Viking Therapeutics Inc (VKTX) 2020 Q3 法說會逐字稿

Welcome to the Viking Therapeutics 2020 Third Quarter Financial Results Conference Call.

(Operator Instructions) As a reminder, this call is being recorded today, October 28, 2020.

I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz.

Please go ahead, Stephanie.

Hello and thank you all for participating in today's call.

Joining me today is Brian Lian, Viking's President and CEO; and Greg Zante, Senior Vice President of Finance.

Before we begin, I'd like to caution that comments made during this conference call today, October 28, 2020, will contain forward-looking statements within the meaning of the Securities Act of 1933, concerning the current beliefs of the company, which involve a number of assumptions, risks and uncertainties.

Actual results could differ from these statements, and the company undertakes no obligation to revise or update any statement made today.

I encourage you to review all of the company's filings with the Securities and Exchange Commission concerning these and other matters.

I'll now turn the call over to Brian Lian for his initial comments.

Thanks, Stephanie, and thanks to everyone listening on the webcast or by phone.

Today, we'll provide an overview of our third quarter financial results as well as an update on recent progress and developments with our pipeline programs and operations.

I will begin with an update on our lead thyroid hormone beta receptor agonist program, VK2809.

During the third quarter, we continued enrollment of patients in our Phase IIb VOYAGE study in biopsy-confirmed nonalcoholic steatohepatitis and fibrosis.

As of the end of the quarter, the majority of our U.S. clinical sites were open for patient enrollment, though coronavirus-related disruptions continued to impact site operations.

We are currently in the process of expanding the number of clinical sites in the U.S. and internationally, and we continue to expect completion of enrollment in the first half of 2021.

With respect to our second thyroid hormone beta receptor agonist, VK0214, during the third quarter, we achieved a significant milestone by advancing this compound into clinical development.

In September, we announced the initiation of a Phase I trial to evaluate the safety, tolerability and pharmacokinetic profile of VK0214 in healthy subjects.

Following completion of this study, we plan to initiate a Phase Ib study in patients with X-link adrenoleukodystrophy.

We are excited to be advancing this important program as patients suffering with X-ALD currently have no approved therapeutic options.

I'll provide additional detail on our development activities after we review our third quarter financial results.

For that, I'll turn the call over to Greg Zante, Viking's Senior Vice President of Finance.

Thanks, Brian.

In conjunction with my comments, I'd like to recommend that participants refer to Viking's Form 10-Q filing with the Securities and Exchange Commission, which we expect to file later today, for additional details.

I'll now go over our financial results for the third quarter and first 9 months ended September 30, 2020, beginning with the results for the quarter.

Our research and development expenses for the 3 months ended September 30, 2020, were $7.1 million compared to $5.3 million for the same period in 2019.

The increase was primarily due to increased expenses related to our clinical studies, salaries and benefits and stock-based compensation, partially offset by decreased expenses related to preclinical studies and services provided by third-party consultants.

Our general and administrative expenses for the 3 months ended September 30, 2020, were $2.7 million compared to $2.2 million for the same period in 2019.

The increase was primarily due to increased expenses related to stock-based compensation, salaries and benefits and insurance expenses, partially offset by decreased expenses related to legal services and travel.

For the 3 months ended September 30, 2020, Viking reported a net loss of $9.3 million or $0.13 per share compared to a net loss of $5.7 million or $0.08 per share in the corresponding period in 2019.

The increase in net loss and net loss per share for the 3 months ended September 30, 2020, was primarily due to increases in research and development and general and administrative expenses noted previously, as well as decreased interest income due to the decline in interest rates throughout the third quarter of 2020 as compared to prevailing interest rates during the third quarter of 2019.

I'll now go over the results for the first 9 months of 2020.

Our research and development expenses for the 9 months ended September 30, 2020, were $22.9 million compared to $17.1 million for the same period in 2019.

The increase was primarily due to increased expenses related to our clinical studies, manufacturing for our drug candidates, salaries and benefits and stock-based compensation, partially offset by decreased expenses related to services provided by third-party consultants and preclinical studies.

