Q1 2022 Cymabay Therapeutics Inc Earnings Call

Good day, ladies and gentlemen, and welcome to the FEMA based <unk> first quarter 2022 financial results and business update conference call. At this time, all participants are in a listen only mode.

Following the formal remarks, we will open the call up for your questions. 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 <unk> website at Www Dot Sema Bay Dot Com now I would like to turn the call over to Mr. Paul Quinlan General Counsel at Sema Bay Mr. Quinn.

Please proceed.

Thank you operator, and good afternoon, everyone I hope that you've had a chance to review the press release, we issued announcing our first quarter 2022 financial results and business update.

You can access that release on our website under the investors tab.

Joining me on the call today are Suzhou Shah Chief Executive Officer, and Dan <unk> VP finance.

Following our prepared remarks, we will open the call for Q&A.

Before we begin I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to <unk> expected future performance business prospects events or plans, including clinical plans regulatory approvals funding and repayment schedules.

Anticipated timeline and trial enrollment date cash runway and planning for commercialization 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 forecast due to the impact of many factors.

The company assumes no obligation to update or supplement any forward looking statements, whether as a result of new information 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 in Sema days quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward looking statements.

This conference call is the property has seen the bay and any recording or rebroadcast is expressly prohibited without the written consent of senior debt.

At this time I'd like to turn the call over to neutral.

Thank you Paul good afternoon, and thank you for joining us today.

As it is less than two months since our 2021 yearend call.

Our updates today will be brief as we turn our attention in the second half of this year to key milestones in our unwavering journey to bring cell Adele part to patients with primary biliary cholangitis or PBC.

Our phase III development program for sell at Alpine N. P. B C include ongoing NDA, enabling PK studies.

I sure a long term safety study to complete a comprehensive patient safety database.

And response, our second phase III efficacy and safety study to support marketing approval.

We believe this program is the most extensive program for any investigational drug currently in development for the treatment of PBC.

These clinical studies draw from the extensive experience we've gained from our prior phase two and phase III development.

Where data have continued to support the potential for cell Adele part to address many of the unmet needs based by patients with PBC.

Results. We previously shared from our 52 week open label Phase II study in over 100, PBC patients dosed with Philadelphia.

Were published last month in the journal of Herpetology.

The opportunity to have these data featured in one of the world's preeminent medical journals for liver diseases elevated sell at El <unk> visibility as a differentiated drug candidate for patients with PBC.

We continue to believe sell Adele par has the potential to address three important unmet needs for patients with PBC.

First many patients need therapies with improved activity against the disease as.

As exhibited in the incomplete responses, commonly observed in their liver lab tests for cholestasis and liver injury.

These tests include levels of alkaline phosphatase believer.

Bilirubin and transaminase by.

Biomarkers that have been associated with histological progression and poor outcomes for patients with PBC.

We believe that offering patients an improved biochemical response.

And especially the opportunity to achieve biochemical normalization should be the aspiration of therapy in PBC.

Second many patients with PBC suffer from significant burden of symptoms, including pure writers.

Currently approved therapies have not address this need.

And the only approved second line treatment a vertical like as it has been associated with new onset or exacerbation of pruritus.

A therapy that can provide symptom relief would improve patients' lives.

Potentially improving acceptability and adherence to therapy.

Lastly, PBC patients encompass a spectrum of disease stage, ranging from those without cirrhosis to those with compensated cirrhosis, including with portal hypertension.

A leading treatment option should be safe across the spectrum of non cirrhotic and compensated cirrhotic stages of disease.

These data along with data from our prior phase III enhance study that we have presented at past medical meetings continue to excite and motivate investigators and their patients to participate in our ongoing clinical studies.

Central to our clinical development program for sell at Alpine PBC is response, our second global Phase III registration study.

<unk> to enroll 180 PBC patients.

Who have had an inadequate response to or are intolerant to first line treatment urso deoxycholic asset.

Since our last call, we have made steady progress towards completing enrollment.

