This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk04: successfully achieved both its primary and secondary endpoints. Patients receiving VK2809 at doses as low as 5 milligrams daily demonstrated highly statistically significant reductions in liver fat content, as well as improvements in LDL cholesterol. VK2809 also performed well on secondary measures in this study, demonstrating significant reductions in other plasma lipids, such as triglycerides, apolipoprotein B, and lipoprotein A. Follow-up data presented at the 2020 EASL conference showed that treatment with VK2809 resulted in durable reductions in liver fat with the majority of patients remaining responders four weeks after completion of the study. Importantly, no serious adverse events were reported in this trial among patients receiving VK2809 or placebo. We believe that VK2809's exceptional low dose potency in reducing liver fat and plasma lipids, its durable effect, and its safety and tolerability profile to date establish it as a best-in-class compound for the potential treatment of patients with NASH and fibrosis. Notably, VK2809's lipid lowering effects may lead to improved cardiovascular benefits in treated patients. This is a critical advantage in a field where multiple competitive mechanisms in development are associated with elevations in lipids that are known to increase cardiovascular risk. Following the promising results observed in our 12-week Phase 2A study, we initiated the Phase 2B study to evaluate VK2809 in patients with NASH. This trial, called VOYAGE, is a randomized, double-blind, placebo-controlled, multi-center trial designed to assess the efficacy, safety, and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis. The study is enrolling patients across five treatment arms, and the target population includes patients with F2 and F3 fibrosis, as well as up to 25% with F1 fibrosis. The primary endpoint of the study will evaluate the change in liver fat content as assessed by magnetic resonance imaging proton density fat fraction from baseline to week 12 in patients treated with VK2809 as compared to patients receiving placebo. Secondary objectives include the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment. Through the third quarter, enrollment and dosing in voyage continued at sites in the U.S. and abroad. We continue to navigate a challenging clinical environment, and we expect to complete enrollment and announce top-line data in 2022. I'll now provide an update on our VK0214 program, which is our second orally available small molecule thyroid hormone receptor beta agonists. BK0214 is currently in development for the treatment of X-linked adrenoleukodystrophy, or XALD. XALD is a rare and often fatal metabolic disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells. The disease, for which there is no FDA-approved therapeutic, is caused by mutations in a gene known as ABCD1, which encodes a peroxisomal transporter of very long-chain fatty acids. As a result of these mutations, transporter function is impaired and patients are unable to efficiently metabolize very long chain fatty acids. The resulting accumulation of these compounds is believed to contribute to the onset and progression of clinical signs and symptoms in patients with XALD. What makes VKO214 a promising potential therapeutic in this setting stems from the key regulatory role played by the thyroid hormone beta receptor on the expression of an alternative very long chain fatty acid transporter known as ABCD2. Various preclinical models have demonstrated that increased expression of ABCD2 can lead to improved and potentially normalized very long chain fatty acid metabolism. For this reason, we believe that VK0214's potent activation of the thyroid hormone beta receptor may represent a potential therapeutic approach to the treatment of XALD. Last year, we initiated a randomized, double-blind, placebo-controlled, single ascending and multiple ascending dose phase one study of VK0214 in healthy volunteers. The objectives of the study were to evaluate the safety, tolerability, and pharmacokinetics of VK0214 administered orally once daily for up to 14 days. This study successfully achieved its primary objective with VK0214 shown to be safe and well tolerated at all doses evaluated. No serious adverse events were reported and no treatment or dose-related trends were observed for gastrointestinal side effects, vital signs, or cardiovascular measures. Treatment with VKO214 demonstrated dose-dependent exposures, no evidence of accumulation, and a half-life consistent with anticipated once-daily oral dosing. A secondary objective of the study was to evaluate laboratory assessments, including a lipid panel, to determine potential pharmacodynamic effects following exposure to VK0214. The results showed that subjects who received VK0214 experienced reductions in LDL cholesterol, triglycerides, apolipoprotein B, and lipoprotein A following 14 days of treatment. Many of the observed lipid reductions achieved statistical significance, though the study was not powered to demonstrate statistical significance on laboratory assessments. Given these positive results, Earlier this year, we initiated the Phase 1b study of VK0214 in patients with the adrenomyeloneuropathy, or AMN, form of XALD. AMN is the most common form of XALD, affecting approximately 50% of those with the disease. Clinical manifestations include progressive leg weakness, incontinence, and sexual dysfunction. Our Phase 1b study is a multicenter, randomized, double-blind, placebo-controlled trial in adult male patients with AMN. The study is initially targeting enrollment across three cohorts, placebo, VKO214 dosed at 20 milligrams daily, and VKO214 dosed at 40 milligrams daily. Depending on a blinded review of preliminary safety, tolerability, and pharmacokinetic data, additional dosing cohorts may be pursued. The primary objectives of the study are to evaluate the safety and tolerability of VKO214 administered once daily over a 28-day dosing period. In addition, the study will assess the efficacy of VKO214 at lowering plasma levels of very long-chain fatty acids and evaluate the pharmacokinetics of VKO214 in this population. Enrollment in this study is