Our general and administrative expenses for the 9 months ended September 30, 2020, were $8.5 million compared to $6.7 million for the same period in 2019.

The increase was primarily due to increased expenses related to stock-based compensation, salaries and benefits and insurance expenses, partially offset by decreased expenses related to services provided by third-party consultants, professional fees and travel.

For the 9 months ended September 30, 2020, Viking reported a net loss of $28.5 million or $0.39 per share compared to a net loss of $18.3 million or $0.25 per share in the corresponding period in 2019.

The increase in net loss and net loss per share for the 9 months ended September 30, 2020, was primarily due to the increases in research and development and general and administrative expenses noted previously as well as decreased interest income due to the decline in interest rates throughout the first 9 months of 2020 as compared to prevailing interest rates during the first 9 months of 2019.

Turning to the balance sheet.

At September 30, 2020, Viking held cash, cash equivalents and short-term investments totaling $255.3 million compared to $275.6 million as of December 31, 2019.

This concludes my financial review, and I'll now turn the call back over to Brian.

Thanks, Greg.

I'll now provide an update on our recent development activities, beginning with our lead program, VK2809 for the treatment of NASH and fibrosis.

VK2809 is an orally available small molecule agonist of the thyroid homeowner receptor that possesses selectivity for liver tissue as well as the beta receptor subtype.

Clinical data to date have demonstrated that VK2809 has compelling potency, selectivity, safety and tolerability profile that may provide benefit in a range of metabolic disorders, including NASH.

Our enthusiasm for this program stems in part from the results of our previously completed 12-week Phase II trial in nonalcoholic fatty liver disease and hypercholesterolemia.

These data demonstrated that patients receiving VK2809 experienced statistically significant reductions in liver fat content as well as improvements in LDL cholesterol, achieving the study's main efficacy objectives.

On exploratory measures, evaluating other plasma lipids, such as triglycerides, apolipoprotein B and lipoprotein (a), treatment with VK2809 also resulted in significant reductions.

Importantly, these results were achieved without any serious adverse events being reported among patients receiving VK2809 or placebo.

In the third quarter, additional follow-up data from this trial were presented in an oral presentation at the international liver conference, or EASL.

The newly reported data demonstrated that patients treated with VK2809 experienced durable, statistically significant reductions in liver fat content that were maintained at week 16, 4 weeks after completion of the 12-week treatment period in the study.

Specifically, VK2809-treated patients maintained a statistically significant 45% median reduction in liver fat content at week 16 compared to a 19% reduction among patients receiving placebo.

Additionally, at week 16, 70% of VK2809-treated patients maintained a response, defined as experiencing a greater than or equal to 30% relative reduction of liver fat content from baseline.

Notably, 100% of patients receiving 5 milligrams of VK2809 dose daily maintained a response at week 16.

In addition to these durability results, new analyses of week 12 study results demonstrated significant reductions in liver fat content among patients receiving VK2809 as compared to placebo regardless of the presence of common NASH risk factors, including baseline levels of ALT above the upper limit of normal, a body mass index greater than or equal to 30, hypertension or Hispanic ethnicity.

The overall data from this study, including these new findings of durability and efficacy in high-risk subgroups, support the underlying promise of VK2809 for the treatment of NASH and fibrosis.

In addition, we believe the broad efficacy observed on key lipid measures may indicate cardiometabolic benefits in this setting, an important advantage as compared to mechanisms that may lead to elevations in lipids known to increase cardiovascular risk.

Based on these positive Phase II results, last year, we initiated the Phase IIb trial to assess VK2809 in the setting of NASH.

This study, called VOYAGE, is a randomized, double-blind, placebo-controlled, multicenter trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis.

The study is targeting enrollment of approximately 340 patients across 5 treatment arms.

The target population includes patients with F2 and F3 fibrosis as well as up to 25% with F1 fibrosis.

Primary end point 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 subjects treated with VK2809 as compared to subjects receiving placebo.

Secondary objectives include evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment.

During the quarter, we continued to enroll patients in the U.S. despite the headwinds created by the COVID pandemic.

The majority of our U.S. sites are open for enrollment, and we expect to open ex U.S. sites imminently.

