All right, good afternoon, everyone. Thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ulz, one of the Biotech Analysts here, and it's my pleasure to introduce Brian Lian, CEO of Viking Therapeutics. Just a reminder, the format for today is a fireside chat. You know, if anyone has any questions, feel free to raise your hand, and we'll address your question. But before we get started, I just need to read a quick disclaimer. "For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative." With that, thanks, Brian, for joining us this morning or this afternoon, rather. We appreciate your time, and maybe I'll just hand it over to you to make some introductory comments.
Yeah, thanks, thanks for the invitation and had a great schedule. We have a great schedule here, so we really appreciate the opportunity to participate. So my name is Brian Lian. I'm the Founder and CEO of Viking Therapeutics. We're based in San Diego. I founded the company in 2012 . We did an IPO in 2015 , and we've always been focused on metabolic and endocrine disorders. I think we have an exciting pipeline of therapeutics or clinical programs. We've got an obesity program looking at two formulations of a dual agonist of GLP-1 and GIP, SubQ formulation and an oral formulation. We have...
And that, that's in phase II and phase I, respectively, hoping to go into phase III, probably early next year. And then we have a MASH program. It's a thyroid receptor agonist that recently completed a successful phase II-b study, and we'll talk to the FDA later this year about what a registration program would look like with that compound. And then we've got another small molecule thyroid agonist that's in an orphan indication called X-linked adrenoleukodystrophy, and that program will probably read out data before the end of the year now. So it's an exciting time for Viking. We've got two end of phase II meetings coming up this year and hoping to move the obesity program forward as aggressively as possible.
Yep. You definitely have a lot going on and have shared a lot of exciting data this year, and, maybe we could start, you know, obesity, VK2735, that's your SubQ formulation. You shared some promising phase II data from the VENTURE study at 13 weeks. Maybe just highlight, you know, what made that dataset so compelling.
Yeah, it was a weekly dosing up to 15 milligrams. We saw up to right around 14% weight loss from baseline in the top dose. I think it was around 8% in the lowest dose, which was 2.5 milligrams. All of the curves appeared to be still downward at the 13-week endpoint, so it suggests that longer dosing windows could achieve greater weight loss, and we saw, I think, really encouraging tolerability. You see the expected GI adverse events with some nausea and other GI observations, but really, they seem to happen early. They don't seem to be sustained, and they typically resolve without any interruption of dosing.
So it was really, I think, encouraging in that, at least in that short study.
Yep, makes sense. On the recent earnings call, you also announced plans to move directly into a phase III, as opposed to a phase II-b.
You know, maybe just talk about your interactions with the FDA during your Type C meeting and kind of what you learned that gave you confidence that that path is viable?
Yeah, after the 13-week phase II data, we were curious if it would be possible to go into phase III. The normal path is to conduct a second phase II, a longer phase II, six to nine months, and see the curves evolve a little bit more. We weren't sure that would give us any really new information. But we weren't sure. So we asked the FDA if it would be okay to go to phase III with the existing data, and the feedback we received indicates that it seems to be okay to go directly into a phase III study.
Yep. And just in terms of the thought process on the phase III design, if you can share, like, the current thinking so far, and I think you have a meeting potentially scheduled with the FDA to kind of discuss some of that. Is there anything, in particular, you're trying to learn from that meeting?
Yeah, well, we would like to propose. The Type C meeting is really to understand, can we go into phase III, or do we, or is it recommended to do a phase II-b? We feel comfortable going into phase III now. The end of phase II would really focus on the trial design. What are the doses? How long is the study? You know, what are some of the enrollment criteria? What are the endpoints? You know, that kind of thing. So much more phase III design specific, rather than the Type C, which was, is this okay?
Any thoughts on, you know, number of patients you might-
Oh.
- want to roll or number of-
Yeah
... studies and duration?
Yeah, yeah. We're looking probably initially at two studies. A study in obese patients, so BMI of thirty or greater or twenty-seven plus one weight-related comorbidity, and the guidance calls for forty-five hundred patients to be in your phase III dataset, with fifteen hundred, at least fifteen hundred in the placebo. So we would probably target somewhere above that forty-five hundred across both studies. Fifty-two weeks of treatment. We'd kind of be right down the center of the fairway on the trial design with both studies.
Can you talk about which dose you're planning to take forward, or could you look at a couple doses there?
We would probably look at multiple doses, and we haven't disclosed the dose levels. We have good tox coverage above the doses we looked at in the phase IIa study, so... But we haven't disclosed what doses. We'd like to wait till after the end of phase II meeting to really-
Talk both studies or-
Total.
Total.
Total, yes. Yeah. Yeah.