ongoing, and we currently expect top-line results to be available in 2022. In addition to our ongoing clinical trials targeting NASH with VK2809 and XALD with VK0214, we have been working hard to expand our pipeline of novel, best-in-class therapeutics targeting areas of unmet need in metabolic and endocrine disorders. To this end, earlier this week, we reported the first data from an internally developed program targeting novel dual agonists of the glucagon-like peptide 1, or GLP-1, and the glucose-dependent insulinotropic peptide or GIP receptors. Agonists of the GLP-1 receptor have demonstrated consistent benefits in diseases such as type 2 diabetes by improving insulin sensitivity, reducing plasma glucose, and reducing overall body weight. As a result of these therapeutic effects, multiple GLP-1 receptor agonists have been approved for both diabetes and obesity. More recently, the focus in this area has turned to the development of therapies that can maintain post-activation of the GLP-1 receptor while also activating other important receptors related to metabolic control. One of these approaches has been to simultaneously target the GIP receptor to provide enhanced stimulation of insulin secretion, thereby improving overall glucose control. The GIP receptor is known to regulate insulin secretion and to provide modest activation of the glucagon receptor. A single molecule with combined activity at both the GLP-1 and GIP receptors may therefore provide improved metabolic benefit relative to activation of either single receptor alone. Indeed, recent clinical data have demonstrated that dual GLP-1-GIP agonists not only provide excellent glucose control, but also potent reductions in body weight. In 2019, we initiated an exploratory program targeting novel dual agonists of the GLP-1 and GIP receptors. This program has evolved nicely, and we have been pleased with our progress and portfolio to date. We are excited to now be in the position to share some of the early data generated by this program. Earlier this week, we presented two posters at Obesity Week, the annual meeting of the Obesity Society, highlighting certain preclinical studies conducted in an in vivo model of obesity. The results of these studies demonstrate that in this model, the addition of GIP receptor activity improves upon the observed effects resulting from activation of the GLP-1 receptor alone. Weight loss, glucose, and insulin effects were enhanced in the Viking series of dual agonists compared with the effects observed with the GLP-1 agonist comparator, semaglutide, when administered at the same dose for the same length of time. In separate studies, the effect sizes observed with the Viking series of dual agonists were similar to those observed following treatment with Terzepatide, a dual GLP-1 GIP receptor agonist currently in clinical development. Reductions in liver fat content were generally numerically larger among animals treated with the Viking compounds relative to the liver fat reductions observed among trizepatite-treated animals. Highlights from the poster presentations include results showing that treatment with our novel dual agonists for 21 days resulted in statistically significant mean reductions in body weight of up to 27% relative to vehicle treatment. In addition, treatment with our dual agonists resulted in statistically significant mean reductions in blood glucose of up to 23% and plasma insulin reductions of up to 57% relative to vehicle treatment. In a separate 14-day study, treatment with our novel dual agonists resulted in statistically significant mean reductions in plasma triglycerides of up to 37% relative to vehicle. In this study, treatment with our compounds also resulted in statistically significant mean reductions in liver triglycerides of up to 49% relative to vehicle treatment. In general, Data from these studies demonstrated statistically significant improvements on these measures compared with the control cohort that received treatment with semaglutide. Results were also comparable to those observed among the control cohort of animals treated with the development stage dual agonist triseptide. We are highly encouraged by these early results and look forward to presenting additional data from this program at future scientific meetings. Based on the results from these and other preclinical studies, We plan to initiate clinical studies with a lead compound from this program in the coming months. We are excited to be advancing this new program, and we will provide additional information on the trial design and other details at the appropriate time. As we advance our clinical programs and expand our therapeutic pipeline, we're also keenly focused on the prudent management of our balance sheet. As Greg noted earlier, we ended the third quarter with approximately $216 million in cash. We believe this provides us with the resources to complete our ongoing clinical studies and advance our programs well into later stage development. In conclusion, we remain focused on the development of first in class and or best in class therapeutics for the treatment of metabolic and endocrine disorders. We believe our clinical track record establishes the company as a leader in the field and we continue to advance our existing clinical programs as well as explore new opportunities to create value for patients, clinicians, and investors. Our lead program evaluating VK2809 for the treatment of NASH and fibrosis is progressing through the Phase 2B Voyage Study, and we expect to complete enrollment and report initial data from this study in 2022. Our second clinical candidate, VK0214, for the treatment of XALD, is in an ongoing Phase 1B study in patients with adrenomyeloneuropathy and we expect to complete this study in 2022. Finally, as a result of our internal efforts to expand our pipeline, earlier this week we announced the initial results from a series of novel dual agonists of the GLP-1 and GIP receptors, which have shown promise in preclinical models. We expect to initiate clinical development of a lead compound from this series in the coming months. This concludes our prepared comments for today. Thanks again for joining us, and we'll now open the call for questions. Operator?
