Q4 2020 Cymabay Therapeutics Inc Earnings Call

Good day, ladies and gentlemen and welcome to cymabay, its fourth-quarter and full-year 2020 Financial results and business update conference calls at this time. All participants are in a listen-only mode following the formal remarks. We will open the call for your question. Please be advised that the call will be recorded at the company's request. It is also being webcast live on the investors section at the time of a website at ww.w. Now. I would like to turn the call over to mister mental Vice President of Finance at time of Mister mental you may

Thank you operator and good afternoon everyone. I hope you've had a chance to review the press release. We issued announcing fourth quarter and full-year financial results and business updates. You can access that release on our website under the investors tab.

Joining me on the call. Today are sujal. Shah chief executive officer, Dr. Chuck mcwhirter. Chief scientific officer. And klara Dickinson Chief regulatory officer who will provide an update on a recent progress in plan on the development program for seladelpar Chuck will discuss updates to other pipeline opportunities and I will provide a brief summary of our financials following are prepared marks. We will all be available for Q&A.

We Begin I'd like to remind everyone that statements made during this conference call including the Q&A session relating to see mabait expected future performance business prospects events or plans including clinical plans regulatory approvals and anticipated time lines and data release dates and cash Runway are forward-looking statements as defined under the private Securities litigation Reform Act of 1995, although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions actual outcomes and results are subject to risks and uncertainties and could differ materially from those forecasts due to the impact of many factors company assumes no obligation to update or supplement any forward-looking statements whether as a result of new information or future events or otherwise except as required by applicable law

Participants are directed to the cautionary statements set forth in today's press release as well as the risk factors set forth and see what paid quarterly and annual reports filed with the SEC four factors that could cause actual results to differ materially from those anticipated in the forward-looking statements. This conference call is property of SEMA Bay and any recording or rebroadcast is expressly prohibited without the written consent of sumabay off at this time. I'd like to turn the call over to sujal.

Good afternoon, and thank you for joining us back for patients with the rare autoimmune liver disease primary biliary cholangitis or PVC as well as the other promising opportunities. We are actively advance in our pipeline.

It is first important to reflect on all that we have accomplished in 2020 and how those efforts position us for success in the coming year and Beyond month after reducing our Workforce by 60% at the end of 2019. We started 2020 actively closing down all of our clinical studies long and winding down all nonessential activities. We did this to aggressively conserve capital and maximize our ability to execute any number of strategic Alternatives. We evaluated including potential in licensing of assets mergers and even liquidation.

importantly, we also launched a rigorous independent evaluation of the potential safety concerns in our Phase 2 study of seladelpar in patients with non-alcoholic steatohepatitis or Nash

by the second quarter the independent safety review conducted at arm's length by a panel of world-renowned liver experts found no evidence of seladelpar related injury in our study and we quickly submitted complete responses to the FDA clinical hold.

in the

Third-quarter the FDA lifted all clinical holds across the seladelpar program and one week later. We announced positive top-line results from our enhanced phase 3 study of seladelpar in TC.

Even though enhanced was halted prior to completing its planned 52-week treatment. Results were available for 167 patients who completed at least 12 weeks of treatment.

These results on the primary and secondary endpoints in the trial.

Results for the week 12:00 revealed a nearly 80% response on the primary endpoint and expected regulatory approval endpoint when measured at fifty two weeks versus 12 and half percent for the 56 patients on placebo.

Further there was an almost 30% response on Alp normalization versus none on Placebo and a meaningful and statistically significant Prestige controlled effect on reducing Puritas in patients with moderate-to-severe Puritas at Baseline as measured by the numerical rating scale or NRS.

As you may know this is a significant and often debilitating clinical symptom of PVC reported to affect up to 70% of patients long as we close out the year. These results were highlighted in a late-breaking presentation at the liver meeting sponsored by the American Association for the study of liver diseases in November.

They were also instrumental in the design for response are Global phase 3 registration study that mirrors enhance.

Responsible study the same optimal 10 milligram dose of seladelpar versus placebo in the same patient population with the same primary and two key secondary endpoints.

Since our last quarterly update in November, we have been focused on the restart of our Global development program seladelpar.

It is important to highlight that every element of our program had been either shut down or paused in an effort to conserve Capital including clinical studies and Drug manufacturing jobs.

A restart of the seladelpar program is a result of the extraordinary efforts. Our teams made in many behind-the-scenes activities in regulatory CMC wage and quality assurance.

In parallel, our clinical operations group has been working tirelessly to enable the initiation of response and are open label long-term study assure.

It is.

Great pleasure and excitement that I can announce today that both of these studies are actively recruiting patients.

I look forward to providing regular updates on these studies as we progress in the months ahead.

For the remainder of our call today, we will outline our plans for the remainder of 2021 including first or primary focus on execution of response assure wage other NDA enabling clinical and CMC activities for seladelpar in PVC. Second pre-commercial planning and market research to support Investments for launch and life cycle management for seladelpar third advancement of our early-stage Pipeline and Business Development opportunities, and finally for continuing management of our capital and human resources.

Completing the development of our top priority.

Although enhance was allowed us to optimize the design and size of response and to leverage our prior experience with clinical sites in more than twenty countries around the world.

Our goal is to complete enrollment by the end of this year despite challenges. We are facing with the ongoing COVID-19 except and increased competition for patients.

We will have a better indication of enrollment timelines as we move past the middle of this year.

In the first quarter, we held meetings in North America Europe Latin America and Asia where we continue to see enthusiasm and support for seladelpar has returned to clinical.

The study is now actively recruiting patients and with increasing numbers of sight activation. We expect screenings and randomization to accelerate in the coming months.

For those not familiar with the design response is a 52-week placebo-controlled randomized global phase 3 registration studies evaluating the safety and efficacy of seladelpar in patients with PBC.

It is intended to enroll 180 patient with an inadequate response or intolerance to acid in a two-to-one randomization to oral 1000 seladelpar 10 milligrams or placebo.

The primary is in which is defined as a patient who achieves an alkaline phosphatase level less than 1.67 times the upper limit of normal with at least a 15% decrease from Baseline and has a normal level of total bilirubin.

Additional key outcomes of efficacy will compare the rate of normalization of alkaline phosphatase and the change in Puritas from Baseline to six months patience with a Baseline and rs of four or greater for moderate-to-severe.

Rytis will be assessed using the same numerical rating scale and daily electronic diary as we use successfully and enhance.