In addition, we plan to add further sites for enrollment with a plan to ultimately enlist over 90 sites globally.

We expect to complete enrollment in VOYAGE during the first half of 2021.

I will now turn to our second clinical program, VK0214, for the potential treatment of X-linked adrenoleukodystrophy, or X-ALD.

VK0214, like VK2809, is an orally available small molecule thyroid hormone receptor agonist that possesses selectivity for the beta receptor subtype.

In preclinical studies, VK0214 was shown to potently activate the thyroid hormone beta receptor, leading to improvement in several in vitro measures that suggest potential benefit in X-ALD.

Additional data from in vivo studies have demonstrated that administration of VK0214 produces a significant and durable reduction of very long-chain fatty acids in both plasma and tissue.

In part as a result of these important findings, VK0214 has been granted orphan drug designation by the FDA for the treatment of X-ALD.

In the third quarter, we announced the initiation of a Phase I first-in-human study of VK0214.

This trial is a randomized, double-blind, placebo-controlled, single ascending and multiple ascending dose study in healthy volunteers.

The primary objectives of the study include evaluation of the safety and tolerability of single and multiple oral doses of VK0214 as well as the identification of doses for further clinical development in the setting of X-ALD.

Investigators will also assess the pharmacokinetics of VK0214, following single and multiple oral doses.

Upon successful completion of the ascending dose trial, we plan to initiate a Phase Ib study of VK0214 in patients with X-ALD.

We currently expect this study to begin in the first half of 2021.

With 2 ongoing clinical programs, it is important to maintain a strong financial position, and we continue to carefully manage our cash resources.

As Greg stated during the financial discussion, we ended the third quarter with approximately $255 million in cash, and we believe this balance provides the runway required to complete both ongoing trials as well as a number of additional clinical milestones.

In conclusion, our primary focus in the third quarter was on the continued execution of our 2 clinical programs.

In our 52-week Phase IIb VOYAGE trial evaluating VK2809 in patients with NASH and fibrosis, the majority of our planned clinical sites are open for enrollment, and we plan to open additional sites in the coming months.

We expect to complete enrollment in the first half of 2021.

With respect to VK0214 for X-linked adrenoleukodystrophy, we were very pleased in the third quarter to move this important program into the clinic.

We are currently executing a Phase I single ascending and multiple ascending dose study and plan to initiate a Phase Ib study in patients with X-ALD in the first half of 2021.

To support these trials as well as a number of other key objectives, we continue to judiciously manage our cash balance, which remains strong at $255 million as of the end of the third quarter.

This concludes our prepared comments for today.

Thanks again for joining us, and we'll now open the call for questions.

Operator?

(Operator Instructions) Our first question comes from Joon Lee from Truist Securities.

I have a question on the additional data you presented at EASL, which I think is notable for a more robust liver fat reduction in patients with higher baseline ALT, where the placebo effects were suppressed in the higher ALT group.

I'm going to guess that the elevated baseline ALT is more in line with the demographics that you're enrolling in the Phase IIb VOYAGE.

Was the powering of VOYAGE factoring in this data stratification specifically?

Or was it based on all the patients -- that effects you saw in all the patients in the earlier study?

And the second question is the durability that you saw, at 16 weeks, does that change how you might strategize around your Phase III development plans, given this durability in terms of the frequency of dosing?

Joon, thanks for the questions.

As far as the subgroups that we looked at in the 12-week study, that didn't change our powering assumptions for the 52-week study.

We were looking at overall assessments on histologic changes for the powering assumptions.

We just thought it was really interesting when you look at pretty much every subset that we could identify that might represent higher risk or typical NASH phenotype that there wasn't any difference in efficacy.

And I think we had another slide in there about baseline liver fat as well.

And it just seemed to be pretty consistent across ALT, BMI, baseline liver fat, hypertension, all of those factors, baseline glucose as well.

So -- but we didn't use that for powering anything.

And as far as your second question, what was the second question?

Durability.

Yes.

No, we just think that that's pretty interesting.

It's useful scientific data for understanding the kinetics of liver fat changes.