However, the COVID-19 pandemic continued to have an impact on screening and enrollment at clinical sites globally.

A cycle of implementing been easing of restrictions as variance emerged and subsided and lingering resource issues at clinical sites have been primary factors affecting our projected timeline for response.

Timelines for enrollment have also been affected by our suspension of activities in Ukraine, and halting of further enrollment in Russia.

Our efforts to mitigate the delay have included increased in person visits with investigators at their sites.

Additional investigator meeting for U S Latin American and European investigators.

Implementation of patient referral initiatives.

And activation of additional sites.

This has resulted in consistent progress over the past few months despite ongoing global challenges.

We now have over 150 sites activated across 26 countries.

As we approach what we project to be the final months of screening we.

We have greater visibility into monthly metrics and now forecast completion of enrollment occurring in the third quarter.

We remain confident in our ability to execute given our extensive clinical and operational experience with Citadel Park development in PVC globally.

Importantly, we continue to expand the clinical experience with sell adult bar in the assure long term open label study.

We have now begun to roll over patients completing response into a sure.

Together with patients that entered into assure from prior studies would sell at El par.

There are approximately 140 patients in this study taking seller Dalbar daily.

This level of investment underscores our commitment to collect data on the long term safety and durability of efficacy of Philadelphia.

We believe this is fundamental to our success in seeking approval and eventually in marketing selling alper.

In addition to fueling our ongoing clinical efforts are.

Our prior experience has provided us rich datasets that has been featured at major medical meetings. Since we began development of Philadelphia <unk> for patients with PBC in 2015.

Through the remainder of this year, we are excited about multiple opportunities to feature data and analyses at upcoming Gi and hepatology Congresses.

In two weeks sell Adele par will be featured in three abstracts presented at the annual digestive disease week held in San Diego from May 21st to the 24th.

The first is an oral presentation in the presidential plenary session by Professor Bettina Hansen from the University of Toronto.

The presentation entitled them sell Adele Park treatment of patients with primary biliary cholangitis for two years improves the globe P. B C score and predicts improved transplant free survival.

Supports that long term treatment with celadon bar was associated with improved prognosis and supports an emerging view regarding the promise of earlier intervention in disease.

Two additional oral poster presentation will also be made.

The first by Dr. Stuart Gordon Professor of Medicine at Wayne State University, and director of the Division of Herpetology and GI research at the Henry Ford Health system.

Describes a pooled analysis of phase two and three data on the efficacy and safety of sell it out bar in PBC patients with compensated liver cirrhosis.

The second presentation by Doctor Alia Gular Hussein.

<unk> Professor at the University of Toronto Centre for liver disease.

Describes an analysis of the efficacy and safety of sell at Alpine in PBC patients, who have had prior treatment with a better coal or gas it or fibrosis.

We look forward to these presentations and further engagement with many of the key experts supporting our ongoing work with Philadelphia N P. B C.

Before I ask Dan to review, our first quarter financials.

Let me provide a brief update on our second clinical program.

Last year advent health initiated patient dosing of Mdx 29, 82, and a two period crossover pharmacology study using a hypoglycemic clamp technique to evaluate the levels of counter regulatory glucagon released under conditions of low blood.

Sugar.

N. Bx 20, 1982 is a G. P. R 119 agonist discovered and developed by FEMA Bay.

It has completed five previous clinical studies, including in subjects with pre diabetes and type two diabetes.

The product concept being investigated for Mdx 29, 82 in the current study is as an agent to potentially prevent or minimize hypoglycemia in patients with type one diabetes.

The study is being conducted by advent help translational research Institute in Orlando, Florida and is fully funded.

By the Liana, EM and Harry B Helmsley charitable trust.

See I'm a bay retains all rights to M. Bx 29 82.

In addition to safety and Tolerability. The primary endpoints are maximal glucagon release, and glucagon area under the curve for Mdx 29, 82 versus placebo treatment periods.

These results will guide our decision on whether to pursue further development for hypoglycemia associated with diabetes.

