Welcome to the Viking Therapeutics 52-week phase IIb VOYAGE Study Histology Results Conference Call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press the star key followed by one on your touchtone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this conference call is being recorded today, June 4, 2024. I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz. Please go ahead, Stephanie. Hello, and thank you all for participating in today's call. Joining me today is Brian Lian, Viking's President and CEO, Marianne Mancini, the company's Chief Operating Officer, and Greg Zante, Viking's Chief Financial Officer. Before we begin, I'd like to caution that comments made during this conference call, today, June 4th, 2024, will contain forward-looking statements under the Safe Harbor Provisions of the US Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, timelines and milestones. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely, and reported results should not be considered as an indication of future performance. These forward-looking statements speak only as of today's date, and the company undertakes no obligation to revise or update any statement made today. I encourage you to review all of the company's filings with the SEC concerning these and other matters. I'll now turn the call over to Brian Lian for his initial comments. Thanks, Stephanie, and good morning to everyone joining us on the call. Earlier this morning, we issued a press release announcing the 52-week histology results from Viking's phase IIb VOYAGE trial, evaluating VK2809, our novel liver-selective thyroid hormone receptor beta agonist in patients with biopsy-confirmed Non-Alcoholic Steatohepatitis, or NASH, more recently referred to as Metabolic Dysfunction-associated Steatohepatitis, or MASH. We are excited to share with you on this call an overview of the histologic and other data collected following 52 weeks of treatment with VK2809. Following my prepared comments, we'll open the line for questions. Before we get into the details, I'd like to remind everyone that we have only recently received these data. We believe that we have enough information to report on the study's success on the histologic endpoints, but we have not yet had time to rigorously evaluate every line item in the data. This was a large data set, and we are still in the process of receiving, reviewing, and evaluating all of the results and sub-analyses generated during the course of the study. We'll provide additional updates moving forward as warranted. We also plan to submit the results for presentation at future medical meetings, so we may wish to reserve certain details until those presentations. As a reminder, VK2809 is an orally available tissue and receptor subtype selective agonist of the thyroid hormone receptor that possesses cell activity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of metabolic disorders. In a prior 12-week phase IIa trial in patients with non-alcoholic fatty liver disease, VK2809 successfully achieved both its primary and secondary endpoints, demonstrating statistically significant reductions in liver fat and plasma lipids. In that study, cohorts treated with VK2809 experienced up to 60% median relative reductions in liver fat content, and the majority of patients receiving VK2809 experienced at least a 30% relative reduction in liver fat. Patients also demonstrated reductions in plasma lipids, including LDL cholesterol, triglycerides, and atherogenic proteins, all of which have been correlated with increased cardiovascular risk. No serious adverse events were reported through 12 weeks of treatment, and VK2809 was well tolerated, demonstrating no differences with respect to placebo on GI measures such as nausea and diarrhea. Based in part on these impressive data, the company initiated a 52-week phase IIb trial called VOYAGE to evaluate VK2809 in patients with biopsy-confirmed NASH and fibrosis. The VOYAGE study was a randomized, double-blind, placebo-controlled, multi-center international trial designed to assess the efficacy, safety, and tolerability of VK2809 in this setting. Enrollment included patients with at least 8% liver fat content, as measured by MRI-PDFF, as well as F2 and F3 fibrosis. The study allowed for up to 25% of enrolled patients to have F1 fibrosis, provided that they also possessed at least one additional risk factor, such as diabetes, obesity, or hypertension. The primary endpoint of the VOYAGE study, for which we reported positive results in May of last year, evaluated the change in liver fat content from baseline to week 12 in patients treated with VK2809, as compared to patients receiving placebo. Secondary endpoints, which we are reporting here today, included an evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment. Today, we're pleased to report that the study successfully achieved these secondary endpoints, with patients receiving VK2809 experiencing clinically and statistically significant improvements in NASH resolution rate, fibrosis stage, and