Viking Therapeutics, Inc. (VKTX) Earnings Call Transcript & Summary

Welcome to the Viking Therapeutics 52-week Phase IIb VOYAGE study Histology Results Conference Call. [Operator Instructions] 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 4, 2024, will contain forward-looking statements under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, time lines 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 nonalcoholic steatohepatitis or NASH, more recently referred to as metabolic dysfunction associated steatohepatitis for 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-analysis 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 selectivity 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 nonalcoholic 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, multicenter 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 possess 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 include 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% to 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 0 or 1 for inflammation and 0 for ballooning. On the secondary endpoint evaluating the proportion of patients demonstrating at least a 1-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 1-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 1 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 1-point improvement of fibrosis. The proportion of VK2809-treated patients achieving both measures range 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 analysis. 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 nonresponders produce similar statistical outcomes. These analyses demonstrate the robustness of the efficacy signal observed in this study. Additional analysis 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 continue to demonstrate reductions in liver fat content with the mean relative reductions from baseline ranging from 37% to 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% to 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% to 25% as well as reductions in triglycerides and atherogenic proteins such as apolipoprotein B, lipoprotein A and apolipoprotein C3, all of which have been correlated with cardiovascular risk. These results align with prior data demonstrating that VK2809 may offer a cardioprotected 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. Patients 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.

[Operator Instructions] Today's first question comes from Steven Seedhouse with Raymond James.

Congratulations on the good results here. I just wanted to follow up on safety. Given some of the warnings and there was different label since the mechanism is shared there. Can you just comment if any signals for hepatotoxicity or gall bladder toxicity we're seeing? And then another question on the beta, just thinking about the placebo response rates or really the response rates across the whole study. Do you happen to know already, Brian, the baseline NAFLD activity score was lower than you might expect for a Phase III, for instance?

Yes. Thanks, Steve. On hepatotoxicity and other liver-related safety issues, there were no signals that I'm aware, we have Joel Neutel, our medical monitor on as well. Joel, do you have any additional comment on that?

No, I think that's an important question. 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 and they were at baseline, and there were no evidence of any cholestatic or any other gall bladder disease throughout the 52 weeks. So extremely well tolerated from a liver toxicity point of view.

Steve, what was your second question?

Baseline NAFLD activity score, was it in 4, was it 5? Was it 6? Just curious what that was?

Yes, I want to say that, that was in our posters from AASLD, I forgot to look it up here. We have I think it was about 5.3, but I'll have to come back to you on that.

Okay. And then just lastly, strategically, it just seems like given the questions around IP on this asset and years to market here with a leader or already on the market being prescribed and all the developments in the incretin space, combination with this and your GLP/GIP-2735 would just seem like CheckMate for everyone else in the world, development space in NASH. So what are your thoughts on that? I mean, is this something you're going to talk to FDA about the development path for a combination? It seems like you've sort of deemphasized that maybe at times. But I'm curious now given these data, what you think about that combo?

Yes. Thanks, Steve. The data are 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.

Congrats.

And our next question today comes from Joon Lee with Truist Securities.

This is Austin on for Joon. Congrats on the data. Now that you have 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?

Yes. Thanks. So the next steps with the VOYAGE data, as I mentioned to Steve, we plan to schedule an end 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.

And our next question today comes from Thomas Smith with Leerink Partners.

This is [indiscernible] on for Tom Smith. Congrats on the readout. A couple of questions from us. So first, focusing on the histology REIT. Do you believe the lack of dose response is due to a small number of subjects in the 1 mg QD arm?

Yes, it's a good point. There 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, every response, a single person is about 7%. So you get 2 people responding, you really boost the response rates there. So I think that's a little bit of artificial enhancement there in that 1 mg dose. When you look at the 2.5 and the 5 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 arms show that fixed on the 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 the 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.

And our next question today comes from Annabel Samimy with Stifel.

Congratulations on data. On the doses, now you've seen all the data for the various doses. You have given any additional thought to I guess, the practical benefits of QD 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. You seem 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 to say single digits for the teens.

Yes. 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 1 day, it's an active, 1 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 in NASH trials, the populations are pretty heterogeneous. The data sets are fairly heterogeneous and the placebo response rates are highly variable. I think the delta versus placebo being statistically significant across the board on the histology end points is very encouraging.

