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

Hello, and welcome to the Viking Therapeutics Phase II VENTURE Study Top Line Data Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded today, February 27, 2024. And now I would 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, February 27, 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 Securities and Exchange Commission 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 describing the results for the primary endpoint from Viking's Phase II VENTURE Trial evaluating VK2735, our dual agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors in patients with obesity. We're pleased to share with you on this call an overview of the initial data and key takeaways from the study at this point. Following my prepared comments, we'll open the line for questions. Before we discuss the results, I'd like to remind everyone that we have only recently received these data. While we believe we have enough information to report on the study's success on the primary and secondary endpoints, we have not yet had time to rigorously evaluate every line item in the data nor have we received all of the results that we ultimately expect to generate from the study. As these data are top line results, there may be differences in certain elements of the data that arise upon receipt of final results later this year. We would not anticipate these potential changes to have a significant impact on the 13-week results that we are reporting today. As additional data become available, we'll provide further updates. We also plan to present the results at future medical meetings, so we may wish to preserve certain details until those presentations. As a reminder, VK2735 is a dual agonist of the GLP-1 and GIP receptors in development for the potential treatment of obesity. Activation of the glucagon-like peptide-1 receptor has been shown to decrease glucose, reduce appetite, lower body weight and improve insulin sensitivity in patients with type 2 diabetes, obesity or both. Multiple GLP-1 receptor agonists are currently approved for use in the United States. More recently, research efforts have explored the potential coactivation of the glucose-dependent insulinotropic peptide or GIP receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Because these 2 mechanisms demonstrate complementary activities, this approach has shown generally improved therapeutic benefits compared with GLP-1 monoagonism. During the first quarter of 2023, Viking announced positive results from a Phase I single ascending dose and multiple ascending dose clinical trial of VK2735 in healthy volunteers. In the multiple ascending dose portion of the study, VK2735 demonstrated encouraging safety and tolerability and positive client signs of clinical activity following 28 days of weekly dosing. All cohorts receiving VK2735 experienced reductions in mean body weight from baseline ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo ranging up to 6%. VK2735 demonstrated encouraging safety and tolerability following repeated dosing. The majority of observed adverse events in the Phase I study were reported as mild or moderate, and the majority of gastrointestinal-related adverse events were also reported as mild or moderate. The results from the Phase I trial were featured in an oral presentation at Obesity Week in 2023. Based on these encouraging early results, during the third quarter of 2023, Viking initiated the Phase II VENTURE trial to evaluate VK2735 in patients with obesity. The VENTURE trial is a randomized, double-blind, placebo-controlled multicenter study designed to evaluate the safety, tolerability, pharmacokinetics and weight loss efficacy of VK2735 administered subcutaneously once weekly for 13 weeks. The trial enrolled adults with a body mass index of 30 kilograms per meter squared or adults with a body mass index of at least 27 who also have at least 1 weight-related comorbid conditions. Due to heightened clinician and patient interest, the size of the VENTURE trial was increased to 176 patients compared with the original target of 125 patients. The primary endpoint of the study, which we're reporting today, assessed the percent change in body weight from baseline to week 13 among patients treated with VK2735 as compared with placebo. Secondary endpoints included an evaluation of the proportion of patients achieving at least 10% weight loss. The doses evaluated in the study ranged from 2.5 milligrams per week to 15 milligrams per week compared to the 10-milligram top dose evaluated in the prior Phase I study. Today, we're pleased to report that the VENTURE trial successfully achieved its primary endpoint and all secondary endpoints with patients receiving VK2735 demonstrating statistically significant reductions in body weight compared with placebo. Additionally, the results showed that treatment with VK2735 was safe and well tolerated in this study with the majority of reported adverse events being categorized as mild or moderate. On the primary endpoint, patients receiving VK2735 demonstrated statistically significant reductions in mean body weight from baseline ranging up to 14.7% as well as statistically significant reductions in mean body weight relative to placebo ranging up to 13.1%. Statistically significant differences compared to placebo were observed for all doses starting at week 1 and were maintained throughout the course of the study. Weight loss in all treated cohorts appear to be progressive through 13 weeks and did not show evidence of plateauing. We believe this suggests that further weight loss could be achieved through extended dosing beyond the 13-week treatment period of this study. A key secondary endpoint was the evaluation of the proportion of patients achieving at least 10% weight loss after 13 weeks of treatment. All cohorts receiving VK2735 demonstrated statistically significantly higher proportions of patients achieving 10% weight loss relative to placebo. The proportion of VK2735 treated patients with at least 10% weight loss ranged up to 88% compared with 4% for placebo. Turning to safety and tolerability. VK2735 demonstrated encouraging safety and tolerability with the majority of observed adverse events being reported as mild or moderate. Treatment and study discontinuation rates among VK2735-treated cohorts were reasonably well balanced compared with placebo. Approximately 4% of VK2735 patients discontinued the study early compared with approximately 6% for placebo. Treatment emergent adverse event rates in the study were marginally higher in VK2735-treated patients relative to placebo-treated patients, driven primarily by expected differences in gastrointestinal-related events. With respect to severity, 95% of observed GI adverse events in the study were reported as mild or moderate. Nausea was also reported among patients receiving both VK2735 and placebo. Among patients receiving VK2735, all reported nausea was characterized as mild or moderate. Vomiting was reported in 18% of VK2735-treated subjects and was not reported among patients receiving placebo. Notably, GI-related adverse events were most prevalent in the first week of the study with observed rates generally declining through the course of the study. One treatment-related serious adverse event of severe dehydration was reported in a patient receiving VK2735. No treatment-related SAEs were reported among patients receiving placebo. In summary, we're very pleased with the results of this study, and we believe they provide support for the continued development of VK2735 for the treatment of obesity. The promising early profile observed at the VENTURE study, combined with the encouraging tolerability and safety profile to date, suggest VK2735 could provide an important future treatment option for patients with obesity. We plan to discuss the clinical development path with the FDA later this year and look forward to outlining our further development plans upon completing those discussions. In closing, I'd like to thank the investigators and patients who have participated in the VENTURE trial and I'd like to thank our employees here at Viking for their outstanding work in successfully executing this study. I'll stop here and open the line for questions.

