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

Hi everybody, my name is Hardik Parikh. I am an equity research analyst for JPMorgan covering large-cap pharma and small cap biotech. I have today, Brian Lian from Viking therapeutics, and he's going to give about a 20-minute presentation, and then we'll jump into a little bit of a fireside Q&A.

Thanks, Hardik. Thanks to JPMorgan for the opportunity to present. We really appreciate the opportunity to be here. I'll make some forward-looking statements today. I would refer anyone hearing this presentation to the Securities and Exchange Commission's website for the most current information on the company. So a quick overview of Viking. We're focused on novel therapeutics for metabolic and endocrine diseases. We have multiple clinical programs ongoing. We'll focus today really on the metabolic disease programs. Lead compound here is a compound we call VK2735, which is a dual agonist of the GLP-1 and GIP receptors. We reported last year positive data from a Phase II study in obesity that successfully achieved the primary endpoint. And we have the Phase III trials planned for the first half of this year. That's a subcu formulation. We have an oral formulation as well, same molecule in Phase I, demonstrated positive proof of concept. And we just announced last week that a Phase II trial was underway with that formulation. We also have a NASH program, VK2809 is a molecule there. It's a thyroid receptor beta agonist. We reported and presented Phase IIb data at AASLD in the fourth quarter that showed a very nice improvement in histology in NASH patients. And then finally, we have a rare disease program. The molecule there is called VK0214, another thyroid receptor agonist that we have been developing for X-linked adrenoleukodystrophy, and we reported positive data from that study, Phase Ib study in the fourth quarter. This is a quick overview of the pipeline. So you can see the Phase III plan for the dual agonist VK2735 with the subcu formulation, the oral formulation in Phase II and then the thyroid agonist in NASH and X-linked adrenoleukodystrophy ongoing. So the near-term events for the company would be the injectable initiation of Phase III trials in the first half and then the oral -- completion of the oral dosing trial likely in the second half of this year. So VK2735 is -- it's a mimic, I guess, of a couple of proteins that are secreted in your intestines after meals, following ingestion of nutrients, peptides are secreted, enter the circulation and then they bind to receptors and various tissues. We're most interested in their activities in the pancreas and the hypothalamus where they stimulate insulin production and induce satiety. And we think this sort of therapeutic profile has a benefit in obesity and potentially other indications like NASH and diabetes. We began to work on this program about 5 years ago, looking at a series of first mono agonists of GLP-1 itself and then moving to the dual agonist where GIP has added to the overall profile. And then also triple agonist, and we -- more glucagon is added, and we really focused on the dual GLP-1 GIP felt like the space was moving in this sort of multi-active agonist mechanism. We couldn't get the triples to work any better than the duals. So we really stuck with the GLP GIP dual agonist. These compounds all have pretty good potency on both receptors. GIP activity seems to vary more. What this slide shows really is just some data from a 14-day study in DIO mice, and you can see -- typically, we see approximately 30% delta from vehicle on weight loss. Pretty clean PK profiles with these compounds, half-life is ranging out to 7 days. This is just an example of one compound VK2745 in primates, but they all show pretty good reproducibility on PK. You can see the curve is really, really tight there group of primates. So we selected VK2735 for further development. We conducted the first a Phase I study, randomized, placebo-controlled stack sort of SAD/MAD, so stack, meaning the SAD starts first. And while the SAD is ongoing, the multiple ascending dose study is initiated, that component of the study was 28 days using weekly dosing -- once a week for 28 days. Primary objectives were safety, tolerability and exploratory objectives on body weight, glucose and liver fat. These data show the results of weight loss from the MAD portion of the study after 4 weekly doses at 28 days. And you can see a nice dose-dependent reduction in body weight, reached at 7.8% at 28 days after 4 doses, placebo adjusted 6%. So we were very happy with the initial signal after 4 weekly doses. Looking at the trajectory of weight loss, we saw a progressive weight loss in all of the dosing cohorts. Even the lowest dose showed a negative slope after 28 days. No evidence of a plateau in this dosing window, and it really suggested that longer treatment windows might lead to a further enhancement of the efficacy signal. Looking at GI tolerability, that's kind of the area that most people look at for this mechanism. Very encouraged by the GI tolerability when you look across at nausea, really not much of a dose-dependent signal relative to placebo. The highest dose looked like the lowest dose on nausea, vomiting, no real dose dependency as well and then abdominal pain and diarrhea and constipation also very mild clinical profile. Majority of the AEs were mild or moderate, and there were no discontinuations related to GI adverse events. So following completion of that study, we initiated a longer study, a 13-week study. We called the VENTURE study, and this looked at obese subjects with a BMI of at least 30 or at least 27 with at least one weight-related comorbidity. We randomized patients across 5 arms: placebo, 2.5 mgs, 5 mgs, 10 mgs and 15 mgs of VK2735. And for the 5, 10 and 15-milligram cohorts, we followed a 3-week titration cadence. So you'd start at 2.5 mgs come up for 3 weeks and then come up to 5 mgs after 3 weeks and then 7.5 and 10. So stepped up in that manner. Primary endpoint of this study was a change in body weight after 13 weeks