This 28 day study is targeted to enroll up to 29 participants.

We are projecting to have these data prior to year end if recent progress in enrollment continues in the coming months.

Turning our attention to financial results for the first quarter.

We have remained diligent with managing our expenses and focusing our activities, where we have near term opportunities to create significant value.

The current market environment has been as challenging as we have seen in our industry over several years.

The capital we raised last year gives us a balance sheet that allows us to advance our global clinical activities for sell at El Par and report topline data from response in 2023.

We believe we are well positioned to weather the pressures of the global market.

As well as those facing the biotech industry today.

Before taking questions I'll ask Dan to review, our first quarter financials Dan.

Thank you Sergio.

As highlighted in the first quarter of 2022, we continue to make additional progress on our PBC development plan objectives.

In clinical development, we made advances in our ongoing efforts to enroll and treat PBC patients and to conduct other required clinical activities and our response for sure and other NDA, enabling clinical studies that are necessary to complete our late stage development of cell Adele par in PBC.

We also made additional progress in manufacturing development as well as in medical Affairs, and commercial where we began early stage efforts to plan for potential future launch of sell adult part in PBC.

Overall, our cash cash equivalents and investments totaled $193 $4 million as of March 31, 2022, and included $25 million of third tranche of funding received from Abbvie worse in the first quarter of 2022.

We believe this cash on hand, together with additional committed capital available to us under the admin worth financing agreement is sufficient to fund our current operating plan through 2023.

I will now turn to a brief review of our first quarter operating results.

Net loss for the quarter ended March 31, 2022 was $27 $8 million or <unk> 32 per share compared to a net loss of $17 $6 million or 25 per share in the quarter ended March 31 2021.

Net loss was higher in the quarter ended March 31, 2022 compared to the corresponding period in 2021, largely due to an increase in clinical trial activities associated with the ongoing late stage development of cell adult bar in PBC as.

As well as an increase in accretion of interest expense related to the Albion worth development financing arrangements.

In particular operating costs increases were primarily driven by an expansion of our site activation and patient enrollment and other clinical trial activities associated with response and assure our two active global late stage clinical trials in PBC and.

And higher employee compensation associated with the hiring of additional personnel to support the PBC development plan.

We expect our operating expenses to increase in the future as we continue to execute on our clinical development manufacturing and commercial readiness plans for PBC.

Let me now hand, the call back to Suzhou.

Thank you Dan.

It has been a long road towards bringing cell Adele par bath to patients with PBC.

And we are as committed as we have ever been to seeing the process through to completion.

Our teams have worked tirelessly against the backdrop of a global pandemic and a market environment that has put pressure on our entire industry.

Our focus has been on managing the things we can control.

Which we believe has positioned us well to create significant value for patients and our stakeholders.

In recent months, we have seen strategic interest in P. B C that we believe underscores the significant unmet needs facing patients today.

We believe cell Adele par has the potential to advance care for PBC patients in a way that is differentiated relative to very few options that exist today.

Philadelphia is now one of the only late stage opportunities in this area that remains fully unencumbered.

As we look to close out enrollment in response in Q3, we expect to have multiple opportunities to highlight important dataset at upcoming medical meetings throughout this year.

We also plan to host an investor day before year end to highlight our vision for positioning sell it out part to advance the care of PBC patients around the world.

We're now happy to take questions operator.

Thank you well now be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question. Kim You May press star two if you'd like to remove your question from the queue for participants using speaker equipment may be necessary to pick up your handset before pressing the <unk>.

Darkies one moment, please we poll for your questions.

Our first question comes from the line of Yasmin Rahimi with Piper Sandler. Please proceed with your question.

Hi, This is Anna on for YOD. Thank you for taking our questions. We have three for you first could you kindly provided us some commentary on how confident you are about finishing response enrollment by three Q 'twenty two what percent of total patients are fully enrolled at this junction second we are certain you were getting and the name of interest on partnering so lots of her M. P.