the combined endpoint of NASH resolution and fibrosis improvement. On the secondary endpoint of NASH resolution without worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution rates ranging from 63%-75%, compared with 29% for placebo. Across the combined VK2809 treatment groups, 69% achieved NASH resolution without worsening of fibrosis. Resolution of NASH was defined as a Nonalcoholic Fatty Liver Disease Activity Score, or NAS, of zero or one for inflammation and zero for ballooning. On the secondary endpoint, evaluating the proportion of patients demonstrating at least a one-stage improvement in fibrosis with no worsening of NASH, the proportion of VK2809-treated patients demonstrating improvements in fibrosis ranged from 44% to 57%, compared with 34% for placebo. Across the combined VK2809 treatment groups, 51% achieved at least a one-stage improvement in fibrosis with no worsening of NASH. Improvement in fibrosis without worsening of NASH was defined as a greater than or equal to one-stage improvement in fibrosis and no increase in NAS for ballooning, inflammation, or steatosis. On the secondary endpoint, evaluating the proportion of patients experiencing both the resolution of NASH and at least a one-point improvement of fibrosis, the proportion of VK2809-treated patients achieving both measures ranged from 40% to 50%, compared with 20% for placebo. Across the combined VK2809 treatment groups, 44% achieved this endpoint. Study results were consistent under various sensitivity analyses. Effect sizes, odds ratios, and P values compared with placebo improved under an imputation analysis incorporating median values for missing data. A more conservative sensitivity analysis, which categorized patients with missing data as non-responders, produced similar statistical outcomes. These analyses demonstrate the robustness of the efficacy signal observed in this study. Additional analyses evaluated liver fat, plasma lipids, and safety and tolerability after 52 weeks of treatment. As reported last year, patients receiving VK2809 demonstrated statistically significant reductions in liver fat at week 12, which was the primary endpoint in this study. At week 52, patients receiving VK2809 continued to demonstrate reductions in liver fat content, with the mean relative reductions from baseline ranging from 37%-55%. The response rate in this study, defined as the proportion of patients experiencing at least a 30% relative reduction in liver fat, ranged from 64%-88%, with all treatment groups demonstrating statistically significant improvement compared with placebo. In addition, across all treatment arms, 54% of VK2809-treated patients experienced at least a 50% reduction in liver fat. These results, in conjunction with the improvements in histology observed in this study, support the concept of lipotoxicity as an important driver of disease. With respect to plasma lipids, consistent with prior studies, patients receiving VK2809 demonstrated placebo-adjusted reductions in LDL cholesterol ranging from 20%-25%, as well as reductions in triglycerides and atherogenic proteins such as apolipoprotein B, lipoprotein(a), and apolipoprotein C-III, all of which have been correlated with cardiovascular risk. These results align with prior data demonstrating that VK2809 may offer a cardioprotective benefit through its robust reduction in plasma lipids. Turning to safety and tolerability, VK2809 demonstrated an encouraging profile through 52 weeks of treatment, with minimal differences compared with the previously reported results from 12 weeks. The majority, 94%, of treatment-related adverse events among patients receiving VK2809 were reported as mild or moderate. Discontinuations due to adverse events were low and balanced among placebo and treatment arms. As we reported in the top-line data last year, one treatment-related serious adverse event was reported in a patient receiving VK2809. A patient with a history of psychiatric disorders reported a worsening of their symptoms. As in all prior studies, and at the 12-week time point in this study, VK2809 demonstrated excellent gastrointestinal tolerability through 52 weeks of treatment, with similar rates of nausea, diarrhea, stool frequency, and vomiting among VK2809-treated patients as compared to placebo. At the 52-week time point, plasma levels of Alanine aminotransferase, or ALT, and Aspartate aminotransferase, or AST, were reduced in every treatment arm receiving VK2809 compared with patients receiving placebo, though not all treatment arms achieved statistically significant improvement versus placebo. Levels of thyroid hormones, such as thyroid-stimulating hormone, free thyroxine, and free triiodothyronine, were relatively unchanged among VK2809-treated patients compared to patients receiving placebo. Changes in vital signs, including blood pressure, heart rate, and body weight, were similar among patients receiving VK2809 as compared to patients receiving placebo. In conclusion, we're very happy to report a successful VOYAGE