I can't overstate the value of enhance and determining the size and design of response, which as I mentioned. Once again, we'll evaluate the same patient population same 10 milligram optimal dose of seladelpar and the same primary and two key secondary endpoints.

In addition to have also initiated a in order to collect additional safety data to support registered.

The study will first enroll patients who have participated in our prior studies of seladelpar and including the patients who completed the open-label phase II study and enroll into our previous long-term study and enhance.

As patients complete response and potentially other future studies with seladelpar. They will also have the opportunity to enroll in a sure.

We expect seladelpar to have one of the most robust safety databases in PVC patients ever submitted for an NDA.

In the background of these two significant Global clinical studies. Our teams have also been executing on Regulatory and clinical activities for numerous and enabling studies and GMC efforts required to meet our filing and launched timeline.

These efforts are often overlooked outside of the company, but are highly valued and resource to succeed as they play a vital role in ultimately enabling the broadest use of seladelpar the benefit as many patients as possible.

On the topic of bringing seladelpar. I want to highlight some of the important pre-commercial planning and market research work. We have been and will continue to conduct through the course of this year.

We have been studying seladelpar in PVC since 2015 having completed for clinical trials studying five doses of seladelpar in over three hundred patients including in both cirrhotic and non-cirrhotic patients and with a subset of these having been treated for two years or longer.

The ten milligram dose has consistently shown anti-static anti-inflammatory and anti-oxidant and good overall safety to date and suggest off the potential of seladelpar to provide patients with improvements and biochemical markers of disease and to reduce symptom burden.

Our aspiration is to help as many patients as possible achieve the ideal response of normalizing their alkaline phosphatase.

We aim to demonstrate that the potential benefits of seladelpar can translate into improved outcomes and quality of life for many patients with DTC.

in the

U.s. Alone. There are approximately 130000 patients with PVC with as many as twenty to thirty thousand in adequately controlled by or intolerant to fiber line treatment with udca.

There are many more who are not currently considered eligible for second-line treatment, even though they have elevated alkaline phosphatase and may also be at risk of disease progression.

There are such a significant negative impact to their quality of life.

Based on current pricing for second line therapy and the potential to deliver even greater benefits are early market research with Healthcare Providers and payers money points to the potential for seladelpar to be the preferred treatment choice for patients and thus an opportunity that may generate significantly greater long-term revenues than ocaliva, which according to recent guidance from intercept is currently projected to have $325 to $355 in annual worldwide net sales in 2021.

As we mature our market research, we will be providing updates on specific details of our projections.

While our core Focus remains on completing development of seladelpar and we continue to evaluate seladelpar and our other early-stage clinical assets off other indications and development opportunities.

Let me turn the call over to our chief scientific officer doctor Chuck mcwhirter to discuss more Chuck.

Thank you. So Jewel last November we announced plans to conduct a study to evaluate MDX 2982 are GPR 119 as an aging potentially prevent hypoglycemia in patients with type one diabetes insulin induce hypoglycemia, and diabetes is a significant cause of morbidity and an important factor that causes many patients to under utilize insulin to control their blood glucose levels glucagon is the counter regulatory hormones secreted from pancreatic alpha cells under conditions of life, but not normal or high blood glucose glucagon serves to raise low glucose levels caused by insulin back into the normal range.

In recently published studies with isolated human pancreatic islets GPR 119 Agonist were shown to enhance glucagon secretion in response to low but not high glucose levels and further. They were able to prevent insulin induce hypoglycemia by increasing glucagon secretion in a rat model. The translation of these findings to the clinic will be evaluated in a phased me proof of pharmacology study examining whether 29.82 can enhance Google consecration during insulin induce hypoglycemia in subjects with type 1 diabetes.

well SEMA Bay retains full rights to

The study will be led by adventhealth translational Research Institute in Orlando, Florida and will be fully funded by the Leona em and Harry B Helmsley charitable trust. We appreciate the opportunity to contribute to this effort to evaluate and the potential to treat individuals at risk for insulin induce, hypoglycemia, one of the most challenging and potentially life-threatening complications of insulin therapy and diabetes are collaborators who are funding and running the study expect it to be completed this year. Although since we are not conducting the study ourselves. We cannot be certain of the timing positive results in this study would provide the option to explore monetizing rights in the program through licensing or to advance the compound further into development on our own or with a partner.

In twenty-twenty. We also began to evaluate cbz 406 the active metabolite of the pro-drug are hello finaid that had previously been studied in diabetes doubt. We initiated a single and multiple ascending do study of CB 0406 in healthy subjects to establish his pharmacokinetics safety and maximum tolerated dose CDC. Rho 406 is a gamma non Agonist Ligon that attenuates the expression of inflammatory genes. It has been shown to block innate immune responses through the bank Kappa B and nlrp3 inflammatory pathways.

In published studies nlrp3 caspase-1 in Iowa 1 beta we're all decreased by CB 0406 in response to inflammatory triggers in macrophages thought it was also shown to attenuate the known nlrp3 dependent pathophysiology of Gaudi inflammation. When dose does the pro drug in a mouse model and also in a phase 2 clinical study and gout patients based on pharmacokinetic studies and monkeys, we believe that CB 0406 may have greater exposure and potentially greater efficacy than does the pro gargoyle open 8 positions on any future development or contingent on it's achieving a favorable profile with respect to safety and exposure the innate immune system plays a pivotal role in many ways besides Scout and thus We Believe 0406 may have utility in various inflammatory diseases and are currently exploring potential opportunities to advance this development pending the results.

Of the ongoing phase one study.

Finally, we continue to explore via Business Development discussions interest in evaluating seladelpar in combination with other promising agents and the impact of seladelpar or fibrosis and Nash pathology and our phase II D clinical study together with promising preclinical studies and combinations suggest the potential for seladelpar to be combined with agent that have effects on weight liver fat and insulin sensitivity. And also with other anti-fibrotic agents discussions of this type often take time to mature as other priorities evaluation, not only seladelpar but their own portfolio and business interests. We will provide updates when there is significant new information that we are able to share

sujal

Thank you Chuck. In addition to the significant momentum behind our efforts to restart and complete development of seladelpar for PVC and the advancement of other opportunities in Iraq pipeline a key highlight of the quarter is the successful management of our overall cost for yet another quarter and throughout 2020 allowing us to start this year took well over a year of cash on our balance sheet.

On that note. I'll ask Dan to provide a brief summary of our key financial highlights, Dan.