When do you plan to have sort of clarity on the design, and when can you sort of move forward there?
Yeah, we would hope to understand what. Well, we get the feedback from the FDA at the end of phase II meeting. And then, as soon as possible, we would like to implement the design to move forward. When we would announce that, unclear yet. It depends on if there's any information requests or things like that from the FDA, and how long those might take to answer. But, so, you know, would it be right away? Would it be sometime in the first quarter? Unclear at this point. We have to get through the meeting first.
Makes sense. You've been talking about weekly dosing, but you'e also indicated there's potential for monthly dosing.
Yeah.
You know, maybe, maybe talk about what data you have there, and what gives you confidence, and then, how are you thinking about moving that forward, or what are some of the potential ways you can do that?
Yeah, yeah. The monthly regimen, I think, is a potentially attractive option in the maintenance setting. Once you've reached some target range, weight range, maybe transitioning to a monthly regimen would be attractive to some patients, and based on the half-life of the molecule, it's generally one hundred and seventy to two hundred hours. It seems like if you were to think about dosing every four or five half-lives, monthly is a possibility. So still trying to understand what would be the right dose for a monthly regimen, but the molecule's behavior would indicate monthly is definitely feasible.
You wanna have a, we think, a therapeutic level of drug in the plasma for the whole month or the majority of the month, and I think we can do that. But it would primarily be in the maintenance setting.
Mm-hmm. When you say maintenance, are you thinking, you know, you know, potential GLP-1 and then convert, or are you thinking maybe even your own subQ , and then you do a maintenance sort of with that, or?
Yeah. Well, I guess we're thinking about is for our own program. You probably induce weight loss with the weekly regimen, and once you reach some target range, transition then to a monthly for a longer maintenance window. Monthly might work for weight loss initially, but it's just gonna take forever to get to that dose. You know, 'cause if you dose monthly, it's gonna take a higher dose, and so take you forever to get there on monthly cadence.
In terms of the timing, and is this a high priority for you to sort of start in, you know, moving that forward, or what's the thought process there?
Yeah, it's a high priority. And the question is, would you bake it into the phase III or do a dedicated phase II-b? And we're thinking about both of those. So I think it's an important option, but a dedicated phase II-b might make sense. We're not sure yet.
Gotcha. Okay. Maybe we can switch to the oral formulation. You know, you shared some very promising early phase I data dose escalation. Maybe talk about the doses you had in the initial update and kinda what gave you confidence to continue to dose escalate?
Yeah. Yeah, we did the twenty-eight-day study with doses up to forty milligrams. I think we had two and a half mgs, five mgs, ten mgs, twenty mgs and forty mgs daily. And once you get to the twenty and the forty mg levels, that's when we started to see weight loss, and at the forty mg, at twenty-eight days, we saw 5.3% from baseline, I believe, and the placebo's 2.1%. So 3% delta there. The AE profile was really attractive, so we decided to dose escalate from there, and we're still in that portion of the study. We recently completed the hundred-milligram cohort and hope to report the data at the upcoming ObesityWeek conference in San Antonio.
Gotcha. Maybe you can talk about what specific data we might get at ObesityWeek. You know, you'll definitely have it through a hundred milligrams. Is that fair?
Yeah. Yeah, and we haven't received the data from that cohort yet, but we would plan to have all of the cohort data from the completed cohorts. And if we were to do another cohort, if it were to enroll quickly, maybe we could have an additional cohort of data as well. But we would have the 40 and the 60, 80, 100 would be, I think, minimally, what we'd report there. And we'd you know, it's a phase I study, so we look at you know, tolerability, safety, and PK, and then everybody's interested in body weight change, so we would look at body weight change as well, or look to report that.
You mentioned very favorable tolerability through the 40-milligram dose. Maybe just talk about what's the driver behind that or the mechanism? You know, I think most people had expected to see more maybe GI tox or something like that.
Yeah, we certainly expected to see more GI-related adverse events. When we first saw the data, we thought, "Oh, nothing happened, you know, it didn't work. There were no, no, no side effects." But then, when you start to look at the weight changes any number of ways, clearly, there was a weight loss signal. Really mild side effects, no vomiting, more diarrhea in the placebo versus treated, so surprisingly well-tolerated. Why is that? I don't know. It just surprised us. It could be that when you dose orally with a dual mechanism, that maybe the GIP feeds in a little bit more strongly relative to SubQ, but I don't know. We don't have a good answer for that.
Yep. And as you dose escalate to 100, you know, up to 100, is it fair to assume you'll start to see some of those, you know, expected toxicities emerge, or is it, you know, not a good assumption?
