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

All right. Welcome, everyone, to Jefferies Healthcare London Conference. My name is Roger Song, one of the senior analysts who cover semi-cap biotech in the U.S. It is my pleasure to introduce our presenting company, Viking Therapeutics, CEO, Brian Lian.

Thanks, Roger. Thanks to Jefferies for the invitation to present. I really have a great schedule today. So I really appreciate it. I'll make some forward-looking statements today. I'd encourage anybody hearing this presentation to refer to the Securities and Exchange Commission website for the most current information on Viking Therapeutics. I'm the Founder and CEO. We're a San Diego-based company. We've got about 55 employees. We are focused on metabolic and endocrine disorders. We think our clinical programs have demonstrated best-in-class efficacy data. And we'll talk a lot today about our metabolic disease program. So VK2735 is a GLP-1/GIP dual agonist that we're developing for obesity. It's currently in a Phase III program we call the VANQUISH program. We have an oral formulation of the same molecule that recently completed the Phase II study, and I'll walk through some of those data today as well. And then we have an amylin agonist that is approaching the clinic, and we expect to file an IND in the first quarter. We have additional programs focused on the thyroid receptor beta, 2 agonists: one, VK2809 that's been through a Phase IIb study in MASH; and one, VK0214 that's been through a Phase Ib study in X-linked adrenoleukodystrophy. We're not actively developing those programs. Here's a graphical representation of the pipeline here. You can see the VK2735 in Phase III with the subcu formulation, and then the oral formulation just completed a Phase II study and then the amylin moving toward the clinic. The additional programs are not being actively developed right now with the MASH program and the X-ALD program. So with the peptide hormone agonist program, we started working on these molecules back in 2019. We looked at the GLP-1 mono-agonist and then a dual-agonist where GIP activity is added and then the triple-agonist where glucagon activity is added on top of those. And we prioritized the dual-agonist mechanism because they just seem to work the best. When we added glucagon, there wasn't any incremental benefit. So we focused on the dual GLP-1/GIP co-agonist. VK2735 was selected as the lead development compound. We have 2 follow-ons that are IND-ready today. The injectable formulation completed the SAD/MAD study in the first half of 2023. And then the -- subsequently, we took it into Phase III called the VANQUISH-2 Phase III programs -- studies. And then the oral formulation has been through a similarly a Phase I SAD/MAD and also a Phase II study with the most recent data reported in the third quarter of last year. I'll move to the oral formulation. It's a little bit earlier stage than the subcu, but it's where we have the most recent data. And these are some data from a 28-day study we conducted with the tablet formulation. This is once-daily dosing. And with this formulation after 28 days, we saw a nice dose response. You can see up to around 8% from baseline at 100 milligrams, placebo adjusted around 7%. So a very nice overall dose response. This shows the trajectory of weight change following 28 days of dosing. And what was interesting in this graph is when you -- it's most obvious in that red line, the top dose, 100 milligrams. You can see the dotted line there showing where treatment was stopped. And for the following 57 days, we saw a pretty good maintenance effect that lasted 4 weeks after that last dose. Actually, we had 8.3% after 57 days and 8.2% after 28 days. So really held on nicely. And it suggested in our view that maybe once someone has attained some degree of weight loss that the maintenance could be feasible with a low dose for a longer period of time. When we look at the GI tolerability summary from the Phase I study, very, very encouraging tolerability and very little titration in these. Most of the cohorts started at the top dose from the prior cohort and just went at that top dose for a week and then went to the target dose for 3 weeks. So for example, the 80-milligram cohort started at 60 for a week and then went to 80 for 3 weeks. And despite that accelerated titration, we saw very nice tolerability. So the Phase I takeaways here from the 28-day study up to 8.2% body weight reduction after 28 days of dosing, progressive effect in most cohorts suggested that further weight loss is likely to occur with longer treatment. The majority of the weight loss was maintained 4 weeks after the final dose. And we saw in this study, excellent tolerability through 100 milligrams with the vast majority of adverse events being characterized as mild or moderate. We saw low rates of vomiting, diarrhea and constipation in the higher dose cohorts. And then we did a -- I didn't have it in the slides