Thank you schedule over the we successfully managed our overall cash expenditures while we completed our investigation obtain the fda's clearance rack start development of the seladelpar program and commenced our response and ensure clinical studies and other NDA enabling studies necessary to complete our late-stage development of seladelpar or overall. Our expense management efforts led to cash cash equivalents and short-term Investments, totaling 146.3 million dollars at December 31st, Thursday. We believe our cash is sufficient to fund our current operating plan including the reinitiation of the full development program for seladelpar and into mid twenty twenty to age.

Turning now to A Brief Review of our operating results net loss for the 3 months ended December 31st, 2020 with 15.8 million dollars or $0.23 per share wage compared to net loss of twenty nine point four million dollars or 43 cents per share in the three months ended December 31st, 2019. Net loss for the year ended December thirty first month was $51 or $0.74 per share compared to a net loss of a hundred two point eight million dollars or $1.53 per share in the year ended December 31st, 2019.

Net loss was lower in the three months and year ended December 31st, 2020 compared to the corresponding periods in 2019 primarily due to decrease in operating expenses, including clinical trial and labor related expenses as a result of the termination of our seladelpar studies and our cost reduction efforts undertaken in response to the fda's clinical hole be replaced on the seladelpar program in the fourth quarter of 2019.

Given the FDA subsequent lifting of the clinical hold and our restart of the seladelpar program and further exploration of other clinical development opportunities are cash expenditures and losses on a spected to increase in the future as we advance our restarted clinical development programs and activities. Finally. I'd like to provide you with a brief update on our current operating environment took to the ongoing impact of the global coronavirus pandemic. We continue to conduct operations remotely for all employees, which is allowed business activity to continue as seamlessly as possible. We will continue to closely monitor pandemic developments and their Associated risks to our business, including our restarted clinical development of seladelpar and and we will continue to take actions available to mitigate these risks where possible further all our actions will continue to be guided by commitment to ensuring the health and safety of our employees as well as patients enrolled in our clinical study.

please

Thank you, Dan. We're now happy to take questions.

Thank you. We will now be conducting a question-and-answer session. And if you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star to age would like to remove your question from the Q4 participants using speaker equipment and maybe necessary to pick up your handset before pressing the star key. One moment, please while we pull for questions.

Thank you. Our first question comes from Yasmeen rahimi with Piper Sandler. Please proceed with your question. Hi team. Thank you so much for sharing all your great progress a number of questions. Very topic. The first one is if you could comment on whether whether the agency has may be modified their view on throttle. He's recently saw that a label revision would be required 440c a potentially. So we wanted to understand if is the agency changing its perspective on the way. We're treating sporadic TC patience. And then the second question is if you could provide some color on maybe how many patients that were in previous Studies have enrolled so far into a short and then I have a quick follow-up.

Sure. Thanks for the question. Yes, I'll start it off and perhaps invite others to join me here particularly on the regulatory side if I miss anything klara can chime in. You know, I think it's important for us to highlight that response as was the case for enhanced and even intercept Space 3 study is really targeting a large proportion of PBC patients that have either early or mild stage disease that which is actually the case for as many as eighty percent of the population approximately off and so in that study, we're largely enrolling patients that that are non-cirrhotic 6, although it is possible or patients who are well-compensated Sera addicts to enroll particularly child patients. And that is a population. In fact, we've studied both in our Phase 2 clinical studies as well as enhanced. In fact, I think it's a key differentiator for us that we have as many yep.

Fifty patients roughly worth of data in well compensated cirrhotic Santa date see very good efficacy as well as safety in the same doses. We're studying in the non in in the non-cirrhotic patient population as it pertains to those patients with more advanced disease. I think one of the advantages we have clearly as ocaliva is been in a market and as we are able to assess the safety risks and concerns for those Advanced patients, we have the opportunity. In fact in studies for patients with it to compare moment in our studies potentially alongside response. And even thereafter to have a better overall safety database and even more advanced patients. So we have a more clear understanding of the potential risks as well as benefits in that population. So I don't believe at least from a regulatory perspective. There's any change from the agency's perception wage?

Getting a label very similar.

So what you see with ocaliva, which is the aim of of our study in response to effectively get a label for second-line treatment treatment for patients that are either non-responders are inadequate responders to udca should say or intolerant that stance has really not changed. But I think we have a greater View and opportunity again to better understand seladelpar overall profile in more advanced patients and ceramics

Thank you, too. And then yeah and then he has mean I think you also asked about progress specifically and assure and you know again here I'll just say we're incredibly excited that both faith and assure are now actively recruiting patients specifically with the sure. We have of course opened up the possibility and opportunity for patients that we're in our previous space. Mm. Most of which in fact had enrolled in our into our prior long-term study as well as patients from enhance. And and so I think as we continue to offer that to a site and two patients Thursday, we're seeing obviously a tremendous amount of excitement particularly on behalf of patients that were previously on seladelpar. That's a process similar to response that's going to take time to get out to the twenty-plus countries that we are enrolling patients particularly in enhanced but we continue to do that work the investigator meetings as I mentioned in the prepared remarks that have now covered really dead.

Geographies are a key step in getting sites informed as well as ultimately activated. So we'll see progress in a shorter enrollment as we see similarly progress and response enrollment really mirroring site activations and really accelerating as those sites get on board.

Thank you. And then a quick one for chuck chuck. Can you elaborate a little bit more on TV? 0406 like what in regards to the mechanism of birth? What are the potentials of being an on a Guinness legen of people are gamma and and and then also what are the indications? You don't have to give me the exact one that what is what are all the possibilities of areas that you could complete potentially interested in so that could be helpful for us. Thank you Jasmine. Well, we're really very excited about 4:06 to start with just for the audience to understand. You know, it's extremely de-risk it's been the pro drug has been studied in a significant number of patients in a significant number of studies and it's clinically validated. So as you may or may not know about gout inflammation or or gout flares.

Are strong inflammatory response it's driven by the nlrp3 inflammasome, which is a very exciting area of research and sterile inflammation with many start-up companies working actively on this and it's known because neutralizing biologics to Iowa and Bettie Page blocked out flares. So our preclinical work with macrophages in Mouse models of the of the the inflammation showed that we blocked that pathway and we did that also in gout patients. So I guess I would just invite you to to consider, you know, the broad landscape that's being described in the literature. If you were to do a pub Med on nlrp3, you're going to return a really large number of indications of Interest with a lot of unserved or unmet need that I think interdicting in these Pathways. Could you know could make sense 40406

So just to recap you know.