trial outcome today. We believe these data clearly demonstrate VK2809's best-in-class efficacy on both NASH resolution and fibrosis improvement, along with the potential for cardiovascular benefit through improvement in plasma lipids. VK2809 has also demonstrated a consistent and very encouraging safety and tolerability profile, which we believe bodes well for longer-term treatment. Finally, I want to thank our clinical team, our CRO, and the patients and investigators who participated in the VOYAGE study. This trial took a long time to complete. It ran through the pandemic and was exceptionally difficult to execute. It's a real credit to our outstanding clinical operations team that it was ultimately such a success. So a big thank you to the team here at Viking. As I mentioned in my opening comments, we plan to submit the results for presentation at a future medical meeting. Thanks very much for joining us today, and I'll stop here for questions. Thank you. If you would like to ask a question, please press star then one on your telephone keypad. If you are using a speakerphone, we ask that you please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Today's first question comes from Steve Seedhouse with Raymond James. Please go ahead. Good morning. Thanks so much for taking the question. Congratulations on the call results here. I just wanted to follow up on safety, given some of the warnings in the Rezdiffra label, since the mechanism is shared there. Can you just comment if any signals for hepatotoxicity or gallbladder toxicity were seen? And then another question on the data, just thinking about the placebo response rates are really the response rates across the whole study. Do you happen to know already, Brian, the baseline NAFLD Activity Score, was it lower than you might expect for a phase III, for instance? Thanks. Yeah, thanks, Steve. On the hepatotoxicity and, other liver-related safety issues, there were no, signals that I'm aware of. We have, Joel Neutel, our medical monitor, on as well. Joel, do you have any additional comment on that? Yeah, no, I think that's an important question, and, and, and there were really no signals at all. As you heard from Brian, the ALT and AST levels were actually a little lower at the end of the 52-week period than they were at baseline, and there were no evidence of any cholestatic or any other gallbladder disease throughout the 52 weeks. So extremely well tolerated from a liver toxicity point of view. Steve, what was your second question? Just baseline NAFLD Activity Score. Oh, yeah. Was it, was it in the fours? Was it five? Was it six? Just curious what that was. Yeah. I want to say, that was in our posters from AASLD. I forgot to look it up here. We have it. I think it was about 5.3, but, I'll have to come back to you on that. Okay, thanks for reminding. And then just lastly, strategically, it just seems like given the questions around, you know, around IP on this asset and, and, you know, years to market here with a leader already on the market being prescribed and all the developments in the incretin space, combination with this and your VK2735 would just seem like checkmate for everyone else in the oral development space in NASH. So what are your thoughts on that? I mean, is this something you're going to talk to FDA about a development path for a combination? It seems like you've sort of de-emphasized that maybe at times, but I'm curious now, given these data, what you think about that combo. Thanks. Yeah, thanks, Steve. Yeah, the data are really, really excellent. We have done some work on co-formulation with VK2735. I think it looks encouraging, but we haven't disclosed any data there. I think the plan now is to just meet with the FDA and receive feedback on phase III trial designs and really what's required for approval today, and then make decisions from there. Yeah. Thanks a lot. Congrats. Thanks, Steve. Thank you. Our next question today comes from Joon Lee with Truist Securities. Please go ahead. Good morning. This is Ahsan for Joon. Thanks for taking the questions, and congrats on the data. Now that you have, you know, positive data, what next steps do you have planned for the program? And then if I can throw in a question on 2735, just curious, when do you think we might get phase II VENTURE PK/PD data and additional data from the oral formulation? Thank you. Yeah, thanks. So the next steps with the VOYAGE data, as I mentioned to Steve, we plan to schedule an end-of-phase II meeting, likely in the second half of the year, just to understand current thinking on trial designs as well as approvable endpoints, and then proceed from there. With the VK2735, we do not have the VENTURE PK data. That's expected imminently. Thank you. Yeah, thanks. Thank you. And our next question today comes from Thomas Smith with Leerink Partners. Please go ahead. Hi, this is Natsuhiko Masuda on for Thomas Smith. Congrats on the readout. A couple of questions from us. So first, focusing on the histology read, do you believe the lack of