It doesn't feed into our Phase III or future development plans, but it is a really interesting finding.

It indicates that you don't necessarily need sustained dosing.

You might be able to pursue an intermittent strategy, that type of thing.

But it didn't really change anything.

We had expected there to be good durability based on the mechanism and the robustness of the initial signal.

The next question comes from Derek Archila from Stifel.

Congrats on the progress.

Just 2 from us.

Just kind of thoughts on the recruitment right now.

I know you're saying and still guiding to completing enrollment by the first half of 2021.

I think having some conversations with some of your competitors, they seem to have more challenges with enrollment.

So I just want to get a sense of how much does your time line take into effect for kind of COVID and where we are in some of the kind of worsening conditions in the EU, where I think you're going to potentially open sites.

So I just want to get your comments on that.

And then second, just give us a sense of the regulatory pathway in X-linked adrenoleukodystrophy and what that looks like.

And could we see data from that Phase Ib study sometime towards the end of 2021?

Yes.

Thanks, Derek.

As far as the enrollment in the Phase IIb study, I don't want to understate the challenges.

And so I didn't mean to make it sound like we're having a super easy time with it.

It's really, really difficult.

I think it's difficult across the board for everybody.

But when we look at the site operations, the screening pipeline, that sort of thing, we still think we can do this in the first half of 2021.

Now that could change if there are statewide lockdowns like we saw earlier this year, but we don't see that right now.

What's really interesting in looking at the individual sites, they're maintaining pretty open operations despite the surges in certain parts of the country.

And I think that weighs more on patient psychology than site operations now compared to back in March and April.

But it's very, very difficult.

And we're still expecting to complete enrollment in the first half of '21, but very, very difficult.

As far as the registration path and X-ALD, we hope to get into patients in the first half of the year provided we get through the multiple ascending dose portion of the ongoing study.

And if things go well, it's possible we would have data next year.

I don't know.

It's possible we could; it'd be certainly later in the year.

And then we plan to talk to the FDA about what the next steps look like.

We would expect the end points and registration to be more functionally oriented, not biomarker oriented, but we won't know for sure until we have those conversations.

Terrific.

And congrats again on the progress.

Thanks, Derek.

The next question comes from Steve Seedhouse from Raymond James.

This is Ryan on for Steve Seedhouse.

Brian, I'm just wondering if you had a time line for presenting any additional data from the Phase IIa study.

Obviously, after the [16-week update] or potentially a publication.

And are you guys planning on having -- presenting any data at AASLD this year?

Thanks, Ryan.

No, we're not going to have anything at AASLD.

We do have a manuscript in preparation on the 12-week study.

Most of the bigger journals are prioritizing COVID things right now.

So it has maybe slowed that process down a little bit, but we do intend to submit that in the relatively near term.

As far as additional data, no plans today to have additional data from that study.

I think we've presented pretty much everything useful that we could present there, but maybe there could be some more in the publication.

The next question comes from Matthew Luchini from BMO.

And congrats on the progress.

So just a couple from me.

I guess, first, on the ex U.S. sites that are going to be opening up, I think when we last connected on the last quarter update, it sounded like those were perhaps a little bit more near term than just kind of opening up this quarter.

So just wondering if there were any bottlenecks there that prevented those sites from actually coming online until it seems like the end of the year?

And then secondarily, on 0214, for the SAD/MAD data, should we expect that to -- how should we expect that data to be communicated when it comes out?

Would that be just press release?

Would -- are you holding that for a medical conference of some sort?

Yes, please, on those 2.

Sure.

Thanks, Matt.

So on the ex U.S. sites, yes, those have been slower than we had hoped to come online primarily due to administrative items.

We had to submit a couple of documents.

We had to correct a couple of typos in one document that required a more substantial resubmission of those documents than we had originally planned.

It's just -- but nothing major.

It was really pretty minor administrative stuff.

And I don't know, it's hard for us to judge how much of that is just COVID-related with delayed communication time lines between our regulatory liaison and the European regulatory agencies.

But that could also play a little bit to those -- the kind of slow time line there.

But I would say we'll be opening some European sites here imminently.

So I think we're on track there.