[Operator Instructions] We will start today with a question from Steven Seedhouse from Raymond James.

Congrats on the definitive result here. It looks like you have a really fantastic molecule on your hands. Just wanted to ask about, first, the discontinuation rate actually higher in the placebo arm than the combined drug arms and only a couple percent higher in your highest dose arm than placebo. So is it fair to say you would look to continue to develop a pretty aggressive titration schema in subsequent studies, like every 3 weeks, 5-milligram steps up? And just in general, how are you thinking about dose titration and dose in subsequent studies?

Yes. Yes. Thanks, Steve. Good question. We don't have the per patient data yet. So I think it's important in determining the different titration rates to look at, for example, in the 15-milligram cohort, where did some of these events happen, the nausea and that sort of thing. If they're early and stacked up, maybe you want to start a little lower, but I don't know, there was a little bit higher rates of nausea in that top dose, but we're not sure if it's because they started fast or higher or if they titrated a little more aggressively. I think the bottom 3 cohorts show really great tolerability. And overall, when these GI-related adverse events happened, they were pretty mild. And so -- and when we look across the time course for the entire study, by far, the most great prevalence was in the first week or so. So -- but to answer your question specifically, we won't know that until we get the actual per patient data, and we can look at more detailed time course results across each cohort.

Okay. And do you think it's possible you could test a monthly dosing regimen here? I think you had been thinking about that now that you have the Phase II data in hand, do you think the PK of the molecule would enable that and just the efficacy support trying that out and seeing how it looks?

Yes. We think so. The PK certainly would appear to support it, but we don't have the PK from this study yet. But certainly, the earlier PK would support it. But that's another piece of data that we'll get when we get the final data tables that will help us determine that. But the PK would certainly support it.

Okay. On manufacturing, I'm hoping you can comment maybe just on where you're at there, the scale of it? Is it sufficient right now to support a large registrational program -- I mean, it looks like this is going to be Viking's lead asset, just given how profound the data is. So I'd imagine you'd want to get into a large expansive registrational development program. So just curious if manufacturing is already sort of prepped to support that.

Yes, thanks. It's an area we're spending a lot of time. We -- there's no issue supplying near-term clinical trials or registration trials. I think the question becomes, is manufacturing at a state that could support a commercial product and the answer to that is no. But we're spending a lot of time evaluating multiple parallel process -- multiple processes in parallel just to understand what's fastest, what's highest yielding, what's cheapest, what's most scalable. And we probably wouldn't be spending as much time on that at this stage were it not for some of the shortages that we're aware of in the market. So huge area of focus. We shouldn't have any challenges for the clinical supply, but -- and by the time it were to be available commercially, I think we should be in a position to supply the market.