dose response is due to small number of subjects in the 1 mg QD arm? Yeah, it's a good point. The really, the 1 mg arm was a very small arm. As we mentioned in the prior call, that was originally intended as a half-size cohort to understand the minimally effective dose, and then in the trial, we reduced it further to accelerate completion of the study. And so every person in there, you know, every response to a single person is about 7%. So you get two people responding, you really boost the response rates there. So I think that's a little bit of artificial enhancement there on that 1 mg dose. When you look at the 2.5 and the five up to the 10, you do see a dose response there, and I think that's probably the more reliable portion of the data to look at. Got it. And based on this information, what's your current thinking on dose selection for the phase III development, given that only the 5 mg and 10 mg QOD arm shows that six on dose fibrosis and NASH resolution? Well, they're pretty small ends, and so to show statistical significance at all on fibrosis is pretty encouraging. We haven't made decisions yet on dose selection. We'll do that once we get some feedback from the FDA. Got it. Last question is: Do you continue to expect to conduct a phase III program with a partner? Well, we've always said that the best outcome for phase III with this program is to have a larger partner involved for execution of a phase III trial. But we need to speak with the FDA in an end of phase II meeting and then make the decisions following that meeting. That's very helpful. Thank you so much. Thanks. Thank you. And our next question today comes from Annabel Samimy with Stifel. Please go ahead. Hi. Thanks for taking my questions, and congratulations on the data. Just following up on the doses. Now that you've seen all the data for the various doses, have you given any additional thought to, I guess the practical benefits of QOD versus QD? Sometimes it's easier to remember daily. So can you just remind us how you chose the every other day type of regimen, and is that something that you still are thinking of definitely taking forward? And then just a quick question on the placebo response. It seemed much higher than what we've seen in some other trials. Was that a factor of the F1 patients you included, or just can you speak to that a little bit, and why we might have seen a placebo response in the 20s, as opposed to, say, single digits or the teens? Thanks. Yeah, thanks, Annabel. With the QOD dosing, there's no issue with compliance. This is administered in a blister pack, so we don't have any concerns that people would forget a dose. It's just that every day you're taking something, one day it's inactive, one day it's a placebo, so there's not an issue there. With respect to the placebo response, it was a little bit higher, but you know, in NASH trials, the populations are pretty heterogeneous, the datasets are fairly heterogeneous, and the placebo response rates are highly variable. I think that the delta versus placebo being statistically significant across the board on the histology endpoints is very encouraging. Okay, great. And then, I guess one other question, and now I know that you haven't really discussed it with the FDA yet, but, are you thinking of taking multiple doses forward in a phase III, or are you sort of fixated on just the most effective dose? Yeah, it's a good question. We haven't decided. It might make sense to take two doses into phase III, but we really haven't decided yet. Okay. All right. Thank you very much. Thanks, Annabelle. Thank you. Our next question today comes from Roger Song with Jefferies. Please go ahead. Great. Thanks, congrats for the data. Quick questions from us. Maybe, to, Brian, if you can talk about the key differentiation for your drug versus the others in the same class, because we're seeing liver fat, lipids, and then how would that inform your end of phase II meeting with the FDA? Because you talk about the study design, primary endpoint, maybe some of, some of the secondary endpoint can be also differentiated. Just try to understand the strategic, strategic kind of decision here more forward this drug. Thank you. Yeah, thanks, Roger. Yeah, so the thyroid activation mechanism is really an attractive mechanism because the thyroid beta receptor is primarily expressed in the liver, and that's the tissue of greatest interest in this disease. Our drug is highly differentiated from any drug in development for NASH because it's a prodrug that is preferentially cleaved within the liver. So you get a truly chemically targeted delivery of the therapeutic agent into the liver, and there is no other agent that has that profile in development today. It is a phosphonic acid when it is released from the prodrug, and because of that, it is highly unlikely to penetrate other tissues through passive diffusion. It's also not a substrate for the active transporter mechanisms that are responsible for the uptake of thyroid hormone. So it doesn't penetrate into