It's a known pathway. We published a paper in in 2018. It's on our website that describes the mechanism as well as we published a paper on the on the couch studying you put those two together with the fact that we believe 0406 will have greater exposure. And efficacy. I think it really sets us up with a lot of you know, very delicious menu of opportunities from which to select one of these uh, uh disease disorders that you'll find in the literature surrounding intellect III and I think the other advantage of touch on you asked what about the the non Agonist aspect, you know people gamma is the target of insulin sensitizers, which of course have their own benefits charm ecology, but they come with a lot of downside with respect to weight gain increasing adiposity electrolyte imbalance edema from action in the kids club.

And and Bone effects So based upon an extensive clinical program the fact that we don't activate genes like the insulin sensitizer to us. Keep keeps the drug. So to speak up Harm's Way with the side effects or the untoward actions of the insulin sensitizers. So that's where the another degree of excitement comes from because it's already been de-risked for this is basically

Thank you.

Thank you. Our next question comes from Steve house with Raymond James. Please proceed with your question.

Good afternoon. Thanks for taking the question. First one. Is this regarding a short or long-term safety data, you're collecting. What is the target enrollment in that study? And do you need a certain number of patients with longer than 50,000 follow up before you submit for approval or will you essentially just submit what you have when response concludes?

Hi, this is Clara. We don't have a specific Target required by the FDA. Obviously them where we have the better to give FDA and Assurance of the overall safety and and side effects of the drug. So we're we're trying to just allow us any patients to come back in to assure that were previously enrolled in the trial as well as those who can participate once they complete the response study. I think the only other thing I'd add Steve is this is a a study that was in fact, I'm going in parallel a long-term study when we were enrolling in conducting hanst. So we're really just rinse and repeat of the clinical development strategy that we had prior this long-term study, of course given enhance enrolled and randomize patients is open for those patients in addition to those in our prior long-term study. And I think as we mentioned again in our prepared remarks, it's what really sets us up even if we get

They half of those patients to enroll in this study.

To have one of the most robust safety databases that time of anticipated NDA in the setting of PVC that any sponsor has actually had at the time of registration. We're quite confident that this really positions us to have another significant Advantage relative to others in the field.

Yep, makes sense. Although the one thing I guess it's not clear is Will assuming that you will apply for Accelerated approval on the basis of response is Asher serving is the long-term outcome study wage full licensure or or is there a sort of a extension protocol that's blinded and randomized because of course, as you know intercept is communicating some some issues with their long-term outcome study Cobalt and maintaining the blinding and and just completing that study in general.

Yeah, the Fisher study is not intended to be the study to confirm the benefit of Philadelphia as part of our required base for study. We we are in June, um continued dialogue with the FDA around the design of that study that we're going to propose so it's not specific to to dish or study.

Okay, so that would so that study is also separate from response. It would be a to be initiated study.

Yes, that's exactly correct Steve. And this is you know, in fact a dialogue we've had with the agency for the last couple of years. I think is you know the pathway to subpart H approval through the accelerated approval package way requires us at least at the time of NDA submission to have that stage four outcome studied agreed-upon and initiated effectively at the time of NDA submission. So we're we're confident again at progress we've made in that dialog you touched upon some of the challenges that intercept is facing and enrolling their face for outcome study. I'll just say here once again though. Nothing here is finalized. We once again have the advantage of learning from intercept some of the challenges. They've had And discussing with the agency a study that we would we would propose to have a best effort of actually enrolling in completing. So it's a challenge in this setting a slowly progressing chronic disease. But again, we have the benefit of learning

Some of the challenges they've faced and approaching it with some potential advantages as we get their ultimately.

Very helpful appreciate that color last question for me just regarding the market research and aspiration. I guess you communicated for greater long-term Revenue than than what's even indicated by the way. How are you thinking about competition like from Ella fiber nor or generic GA or even combo plus bezafibrate and what impact from Noah's Ark zooming in that optimistic long-term Outlook that you communicated. Thank you.

Yeah.

It's a great question. So, you know, we've initiated some work and there's much more for us to do here as we set ourselves up for potential success than we certainly believe in that and so, you know, when you look at Iraq and a mentally Steve, I think it's all starts with the profile and the data set and at least today we're seeing a profile of Greater efficacy on the composite primary endpoint again, I'll speak often as I make these comparisons. They're not coming from head-to-head data, but just respectively in the development of these various different targets that you had mentioned, but we're seeing very robust efficacy and biochemical markers of disease that have in fact been correlated to improvements and outcomes based on Rich historical data set as you know, the global study group data, for example, we're seeing a significant effects on inflammation some of the effects that we're seeing certainly could lead to improvements overall in Liver Health potentially liver still dead.

Esther fibrosis things again that long-term have the potential to impact outcomes for patients. We're also seeing not just significant effects on biochemical markers of disease or actually seeing a good proportion of patients up to 30% in our phase II in our prior phase three work actually normalize their alkaline phosphatase and this is something in the medical community that has been coming ever more important. I think there's a a stronger desire in the medical community and PVC to treat patients to normalization. That's not yet something we've seen certainly to the degree. We have thus far in our studies with seladelpar necessarily with other agents, like ocaliva, you know, of course the bees urso study has shown some promising data feed the vibrate on top of udca these wage rate, of course is not available in the US. It is a generic elsewhere. I think fundamentally the bees urso data once again validates. The people are mechanism in fact as a preferred phone number.

Align mechanism and really only for those patients potentially that need additional biochemical normalization or lowering to reduce risk of disease progression. You might consider adding a XR for those subset of patients, but we believe again based on our data set that a fair proportion of patients can get to goal and reduce risk of disease progression in a meaningful way. Perhaps would seladelpar really as a Preferred Choice. So as these other competitors really come online, once again, I think it's the overall profile and and I'll add two other elements to the profile obviously wage and benefit on reducing the key clinical symptom burden of the disease itself on Puritas. We've shown it in a statistically significant fashion versus placebo in the enhanced data set. Once again, I think that's a differentiated data set relative to the many competitors that you highlighted even some of those other people's that have shown some potential benefit on reducing Puritas. We have no reason to believe they wage.

but once again, I think the strength of our

Data set largely. Uh, I think solidified seladelpar is having this effect. If we're able to show this once again in response in a meaningful fashion. We think again, it's a different date or versus these other data sets and then finally overall safety. I mentioned that we've studied not just early stage and patience with mild PVC if she will based on biochemical markers of disease and the stage where we see very good overall efficacy and good safety. We've of course also studied patients with with compensated cirrhosis those child to AIDS as I mentioned. That's a a patient population where for example with bruenor, we're not aware of any data existing in that patient population. And so when you talk about overall safety, we believe that's another key differentiator and potentially positioning seladelpar as a preferred treatment alternative. So, I think these things matter, of course it is. Yep.