As far as the VK0214 SAD and MAD data, we would hope to have some of those results in the first half of the year.

And good question on the disclosure strategy.

I mean, minimally, a press release, but depending on what the data looked like, we might try to submit something to a later conference in 2021.

But I think that will be driven on what we see.

If there's anything really exciting or interesting, we might want to save that for a conference.

But I would say, minimally a press release though.

Okay.

And then just one last one, if I could, on the numbers.

Both -- operating expenses have been quite flat now through 3 quarters this year.

And I guess we've been expecting perhaps a little bit more of a step-up as things had picked up with the Phase IIb.

So just wondering how should we -- we should be thinking about at least maybe the last quarter of the year?

And anything you can say, loose or otherwise, as we start thinking forward to '21.

With that, I'll get back in the queue.

Matt, Greg here.

Yes, I think -- yes, they have been a little bit flat, but we do expect them to continue to increase from here as the trial continues along.

So I think nothing to read into the flatness through this point.

I think it will continue to pick up going forward here.

We always try to be conservative on the estimates, but I think it is certainly going to tick up.

Yes.

Okay.

Great.

Congrats on the progress.

Thanks, Matt.

The next question comes from Michael Morabito from Chardan Capital Markets.

I just had a question here.

I wanted to know if there was anything put into place for the VOYAGE trial to track patients who at any point during the trial test positive for COVID during the trial.

And if there's any kind of a protocol that you put in place for what would constitute rationale for excluding patients that have been affected by COVID, do you have anything like that in place?

Yes.

Thanks, Michael.

This is a great question.

We treat COVID like you would treat the flu in this situation.

If someone gets so sick that they can no longer participate or no longer are willing to participate, then they would discontinue.

But that's no different from a pneumonia -- in this specific context, no different from a pneumonia or some sort of injury that would preclude them from completing the study.

So there's nothing COVID-specific in those discontinuation or withdrawal procedures.

It's just treated as another potential illness or injury that might lead to withdrawal.

Okay.

Would you consider tracking patients that have tested positive to potentially stratify the post hoc analysis after the fact?

Yes.

I don't know that there would be a meaningful number there, but I think we could certainly look at how those patients responded relative to the COVID-free patients.

Sure.

The next question comes from David Bautz from Zacks.

Brian, we've heard other NASH companies talk about moving their compounds directly into a Phase II/III trial.

And I was wondering if you could just remind us why you chose to go with a separate Phase II and a separate Phase III instead of doing a combined trial?

Yes.

Thanks, David.

Well, the published guidance calls for a 12-month biopsy prior to Phase III unless you've got some compelling biological rationale to propose otherwise.

And when we were planning the Phase III, we had originally wanted to do a Phase II/III, but then the guidance sort of suggested that might not be a good idea.

We didn't have long-term biopsy data as well.

And I think most importantly, and I think I said on these calls before, we could not find a single KOL to support that plan.

Maybe that's different for other organizations, but that was certainly our experience.

It was -- there was no exception to that.

It was absolutely 100% consistent.

So it sounds like a great idea.

I wanted to do it.

But at the end of the day, we didn't have the biopsy data that the guidance called for, and we had no real positive feedback from those who we proposed the structure to.

Okay.

And for 0214, I understand you're in a PK study in healthy volunteers.

And I'm just curious if there is some biomarker or other assay that you could look at to see if the drug is hitting the target in these individuals before you move into patients?

Yes.

Yes, it's a good question, David.

So I think the target engagement evidence will come from changes to triglycerides and LDL cholesterol.

We are also looking at some of the very long chain fatty acids, but it's really unclear that those will generate useful data because most healthy individuals have low levels of very long chain fatty acids, so it's not clear that you would see any change there.

But we're looking at all those.

And I think the target engagement will certainly be answered by the changes to LDL and triglycerides.

The next question comes from Yale Jen from Laidlaw & Company.

Congrats.

This is for the VOYAGE trials that you do have a couple of arms, which is a lower doses.

What I'm trying to get is what might be the assumptions or expectations of these lower dose will provide to you versus the more higher dose which you have tested in the previous Phase IIa study?