D C could you walk us through at what juncture and think it is most appropriate to pull the trigger and third congrats on securing three D. DW presentations, including the present presidential plenary session could you. Please kindly tell us if there are any new aspects of this what was the part data that you'll be presenting and we've not yet seen and the significance of this new data set.

Yep.

I appreciate the questions and I'll answer the first two and I'll ask Chuck to provide some additional context on the presentations at D. D. W.

I think as most folks know as I mentioned in the remarks, you know we've been 100% focused on advancing Philadelphia for patients with PBC.

And over the last year have done everything in our control effectively to deal with the pressures that we've faced relative to the pandemic.

And additional competition for patients.

As mentioned one of the biggest challenges has been the waxing and waning of restrictions in various geographies at different periods in time.

Now the positive is over the last few months, we've now started seeing very steady and consistent progress. So it gives us a greater ability to now predict the completion of enrollment than we had previously over the last year I'll remind you that first patient randomized in response occurred in April of last year. So we're a little over 12 months.

From the first patient coming into the study.

It's not a typical as we reached a crescendo in the number of sites activated and as broad of a program as we have in response across 26 countries around the world you know to start to see an increase in that enrollment and what's not a typical absent some of the challenges presented by the pandemic has to start seeing a meaningful acceleration.

<unk> as you get to a critical mass of number of sites.

That's one of the things that's been different with the backdrop of the pandemic harder to see consistent acceleration, but as I mentioned, we've started to see several months a very consistent steady enrollment that gives us the ability now to project towards the completion of enrollment now these are projections.

But again this is a an indication in which we have been experiencing development of Philadelphia since 2015.

Strong relationships with sites globally, we've done this before we've fully enrolled our prior phase III study. So we're quite confident in execution and how we need to do what we need to do over the course of the coming months with this greater visibility to the timeline really comes this vision and view around completing enrollment.

In the third quarter, we don't tend to have much it provide any percentage around enrollment, but again I think I would take the comments just given where we are in this study and a view towards what's necessary to complete enrollment.

Really as a guide towards the confidence that we have in executing and completing enrollment in the third quarter much greater visibility today than we had even several months ago.

Now you talked a little bit about M&A and partnering interest in this space as well obviously in the last six months.

We've seen two separate transactions in the P. D C space.

And as I mentioned again in the prepared remarks, you sell a delta or we believe is really one of the only fully unencumbered late stage assets in PBC.

Now our development program as extensive as it has been in the program inclusive of both assure an response, we believe will provide us with the opportunity to register cell Adele part not just in the U S. But also in Europe .

And so we certainly have the balance sheet and the wherewithal to execute through completion of the program.

But it's the principle of ours to always evaluate strategic interest as an alternative to ultimately putting cell Adele par in the hands of as many PBC patients globally as we possibly can and I think we are sitting in a very strong position ultimately to capitalize.

On the meaningful amount of interest we've seen in the space.

The highly differentiated and derisk profile of Philadelphia in PBC to ultimately execute on a strategic plan that creates the greatest value and as I mentioned puts philadelphia or in the hands of as many patients globally as possible. So those types of discussions remain ongoing.

And I would simply say that we're very excited.

Excited frankly about the opportunities to partner or potentially to really bring cell Adele PARP to patients globally. We certainly again have it within our vision to bring cell Adele part two patients throughout the U S.

But this is an important global strategy for us. So we'll continue to evaluate ongoing discussions with various parties.

Okay.

Thank you very much and the last one about the D D W presentations.

Could you kindly tell us if there's any new aspects of the slope of hard data that you'll be presenting that we may not have seen yet and the significance of the new dataset.

Yeah, Matt This is Chuck I'd be happy to take that question. Yeah. We were very very excited to get selected for the presidential plenary section.

And what we're presenting here I do have to respect the embargo for D. GW. So there's limitations in what I can tell you, but I do hope I can.

Peak your interest to really go see something that I think there's going to be quite interesting.

We're using the globe score, which is a validated prognostic risk tool.

But basically comprised of five factors age.