spk00: Yes, thank you. At this time, we will begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble the roster. And today's first question comes from June Lee with Truist Securities.
spk09: Hi, thanks for the update and for taking our questions. The first question is, are you able to disclose where you are in the enrollment of Voyage? And can we expect the data in the first half or second half of 22? And I have a follow-up.
spk04: Hey, June, thanks for the question. We aren't in a position to really disclose the enrollment numbers, and I think that's consistent with what we've done in the past. Right now, I would say, you know, middle of the year would be probably on the early edge of when we would have the initial data available.
spk09: Got it. And regarding your dual agonist, just really curious if that 27% weight loss you saw in mice could be translated into maybe 10% or greater weight loss in humans. Only asking... because that seems to be the bar set by another dual agonist that reported recently.
spk04: Yeah, you know, it's always hard to extrapolate, but we had terzepatide in the studies, or the second poster anyway, as a control, and we seem to be essentially right in line with the terzepatide efficacy level, which I think generally is in that 10 to 12% range, maybe a little larger depending on the population. But I think it's, again, this is mice, but it looks competitive at this point.
spk09: Right. Actually, the drug I was referring to is ALT801 from Altimmune. Theirs is oral. I mean, how important is it that drugs like ETH are oral versus sub-Q? Any lead-throughs from experience from the oral versus sub-Q semaglutide? Thank you.
spk04: Sure. You know, I think orals generally would be preferred by patients, especially, you know, as you get a little older. But, you know, given the efficacy and the therapeutic benefits, it's hard to say. If you have something that's maybe dosed less frequently, that might be preferable. But really, you look at the size of this the markets that this mechanism could apply in. And I think you'll see multiple modalities and multiple different compounds really being able to be successful.
spk00: Thanks, Mark.
spk04: Thanks, Jim.
spk00: Thank you. And the next question comes from Matt Lucchini with BMO Capital. Hi.
spk08: Good afternoon. Thanks for taking the questions and for the nice update. First, I guess on voyage again, you know, just thinking about your expectations where we were versus last quarter, if there's anything different in your thinking. In other words, is patient recruitment environment at this point better, worse, or in line with your expectations? And then on the dual agonist, you know, I just would like to get some thoughts on how you're thinking about indication selection here. Obviously not afraid of markets with big development programs, but as you look at the therapeutic and competitive landscape, where do you think a product like this could have the greatest impact? Thank you.
spk04: Yeah, thanks, Matt. With the voyage enrollment, I think it's been continually challenging. It's been pretty steady since the summer, and we've continued to expect an uptick in enrollment as the COVID pandemic sort of winds down at least in the U S uh, and we haven't really seen that. Um, we think, uh, you know, there's, there are a lot of unexpected challenges with COVID. I think, um, there are staff shortages at sites, staff shortages at, uh, at CROs. Uh, we have also surprisingly the impact of COVID studies on, on site operations has been, uh, larger than I think we would have ever expected. But, uh, It's been consistent. We've been enrolling steadily, and it's not as fast as we'd like or anybody would like, but it's moving forward. With the profile of the dual agonists, I think what generally you see with the dual agonists is efficacy that looks to be a little bit better than the single GLP-1 agonists, even if you dose up with the GLP-1 agonists. I think the therapeutic profile will be really attractive if any of these are ultimately approved. And that would hold really in any indication in obesity or diabetes or NASH.
spk08: Okay. I guess, well, okay. I guess maybe the last question then would be, you know, it looks like spending is down pretty decently, sequentially. Just wondering, you know, in the past, there's been a talk about 50 to 70% step up and up X this year. You know, that obviously implies a hefty lift in the fourth quarter. Just wondering how we should be thinking about that going into year round.