Yale, thanks for the question.

So the dosing, the Phase IIb overlaps with the Phase IIa on that higher dose, 10 milligrams every other day arm, where we saw 58% or so, 57% reduction in liver fat.

And as you look at those data, it seemed to us that all of those doses, just if you look at the totality of the data, they were all pretty similar.

And so we felt that we had room to come down in exposures and likely still see some therapeutic benefit.

And so to better understand the dose response and to also identify the minimally effective dose, we added some of those lower doses.

And so we would expect to see efficacy at the higher doses, certainly.

I think when you get down to 1 milligram, it's a little more questionable whether or not you'll see a major effect there, but we'll certainly find that out in the study.

But that was the reason for the spread of doses.

And coming down, we -- the reason for the -- coming down in the doses was just due to the fact that all those doses pretty much looked indistinguishable in the totality.

Maybe just follow-up a little on that.

I mean we've talked about earlier that there could be the option of or at least contemplating a loading dose and subsequently with a loading dose.

With this data, let's say, next year, first half of next year, how would that help you to think whether to design the subsequent trials or the Phase III trials in this regard, although we certainly have that -- have the data yet?

Yes.

It's an interesting question, Yale.

We had actually considered the sort of loading dose/maintenance dose in the VOYAGE study.

It was just a little complicated, the trial would be difficult enough as it was so we decided not to implement that sort of a design.

I think in looking at the Phase III, if we were to choose something like that, I'm not sure that we would do that, but we would want to know what the histologic benefit is from the lower doses.

So if you thought about starting somebody at a high dose for 12 weeks to induce a robust liver fat reduction and then transition them on to a lower dose.

You'd want to make sure that if you were to do that, that the low dose generates some histologic benefits.

And so we'd need to see the longer-term data there to make that call.

But it is something we've talked about here internally.

I think it's a really interesting idea.

I'm just not sure that we'll pursue it immediately.

Okay.

Great.

And again, congrats on the progress.

Thanks, Yale.

The next question comes from Jay Olson from Oppenheimer.

Brian, congrats on the progress.

I'm curious if you could comment on some of the recent findings suggesting that liver fat reduction, as measured by MRI-PDFF, is predictive of both NASH resolution and fibrosis improvement?

And maybe comment on your target level of liver fat reduction in the VOYAGE study?

And then on VK0214, I was wondering if you could comment on -- assuming your Phase I studies go well, how soon could you initiate a registrational study in X-ALD?

Thanks, Jay.

With the second question, we're not sure how soon we'd be able to initiate a registration study.

I mean everything -- if everything went well, we would target 2022 for that, but we would need to have input from the FDA and have a trial design and everything, but that would probably be the time frame.

And with the first question on liver fat reduction, it sure seems like the more data that are reported, the more supportive it is that the reduction in liver fat sort of indicates the resolution or at least a higher probability of a resolution of NASH and a regression in fibrosis.

Now, I would say that's most important for compounds that target liver fat.

If it were a pure anti-inflammatory mechanism, you wouldn't expect to see that, so that might lead to a regression of fibrosis by some other means.

But for compounds that reduce that lipotoxic load, the data, I mean, really seem -- going back to the FLINT study, the data seem to be supportive of the notion that when you have a 26%, 28% or more reduction in relative liver fat content, you greatly increase the odds of histologic benefit on the other features.

Next question comes from Andy Hsieh from William Blair.

So Brian, I think last quarter, you mentioned about, in the European region, you're looking at maybe 15 sites.

And you also gave kind of a breakdown between U.S. and EU.

You said something closer to 4:1.

So given the fact that I think you increased that projection from 80 sites to 90 sites in this quarter, would that ratio be roughly the same?

Is that how we should think it about -- think about kind of the geographic distribution?

Yes.

I think the ratio will be pretty consistent.

I don't think there will be any overweight in ex U.S. sites and underweight in U.S. as far as the additional sites.

No, I think it's going to be pretty stable there.

Okay.

And then for the EASL presentation, if you look at the weight loss at the end of the study, placebo was probably plus 1. And then across all the dosing arms is about minus 0.5 kilo.