I would expect it. We're being a little aggressive, you know?
Yeah.
Every cohort, as we dose up, since it was so well-tolerated, has kinda started at the prior high dose. So, like, the 40 mg dose started at 20 for a week, and then went to 40 for 3 weeks. The subsequent 60 mg cohort started at 40 for a week, and then went to 60 for 3 weeks. So, I mean, I would expect that... Maybe not, but I would expect some AEs to start to materialize as you go up. And then, that allows you to then think about the phase II design and-
Right
Titration scheme to impose there. But, it would be a surprise if there weren't any-
Yep
AEs. But it was a surprise at 40 there weren't any.
Yep. And can you talk about the decision to continue to dose escalate beyond a hundred, and just, you know, some... What are the factors that go into that, and when might we, you know, hear about that?
Yeah. Yeah, we, there's a dose level review team that reviews the data after each cohort's completed. They have not yet met to discuss the hundred-milligram cohort. So they primarily look at tolerability and safety, and they don't, they don't care about weight change. And then they make a recommendation, or, "Okay," as to go to the next dose, and then suggest a dose level. So it's a balance. You know, we wanna be able to start the phase II study this year, and we've got a kind of an idea on the doses that we would use in the phase II study. If we were to go, you know, higher than the doses, now, we have some precedent for that.
We did the multiple ascending dose study with the SubQ formulation, went up to 10 milligrams. We decided to stop there and put a 15 into the phase II, and we had good tox coverage, so we were able to do that. Maybe we could do something like that with the oral, if you know if that would make sense.
And how high might you go on the oral? I think, you know, at some point, you know, in the past, you've mentioned maybe it doesn't make sense to-
Yeah
Continue dose escalating. What's that threshold and-
Yeah, that's an unknown. Probably, you don't wanna go too high, it becomes not a feasible commercial product. But, so that's a hard question to answer. I think we may be able to go above a hundred, but how much further, unknown just yet, before we get some of the data from this hundred-milligram cohort.
Maybe just to follow up on one of your earlier comments. You know, as you think about selecting the dose for the phase II, you know, maybe talk about, you know, how you go about selecting the dose, and you mentioned sort of aggressive titration. So maybe if you're seeing more tox at a higher dose, maybe you slow down the titration.
Yeah.
Is that sort of-
Sure, sure. You know, you'd probably wanna start at a dose that's low or minimally effective, and then scale it up from there, and you know, if the hundred's well-tolerated, maybe push above that a little bit in the phase II, if we don't do another phase I cohort, so you'd wanna spread them. We'd probably look at four or five doses in the phase II study, and depending on what the tolerability profile looks like in the higher dose cohorts, we would then adjust the titration regimen to accommodate where AEs begin to show up and how you would titrate into those dose levels.
Yep. Mm-hmm. Maybe just talk about the duration. What potential duration of a phase II that-
Yeah. This would parallel the SubQ study, which was a thirteen-week study, the VENTURE study. So just thirteen weeks of higher doses would titrate in, the lower doses might be flat.
Yep. And just to get that study ongoing, you mentioned, you know, start by the end of the year. You know, what has to happen from now until then to kinda hit that timeframe?
We'd like to get the data from the 100-milligram cohort, and whether or not we add another cohort's an open question. But making the dose forms that we would use in the phase II, and getting it packaged and everything like that, all that needs to start pretty quickly if the study's going to initiate this year, and we do expect it to initiate this year.
Yep. Okay.
So the gating factor is really getting the data from this hundred-milligram cohort, and then having the product manufactured.
Is there a particular bar in terms of weight loss you're looking for? You know, we get that question quite a bit.
Yeah, so really hard to know the 28-day studies are not a useful metric, really. I know everybody looks at them. I do, too, but it's such an early part of that longer-term treatment window that it's hard to make comparisons. We know the accumulation is kind of gradual with the oral formulation, so unlikely we're really at the therapeutic levels in as short as 28 days. I don't know what the hurdle. We were happy to see 5% in 28 days. I would expect that to continue as you dose longer with a higher dose.
Yep. Makes sense. How do you see the sort of oral fitting in, right? You mentioned monthly could be sort of a maintenance dose. You know, how does the oral fit in?
Yeah, we kind of see the oral in the same, in the same way, that it would be most attractive in the maintenance setting. You reach a target weight range, and then you transition from your SubQ weekly, either do a SubQ monthly or to an oral formulation daily. And this just gives people more options, I guess, for treatment. And the one attractive feature is the same molecule, so it's. You don't have to worry about maybe inducing new side effects with a different molecule or anything like that, you would transition. And that, you know, if you were to go from the SubQ to the oral on a maintenance, the oral dose there probably doesn't need to be as high as the dose required for weight loss.