versus placebo. Study demographics outlined here, pretty well balanced across the dosing arms more women than men, which is typical, mostly white, weight and BMI also reasonably well balanced across the treatment arms. We reported these data last spring. The study was successful on the primary endpoint. We saw success -- a significant reduction in body weight after 13 weeks, ranged from around 9% at the lowest dose from baseline up to 14.7% at the 15-milligram dose, placebo adjusted a little over 13%. So nice dose dependency significant at every dose level. This shows the trajectory of weight loss over the 13-week window. All of the dosing cohorts were statistically significant, starting at the first week and then maintained throughout the 13-week window. And you can see the nice spread in efficacy. Each dose, each successfully higher dose resulted in a greater degree of weight loss. And like the 28-day study, there was no evidence of a plateau here at after 13 weekly doses. So suggested further extension of the dosing window might lead to in a further improvement in weight loss. A secondary endpoint in this study was a proportion of patients who experienced greater than equal to 10% weight loss, and what we saw here also a nice dose-dependent improvements in the proportion who experienced at least a 10% reduction in body weight. The highest dose was that 88% had at least a 10% reduction in body weight. One thing we were interested in is how durable the weight change was. So in a subset of patients who elected to participate in the PK assessment of the compound, we had them come back 4 weeks after the last dose. And this slide just shows the body weight change comparing the week 12 assessment and the week 16 assessment on body weight. And you can see across all the combined cohorts 94% of the overall weight loss was maintained 4 weeks after the last dose, and that persisted out at the week 19 as well. 83% had -- 83% of the week-12 weight loss was maintained. So we think this suggests that possibly we could dose less frequently than weekly raises the possibility of potentially a monthly regimen. Looking at some of the safety and adverse events in the VENTURE study, discontinuation rates on the top line there, pretty well balanced across the treatment arms for both the treatment and the study. Overall, treatment-emergent adverse events, that's TEAEs. You do see a dose-dependent increase, primarily driven by the GI adverse events, which you would expect from the mechanism. And then the drug-related treatment emergent adverse events leading to study discontinuation very low across all of the treatment arms. Majority of the treatment-emergent adverse events were mild or moderate. There was one SAE of dehydration that was considered probably drug related. Looking at the GI tolerability summary. Again, pretty mild GI profile, majority of these were characterized as mild. There were some moderate when you look at nausea, for example, a little bit of a dose-dependent uptick what you would expect, but overall, not to be unexpected with this mechanism and no severe nausea. Vomiting, you do see a slight dose-dependent increase in vomiting. Otherwise, abdominal pain diarrhea constipation really not out of line with what would be expected from the mechanism. Something that was kind of interesting in this study, when we look at the time course of GI adverse events, this slide shows all of the cohorts combined here. And what you see is the green bar is constipation, the aqua colored bar is diarrhea, blue is nausea and gold is vomiting. And what you can see in the graph is by far, the majority of GI-related adverse events happens early in the treatment window and then wanes to near zero for the remainder of the study. You do see a slight uptick here. These were 3-week titration blocks. So here is the first week where a dose was increased in those arms that did increase their dose. So you do see a little bit of an uptick in nausea. But again, 95% had no nausea at the week 4 endpoint -- time point. So the study takeaways from the VENTURE 13-week study up to 14.7% main weight loss after 13 weekly doses, very promising tolerability. But more than 90% of the efficacy was retained after 4 weeks after the last dose. The PK, we think suggests the potential for a monthly regimen. The majority of the GI-related adverse events tend to occur early in treatment and then resolved with no recurrence and we're now planning to move to a Phase III development with the program. So what we had in the fourth quarter, we had an end of Phase II meeting with the FDA. We received, I think, very encouraging feedback. We are planning to conduct two Phase III studies. One will be in patients with obesity, one in patients with type 2 diabetes and obesity, and we expect both of these to begin in the first half of this year. So we are also developing an oral formulation of VK2735. We, last year, announced data from -- the first study, called the 101 study. It's a multiple ascending dose study design and really was an extension of the subcu study to look at the oral formulation. So you can see here the way this trial started, people started the lowest dose cohort was 2.5 mgs and then once that cohort was completed, there's something called the dose level review team that reviews the data and then makes a recommendation to proceed on to the next dose. And we went ultimately up to 100-milligram doses. And then we added an exploratory cohort that looked at 80 milligrams daily transitioning to 80 milligrams every other day. When we look at body weight change in this study after 28 days, like with the subcu, we saw a dose-dependent reduction in body weight, ranging up to a little over 8% from baseline after 28 days. Placebo adjusted approximately 7% at the top dose. When we look at the trajectory, this slide is showing two things. First, the trajectory of weight loss through the 28-day dosing window, and then right here was that last dose, so from this dash line here out through the rest of the graph was the weight change through 57 days. So 4 weeks following the last