That how the ultimate competitive environment plays out with respect to pricing and generics will also impact future decisions. But we think once again seladelpar is incredibly well-positioned based on this data set and really the opportunity for us to continue investing in life cycle Management in additional data sets that may highlight an advantage of seladelpar unethical Dion tolerability as well as potentially and safety.

Kudos on remarkable turnaround in 2020 and getting back to his face three, really really remarkable. Thanks for taking the question. Thank you Steve. Thank you. Our next question comes from alethia Young with Cantor Fitzgerald. Please proceed with your question. Hi, this is Nina on fairly. Thanks for taking our questions. We would know a little bit more about the CB 0406 program and and had a few questions there. We were wondering if this program was discovered in house or or was it in licensed off? Also how selective is 04064 gamma versus other isoforms and and last question. What does 0406 need to show in the multiple-choice do studies for for you guys to be comfortable with this profile? Thanks.

Yeah, those three great questions. Thank you for that. So, you know, I think with respect first of all to the selectivity we've extensively profiled it for example using Chrome and it's it's very specific four people gamma. There is no off-target effects with respect to Aur Aisa type effects with respect to people are alpha or or people are Delta. So it's it's very it's a very narrow range with respect to that you you asked about the what the access factor is. I think if you look at the publication, we had a good effect on gout flares that was a little bit less than the standard of care colchicine so I could call it maybe eighty percent. We think that if we could get a a significant Improvement in exposure based upon what we understand we should be able to log

to my side effect and culture scene

In the setting of gout flares, which is I mentioned is a nlrp3 driven process. Although culture cmax Downstream be a different mechanism essentially represents the maximum effect that you'll see in the pathway. So we think if we could get a significant increase in exposure and I don't I don't want to provide a specific guidance about what that increase in exposure needs to be but I can suck then in the monkey studies where we did we compare 0406 directly to the pro-drug. We saw significantly higher exposure 40406. So we're just really suggesting to confirm that will hit that that Target and if we do then we we have some we have some very good confidence that that that'll give us the best the best chance moving forward. I'm sorry I missed a I've already lost track of the first part of your question. Someone can remind me.

Yes, so so was this program discovered in hell? Yes. This is an in-house program.

And I think neither one other thing. I just wanted to add to Chuck's comments as we think about potential indications is Chuck mentioned. There are many that are impacted by this pathway. I think fundamentally our focus and priority is in identifying rare diseases and potentially even diseases in which you could gain orphan drug designation. So really fitting into our current strategic Focus overall.

Thank you. This is really helpful.

Thank you.

Thank you. Our next question comes from Patrick with lifesci capital. Please proceed with your question.

Thanks for taking the questions and congrats on all the progress just a couple more on 046. If I may you mentioned, you know, some of the safety effects of influence in a position might be averted considering the non Agonist nature of this compound, and I'm just curious at the same time. Does that mean that some of the beneficial effects you've seen with people gamma Agnes would be lacking off or do you anticipate some translate ability on the opposite side of things via the channel rp3 pathway, and obviously totally totally understand that it's early and, you know without an indication selected. This might be a loss event in question, but uh, just just curious as we think about potential liver indications. Thanks.

Jo thank you. Patrick know it's a it's a question that makes a lot of sense. And so you can find we had studied our hello finaid the drug for diabetes and we were always interested in both the insulin sensitization as well as the anti-inflammatory effects. So I think what we found in diabetes is that the drug was safe wage, we've completed a 17 clinical studies more than 1,700 subjects were exposed to the pro drug and we did see some benefits on insulin sensitive wage, but they weren't competitive commercially. We didn't see the team that we didn't see weight gain. We don't see effects on bone fracture biomarkers that you see with tzds. And so for that reason, it just didn't make sense to continue development for for diabetes thought that time we learned about the anti-inflammatory effects and and at some point if we have an R&D day, it'll be really nice to age.

Health explain the trajectory of the of the program

And how we moved into inflammation that's driven by the the non Agonist transfer oppression of jeans. So transfer press is nf-kappab as well as a one-off inflammatory jeans and of course nf-kappa be drives nlrp3. So it's basically One Step Up stream from 53 and that also gives in our mind an additional degree of selectivity and potential safety. One thing that I didn't mention is that you know, anti dial 188 at biologics are effective and they're registered for a number of indications including recently just this last week we're alone except was which is Anaya 1 beta kombe Ki Kore receptor was registered for the card itis recurrent pericarditis. They come with an infection risk, in fact even serious in and occasionally fatal infection dead.

De depressed through the mechanism neutrophils so you can get occasional grade three and great food or for neutral neutral Celia or neutropenia. Sorry, and we we don't see that. It's any of our studies with with the pro-drug. So I think being One Step Up stream gives you a kind of tissue selectivity, but still allows you to get to the anti-inflammatory effect. If you'd like to have, you know, without having a basically a systemic suppression. So hopefully that helps you give some of the insights around additional excitement. We have harnessing transfer pression in a tissue specific way.

Absolutely. Thank you.

Patrick

thank you. Our next question comes from J Olsen with Oppenheimer. Please proceed with your question.

Oh, hey congrats on all the progress including getting those two is up and running. Can you just talk about what impact you expect if any from the pandemic on enrolling the response trial and you should expect to see data from that study and then separately if you could comment on how we might extrapolate the shortened enhanced results out to 12 months of treatment for a response.

Yeah, sure. I'll start off and answer the first part of your question. I appreciate it. You know, there's no question that the pandemic presents challenges not just for us but I think any enrolling patients in in other studies globally and so, you know fundamentally it presents challenges often and getting patients to screening and patients that might otherwise and roll instead of the good thing for us here is during the height of the pandemic. In fact, we are largely in planning stages of getting the protocol approved by Regulatory Agencies Arby's and ethics Commission in the various countries in which we are targeting initiating sites and then even getting site contracts in place that's really been the Crux of the work at the end of last year and early this year. So it's a heavy lift. And so many don't quite appreciate the fact that when you finally have a protocol for a global study, there's a lot of leg work before you start getting patients into screening and ultimately true.

