wondering if you have a good read on what fraction you expect oral preference to be in hidradenitis and axSpA. Yeah. I think we can admit that we don't have definitive semi-quantitative marketing research back material, things like that. These are still early days for our 881 asset. But the KOLs that we talk to, they don't just treat psoriasis. They treat all derm conditions. And they are clearly mentioning that, "Hey, don't ask us why necessarily." But it's like in our space, oral is strongly preferred. Yeah. As was mentioned earlier, the slice of this market is the rheumatology community, and that's a little bit different doctor population, and that will need to be addressed as well. Excellent. Very helpful. Thank you and congrats again. Thanks, Julian. Thank you. Our next question comes from the line of Douglas Tsao with H.C. Wainwright. Please proceed with your question. Hey, good afternoon, and Dinesh, congrats on all the progress. I guess maybe as a starting point, you noted in your comments specifically about dermatologists' sort of preference for oral agents, certainly over injectables. And so does that lead you to sort of focus on dermatology-focused indications for the IL-17 program initially? And then I guess the other question I have is when you mentioned sort of your position or sort of the strength of your balance sheet to take this further into proof of concept, how do you think about that versus finding a partner who may have a bias in terms of sort of input in terms of the strategic direction they want to take the asset potentially? Meaning that if you go one direction with your own proof of concept program, that might diminish somebody's interest because they would have preferred to go in a different direction at first. Thank you. Yeah. No, I think those are excellent considerations. And again, as I mentioned before, we will be very carefully evaluating all different options at any given time, and then we will do what is in the best interest of stakeholders as well as the program, as you are pointing out. Now, the good thing, though, is like as I also mentioned in my prepared remarks, we are working on those targets that have ample validation through both clinical and commercial validation, right? So this is a path that in a way has been well-traveled before us, but with injectables. But that kind of takes away the strategic suspense from our approach, meaning it's already known that with a new agent, with a new IL-17 blocker, you would do a psoriasis study first, get an understanding of the PK/PD, the biological effect, that kind of thing. And then that will give you a very nice translation into how to go after not just psoriasis, but with other indications. So we'll be tempted to follow that kind of recipe and that kind of approach over here. Sure. I'll make a couple of comments. Number one, I don't think that the oral preference is limited to psoriasis. I think it's across all indications. So I think that this strategy will be appropriate for all the IL-17-mediated diseases. The reason we chose psoriasis first is because that's how we can learn the quickest and develop this molecule the quickest. So that underpins most of our thinking as to why we're going into psoriasis first. It has the highest response rates. So other people with injectables have used it the same way we are as a target validation because you need to see very high response rates to be able to play in that pool. So it only takes a small number of patients to know what you've got. And I had mentioned that we will leverage the psoriasis data to gate rapid decisions about other indications. We think studying psoriasis is enabling for other indications as well. Of course, we get safety information, which we would think would largely extend. Thank you. Our next question comes from the line of Yun Zhong with Wedbush. Please proceed with your question. Hi. Yeah. Thank you very much for the questions, and congratulations on the progress. Maybe a follow-up question on indication selection. I hope it's not redundant. So I just want to confirm that it is possible that after phase, sorry, the next study in psoriasis, depending on the profile, you might make a decision to switch to a different indication if you deem it to be more appropriate. I think given that there is going to be probably IL-23 oral for psoriasis, and I think Sam talked about this advantage of 23 inhibition versus 17 inhibition in psoriasis. Yeah. No, absolutely. The idea would be that once we get the signal that we want to achieve in psoriasis, then as Newman mentioned before, we would be very tempted to trigger multiple studies in all the relevant indications, meaning HS and spondyloarthritis in particular. As you know, we don't have cash constraints. So that's a wonderful thing. And of course, we have all the resources, and our employees are used to working very, very hard anyway. Okay. Then another question on the partnership. So your existing partnership with J&J, does it provide J&J with any advantage when it comes to partnership discussion for this IL-17 oral program? Well, the way I would answer this question is IL-17 is fully owned by us, and none of our partners, whether J&J or Takeda, has any privileged rights to IL-17. Okay. Great. Yeah. Thank you very much. Thank you. Our next question comes from the line of Catherine Okoukoni with Citizens JMP. Please proceed with your question. Hi. This is Catherine on for John. I just have a quick question about potentially any benefits and safety that you might expect to see with your candidate relative to kind of what's out there given the potency. Is that kind of, yeah, I guess that's just my question, on any safety advantages you might expect? Yeah. I think clearly when we were creating the target product profile, what we want to achieve was combine the best of both worlds, meaning try to grasp the extraordinary potency of the best antibody that is out there, and that is Bimzelx, which has amazing potency, not just against IL-17A/F dimer, but also against the AF and FF dimers, and we believe we have achieved that with 881 in our product profile. Now, how this translates to its own unique advantages as an oral agent, that is something we will learn over a period of time, but I mean, to make it very clear, and you are pointing out a good thing, this is about as good as it could get with an oral agent, and our team has been able to achieve that. Sorry, Sam. Go ahead. When you add the F activity to the A activity, what's been known clinically is you get a small increase in the rate of oral candidiasis, or it's called thrush, which can be easily treated. The KOLs don't think it's a big deal, but that is one thing you get a little bit more of when you add the F activity. Could our product have a little bit less of that? It's possible, but it's way too early to say that. But we have no reason to believe it would have any more of that than other agents like Bimzelx that have the F activity. I think that's a great point because by virtue of being an oral agent, right, unlike injectables, where there is a huge high-concentration bolus injection on day one, we don't go through that. We go through very steady-state dosing and exposure of our drug. But too early to say. Thank you so much. Thank you. Thank you. We have reached the end of the question-and-answer session. I would like to turn the floor back to CEO Dinesh Patel for closing remarks. Yeah. No, again, thank you, everybody, for participating. As you can tell, this has been a great day, actually a great week for the Protagonist team. And we are at a very promising and powerful junction, and thank you all for your support to Protagonist today and in the future. And we will try to do justice to our assets over the coming months and years. Thank you. And this concludes today's conference, and you may disconnect your lines at this time.