Okay. Great. And then I guess, one other question. And I know that you haven't really discussed it with the FDA yet, but are you thinking of taking multiple doses forward in the Phase III? Are you still -- are you sort of succeeded on just the most hyper dose?

Yes, it's a good question. We haven't decided it might make sense to take 2 doses into Phase III, but we really haven't decided yet.

And our next question today comes from Roger Song with Jefferies.

Great. Congrats for the data. Quick questions from us. Maybe 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 in the Phase II meeting with the FDA because you talk about the study design, primary endpoint maybe some of the secondary endpoint can be also differentiated. Just trying to understand the strategic kind of decisions here move forward this...

Yes. Thanks, Roger. Yes. 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 hepatocytes. 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 it plays this key regulatory function in moderating plasma lipids. So what we've seen in all of our studies is reduction in LDL and triglycerides in ApoB and Lp(a) and ApoC-III. And 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.

Maybe just a comment on the Phase III design, how you will be able to kind of incorporate all those kind of differentiation into the Phase III? And then as you discuss with your potential partners, is that kind of really attractive from the former perspective as well.

Yes. 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 would 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 these agents.

[Operator Instructions] Today's next question comes from Andy Hsieh with William Blair.

Okay. Congratulations on the data. 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 increase, right? So usually, you up titrate. So I'm curious if that could potentially be incorporated in a Phase III just given the very, very benign safety profile and the potential to extract a little bit more efficacy there?

Yes. Thanks, Andy. It's a great question. Generally, the Phase III trials 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 further up titration 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 on Annabel's question about histology. Looking at [indiscernible] back in 2018, the Phase II base results, I think they required a 2-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 various different definitions and its contribution to the placebo rate?

Yes. Thanks, Andy. It's a good point. When you apply the 2-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, we haven't looked at all -- when we do look at the placebo drops, the delta increases and the response among the treated arms increases that 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, F3 population.

Yes. 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% to F1s, but it was right in that range. We had 2 posters at the AASLD conference. I'm sorry, 1 poster the AASLD conference in November, where we looked at the subpopulations with and without type 2 diabetes and F2, F3 versus F1. I think F2 versus F3 as well. And you really didn't see a difference in efficacy when you went to diabetics versus nondiabetics or severity of fibrosis. So the mechanism seems to hold across the spectrum of severity, at least from what we could see.

Great. That's helpful. Congratulations again.

And our next question today comes from I-Eh Jen with Laidlaw & Company.

Add my congrats on the great data. Just 2 questions here. The first one is on safety, particularly on the GI side, is that it seems from absolute number percentage perspective, that the treatment that could have lower than the receivable. How would you contribute that? And what do you think, whether that's something to be differentiated from other drugs or development turning in place?

Yes. Thanks, I-Eh. It's true the placebo rate was higher than the treatment rate, but I think on GI overall and nausea as well, I don't know. 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. What you -- is that you mentioned the higher as 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, each breakouts versus maybe the approved drug or other [indiscernible] in place to see the differences and facts.

Sorry, I don't think I've followed everything there, can you repeat the question?

I'm sorry. In terms of the patient makeup that leads to the potential higher absolute value of the placebo was treatment groups. Could you give us a little bit more color in terms of the patient breakdown of potentially plus potential reason to have that readout versus competitors?

Yes. Well, when we look at the study demographics, we were pretty well balanced across the board. Average age was 52 to 53. It was more women than men about 60-40, mostly whites about 1/3 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. As Steve asked that earlier, I think we're about 5, 5.3, something like that on average NAS. But -- so there's nothing that is obvious there that would 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 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.

And our next question today comes from Jay Olson at Oppenheimer.

Congrats on these results. Can you talk about any initial thoughts on how you might segment to 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?

Yes. Thanks, Jay. Based on the fibrotic benefit, I think it should be effective or beneficial across the 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 disregulation, 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 means to really make those decisions.

Okay. And then can you talk about the most common AEs that led to treatment discontinuation and maybe especially in the 10 mg QOD group, where it seems like there's a little bit more discontinuation?

Yes. 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 drop that amongst placebo than active arms as far as the AEs that led to discontinuation, minimal difference this year. So we didn't really focus on those, I'd say, headache and I think it 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 noninvasive primary endpoint? And is that something you plan to discuss with the FDA?

Yes. Thanks, Jay. 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 noninvasive 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.

Congrats on the results.

And 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.