Oakland phosphatase levels bilirubin levels, platelet count and albumin in all all of those are factors that are known to be related to <unk>.

Risk of progression and this this continuous score system is now being used to not just.

<unk>.

Identify the risk for progression, but to look at treatment response.

And so the story in the presentation is that the data suggests the club score changes suggest that are.

Theres been an improvement.

And event free survival in those patients treated for two years with cell Adele par and so what's different here why is this important well the globe score as a continuous variable and it is basically an online tool that's available to physician can can type in the patient's numbers and get a prediction for risk.

It's different than it's used for regulatory approval, which has also been validated in the sense that it makes more scientific sense. If you have a patient who's alkaline phosphatase level is close to the regulatory threshold of 1.67 and they change very very small amount.

It doesn't make sense that theres really been that much of a change in the risk or the other.

Their hand, the globe score with being a continuous variable if you get a large change, but theyre not below that $1 67, you're really established that they've had an improvement in their their outlook and their outcome.

And so we believe that well work continue to anchor on the regulatory endpoint for approval, we think the globe score this continuous score system.

Will likely become part of medical practice and it may be incorporated into future clinical research. So I think we're really.

Paving the way there and I think if you were able to attend the session proposed in the audience that can I think youre going to see some analysis that looked at different aspects of the patient population and give us some real insights into where sell adult her might be directed once it.

Hopefully it gets to the market.

Thank you very much.

Thank you. Our next question comes from the line of Stephen seat House with Raymond James. Please proceed with your question.

Good afternoon. Thank you for taking the question Suzhou you are speaking.

More about sort of strategic interest in how you're thinking about that than Ive heard you in the past and it's pretty interesting given.

What we just saw with Ocala, but ex U S.

It's basically being sold somewhere between 400 and $500 million depending on.

Milestones coming through so I wanted to ask just without pegging. The ground. What do you think of that price and how are you thinking about the ex U S value and opportunity.

The way to.

Capitalize on that first name of it.

Yes, I appreciate the question Stephen you know I think as we've continued to progress with our own development.

We're certainly anchored by our ability to carry forward and complete the development program for sell Adele part not just in the U S, but for a registration.

As I mentioned, even in Europe , but.

But clearly as we do more work and well look forward in the second half of this year as mentioned to share a bit more of the market research and commercial strategy that we're putting together to prepare ourselves upon potential success for salad out part of the development program.

But we're really excited about opportunities, we see a to deliver oh.

Solution, if you will to patients that meet a significant number of consistent unmet needs today.

As well as an opportunity to really expand the addressable patient population I think some of what we've seen.

With other transactions you mentioned the sale of the rights to a vertical like asset outside the U S.

For a little over 400 million to <unk> pharma.

I think really underscores what.

What we believe to be an opportunity again to expand addressable patient population here specifically in that translation transaction outside the US This is something that we believe is absolutely an opportunity for sell at L. Par to really capitalize on and so as we've progressed, it's always been an important priority for us to a value.

A host of different strategic alternatives and so yeah, I'd simply say that you know the fact that we've talked a bit more about it.

Positions us in a position to think about you know as I said capitalizing on the right alternatives for us as we move forward.

Alright, I appreciate it a couple of sort of more housekeeping questions I wanted to ask because I noticed the inclusion exclusion criteria entry for response on controls that go along with.

Expanded a little bit on March 21st I would say, but it just looked like it was adding more details.

Verify what was already there so I wanted to.

Ask if there's been any material changes to inclusion exclusion criteria in that study and then second.

Want to know if you expect data for Mdx to 982 in the first half this year.

Sort of reporting of data is actually in your hands are in.

With your partner.

Okay.

Yeah happy happy to answer those two questions. You know I think are not atypical in the in a global protocol like response to see some amendments throughout the conduct of the study I think the most significant of which recently has come out of some of the work we've done in renal impaired patients.

This lowered the the GFR threshold for exclusion criteria for patients that obviously makes it easier.