Last question for me. Just -- it looks like the weight loss signal you're seeing is, even if you account for the titration scheme of differences, it just looks more potent than tirzepatide head-to-head using SURMOUNT-1, for example, as a comparison. I'm wondering if you can comment at all on just anything about the molecular design of your molecule that you'd attribute that to or -- is that still something that you're keeping proprietary or trade secret for now?

Yes. Thanks, Steve. No, we haven't disclosed the structure. We know that the PK profile provides very good exposures and the half-life is quite long. So those 2 are tied together. So we think that, that helps drive this level of efficacy. And I think it also, going back to your earlier question, likely supports a monthly regimen just because the half-life is so long.

Congratulations on the great result here.

Thanks, Steve.

And we will follow with the question from Joon Lee from Truist.

Congrats on the impressive data. Can you elaborate a bit on the single SAE on the drug arm like dehydration, for example, which dose was it? And were you tracking also any LFTs during the study? And I have a follow-up.

Yes, we were tracking liver function tests, and I don't think there was anything of issue there or any challenges there. With the severe dehydration, I believe that was in the 5-milligram dose. And I don't know if there's a -- Joel Neutel is our medical monitor. He's on the line as well. And Joel, do you have any additional color on that dehydration person?

Yes, sure. So like you said, he is a patient on a 5-milligram arm who presented to the hospital with symptoms of dizziness and was determined at the hospital to have dehydration and patient was admitted and recovered pretty quickly after that.

Okay. Okay. And what are your next steps in terms of clinical development? Do you have a Phase IIb in mind? Or are you more focused on BD at this point with this impressive data on hand?

Well, we're planning to having a Type C meeting with the FDA at our earliest convenience. That's probably going to be around the middle of the year. And then outline the path forward from there. It seems more than likely that a Phase IIb will be the next step here, but we'll have a better idea after we speak with the FDA and get some guidance.

Great. And last question. What additional data are you waiting for? And what could that disclosure look like in terms of timing or setting up the disclosure?

Yes, it's a good question. We don't have all of the clinical chemistry, the labs, that sort of thing. So we will -- lipids, detailed LFT stuff. We don't have that just yet. We just know that there weren't AEs associated with those sorts of things. And the PK, so PK not yet available. We should have all of those details, the full set of data in the second quarter.

And now we have a question from Jay Olson from Oppenheimer.

Congrats on the stellar results. Can you just talk about the trajectory of weight loss over time? The press release says there was no plateau reached at any dose. Is there any color you can provide on the shape of the weight loss curves? Or does that mean that they were essentially linear?

Yes. Thanks, Jay. They were -- the slopes were -- of all of the cohorts were pretty negative at 13 weeks, so indicating a continued downward trajectory, nothing had flattened out. And there wasn't really an indication yet of a plateau signal. The 2 higher doses, the 10 and the 15, 1 of them appeared to maybe be accelerating a little bit. But I mean, it's hard to know. These are weekly reads. So you get a little bumpiness as the curve evolves. But just very, very interesting at this point, very promising.

Okay. Great. And also, really low placebo dropout rate, super impressive. Any, I guess, lessons learned there that you can apply in Phase III to continue to keep that placebo dropout rate so low?

Yes. I think that's probably -- potentially -- I mean, partly anyway, a function of the duration of the study. Shorter studies tend to have lower placebo drops than the longer study where there's more of a risk of that. But I don't know if there's any learnings at this point. We feel it's probably just a function of the duration of the study.

Okay. Great. And if I could just ask one last quick question. If you could please just remind us the patent and IP status for 2735?

Yes. The IP coverage for this compound and its follow-ups extends beyond to 2040.

Great. Congrats again.

Thanks a lot, Jay.

We have a question now from Annabel Samimy from Stifel.

Congratulations from us as well. I guess 1 question I have is, given the potency of the compound and its ability to, I guess, exceed the weight loss already established by current treatments at this specific time frame. Are you giving any thought as to whether you contain the dose at 10 milligrams in future studies just to maintain a pristine profile? I guess how rapid weight loss curve do you really need to be competitive? So that's my first question. Essentially, what you can do to maintain this pristine profile?