spk01: Hey there, Matt. I think the spend and expenses for the fourth quarter will be pretty similar to what we've seen here in the third quarter. So, you know, I think our pickup, we might see a bit into next year, but for now, you know, I'd say for the upcoming quarter, you can think of it similar to the third quarter.
spk08: Great. Thanks for taking all the questions.
spk01: Thanks, Matt.
spk00: Thank you. And the next question comes from Steve Seedhouse with Raymond James.
spk02: Oh, thank you. Good afternoon. It seems that the FDA, just with respect to NASH and you know, what the FDA is looking for from pathology assessment protocol. There seems to be some clarity coming there. These three pathologist panels are being used now by Intercept and others. I'm just curious if this is something that you've heard from the FDA directly, if it's something that you plan on incorporating into phase two, or, you know, is this only a relevant protocol to consider as you think about a phase three study? Thanks.
spk04: Thanks, Steve. Yeah, I think it's probably more applicable to phase three than phase two. We are using multiple pathologist reads in cases where we have close calls. I mean, sometimes if someone's got, you know, clear NASH and ballooning and steatosis and inflammation and fibrosis, I mean, there's no need for a second opinion there. But in the close calls, It's very helpful, and we're doing that. And, you know, I think moving into Phase 3, we and everybody else would probably skew toward that multi-reader approach because it just reduces the variability. At least you have to get the consensus as well.
spk02: Okay. And just the only other question I had is, if you think about this dual agonist and, you know, the nice data that you – presented preclinically and your plans to move this into the clinic in the coming months, would it be safe to say that this sort of takes priority as the next pipeline asset over, like, the BGAT-1 inhibitor and the FBPA's inhibitor and other things in your pipeline?
spk04: Yeah, that's a great question. Yeah, yeah. I think right now it is. The data were probably a little better than we expected, and so We prioritized it, and we're moving toward the clinic as quickly as we can. But that doesn't mean the other programs are unimportant. This is just bumped ahead of them based on what we've seen so far.
spk02: Great. Thanks, Brian.
spk04: Thank you. Yep. Thanks, Steve.
spk00: Thank you. And the next question comes from Jay Olson with Oppenheimer.
spk05: Oh, hi. Thanks for taking the question. For VK2809, Are there any competitor dynamics that you're looking out for in the near term that you think could provide important read-across? And then I had a question on your GLP-1 kit as a follow-up.
spk04: Yeah, sure. I think the big data set for the thyroid beta mechanism is expected sometime in the second half of next year. that's what we would certainly be looking for. And I think most people will be looking for that, you know, validation of the mechanism and, you know, a way to gauge the impact on fibrosis and NASH resolution in a larger population. So I think everybody's interested in that data set next year.
spk05: Okay, great. Thank you. And then I think you said that you were looking forward to initiating clinical development for your GLP-1 Get program. Does that mean that you have nominated a candidate? And can you just talk about the IND filing timeline?
spk04: Yeah, it does mean we've nominated a candidate. We're not in a position right now to identify it, but we do have a candidate in mind. And we said we'd... start the study, you know, hopefully in the next few months. So I don't want to give any timing on an IND filing or anything like that, but that, I think, guidance, you know, within the next few months is safe to say for initiation of a study.
spk05: Okay, great. Thank you, and congrats on the progress.
spk04: Thanks a lot, Jay.
spk00: Thank you. And the next question comes from Andy Shea with William Blair.
spk10: Thanks for taking my questions and congratulations on really extending your pipeline. So maybe a high-level question, Brian. Maybe highlight your R&D capability. This is something that we just haven't heard a lot about. You know, maybe, you know, a hit-to-lead optimization. you know, screening regarding, you know, base displays or something like that. Just kind of educate us on where you are in terms of your R&D infrastructure.
spk04: Thanks, Andy. That's a good question. So just to reiterate, the vast majority of our efforts are on the clinical side with VK2809 and VK0214. But we do spend a fair amount of time in the literature and watching the competitive landscape And the company's always been sort of modeled on this virtual outsourcing approach. So when we find an interesting target or an interesting area to look at, we contact the appropriate vendors and get really targeted on the specific studies that would be the most useful for us in order to avoid a huge incremental uptick in spend. And it seems to work. We've dabbled in a lot of areas. Not everything seems to stick, but this one seemed to look pretty nice. And the more we learned about it, it seemed to rise to the top of some of the other things we've been looking at. So that's why we've decided to put a little more effort into this. But it really is compound and project-specific regarding how we approach the development path.