Innovation and that's really been the effort that we haven't faced in.

Sincerly challenge with for the most part there are some times in which uh, you know, regulatory bodies and agencies may have delays. Those are some of the things that we absolutely have faced will face and will continue to Faithfully with less severity as things potentially improved as vaccinations themselves are rolled out globally as well. Now fundamentally what we're doing in response, although the study is targeting 80 fewer patients than we had randomized enhance enhanced. We had randomized 265 patience as you recall in just under a year. We're targeting 80 fewer patients the scope of our effort mirrors the scope of the effort that we had enhanced. If not potentially larger when I refer to the number of countries and number of sites that will Target it'll be a similar if not large or a number of countries insights. Then we targeted in enhanced with an effort as we discussed in our prepared remarks to get responses.

Enroll, by the end of this year that would allow us to have top-line data by the end of 2022 or very early 2023 that remains our objective J. And I think even less of or I should say respective of the pandemic in any study of this size and magnitude globally. It would take a couple of quarters for us to really assess home on that timeline. It's a hockey stick pattern in clinical studies is more and more sites. Come on board. You see an acceleration. That's what we observed enhance. That's what we expect to observe and responsive. And again, we're excited that we've been able to kick this off in the study. In fact is actively recruiting. So we're going to Hope clearly to hit those timelines ultimately.

Excellent. Thank you for that. Thank you. And then maybe if I could just on can you talk about the registration all pathway? There is a hypo prevention claim going to require an event-driven trial.

Well, thanks for that. It's a little early. We you know, I think we haven't even had a regulatory discussion yet. So I don't think we you know, maybe klara would want to help me answer the question where we are really Jay is really establishing proof of pharmacology, you know, does the do the results that we're seeing with human eyelets and rats can we recapitulate that in in a basically a mechanistic study, you know, then of course we would begin to have some dialogue with regulators and would move to a phase to be home which you know, currently you may know that there was just a another glucagon approved for a a rescue therapy. So that's all that's available right now, you know a safe wage preventive would really be helpful. I think for a lot of patients who who are concerned about how aggressively to use their insulin because of hypoglycemia there many patients who are a dog

License are teenagers and you know their their parents worried.

You know because a lot of these hypoglycemic episodes occur, nocturnally, so having something that they could safely and confidently use and and then took insulin appropriately to manage their glucose levels. I think would be a significant step forward but we're a little early in terms of assessing. You know, what endpoints would be that phase two people probably use continuous glucose monitoring. So it would probably be events of moderate to severe hypoglycemia. I speculating here and then again to speculate not even a little further than of course, I think phase three would would probably seek just to to confirm what you do you're learning you're learning phase phase to be but you know, it's it's a pretty that's pretty intriguing opportunity we feel and in 2982 it which was a homegrown a compound really came out of our efforts through Medicinal Chemistry and dead.

And the like I think is is one of the best cheap yarn 119 that has been studied. We have five clinical studies more than two hundred subjects have been exposed to the drug in a pretty good nonclinical package. So getting some data here should should allow us to move forward more quickly.

Great. Thank you very much for taking the questions.

Thank you. Our next question comes from Thomas Smith with s v b lyric, please proceed with your question.

Hey guys, good afternoon. Thanks for taking the questions and let my my congratulations on the progress first. Just a question on the face three response that he can you please verify the number of study sites you're targeting and how many are activated this point. And then can you also talk a little bit about your current thinking on seladelpar indication expansion. Um, I appreciate the comments on on a HDD, but also wondering whether you can speak to how you're thinking about potential plans and other rare cholestatic if your diseases like PS3, thanks.

Yeah. Sure. Thanks for the questions Thomas, you know as it pertains to the to the progress in the study. It's obviously very fluent. So every day there's progress every week. We're making progress. I think their own number of sites that you can see on clean trials. I want to say just just under half a dozen does far but once again, there's not a seamless timeline as sites get up and running and the information necessary. I'm getting uploaded there. So we've made really good progress in terms of overall sites as we continue to get things up and running, you know, we talked about a scope as large as we had in enhanced off hand. We had activated nearly a hundred and fifty sites not all of those enrolled patients in a setting like PVC. We typically see between one to two patients per site. There are some sites. We talked to a super in rollers with four or five patients. Of course, there's some sites that ultimately are not able to enroll patients. Just don't meet the enrollment criteria for for this type of wage.

And so we we fail we've got vast experience now, you know of those sites we had enrolled in enhanced. We know those that you know, likely won't have paid.

So it'll give us some efficiency and not going back to some of those regions and site specifically where where there weren't patients that met the that met the criteria. There were sites that we learned off of at the last stages of randomizing enhance and completing that enrollment that in fact had interest and unfortunately, we couldn't get them in in that time and I think that also gives us a little bit of advantage to just know off some of the additional centers that we want to ultimately Target but you know, I think this this is going to be once again as it was an enhanced north of a hundred sites that we hope to even be activated into the office study and contribute to getting us to this goal again, hopefully by the end of this year.

Okay, great. I appreciate that color sujal. And then maybe if you could just talk a little bit about the the business development and I guess how you're thinking about plans in ntsc at this point. Yeah, no, sorry good good follow-up question. So as we had discussed, you know, we continue to have dialogue around opportunities to potentially study seladelpar in combination with other treatments for Nash as Chuck mentioned in in their prepared remarks. Once again, very challenging for us to really pinpoint a timeline on this it does involve third parties evaluating not just seladelpar, but also their own programs and their own strategy game but to give you an example, they're really quickly and then move on to other opportunities that we remain excited about, you know, you look at what Novo and Gilead are doing for example combining glp-1 plus FXR off a collaboration which they in fact expanded recently announced an expansion of that collaboration. They could many ways. We look at seladelpar profile and I would argue and even better combination with

Glp-1 and ethics are could. In fact be seladelpar. So there's much to dig through and discuss their and we're committed to that ongoing dialogue and potential additional opportunities outside of those Thursday. We have specifically decided would only Advanced with a partner with significant resources on board are in fact opportunities. You alluded to other potential indications in rare disease PSC clearly potentially one of the most obvious ones would seladelpar. There are others that Chuck and his team have continued to evaluate pre clinically as well. Do think this mechanism May lend itself to inflammatory diseases within liver rare diseases as well as potentially outside of liver. So those things are early too early for me to be able to comment on a you know, I can tell you with respect to PSD. Obviously. This is high unmet need patient population a smaller patient population than PVC but a patient population for which there are no wage.