peripheral tissues well, but when it recirculates to the hepatocyte, it is actively transported back to the hepatocyte. So it has a number of different characteristics that make it exquisitely targeted to the liver. The mechanism is really attractive for this population, because the thyroid beta receptor plays this key regulatory function in moderating plasma lipids. So what we've seen in all of our studies is a reduction in LDL and triglycerides and ApoB and Lp(a) and ApoC-III. In this population, many of these patients have some form of dyslipidemia, and having a pan-lipid-lowering effect is a really attractive feature for something like this. Yeah, thanks. Maybe just a comment on the phase III design, how you will be able to kind of incorporate all those kind of differentiations into the phase III. And then as you discuss with your potential partners, is that kind of a really attractive from the pharma perspective as well? Thank you. Yeah. No, thanks. It's a little premature to talk about trial design because we haven't yet had our end of phase II meeting. We know what the guidance stipulates on patient characteristics, but it'd be useful to hear from FDA what the current thinking is on endpoints and approval requirements. We do think the impact on plasma lipids is a very valuable characteristic because it should augment an outcome signal, which is required for full approval of all of these agents. Excellent. Thank you, Brad. Thanks, Roger. Thank you. And ladies and gentlemen, as a reminder, if you'd like to ask a question, please press Star then One at this time. Today's next question comes from Andy Tsai with William Blair. Please go ahead. Okay, congratulations on the data, and thanks for taking our questions. So, one question, maybe about the dose. This has to do with how much leeway from a regulatory perspective, do you think the FDA will allow? So, I guess the basis of the question is basically learning from incretins, right? So, usually you uptitrate. I'm curious if that could potentially be incorporated in a phase III, just given the very, very benign safety profile and, you know, the potential to extract a little bit more efficacy there. Yeah. Thanks, Andy. It's a great question. Generally, the phase III trials, you know, are based on the dose exploration in the phase IIb study or a prior study. I don't think at this point we would pursue a further uptitration, though, to your point, given the tolerability and safety profile, it seems like it could be achieved without an incremental risk to safety or tolerability. But at this point, I think we've got very promising efficacy at the current doses, and those will be the doses we'll discuss with the FDA. Great. Great. And going back to Annabel's question about histology, looking at Madrigal's paper back in 2018, the phase II results, I think they required a two-point reduction in NAS. So I'm curious your view on potentially that requirement in reducing their placebo rate versus your definition and the placebo rates, kind of how you think about, you know, various different definitions and its contribution to the placebo rate. Yeah. Thanks, Andy. That's a good point. When you apply the two-point NAS, you do see a reduction in the placebo rate. And we haven't looked at all of those permutations, but typically, when we look at that, and we haven't looked at all of them, but when we do look at that, the placebo drops, the delta increases, and the response among the treated arms increases, so it further enhances the delta. But again, we haven't looked at every permutation, but it helps the spread for sure. Got it. And then last question, do you mind reminding me your ultimate enrollment percentage for the F1 fibrosis? And I realize that you haven't really looked at details of the subgroups, but I would be very curious to know if there's any sort of directional difference between the F1 and the F2-3 population. Yeah. Thanks, Andy. So the trial was designed to target, 75%, at least 75% F2 and F3 and up to 25% F1, and that is, pretty much how it distributed. There may have been just over 25% F1s, but it was right in that range. We have, we had two posters, at the AASLD conference. I'm sorry, one poster at the AASLD conference in November, where we looked at the subpopulations, with and without type two diabetes and, F2, F3, versus F1, I think F2 versus F3 as well. And, you really didn't see a difference in, in efficacy when you went to diabetics versus non-diabetics or, severity of fibrosis. So the mechanism seemed to hold across the spectrum of severity, at least, from what we could see. Great. That's helpful. Congratulations again, and thanks for taking our questions. Thanks a lot, Andy. Thank you. Our next question today comes from Yale Jen with Laidlaw & Company. Please go ahead. Good morning, and my congrats on the great data. Just two questions here. The first one is on safety, particularly on the GI side, that it seems from absolute number, percentage perspective, that the treatment actually has lower than the