spk10: That's very helpful. And just, again, probably a longer-term question, just regarding the strategy here, obviously, you know, if you look at the surge appetite program, you know, five large-facing programs, so maybe kind of provide us with your longer-term vision. Are you going to, you know, combine with 2809 and NASH, just have basically an in-house combinatorial optionality and then partner out the larger ones to a big pharma, that kind of stuff?
spk04: Yeah, that's a good question. So I think this fits within the way we've always thought about VK2809 as well, and that is these big markets are probably best addressed with a partner. And so whether that's before Phase III or after Phase III, These large markets that require large infrastructure would, you know, first choice would always be to partner. And we've always been open to partnering discussions. Where these programs could work internally most feasibly is on the orphan side. So we think for rare diseases we could launch and commercialize a product there without a massive uptick in infrastructure. But the GLP-GIP program would fit, you know, more along the lines of the way we think about our VK-289 asset where partner would be preferred for the much larger expensive programs or, yeah, clinical development programs. Got it.
spk10: Okay. That sounds good. Thank you so much for answering my question. Thanks a lot, Andy.
spk00: Thank you. And the next question comes from Yale Jen with Laidlaw & Company.
spk06: Good afternoon, and thanks for taking the questions. I just want to confirm in terms of the 0214, in terms of the potential sort of data readout from the Phase 1B, would that be in the second half of this year or next year, or that could be pushed out to 2023? Hey, thanks, Gail. No, we would...
spk04: hope to have it next year, probably in the second half of next year, but the plan is to hopefully have the top line available by the end of the year in 2022. Okay, great.
spk06: And one more question in terms of the dual agonist. As you indicated that the study will start in a couple months, is that referring that or suggesting that the GLP-TOCS auto study has been done or is still ongoing?
spk04: That's a great question, Yael, and I don't want to get into that level of detail, but obviously we have to do some talks before we go into humans, and so it would be reasonable to assume that that's underway or enough has been completed to allow us to consider moving into humans. But good question. We're just not going to give that level of detail right now.
spk06: We try, and thanks for the comment.
spk04: Thanks, Yael.
spk00: Thank you. And the next question comes from Justin Zelen with BTIG.
spk11: Hi, Brian and James. Congrats on the progress this quarter. Thanks for taking the question. So first on the dual agonist, I was just curious on, you know, the PKPD front, whether we should expect the frequency of administration of the drug to be comparable to trisepatide, or do you think there's potential to potentially push the duration of effect to more than a once-weekly dose?
spk04: Yeah, this is a good question. We'll have more insight on that after we get some human data, but I would say it's not a daily. It would be a longer acting agent, but just how long that is, we really won't have a good handle on until we start looking at some of the human data.
spk11: Great. Okay. That makes a lot of sense to me. And, you know, you mentioned that you're also looking at the competitive landscape and are scouting new mechanisms. Is there anything of interest at the upcoming liver meeting that particularly stands out to you?
spk04: Not with regard to new mechanisms we're looking at, but, you know, I think the, you know, the semaglutide data will be interesting. The FGF21 data will be interesting. So, Those would be the areas we'd probably be most focused on with respect to the ASLD meeting.
spk11: Great. Well, congrats again on the progress and thanks for taking the questions.
spk04: Thanks a lot, Justin.
spk00: Thank you. And the next question comes from Thomas Smith with SVB Larrick.
spk07: Hi, everyone. This is Mike on for Tom. With respect to the dual acting program, how are you thinking about the potential anti-fibrotic benefit for the mechanism? And then separately, do you have an initial sense of what that early study design could look like and if we might be getting some type of efficacy results?
spk04: Yeah, good question, Mike. So what we've seen, you know, with the studies of semaglutide is that you see a really terrific effect on NASH resolution and what look to be trends in fibrosis improvement that might be become clear with longer exposures. So all of the arrows sort of point the right direction on fibrosis, but the effect seems to be at least early most pronounced on NASH resolution. With respect to Phase I study, I think the template would probably look like the SADMAD study that we did with VKO214. So you're able to parallel track both of those. And, you know, you could probably look at some early pharmacodynamic signals from that sort of a study.
spk07: Great. Thanks very much.
spk04: Thanks a lot.
spk00: Thank you. And this concludes the question and answer session. And I would like to turn the call to Stephan Diaz for the closing comments.
spk03: Thank you again for your participation and continued support of Viking Therapeutics. We look forward to updating you again in the coming months. Have a great afternoon.
spk00: Thank you. The conference has now concluded. Thank you for attending today's presentation. May now disconnect your lines.
Disclaimer