Approved treatment Alternatives those patients are more heterogeneous than you see overall in the PVC population. So we continue to have dialogue with experts with advisors as we think about the right time line the right types of study designs to potentially explore PSC. But certainly that's an area of high interest. The real question right now is timing and right now we're committed to making sure that we not only get back into the clinic in PVC as we have this quarter, but really drive to a completion there because we think there's real near-term opportunity to advance care and and significantly even grow the patient population as we've discussed.

Got it.

Got it. Okay, great. Thank you. I appreciate the the color. Yeah. Thanks, Thomas.

Thank you. Our next question comes from a yank mamtani with B Riley security. Please proceed with your question. Good afternoon. Thanks for taking my questions and and congrats on an incredible job. And so just maybe sujal. If you could comment on what you said in your prepared remarks and you you know, the overlooked ND enabling activities and I mean, are there any drug drug interactions that you that you may have to do and and and maybe just thinking about combinations are if you could comment also, you know just summarize your work you may have done in Nash to date uh from a combination standpoint with seladelpar. I think that could be really helpful.

Yeah, certainly. So I'll start off with the first part and then I'll invite more specifically talked about potential combinations, you know, the NBA enabling studies that Clara and and all the team internally are really spearheading are really the standard ones. So looking across BBC at the treatments that patients are typically on and you know ensuring that we look at drug interaction studies for those commonly prescribed medications that this patient population can be on as well. Uh, you know, they they include renal impairment Paddock impairment studies. So just a lot of blocking and tackling my own nothing outside of the norm fundamentally then then what would be expected in this setting? So those are just ongoing activities as we drive towards, you know, looking for wage able to meet the timelines that we set forth. We would anticipate being in a position to file an NDA potentially in mid 2023. And so making sure that we have a game.

These things completed by the time of that NDA submission is also a priority, of course alongside the phase 3 study in the long-term study as well. Maybe Chuck. Do you want to talk more specifically about the second part of my question? Yeah. Sure happy to do that. So if you have an opportunity, you can look on our website. We have some some posters that we presented looking at Subway combinations in a pretty aggressive fiber optic model in my and we've looked at a variety of Agents. We looked at GOP one receptor Agonist. We've looked at we looked at Salon I you would because it was in phase three. We've looked at a cement I diabetic agents and the like I think what's really emerged for us is so far is the agents that have effects on a metabolic features. So for example, if you look you'll see that we we looked at which has its own human data where there's some good effects on Nash pathology but limited time.

Effects on fibrosis you probably know that it's Immaculate. I'd also has recently released some Nash date as well which has pretty much a similar pattern some some very very convincing a pathology but really nothing available on on fibrosis. At least for the duration of the studies that have been examined to date in my sillies with the caveat the difficult Choice translation. We see a very strong complementarity. So seladelpar has some metabolic effects, but it has some strong antibiotic affects. Those metabolic effects is selling a part added a very nicely to the effects of the glp-1 receptor Agonist while maintaining the anti-fibrotic affects. So the thinking is that off of two agents you put it together, you take away some of the disease driving from the metabolic side and you supplement that with the known histological feature that drives live a relay. Yep.

How come you you basically?

Stop that in its tracks. You you'll have an early effect on on events. Those two together could be quite intriguing to study and I think that's probably the similar concept that Gilead then had a novel or looking at we just think that if you look at the our Nash clinical data where we had 26% Nash resolution in 37% off stage fibrosis Improvement in Nash patients that we we believe seladelpar would be a very strong player in that kind of combination and and with the caveat it's not head-to-head. I think it really suggests at least one should think about that combination with the GOP one receptor Agonist.

Thank you, very helpful overview on on both those topics and and quickly on on 0406 if you know understand the mechanism very well, but but I'm on the attributes on the specific molecules. It seems like a lot of those like almost you're going up to 1 kilo. Can you just maybe comment on why is that and and when you think about your next Thursday, the is your mid 2022 cash Runway include, you know, whatever. You may do next in with this molecule. Just curious.

I'll handle the first part and then as soon as you can help you understand the the balance and the the capital allocation. So in in gout we studied an 800 milligram dose and in and of course, I've already mentioned that we expect that 0406, you know would be a lower dose because of its higher exposure. The authors thing to appreciate is that 0406 is the is the basically the intermediate right before the synthesis of the pro-drug. So all of the box has been worked out in you know under GMP at the half metric ton scale and the molecular mass of 0406. Of course is is smaller than our whole open 8:30 the total overall dos, you know could well be less and and of course, they'll be some some cost of goods advantages because there's there's one less step in the process.

Yeah, Mike is as it pertains to the forecast on the cash Runway. It includes completing the phase one. It does not yet include, you know thinking through a phone number of potential phase two studies that we would look to execute. I think again here we want to make sure and understand the indication that we think merits further investment. May I will say one thing as it pertains to obviously the balance sheet, you know, we're we're quite pleased with the fact that we've been very cost-efficient through the last year and half continue to have as I mentioned well over a Year's worth of cash on the balance sheet. We feel that there's nothing we're restricted from accomplishing throughout the rest of this year. We also firmly believe that we have access to Capital through various means life and we've been evaluating these periodically as we always do even in years past continue to see a lot of support from investors again through various different wage.

and fundamentally, you know, we'll make the right decision at the

Flight time around ensuring not only our ability to get seladelpar through phase three but to NDA filing and subsequently prepare ourselves for at least a US commercial launch. We continue to evaluate potentially other geographies and whether or not we met out license rights to other geographies and and that may come down the road in the future. But of course again, we'll make sure that we have the balance necessary not just to move seladelpar through the completion, but obviously these other programs should we see real opportunity to create significant value there and again near-term at least with 2952 is you know the phase to a study that's ongoing is being funded fully as we mentioned by the Helmsley charitable foundation. And so that's not actually taking capital from our parents balance sheet today.

Thank you. It's it's it's again incredible what you've been able to do with what you had a year ago. Thanks for taking my questions. I appreciate it. Thanks Maya.

Thank you. Our last question comes from Ed with HC Wainwright and Company. Please proceed with your question.