Mm-hmm.
The amount of drug required to prevent weight gain is likely to be lower than the amount of drug required to induce weight loss, so it reduces that sort of API demand for the maintenance product. That's where we see the biggest bucket in the oral with the maintenance setting.
Can you maybe just talk about the market opportunity here in obesity? I think expectations are, you know, fairly large, and-
Mm-hmm
You know, where do you see your programs fitting in? And then, how do you sort of compete with these, you know, larger pharma companies?
Yeah, it's a large market. Yeah.
It weighs off, too.
Yeah, yeah, it's a little ways off. But I think on efficacy the molecule looks pretty potent. And if we have some differentiation on tolerability or convenience, I think that would help drive uptake. It would be something we'd prefer to be engaged with a larger party as far as commercialization. So that would be kind of plan A, to have another larger company involved. But we'll have to see how that evolves.
Yeah. Just for the oral to sort of be competitive, what do you kind of see as the profile that you need to sort of hit there? And maybe not necessarily in this phase I study, maybe in the phase II-b, but.
Yeah. Well, we would hope in the phase II, if the curves were to continue, that we would, you know, see, you know, greater than 5% weight loss-
Yep
... over 13 weeks. And if the tolerability profile is what it looked like in the 28-day study, I think that would be a really competitive profile versus what we've seen. So, but we'll have to do the study to really see.
Yep. Another question that's sort of been a focus is just manufacturing. There's obviously been some capacity issues currently, and there's efforts to sort of expand that. But how does that impact you, or how do you think about preparing for that in the future?
Yeah. Today, it doesn't impact us at all. We have clinical supplies for phase III for the SubQ, for phase II with the oral, and there are multiple batches kind of being made as well. So we're okay as far as the clinical trial supply. Where it becomes an important question is in commercial launch, where the amounts will be much, much greater. And we're working with multiple suppliers, looking at various synthetic routes, and we would hope to, by the end of the year, choose one of the routes. That's one of our goals this year, is choose one of the routes that we would like to scale up on a commercial scale. And so, a lot of focus on that right now.
Hope to enter into an agreement by the end of the year.
Yep. Okay. You think multiple, multiple agreements or one agreement initially, or?
Preferably one.
Yep.
Yeah, and preferably be one for both the API and the tablet, and the fill and finish, so you've got everything in one house.
Yep. Makes sense. So we've been talking about 2735 , but I know you have other opportunities in the clinic for obesity, you know, one being amylin, so maybe we can start there, and if you could, you know, touch on that program and where you're at.
Yeah, yeah. We've been working on that program for a little while now. Really interesting mechanism. In some of the in vivo work, it probably looks a little more effective than the 2735 compound. So really attractive mechanism. We would see the amylin program more of a, as more of an add-on to another mechanism. So, to the extent you could combine with a dual agonist on GLP and GIP, it'd be a nice triple agonist.
Yeah.
That's kind of what we're thinking longer term, so we hope to bring a compound into the clinic next year, and then follow it with a combo, so they would be kind of- we'd like to understand the single agent's profile first-
Yep.
and then look at how it plays with the GLP/GIP dual agonist as well.
When you say advance in the clinic next year, is it possible we might see some data maybe towards the end of the year, or is that too aggressive?
That's possible. Hard to predict, but that's possible, yeah.
Mm-hmm. Okay. Maybe other pipeline assets in obesity. I know you haven't said too much about it-
Yeah.
but I think there's others, so maybe just if you make comments there and sort of how you think about advancing those or not advancing those.
Yeah, well, we have other programs that we haven't publicly disclosed, and we typically have been pretty quiet about programs until we're pretty sure we're going into the clinic. With the amylin, we're pretty sure we're going into the clinic, so that's why we disclosed those data at the American Diabetes Association Conference. With others, we'll probably continue to be quiet until we get closer to a decision on filing an IND.
Yep. We touched on this a little bit earlier, but just, you know, commercial-type strategy or thinking in terms of, you know, trying to go on your own or partnering, and I know it's early, but is there a preference for type of partner? You know, is it geographic? Is it worldwide? Those types of things.
Yeah, if it were a partnering opportunity, I think a global partner would be the ideal partnership. And, I guess, the second preference would be a sort of regional, you know, Asia, Europe, North America. We probably wouldn't be interested in the country-specific partnerships.
Yep. Obviously, partnering is one way, but another option is, you know, potential sort of acquisition. I don't know. Can't make much comment there, but just anything, any kind of comments, 'cause that's, like, one of the most common questions we're getting.