placebo. How would you attribute that, and what do you think, whether that's something to be differentiated from other drugs or developments currently in place? Yeah. Thanks, Yale. It's true, the placebo rate was higher than the treatment rate, but I think on GI overall and nausea as well, I think the way we interpret that is that we're no different from placebo. I don't think there's any GI activity for the agent, so I don't think it helps with GI. It just is very benign on GI. Okay, great. Maybe just one more question here, which is that you mentioned the higher SO readout value of placebo, maybe due to the patient differences. Could you drive a level down deeper in terms of the specifics of the patient breakups, base breakups, versus maybe the approved drug or other development in place to see the differences? And thanks. Sorry, Yale, I don't think I followed everything there. Can you repeat the question? Yeah, I'm sorry. In terms of the patient makeup, that leads to the potential higher absolute value of the placebo vs. the treatment groups. Could you give us a little bit more color in terms of the patient breakdown, so potentially as a potential reason to have that readout versus comparisons? Oh, yeah. Well, when we look at the study demographics, we were pretty well balanced across the board. Average age was, you know, 52-53. It was more women than men, about 60/40. Mostly whites, about a third Hispanic. BMIs were pretty well balanced, so there's not an obvious factor you can point to. And the NAS was pretty evenly distributed as well. And Steve asked that earlier. I think we're about 5.5, 5.3, something like that, on average NAS. But so there's nothing that is obvious there that would, you know, indicate a difference in treatment arms. I just think when you look across NASH studies, there is some volatility to the placebo response rates, and and we happen to see it here as well. But, the more important thing is we see statistically significant and large differences between the placebo and treatment arms in a relatively modest-sized trial. Okay, great. That's very helpful. Again, congrats. Thanks, Yale. Thank you. And our next question today comes from Jay Olson at Oppenheimer. Please go ahead. Oh, hey, congrats on these results, and thanks for providing the update. Can you talk about any initial thoughts on how you might segment the target NASH population? For example, would you conduct a study in NASH patients with F4 fibrosis or patients with F2, F3 fibrosis and cardiovascular risk factors? Yeah, thanks, Jay. Based on the fibrotic benefit, you know, I think it should be effective or beneficial across a range of fibrosis stages. I don't know, though, that we would necessarily target the cirrhotic population. The F2 and F3 population is the population of greatest interest in the setting, so that would be probably the area to focus on. As far as patients with lipid dysregulation, something we haven't really gotten into as far as design details at this point. We'll wait for feedback from the FDA at the end of phase II meeting to really make those decisions. Okay, thank you. And then, can you talk about the most common AEs that led to treatment discontinuation, and maybe especially in the, the 10 mg QOD group, where it seems like there's a little bit more discontinuation? Yeah. The discontinuations were pretty well balanced. Discontinuations due to an adverse event were actually higher in the placebo than in the 10 mg arm and in the total number total combined arms as well. So more AEs leading to dropout amongst placebo than active arms. As far as the AEs that led to discontinuation, minimal differences here, so we didn't really focus on those. I'd say headache and... Headache was a common one. Fatigue also was a common AE. No difference in treated versus placebo, but fatigue was a common AE reported in the study. But neither of those are what we would consider problematic adverse events, and there was no difference between treated and placebo. Okay, great. And, maybe one last question: Is it possible to design a phase III study that could use a non-invasive primary endpoint, and is that something you plan to discuss with the FDA? Yeah. Thanks, Jay. Yeah, it's we don't know if it's possible. The guidance currently requires a biopsy. If there were a way to incorporate a panel of non-invasive tests and do a biopsy in a subset, that would be of interest to us. That doesn't seem like an unreasonable approach, but again, we don't know because the guidance currently stipulates that everybody needs a biopsy. Great. Thank you, Brian. Congrats again on the results. Yeah, thanks a lot, Jay. Thank you. Ladies and gentlemen, this concludes our question and answer session. I'd like to turn the conference back over to the management team for any closing remarks. Thank you, everyone, for joining us today, and thank you for your continued support of Viking Therapeutics. With that, we'll end the call. Have a great day. Thank you, ma'am. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.