here, but an exploratory transition cohort where people were titrated up to 80 milligrams daily for the first 2 weeks, and then they transitioned to an every other day regimen. And these people also continued to demonstrate weight loss. So it suggested that, again, you might be able to transition people to a lower daily dose and continue to see weight loss. So following this study, we conducted a Phase II study called the VENTURE oral dosing study. And this was a dose-ranging study, went from 15 milligrams up to 120 milligrams daily. The green cohort at the bottom of the diagram there was an experimental cohort where people were titrated very quickly up to 90 milligrams and then down-titrated to 30 milligrams for the final 7 weeks of the study, and that was to further explore this maintenance concept. These are the weight change data. These data were reported back in August, and we saw a really nice dose response here up to a little over 12% after 13 weeks of daily dosing, but every dose cohort showed a successively greater impact on weight loss. So we're very happy with the efficacy profile here. And when we look at the likely target doses moving forward, we're expecting to really focus on that 20 to 75-milligram range in future studies. And we feel that the profile and the weight loss profile here is very competitive after 13 weeks. This shows the trajectory of weight loss through 13 weeks, showing up to 12%, so 7% to 12% progressive in every cohort and statistically significant versus placebo at every time point after the first week for every cohort above 15 milligrams. When we look at the follow-up data here, here are some data that we received later on in October. And we can see in this range that we're really interested in that 20 to 75-milligram range, a nice maintenance of weight loss for the 3 weeks following completion of dosing. And this further supports this concept of durability that we see. Here are the results from that exploratory maintenance cohort. So the gold line here shows the cohort that was just titrated up to 90 milligrams and held there through the 13-week window and showed around 11% weight loss. The green line here is that cohort that was transitioned from 90 milligrams to 30 milligrams. So at week 6, these people were down-titrated back to 30 milligrams and held there for the following 7 weeks. And we were gratified to see that they had lost 8.1% after the first 6 weeks. And then after the transition to 30 milligrams, they continued to lose weight very gradually and ended with 8.2%. So it suggested to us that this concept of a lower maintenance dose is very promising. When we look at discontinuations here and treatment-emergent adverse events, really not a lot of difference. When you go to the far right on that 120-milligram cohort, you do see an uptick in discontinuations and overall treatment-emergent adverse events. But when we look at the range that we're expecting to focus on in future studies, really not a great deal of difference between the treated cohorts and the placebo cohorts. Majority of the treatment-emergent adverse events were mild to moderate and discontinuations probably due to this accelerated titration rate here. We -- based on the Phase I data, we had used 2-week titration blocks, and we started at 30 milligrams. I think in future studies, we probably start a little lower and extend the titration block to 4 weeks. And most of the treatment-emergent adverse events that led to discontinuation were GI related. When we look specifically at the GI tolerability summary, again, a little bit higher as you go to the far right of the table relative to placebo. But overall, when we focus on the dose range that we're most likely to utilize in future studies, really no significant difference from placebo on nausea or other GI adverse events, a little bit of an uptick in vomiting, but we think that starting low and going slow is likely to address that. Again, most of these mild. This is an interesting histogram that shows the time course of GI adverse events. And this is consistent with what I'll show in a few minutes on the -- from the subcu experience, and that is that usually when GI adverse events are observed, the most common occurrence is in that first week of treatment when people are first exposed to the mechanism. The second most common window of GI adverse events is in the first step in up-titration. And you can see that here. Week 1 was the initiation of treatment, then week 3 is your first step up, and that's where you see the highest rate of nausea in blue. Following that then after you get to week 4 and beyond, really very little difference from baseline and background rates on constipation, diarrhea and vomiting. So the Phase II study takeaways and next steps. We saw up to 12.2% reduction in body weight after 13 weeks of oral dosing, progressive dose-dependent weight loss across all treatment cohorts. The maintenance cohort is exploratory, but it was very