study dose. And it was interesting that we did see, for the most part, the weight loss was retained. And in the highest dose, really pretty flat, 8.3% after 57 days, 8.2% after 28 days. So what we think that suggests is that maybe you can maintain weight loss at a lower dose than was used in the induction phase. So you can think of maybe somebody transitioning from a subcu formulation onto a low dose oral to prevent weight regain or rebound. This slide shows the experimental cohort that I described where people transitioned from a daily 80-milligram dose to an every other day 80-milligram dose. So the overall exposure is cut in half. The maroon line shows the 80-milligram daily through the course of 28 days, 5.2%. The green line starts for the first 2 weeks at 80 milligrams per day and then transitions at this point to an 80 milligrams every other day. And you can see there's some separation even though the regimens are identical here for the first 2 weeks, a little bit of separation there. And that separation is kind of retained. The curves still are largely parallel through the following 2 weeks despite cutting the dose by 50%. So again, it was just kind of a quick and dirty way to evaluate can you reduce the dose once you have some inertia and still maintain efficacy. And it seems to suggest that, yes, it's possible. Looking at the proportion of subjects in this study who experienced at least a 3% reduction in body weight, that's the blue bars or at least a 5% reduction in body weight. That's the gold. Again, we see a nice dose-dependent improvement in the proportion of 3% and a proportion of 5% at the 100-milligram dose, all subjects experienced both 3% and 5% reduction in body weight. This slide is interesting. It looks at the relationship between reduction in appetite or increased satiety, which is what you would hope to see with this mechanism and body weight. And so the blue shows the proportion of subjects experiencing increased satiety or reduced appetite, the gold shows the reduction in body weight. And just interesting to see that they mirror each other like you would expect if someone is -- their appetite is being suppressed, they should experience greater weight loss. So interesting to see that. Looking at the Phase I study, adverse events and discontinuation rates, really very few discontinuations and no real dose dependency relative to the control arm, the placebo arm. Treatment-emergent adverse events tended to be slightly higher, and that's primarily driven by potential GI adverse events. Drug-related treatment emergent adverse events, some dose dependency there. And there were no serious adverse events in this study. The majority of these were mild to moderate. When we look at the GI tolerability summary here, we were pleasantly surprised that the overall GI profile was very mild. We do see some increase in nausea at the higher doses, but we don't think that's necessarily reflective of what the real world would show. These subjects were titrated at an artificially accelerated rate. So -- for example, the 60-milligram cohort started their first week at 40 and the final 3 weeks at 60, 100 mgs started 3 weeks at 80 and then -- or 1 week at 80, 3 weeks at 100. So probably would be more gradual in the real life with the titration rate there. Nonetheless, the nausea rate was very low. Vomiting as well, also very low and other GI adverse events surprisingly low in our view. So we think tolerability consistent with the subcu formulation is very promising. So the oral study takeaways up to 8.2% reduction in body weight after 28 days of daily oral dosing the progressive nature of the weight loss curve suggests that we may see further weight loss with the longer treatment windows. Majority maintained 4 weeks following the final dose. We do see dose-dependent exposures with daily dosing. And we think that based on the PK curves, we're probably seeing a continued accumulation at day 28. Great tolerability so far, small short study, but looks promising through 100 milligrams. 99% of the adverse events are mild to moderate. A mild nausea was observed at the higher doses. We think that's probably addressable with a different titration rate. and really minimal GI adverse events, lower rates of vomiting, diarrhea, constipation at the higher dose cohorts. And then the exploratory arm where we went from 80 milligrams daily to 80 milligrams every other day, really does indicate there is some feasibility to a lower dose maintenance regimen following a higher dose induction regimen. And last week, we announced the initiation of a 13-week study. We call it the VENTURE study. This is a 7-arm study where we look at dosing, 15 milligrams is the lowest dose, 120 milligrams is the highest dose. At every dose above 30 milligrams, you will start at 30 for 2 weeks. And then like for the 60, you'd go to 60 for the remaining 11 weeks. The 90-milligram is 30 for 2 weeks, 60 for 2 weeks and then 90 for the remainder of the study. We have an exploratory arm in here where you titrate up to 90, just like in the 90-milligram cohort. But then after 8 weeks, you transition down to 30 milligrams for a maintenance dose. And then the highest dose is you titrate up to 120-milligram in those 2-week steps. So we just started this study announced it last week, and hopefully, we will be in a position to report data toward the end of the year from this study. Moving to our financials. We ended the third quarter in a really strong financial position of over $900 million on the balance sheet, and we think that will support completion of the Phase III program with both the subcu and the oral formulations. And that's the story. So we're focused on novel therapeutics for metabolic disorders. The VK2735 program for obesity is currently sort of the flagship program moving into Phase III in the first half. The oral formulation in Phase II today, hopefully, reporting data from that study in the second half of the year and then the NASH program and the rare disease program available for licensing. And I can stop there. Thanks very much for your attention.