Hi everyone. Thanks for taking my questions and let me add a congratulations on a remarkable turnaround throughout all of last year's with with seladelpar across your programs some of the questions. I have already been answered. But I do have a couple one is with regard to response your pivotal study. Clearly, you're leveraging off many of the sites that you had previously used for enhanced as well. As you know, optimizing the study design and everything from from the enhanced data, but I'm just wondering if perhaps just qualitatively you can discuss in addition to birth.

The ongoing pandemic what you know, what potential obstacles or dead or challenges do you see with enrollment? And I'm just wondering although this may be unlikely to to to really affect anything. But I'm just wondering if perhaps while there's a lot of patients that had good experiences in Prior studies. If there was a sense that you're hearing of of hesitancy from from either patients or Physicians given the clinical hold and and everything during that episode and then I have a follow-up. Thank you.

Yeah, thank thank you for that at well. Let me first just start out and I think just to say that you know, in terms of medication for we're able to kind of Leverage a lot of experience that has emerged, you know, for other sponsors and with our partners cro as we've gone through various waves and surges around the world. So there have been a lot of experience has developed that allowed us to put in place various things that you can do to mitigate things like Home Health visits where needed things like being able to dispense drug directly to patients in their homes. So they don't have to travel to the site things like offering Transportation, you know, if patients were uncomfortable using public transport things of that nature. So there there's a lot that we've we've learned and we put in place and were able to incorporate this into the protocol. So if we need it as an odd

Can we we can use it? It's not to say we are going to use it. It's just there in all territories. So that that's that's kind of one question II you're asking about is I you know, you know is is there some kind of lingering concern some trailing concern about the experience and I I can just say unreservedly know our approach really has been to be in close contact not only with key opinion leaders, but with really with investigators who have been in all of our studies, there's not a week that goes by that I'm not speaking with them talking about them. You know, I think our best our best tool really for enrolling the study is the data and from enhance and the enthusiasm that I took received comments that I received the discussion that we've had with kols around what we found as a result of the investigation it really wage.

Hardening and from the patient perspective. For example, I just had an email last night, you know a site that really has many patients that are just really excited hopeful they can come back in in the treatment with seladelpar. So I think I think I I really have no reservations about you know about a concern that that we that we Monday through with respect to what happened in Nash.

Okay, great. Fantastic. Glad to hear that second question is with regard to the two key secondary endpoints you talked about before in the past certainly about what you would like to see in terms of, you know, potential labeling where you to see significant reductions in Puritas, but also wondering about Alp normalization given that there is no data to certainly support the the idea that you could see significant some normalization. How should we think about um, uh, you know the exact options that you may pursue in terms of labeling, especially from a differentiation a marketing perspective there.

Yeah, thanks for the question really thoughtful. I'll start it off and invite, you know, Clara and Chuck perhaps to chime in I think fundamentally with respect to Al class normalization there really isn't necessarily a regulatory Pathway to recognize Alphas normalization from a labeling claim perspective. We do think that the data set itself and having the ability to have data sets from enhance and even response demonstrating a good proportion of patients that actually experienced normalization. Nevertheless is is a key differentiating feature off certainly from the only existing second-line treatment alternative ocaliva and potentially even others that are being evaluated. So, you know, it's it's a prime interest not only to us but reject the entire medical community and we think could be a key factor in in driving, you know potential use. Should we be successful in getting seladelpar registered? Of course.

Pure itis I I think it's a bit more straightforward than even uh class normalization, you know, this is a known clinical symptom of the disease. It affects quality of life significantly. I think in many ways you might consider a symptom burden to be an outcome of the disease itself. And so here of course, we have aspirations. We think there are various ways to page here, you know, clearly having a data set strong enough that The Regulators would do as as being able to provide, you know, some indication on a label of treating patients with PVC trading. It's for patients with PVC is probably at the top of that wind list, but but there are others, you know, having the data set itself in the label a strong data set continuing to be able to invest in evaluating patient-reported outcomes the appear itis or even fatigue just something we've done consistently in our clinical studies all of these data log.

As we think as we look to publish and continue to invest in life cycle management to really have data to support broader use of seladelpar. I think can be quite valuable overall as we continue to progress even in the absence of a specific label claim. Of course, you know, we continue to be hopeful that that will be successful here and show kind of effect as we shown in enhance and continue to think about opportunities even beyond the phase 3 study to invest in these types of data sets.

Okay, great. Final question then for me is if you could perhaps this is a question for Dan, but if you could help us think through, you know, the potential trajectory trajectory or or Cadence of topics spending throughout this year and perhaps into early next year off both G&A and R&D. Especially perhaps later this year as you look to get readouts from your early life Pipeline and think about, you know, pursuing further development with those compounds.

Yeah, thanks for the question. Ed. You know certainly as we highlighted in the in the remarks you we are seeing a an uptick in our spending as you would clearly expect as we as we react of these programs across the number of of of trial fronts and initiatives and so we're we're we're projecting a 20 and twenty million and growing to sort of twenty-five million dollars off per quarter sort of run rate and a little bit more towards the back half of this this year of unless so towards the towards the first half. So that's sort of the progression and as we took us a little bit earlier on this on this particular call here. Um, you know, if you consider some of these other programs they are they see the 406 for example, we're we're we're off we've got funding in the budget for those but we'll we'll take a look at you know, what where the data leads us there and and consider, you know, the capital needs beyond that. Um, and and yep.

I'll just turn it over to schedule as well for any other color. Yeah. No, I think that is as Dan mentioned if you look back at historical effects when we were enrolling enhanced, I think it mirrors am projecting here with respect to twenty to twenty-five million per quarter and it won't get to the high end of that range until we get much deeper into enrollment and that's what really provides the cash Runway guidance to mid-2012 to uh, and and the strength of the balance sheet that we have here today obviously will evaluate opportunities to continue advancing the pipeline programs as we progress and and certainly look to do so in the future.

That's helpful and congrats again.

Thank you.

Thank you. There are no further questions at this time. I would like to turn the floor back over to management for any closing comments.

Thank you operator. I'll just leave everyone here with one sentiment one year ago today. We had shut down all clinical activities while we took on the important work off of ensuring patient safety before dosing another patient with seladelpar today. We have four active clinical studies on going across three different programs and multiple significant opportunities to create value for patients and our shareholders. We would not have accomplished what we accomplished in the past year without the grit resolved hard work and dedication and really by everyone at SEMA Bay by our partners our expert advisers. And of course the patients that continue to inspire us in our most challenging days off. I think all of them, I thank you for joining us today, and I look forward to providing you with many more updates in the month ahead.

Thank you.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Have a wonderful evening.