promising. It showed a proof of concept there after you transition to a lower dose, you continue to see some weight loss. We thought excellent tolerability through the 120-milligram dose with the majority of treatment-emergent adverse events characterized as mild to moderate. And we think that starting low 10 to 15 milligram starting dose and then 4-week titration blocks are likely to greatly improve the tolerability profile observed here. The majority of the GI adverse events also were mild to moderate. I'll talk in a few minutes about a study that we have ongoing today, which is a transition study where people start with a subcu dosing regimen and then transition to oral daily, a low-dose oral daily regimen. That study is ongoing. And we currently, with this formulation, plan to talk to the FDA by the end of the year and have an end of Phase II meeting and then decide what the appropriate next steps are for the oral tablet. Now I'll move to the subcu formulation. This has been through a SAD/MAD study and also a Phase II 13-week study. This is just a brief summary of the SAD/MAD takeaways from the SAD study, single ascending dose study. We saw a T-max of about 72 hours, which indicates a fairly gradual onset of action. Half-life, 170 to 250 hours, which we think makes the formulation amenable to weekly dosing and potentially monthly dosing. In the MAD study, we saw a dose-dependent improvement in weight loss up to 7.8% after 28 days, and that was in subjects with an elevated BMI. And then we saw durable weight loss 21 days after the last dose. In this -- in the MAD study, we also looked at liver fat. We saw up to about a 50% reduction in liver fat in the patients who received MRIs. And we think it's a pretty rapid effect and indicates a broad metabolic benefit from the mechanism. And then really excellent exposures from weekly, suggesting that a monthly is certainly a possibility. And then finally, excellent tolerability with 98% of the adverse events characterized as mild to moderate. Following the Phase I, we designed and initiated this Phase II study, we call it the VENTURE study, very similar to that oral study I just talked about, but was used weekly injections, dose range from 2.5 mg up to 15 milligrams. And the 2.5 was a flat dose, the 5, 10 and 15 utilized titrations every 3 weeks. The primary endpoint here was change in body weight at week 13 versus placebo. This slide shows the primary endpoint in that study, looking at change in body weight after 13 weeks, very nice dose response ranging from 9% to approximately 15% from baseline, statistically significant starting at week 1 and maintaining all the way through the 13-week endpoint. And that's shown here, the progressive weight loss over 13 weeks. You can see a very nice initiation of weight loss and then sustained trajectory through the entire treatment window. No evidence in any cohort of a plateau, and we think that suggests a further improvement in body weight with longer dosing. Here's a GI tolerability summary. And we can see here, like with the oral, generally, you see an increase in GI adverse events, nausea, vomiting and diarrhea as dose increases, but it's not always purely dose dependent. You can see the -- for example, the 10 mg is maybe a little bit better than the 5 mg. So a general increase, but we don't think a significant issue with GI or anything that's different or unexpected from the mechanism. This is an interesting slide because it shows the time course of GI adverse events in 2 cohorts. The 10-milligram cohort is on the left and the 15-milligram cohort is on the right. And the big difference in these 2 cohorts is that the 10-milligram cohort started at 2.5 mg. And so you can see in that first week, just like we saw with the oral, an elevation in nausea and a little bit of constipation there in that first week, which then declines very rapidly and then ticks up again when you hit week 4, which was the first titration step. So the difference between the left-hand graph and the right-hand graph is the 15-milligram cohort started at twice the dose. The 15-milligram cohort started at 5 milligrams. And you can see here a large increase in nausea and it really speaks to that -- just that mantra that everybody talks about with this mechanism, start low and go slow. When you look out on the right-hand side of that right graph, you can also see when they were titrated to 15 milligrams, you see another uptick in nausea. Well, this was the largest uptick because people went from 10 milligrams to 15 milligrams. They skipped the 2.5 mg dose. So we learned 2 things from this cohort. One, you want to start below 5 milligrams; and two, you don't want to jump more than 2.5 mgs in each titration step. So very valuable learnings from this cohort, again, to start low and go slow. So the Phase II study takeaways are summarized here up to 14.7% mean weight loss after 13 weeks. We think very promising tolerability with over 90% of drug-related treatment-emergent