Easier for some patients to enroll into the study because we didn't see as much of effect on them and that study from cell Adele par. So that was a positive and again opens up the opportunity for some patients that come across that threshold to enroll into the study. There is also a shorter period for washout for those patients that had been on prior.

Treatment, specifically, a vertical like asset <unk> five rates.

Historically, and so again that just helps us at least offer up an opportunity for patients to come into the study more quickly again, if they are eligible to enroll so I think those were probably the two most significant that we believe certainly have helped us and will continue to help us completing enrollment in response with respect to MBS.

<unk> thousand 982, you know here again, we've seen some positive trends recently and enrollment in that phase Iia study.

You mentioned correctly. This study is being run by advent health and fully funded outside of Sema Bay, but.

But we retain the full rights to the program, we certainly will be involved with those groups and actually sharing and publicizing. The data. So you should expect to see that come from all the parties involved inclusive of Sema Bay and we're really excited about the potential for that study to complete enrollment in the coming months.

In fact, we can be in a position to share that data before yearend.

Thanks, So to appreciate all the.

Hey, Joe.

Thank you Steve.

Thank you. Our next question comes from the line of Patrick Dolezal with Wifi Capital. Please proceed with your question.

Hi, Thanks for taking the question I guess on the topic of business development I'm curious, how you're thinking about pipeline expansion if at all and if so would there be a focus on earlier stage assets or would you ever consider a more transformative transactions, especially some merger kind of.

A later stage company in a similar space perhaps.

And then the second question is.

Just really on pre commercial pre commercialization preparations.

Other you've engaged the physician community or payers and kind of what the response has been thus far so.

Yeah, Patrick I appreciate the questions. You know look I think we're grounded first and foremost by near term opportunity to create value.

For patients of course for our shareholders as well and so the center of that is execution on sell it out bar and so we are unwavering in our level of focus and completing enrollment in response executing on the global clinical program. That's inclusive of a sure a study that we think adds to our phase III development program and our prior history.

We have development to really position seller dalbar as really being the most extensive program in PBC in development today, that's where we're grounded because we know as derisked and differentiate it as a profile for cell Adele par is today.

That the greatest amount of value in the near term will be created off of us really executing well on that program. So that's first and foremost our priority Theres no question that as we think about future opportunities to create value. We certainly build teams here at Sema Bay with extensive experience from research to clinical.

Operations in clinical development regulatory quality CMC and as we add that final lag if were successful would sell at alpine around commercial we certainly believe we have the infrastructure internally and expertise to capitalize on additional opportunities you talked a little bit about opportunities in similar spaces of course, theres a depth of offer.

Our depth of experience here inside the company around inflammation and fibrosis.

Tremendous amount of focus obviously here today near term in liver and Gi.

But we certainly could envision ourselves opening up and expanding to other differentiated opportunities I think they'd have to fit well with our areas of focus and internal expertise.

And they'd have to be the right timing and the right opportunities. So again I wouldn't take away our focus from cell Adele par in the near term opportunity to create value, but certainly as we think beyond that.

We believe we're well positioned to continue to feed pipeline and growth opportunities longer term.

That's absolutely an inherent thought process of ours as we continue to progress.

With respect to just the inputs that we've had from a pre commercial perspective, we've started to do a fair bit of market research we've talked to physicians. Obviously, we've been closely involved with experts in the PBC PBC community globally for many years.

But we've continued to gather these data and internal advisory meetings, we've gathered a fair bit of market research data that continues today Steve.

I'd say, we've been seeing a tremendous response and much of it is anchored again on the on the significant amount of data that we've collected to date data demonstrating anti cola static benefits of cell Adele par anti inflammatory benefits in Philadelphia as well.

Importantly, as effects on improving key clinical symptoms of disease, including fatigue as well as importantly pruritus.

That profile I think is at the center of the positive response that we see from the medical community. The payer community will continue to do that work and ultimately the final dataset. It shouldn't really support the profile, we've seen with the drug thus far as al mentioned in North of 300, PBC patients that we've dosed with.