Yeah, yeah. Well, me too. So, no. No real comment there, yeah. Okay.
Anything about obesity, in your program, do you think goes underappreciated by investors, or you think that the story there is well appreciated, given your sort of multiple, you know, options with SubQ, oral, and-
Yeah, I mean, I think the compound presents a portfolio of options with the, if the monthly were to succeed, that gives you a nice maintenance regimen that might help with, you know, retaining patients on therapy. The oral, I think, also gives you the same molecule in a different, dosage form, which might be attractive to both the clinicians and patients. And so, I think it gives you a variety of products from the same molecule, which is differentiated. Next generation would be if you were to combine with the amylin agonist. Typically, you see, you know, 40%-50% improvement in efficacy when you add amylin on top of, say, a GLP-1 agonist.
So, if you were to add it on top of a dual agonist, you'd see the same... If you saw the same bump-
Mm-hmm
... it would represent a really meaningful weight loss signal.
Yep. Maybe last question on obesity. Obviously, you have a lot of things moving forward. Just, you know, how do you think broadly about the key priorities as you move forward into next year?
I think the key priority is to get through the end of phase II and understand how the phase III will look design-wise.
Mm-hmm
... how long it's going to be, the doses to use, whether or not the monthly would fold into the registration program or not. Those are all important. All the design elements around phase III, really important, focuses for us, for the next three to six months. And then getting that study up and running and executed as quickly as possible.
Yep.
With the oral, big focus on getting the study up and running by the end of the year, and then if it followed the same trajectory as the SubQ, hopefully, we would have data, you know, toward the second half of next year with that program. So both of them progressing pretty quickly, and then the amylin program moving to the clinic, hopefully next year as well.
Yep, makes sense. You know, we got about five minutes, so maybe just touch on 2809
Mm-hmm
And kind of the current thinking there or next steps.
Yeah, 2809 is our small molecule thyroid receptor beta agonist. We completed a phase II-b study, called the VOYAGE study, earlier this year. We showed a really nice reduction in the fibrosis, and we saw a nice NASH resolution rate, as well as the combination reduction in fibrosis and NASH resolution. The plan with the program is to have an end-of-phase II meeting, likely in the fourth quarter, to understand current thinking around registration trial designs. And really, in particular, does everybody need a biopsy, or can you biopsy a subset? I think that's an important question for us to understand. With the program, I think-...
You know, we're looking at likely partnering would be the path forward there, but we wanna see what the FDA says at the end of phase II meeting.
Yep. And previously, you sort of mentioned, 0 214 , that's your X-ALD program. You're gonna have some data, I think, by the end of the year.
Yeah.
Maybe just give a little quick background there.
Yeah
and maybe the size of the opportunity and what-
Yeah. About 8,000 patients in the U.S. have X-linked adrenoleukodystrophy. We would be looking at a subset of that X-linked adrenoleukodystrophy population called the adrenomyeloneuropathy. It's about half of the patients, somewhere 40%-60% of that. So 4,000-5,000 you would consider in the U.S., and similar number in Europe. Thyroid beta agonists regulate the expression of a receptor peroxisomal transporter that shuttles very long-chain fatty acids into the peroxisome, where they get metabolized and discarded. So the thinking is you treat... And these patients, one of the drivers for onset and progression of the disease is an accumulation of very long-chain fatty acids, which causes axonal damage.
So if you can treat with a thyroid beta agonist, induce the expression of these peroxisomal transporters, and reduce very long-chain fatty acid levels, maybe you could mitigate, slow the onset and mitigate some of the symptoms that these patients experience. So right now, we're doing a 28-day study in adult men with adrenomyeloneuropathy, and we're looking at the change in very long-chain fatty acids. It's phase I, so it's mainly safety, tolerability, PK, but we're looking at the changes in the very long-chain fatty acid levels as well.
Yep.
I think we would seek a partner with a specialization in orphan diseases, following that study.
Okay. Makes sense, and maybe just last question, if you can comment on your current cash position, you know, what that covers, and then kinda what the runway looks like from here?
Yeah. With the current cash, I think we ended the second quarter with $940 million in cash, and that would get us through a phase III program with the SubQ formulation and a phase III program with the oral formulation. And I think a little ways beyond that as well. So, I guess safe to say minimum of two years of cash where we sit today.
Yeah. And can you maybe talk about the cost for each of those phase III studies?
For the phase III programs, together, we're kind of assuming around a $300 million range. So for each one would be about, our assumption is around $300 million.
Yep, makes sense. Okay, great. Looks like we're out of time, so why don't we end it there? Thanks so much, Brian.
Thanks a lot.
Appreciate your time.
Yep, thanks.