Thanks for that, Brian. So I'll get into a couple of questions about the clinical trials. But I think last week, we got a number of questions from investors about the FDA putting out their revised kind of guidance for obesity clinical trials. To me, it kind of seems like it was much more than just putting more details around their policies as opposed to changing anything. But I just wanted to get your thoughts on that. And what's most relevant towards the Viking's programs there?

Yes. Well, we felt the same way it was -- seemed like a refinement of prior guidance, but that guidance had gotten pretty, pretty old. So not a lot of game-changing updates in the new guidance. I mean there was detail around -- one thing that was interesting, the comment that the 52-week treatment period in Phase III is at the maintenance dose. It doesn't include the titration. That was not clearly delineated in the prior guidance. More detail on pediatric obesity studies, things like including a diversity plan in your Phase III program. So a lot of fleshing out of things that people are doing, but hadn't necessarily been formalized in the prior guidance document. It didn't impact our study designs at all. We had just come out of an end of Phase II meeting. So we had a pretty good idea on where the FDA stood with these things. So there was nothing different in the guidance versus what we had already assumed would be required for a Phase III program. So not a lot of big updates.

Yes, which is kind of my second question was just everything that you've gotten from those Phase II -- end of Phase II meetings, nothing counter to that, you're still on track to kind of move into Phase III for the subcu?