Zelle Dalbar today, many of which have actually gone even out to two years of treatment.

So we're excited about this opportunity from a commercial perspective, and again I think you'll see us share a lot more of that insight.

As we complete enrollment in the third quarter and we get to the later part of this year.

Thanks I appreciate it.

Thank you Patrick.

Thank you. Our next question comes from the line of Ed Arce with H C. Wainwright. Please proceed with your question.

Hi, everyone. Thanks for taking my questions and congrats on the progress with enrollment in the face of a.

Multiple challenges here lately.

Four questions for me if I may firstly.

Enrollment of response.

Uh huh.

How many patients have.

Been enrolled.

Now that youre looking at less than 30.

Additional.

To get to full enrollment.

Hum.

C.

Acceleration.

And.

To some degree of over enrollment and is that something you would actually be interested in.

Secondly, with regards to the assure study the long term open label study I think you said there were 140 patients now rolling over from response, just wanted to confirm that.

And more broadly.

As it's part of the NDA filing and you were looking at I think a total of 500 patients in that study.

B some submit the data.

The table at the time of filing.

Third thirdly, I wanted to ask about the.

The initial efficacy and response that you were looking out from <unk> 2982.

And specifically the maximum glucagon release in the area under the curve that you mentioned.

And any sort of benchmarks that you're looking for either qualitatively or quantitatively.

And then lastly for Ford.

It was just.

Uh huh.

Hum.

Financials are looking throughout this year is it reasonable to expect that while we would see steady increases in R&D through the year.

G&A should be relatively flat.

And thank you for answering my questions.

Absolutely and I think I've got all that here written down if I Miss anything you can catch me up here first of all with respect to enrollment in response, we've not indicated specifically the number of patients that are randomized into the study I think you mentioned a number of less than 30.

Yeah, if I, if I read that correctly I heard that correctly, what we did mention is that we've got 150 sites activated.

So not specifically patients randomized, but 150 sites across 26 countries around the world I would simply tell you. This you know.

Projecting enrollment timelines.

He is a bit tricky and always carry some risk in and I think that challenge is no more so than today given the backdrop of the pandemic as we've talked about on prior quarterly calls as well as today.

Where we sit today is at a point in time, where we know we have at least a consistent level of data over the last three or four months. If all we do is maintain that consistent level of enrollment than we project. The study to be enrolled in Q3, clearly internally our objective is to try to accelerate enrollment.

You've talked a little bit about the fact that one of the key activities over the last two months has been for various members of our team to be face to face at investigator sites.

Actually been face to face with almost 80% of our S. U S European investigators.

Have been largely across North America, Latin America, Europe and APAC.

All over a majority of sites that we visited ourselves at Sema Bay, not just our CRO, but seem a bay representatives Theres no question that that level of engagement.

It takes commitment, but clearly we think will generate result, so we're actively involved with every site actively working through.

The needs of sites to try to get this study enrolled as quickly as possible in all of our initiatives are anchored around trying to accelerate that level of enrollment, but we're certainly as I mentioned quite positive around what we've seen recently over the last few months and again, if we just maintain that consistent level of enrollment that we've seen in the last three.

Going forward, we do expect this study to complete enrollment in the third quarter.

Now you also asked a bit about our shore, where we do have about 140 patients now on the assure long term study a study that again just gives us a tremendous amount of data both safety as well as long term efficacy of cell Adele par importantly, the first sets of patients complete.

<unk> response, I mentioned, the first patient into the study was April of last year. So clearly we were beyond the 52 week treatment period, and I'm happy to say that we've already started rolling over those first sets of patients that came into response into assure the vast majority of that 140, <unk>. However, our patients that had been in prior clinical studies.

Neither our phase two open label study or our prior phase III enhance study that's where much of that population comes from you also mentioned the number 500 I'm not sure quite what that refers to.

We don't expect to see that many patients from a sure again, we had north of 300 patients that had been dosed with cell Adele par even as we started response.