So just curious about your interpretation of that, is that pretty clinically significant given the short treatment period?

Or how do you think about that piece of data?

Or what are you going to do with that data?

Yes.

Yes.

That's -- it's an observation that's not lost on us.

We've noticed it.

The data -- the ends are pretty small here.

It's obviously interesting to see.

But I think when you look at this mechanism, generally, you don't really want to see weight loss, at least in these sort of early studies because weight loss is sort of a proxy for thyroid alpha activation.

And so if you have a nonselective compound, you see a pretty pronounced weight loss.

And so that was one of the reasons we were hoping not to see any significant weight loss.

But we do -- all of the arms do have this little delta from placebo.

We'll see in the VOYAGE study if that's real or not, but we certainly noticed it, and it's -- thanks for pointing that out.

I don't know -- I don't know if it's clinically significant, Andy, but we'll see over a longer time period.

Yes.

Okay.

Yes, fair enough.

Cool.

Congrats on all the progress this quarter.

Thanks, Andy.

(Operator Instructions) The next question comes from Scott Henry from ROTH Capital.

Brian, just a question on the 16-week durability of liver fat content reduction.

How long would you typically expect a rebound to take place upon ending treatment?

Just trying to get a sense of how to interpret 4 weeks in the context of when a patient's liver would normalize?

Yes.

It's a good question.

I don't know that that's really ever been demonstrated in the literature.

That's why this was a really interesting check after 4 weeks.

I know that has also been done with one of the FGF analogs.

And I think we see somewhat similar data on the kinetics of that liver fat returning.

How long it would take?

I don't know.

If you just do sort of a linear extrapolation, it would suggest that it's going to stay off for 4 to 6 months.

Could be longer.

But I don't really know and I don't know if that's been reported anywhere.

Okay.

And will you look at data beyond 16 weeks with that trial?

Will we get updates in the future?

Oh, no, for the 12-week study, the 16-week visit was the last visit.

Okay.

And then shifting gears to the X-ALD program, the Phase I trial is certainly more involved than a typical Phase I, typically a healthy patient.

Hopefully, it doesn't hurt anyone.

But this Phase Ia is randomized and placebo-controlled.

Could you just give us a sense of -- obviously, there's a lot more effort going into this with the intent of getting more out of it.

And I think you hit on this a little earlier, but what are the main markers that we should be focusing on when we do see that data?

Thanks, Scott.

So I don't know that it's any more complicated.

It's maybe a little more complicated in the stack design.

So we do a SAD and a MAD sort of simultaneously, with the MAD one cohort behind the SAD, but that's not an unheard of design.

And it's 8 patients or 8 subjects per cohort.

It's a pretty simple multiple ascending dose structure there.

So it's not highly unusual by any means.

We'll look at, obviously, safety, tolerability, those sorts of things.

But we'll also be looking at thyroid hormone access, the liver panel, everything that you would typically look at, as well as some of the early potential signals of pharmacodynamic effect on LDL, trigs and the very long chain fatty acids.

We wouldn't expect to see much on the very long chain fatty acids, but we're still looking at them just out of interest.

The next question comes from Julian Harrison from BTIG.

Congrats on the steady progress.

On the X-ALD Phase Ib teed up for next year, I'm curious if you will be screening out AMN with cerebral involvement.

And if that's the plan at first, at what point do you think you might be well informed enough to make a decision on whether or not to broaden development to this more severe subset?

Thanks, Julian.

Yes.

So we won't be targeting patients with cerebral involvement.

That's a more serious phenotype.

And in a 28-day study, I think they're better off considering other options.

We'll target the adult male population with AMN and just monitor the markers.

Moving forward, I don't know.

I think the cerebral cases are more common among children.

And so I think that would be something that we'd probably look at quite a bit further out than the registration study, which we'd probably target the same population as the 28-day study, which would be the -- more of the adult population.

There are no more questions in the queue.

This concludes our question-and-answer session.

I'd like to turn the conference back over to Stephanie Diaz for any closing remarks.

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 good afternoon.

Bye-bye.

The conference has now concluded.

Thank you for attending today's presentation.

You may now disconnect.