adverse events mild to moderate. The majority of GI-related adverse events occur early and then resolve. And then we see good durability here. We don't have the slide in this deck, but when we look 4 weeks after the last administration of study drug, more than 90% of the efficacy was retained, which further suggests that possibility of a less frequent than weekly dosing. And to that end, the PK profile suggests that a potential monthly regimen would be worth exploring. Where we are today with the subcu formulation? We initiated 2 Phase III studies in the second quarter. The VANQUISH-1 study is enrolling patients with obesity and the VANQUISH-2 study is enrolling patients with obesity and type 2 diabetes. Both of these studies include an extension to look at long-term safety and efficacy, a 52-week extension. VANQUISH-1, we just announced before this presentation this morning. We've completed enrollment, and that was over-enrolled versus the target enrollment number there. And VANQUISH-2, we expect to complete enrollment in the first quarter. This is a diagram of the study design for both studies. The -- 3 treatment arms versus placebo, 7.5, 12.5 and 17.5. All of the cohorts started 1.25 milligrams. They're held there for 2 weeks, and then they undergo 4-week blocks at 2.5 mg. So it takes about 26 weeks for the 17.5 mg to reach that top target dose. And then once that 17.5 mg dose is reached, they're held there for 52 weeks. Primary endpoint is a change in body weight from baseline and secondary endpoints look at proportions with the 5%, 10%, 15% and 20% weight loss. And then finally, this is a maintenance study that we kicked off in October. Complicated slide, it's a complicated study. But if you focus on the top hand -- or the top part of this diagram, you can see cohorts are titrated on a weekly basis up to a range of weekly doses, and they range from 15 milligrams weekly up to 22.5 milligrams weekly. At week 19, then cohorts are transitioned to a monthly regimen. And the monthly regimen ranges from 15 milligrams up to 22.5 milligrams. And we have a control in there that keeps 17.5 mg weekly through the whole window. Another control that titrates up to 17.5 and then transitions people to placebo and then a placebo, the entire duration of the study as well as a control. The bottom hand -- the bottom half of the study of the slide shows an oral set of cohorts here. So these cohorts are titrated up to 17.5 mg weekly. And at week 19, they are transitioned to either 17.5 mg daily oral, 27.5 mg daily oral or 110 mg weekly oral once a week. So a lot of really, really useful information will come out of this study, and we expect to report the data around the middle of next year. Finally, I'll wrap up with the financial summary. We ended the third quarter with a little over $700 million in cash. We expect that to get us through the VANQUISH Phase III data readouts and really fortunate to have the runway that we have today. So that's the story. So we're focused on metabolic and endocrine disorders. The metabolic disease program highlighted by VK2735. That's the dual agonist for obesity, currently in the VANQUISH Phase III trial program with VANQUISH-1 completed enrollment as we announced this morning. VANQUISH-2, we expect to complete in the first quarter of next year. The oral formulation completed Phase II. We will have an end of Phase II meeting by the end of the year and then make a decision on what the next steps are with the oral formulation. And then I didn't talk about it, but we do have an amylin agonist that's moving towards the clinic, and we expect to file an IND in the first quarter of 2026. So I'll stop there. Thanks very much for your attention. Really appreciate it.

Just one quick question. I think one of the new information I picked up is the oral formulation, the Phase II, you decided to focus on the low end of the -- the middle end of the dose cohort. So is that guided by the PK and the GI? Or what -- and then what's the TPP for that dose cohorts?

What's the what?

What's the target product profile?

Yes. So we focused on those mid-range doses. So what I did mention is that this -- the VENTURE oral study, everybody took 4 tablets, even the placebos. And the tablets were 30-milligram tablets and the 30 mg is -- it's a lot to put in 1 tablet. So when we thought about doses to take forward, we wanted to -- kind of a lot of things went into that decision. What's the right tablet size, how many tablets do people want to take? What are the margin considerations as you go up in dose? And that 25 to 75 is really kind of the sweet spot for all of those items. So that's why we decided to stay in that range. We have that weekly dose in the maintenance study. That should be really interesting because the half-life is around 8.5 days. So it's possible that once you reach a target dose with the subcu, you could transition to that once-a-week dose and maintain body weight.

Thank you. Thank you, everyone.

Thanks.