Yes. Yes. And there was nothing. We had asked questions that were sort of related to some of the guidance topics. So we had, had a little bit of a heads-up on those -- not knowing guidance was coming, but just the language is pretty similar in some of the responses we got versus what was in the updated guidance.

Okay. Okay. So you recently -- just last week initiated the Phase IIa trial for the oral?

Yes.

When you look at the kind of patient numbers, I think on clinical trials, it's about 280. So it seems sized enrollment-wise to be like almost like a Phase IIb. Any thoughts on having the treatment duration a little bit longer than 13 weeks? I think orforglipron had theirs at 36 weeks for Phase III.

Well, both of the subcu formulation and this trial are 13 weeks in duration, and that's really driven by the tox package that we have, both the formulations have their own tox packages. So yes, that's 13 weeks because that's the tox coverage we have.

Okay. And then you mentioned -- I don't know in terms of the titration in Phase I, you could say it was very impressive even despite the quick titration, what are the thought process behind kind of slowing it down? What do we think is the risk benefit there? If you're already getting good tolerability?

Yes. I don't think we necessarily needed to, but when you go into larger numbers, maybe someone has more sensitivity to the mechanism. So we thought we could find a nice intermediate where we keep flat dosing at the lower doses of 15 and the 30 because there just seems to be a minimal risk of an adverse event there or GI-related adverse event. And then when you step up to 60, 90, 120, maybe we could just start at 30 -- I mean just a real -- a quick titration but a little more gradual than starting at 120. And again, I don't think that's mandatory, but if anything, it should help the GI profile.

Okay. Okay. And then you also mentioned that you're doing on exploratory arm where you are similar to the previous Phase I. I think you had 80 milligrams and you switched it to 80 every other day, not doing 90 for the first 8 weeks switching into a 30-milligram maintenance dose. What are you looking to achieve from that trial? What would be like something that kind of gives you a good amount of confidence that you can move that forward as well.

Yes. Well, it's just another -- we'll have to do a more detailed maintenance study, but this is just another kind of exploratory arm to look at if you dose for some period of time at a high dose and achieve some degree of weight loss and then you transition to a much lower dose. Can you prevent weight gain? Do you still see continued weight loss but at a lower rate. Those just kind of gives you a little bit of a feel for that. And we think overall, the oral formulation probably will be best used in the low-dose maintenance setting. So this gives some indication as to what dose might be utilized in that setting. So you transition with the subcu or the oral?

When we spoke right after obesity, you've said there is a possibility that similar to the subcu formulation, the oral could also potentially skip from Phase II to a Phase III. Just wanted to get your thoughts -- your latest thoughts on that. And then...

Yes. Yes, premature right now, we don't know. In this study, the oral, like I don't think we reached steady state at all in the 28-day study. So we need to understand what the PK profile looks like and see what the weight loss trajectory looks like. So I mean, in a perfect world, yes, we could proposed moving to Phase III, but I think it's premature. We want to see what the data look like first.

Okay. What do you think the FDA has generally been looking for when they're making these types of decisions when you're thinking about the preclinical studies and then as well as kind of the Phase I? Is there a certain types of data packages that they are -- they just -- they need to kind of make those decisions?

I don't know. We submitted everything we had. We had a Type C meeting back in June where we asked, does the data support moving to Phase III, if that's what we wanted to do. And we -- I think it was an encouraging response from them. The guidance at the time and the guidance last week, the guidance has not changed on this. The guidance says that prior to Phase III, sponsor should understand the maximal or near maximal efficacy. And we had treated 13 weeks. So the curves are still declining pretty strongly. But we had an understanding of the tolerability. I think it's understood at the FDA that AEs tend to have an early in treatment and the profile looked reasonably safe and well tolerated after 13 weeks and so we had proposed going to Phase III. And so I don't know what they typically use, but we just gave them everything we had all of our animal data and all of our human data, and they weren't receptive.

Okay. Okay. A little bit of an unfair question, but on the oral, I know you said it's premature to have that discussion yet. But where is your mindset in terms of -- you had to put a probability on going to Phase III 25? Is it more than 25? Is it around 50-50.