Yes. Thanks, Annabel. And it's a good question. That's why I think understanding individual patient data from all of the cohorts will be really important because the top dose -- it just had a higher starting dose and a more aggressive titration schedule. So does that mean the top dose is any worse on tolerability. We're not sure. Maybe if you started at slower and titrated from 2.5 mg you'd see the same type of profile as the 10, but just better efficacy. But those types of nuances we'll learn once we get the more detailed data set.

Okay. Great. And just to clarify, can you just tell us about the titration schedule? How many -- how frequently were they moving up in dose? Was it consistent across doses? And do you feel that there's more work to do there in terms of managing a titration schedule, I guess, more personalized to a patients? Or is that just something that's going to happen in the real world?

Yes. Well, the -- all of the cohorts started at 2.5 milligrams, except the top dose. 15 milligrams started at 5 milligrams. And the titration blocks were in 3-week increments. So for the 5 milligram, for example, 2.5 milligrams for the first 3 weeks and then 5 milligrams for the remainder of the study. And so -- and again, just going back to the individual patient data, we'll have a better understanding on the comparison between that 2.5 mg and 5-milligram starting dose once we get the individual cohort data so that we can understand, did the 5-milligram actually lead to more AEs early or not. And so -- the schema is actually outlined in the press release underneath the efficacy table, I think.

Okay. All right. Great. And then just, maybe you don't have the data yet, but were there any other AEs that you can -- that stand out or lack of AEs that you can stand out relative to competing products already available on the market that you think differentiate 2735 over, say tirzepatide or [indiscernible]?

No. I mean the AEs we focused on really are the GI AEs. There were no other buckets of significance in the study, pretty recent data. So we haven't gone through every lab and line item. We don't have all the labs. So -- but there was nothing as far as an unusual cluster of AEs or an unusual characteristic AE that's different from what's known to be associated with GLP-1 agonism.

Okay. Great. Congratulations, again.

Thanks, Annabel.

And we'll follow with the question from Joe Pantginis from H.C. Wainwright.

So first, Brian, a logistical question. Obviously, this is ahead of the Type C and your next clinical plans, but I wanted to see if you could take any first passes at potential designs, number one. And then number two, when you look at the AE profile and the dropouts, albeit at very low rates, can you share anything with regard to, say, investigator feedback and manageability of these AEs, say, GI in the clinical study versus what you might see in real-world practice? Meaning, are these -- are the physicians may be erring on the side of caution based on the protocol, whereas in the real world, there might be able to be like if these events are only happening in the first week or so, just being able to have their patients stay on a little longer to get past it?

Yes. Thanks, Joe. Great questions. With the trial design, I mean, we're going to have the Type C meeting and have a better understanding coming out of that. It seems likely that a Phase IIb of 6 to 9 months in duration would probably be the next step. And what doses we choose there probably driven by a thorough analysis of the final data from this study, titration schema as well. But duration, we'd probably look into 24, 36 weeks. With respect to the AEs, I think most clinicians are fairly aware of and familiar with the GI induced AEs associated with GLP-1 agonism and incretin access in general. So how that impacts the reporting, I'm not sure. It could be that there's a little bit more sensitivity to it. As far as management of it, it doesn't seem like there's any intensive management required, to your point, most understand that these things happen early in the course of treatment. But I think it's maybe better to have Joel Neutel, our medical monitor, provide a comment, if you have any comments on AE's manageability expectations, Joel?

Yes, sure. And I think that's an important question. I mean -- I think the general sense of most clinicians in the study was that the GI side effects that occurred early, they were mild for the most part and disappeared very quickly with continued treatment to these patients. And I do believe that with increasing use of these drugs, there's an increased sensitivity -- patients or physicians are looking a little bit more carefully and asking patients a little more aggressively for the presence of these adverse events. But this -- generally, I think the physicians felt it was extremely well tolerated, and the side effects were mild and of short duration.

I appreciate all the added details.

[Operator Instructions] And we'll follow with a question from Andy Hsieh from William Blair.

Great. I think if you [indiscernible] 4:00 in the morning, quite like a 13% placebo [indiscernible] in weight loss. So really happy for the -- both for you and the entire Viking team. So it's 3 for us, just -- maybe a follow-up to Steve's question earlier. I know that there's a 6-week kind of follow-up period. I'm just wondering if that data is available or you can comment on kind of the durability based on the PK profile that you provided. And second question is kind of a clarification question. I think you mentioned in the discontinuation rate row of the table. There's a difference between discontinuation of the treatment and the study. So I just want to clarify the treatment, so can patients come back on after interruption. We're just -- basically give us more information about that. Lastly, I wanted to also ask kind of a trial design, philosophical question. If you look at the plateau effect of these existing drugs, for the more potent ones, it might take longer for them to plateau. So just curious about that 20- to 30-week duration. Is it important for a Phase IIb study to see kind of an obvious sign or plateauing? Or this is basically kind of just wanted to track patients from a safety tolerability perspective?

Yes. Thanks, Andy. I'll try to remember those. So the 6-week follow-up window is complete for everyone. We don't have those data tables yet. We should receive them in the second quarter. With respect to the treatment discontinuation versus the study discontinuation, sometimes this is an area that can be gamed a little bit. You can discontinue treatment, but stay in the study and complete all of the scheduled visits, but you're just not receiving treatment anymore and that's different from dropping out of the study completely. And so we just listed both to avoid any confusion. With treatment discontinuation, you could miss up to 2 doses. If you missed more than 2, you were discontinued from treatment. And so -- and I don't have the breakout of those details. But if you miss more than 2, you couldn't like come on -- come back on. With the plateau question, Yes, it's an interesting question because the guidance would indicate you should understand where your maximal efficacy is, something along those lines prior to Phase III. But if we look at the Phase II studies of other approved agents at their Phase IIb data sets, we did not yet see plateau. So hard to know in the absence of a discussion with the FDA, what the real rule is there, and that's one of the things we hope to get from the Type C meeting. I hope that answers your question.

Great. That's very helpful.

We'll follow with a question from Thomas Smith from Leerink Partners.

My congrats on a really strong data here. First, Brian, can you comment on whether these strong results change in any way your expectations for the Phase I oral 2735 data that you're expecting to report later this quarter. And then are there any learnings from the subq Phase II experience here that you expect to incorporate in the potential future studies with the oral 2735?

Yes. Thanks, Tom. Well, we're still expecting to have those oral data later in the quarter. I don't know if there's anything to translate from this study. It's just a different study. This is a Phase II, really a preliminary efficacy study, whereas that's a safety PK tolerability study. So I'm not sure if there's anything yet to translate. We don't yet have all of the cohort related data, patient-specific data, from this study. So hard to say exactly what it might do to the future plans with the oral formulation. I think right now, let's see what the data look like, let's see what the tolerability looks like, if there's -- what the PK looks like. If there's any signal of efficacy and then go from there, from that data set alone.

Got it. That's helpful. And then it sounds like you're planning the Phase IIb and obesity is a reasonable next step here. Can you just comment at all on how you're thinking about positioning and maybe the potential to evaluate subcu 2735 in additional indications here beyond obesity.

Yes. We did look -- 1 obvious additional indication is the NASH or NASH indication. And we think the mechanism seems to be applicable there based on what we've seen recently. So that would be 1 area. I think for now, we're going to direct our resources in obesity but that would be 1 obvious indication that could see some benefit from the mechanism. And we know it seems to be applicable there.

Got it. That makes sense. Congrats again on the really stellar data.

Thanks a lot, Tom.

And now we have a question from Justin Zelin from BTIG.

Congrats on this really strong data here. Just a few questions for me. Brian, have you seen any incidence of pancreatitis in the study? And are you measuring biomarkers such as cholesterol or waist size in the study as well that we might get some data from?

Yes. Thanks, Justin. No, I don't think there was any pancreatitis reported in the study. And we are monitoring lipids and all of those things, lipids, liver panel, clinical chemistry. We just don't have that level of detail at this point. In the Phase I, look, encouraging though, we did see LDL cholesterol and I think ApoB was reduced as well in 28 days. So that was an encouraging early data, but we just don't have it yet from this study.

Great. And just given the strong data here. I know in the past, you've talked about potential BD with this asset. Does that change your thinking moving forward and potentially looking to run pivotal studies on your own?

Yes. Thanks. It's a good question. I think our plan is to proceed aggressively with further clinical development. we're always open and always have been with all of our programs to BD discussions, and we'll pursue what would make sense for the company and our shareholders and patients in particular. But we're right now really focused on next steps of the program for us and remain with the open door policy for discussing opportunities.

Congrats once again.

Thanks, Justin.

Thank you very much. This concludes our question-and-answer session. And now I would like to turn the conference over to Stephanie Diaz for any closing remarks.

Thank you, everyone, for joining us today. Thank you for your continued support of Viking Therapeutics. And with that, we'll end the call. Have a great day.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Have a good day.