We're excited to see almost half of those already come into the assure study I think ultimately beyond response and assure we do have a commitment because improved approval in PVC.

Occurs from an accelerated subpart H approval pathway to commit to a long term outcome study again, we're in the final stages of agreement with regulators around what we think will be a very novel approach to that outcome study relative to what we've seen historically in PBC and so we'll have more to share.

On that as that process is.

Is finalized and as we again complete enrollment and eventually complete.

The response phase III clinical study, but that's yet to come and we're completing that dialogue with the agency as we speak.

Your third question I think had.

Really around initial efficacy and response around expectations with Mdx 29, 82 in the proof of Pharmacology study and you know here I'll I'll again ask Chuck to jump in and give you some context around.

This study.

Yeah, I had sorry, I think the basic design that we used was good.

Good one in the sense that we are also including healthy subjects. So the healthy subjects, who will give us a good benchmark for what you know what we expect from the mechanism in terms of its ability to elaborate glucagon and of course, then that is related to its ability.

To restore normal glucose levels from from a low low blood glucose levels that we induced with the hyper.

Insulin they make clamps.

Yeah.

And then I'll ask Dan to answer the questions around financials through the rest of this year.

Sure Yes. Thanks for the question you know.

Without a doubt.

As you noted we will be focused on executing the development of the R&D.

Investments there are unwavering will be.

Spending.

For the completion of response and a sure.

And in other NDA, enabling studies.

With respect to G&A.

It will be largely flat throughout the year, we really wanted to be thoughtful through this time of of completing our enrollment and really thinking through that and the trajectory towards ultimately towards data. So we're gonna be vary.

Watching our our costs as we move forward.

Yeah.

Thanks for taking my questions guys I appreciate it.

Thanks, Ed.

Thank you. Our next question comes from the line of Jay Olson with Oppenheimer and company. Please proceed with your question.

Like to follow up one on response study and the other probably on the M&A front.

So for the small study just want to confirm or have more colored song.

This action to complete enrollment in Q based on your current employee acts at 155, where you need to or you need to open additional sites at a post out a week he in the past few months.

And on the M&A I'm just wondering what's your view of U S and ex U S. P. D C markets.

We're still at ballpark do you see that as like separate Opportunely Detroit's like one package and also if you can comment on whether the cash runway projections also include the.

And in building the commercial infrastructure and also prelaunch preparation. Thank you.

Yeah. Thank you for the question so with respect to response, we do as I mentioned expect to complete enrollment in Q3, I think you asked whether or not that's predicated on additional side certainly we believe that the sites that are activated today can allow us to accomplish the completion of enrollment based again on where we are today and what we <unk>.

Checked into the future.

That's one of the things that we actually have at our disposal as well to mitigate some of the challenges of the pandemic and so you may very well see even additional sites than what you're currently represented on clinical trials Dot Gov.

Once again to ensure that we hit these timelines, but I think fundamentally where we are with our plan. We're confident that the plan will allow us to execute to complete enrollment here in the near term.

With respect to M&A U S versus ex U S. I think we ultimately look at geographies somewhat independently the goal within FEMA Bay is clearly to get Philadelphia to patients globally that can benefit that includes the U S. That includes Europe . It includes geographies outside of those jurisdictions Asia Latin America.

And so I think ultimately we're going to develop a plan and continue to execute on our plan that is likely to involve partners, particularly in geographies outside of where were base today.

Clearly the significant the most significant opportunity is in the U S alone there our strategy is to execute and ultimately build our opportunity to commercialize and bring sell at all parts of patients on our own. We can certainly do that in regions outside the U S. But we recognize the challenge that exists there from an infrastructure perspective.

And so once again, we're actively involved even today and we will continue to be in thinking about potential strategic partnerships that can allow us to do that effectively in a cost effective manner and still create significant value obviously for all of our stakeholders.

Finally, you asked a little bit about cash runway the cash one way we've provided to date in fact doesn't include commercial launch. So ultimately we're expecting our cash to last through the end of last cheating. The end of next year clearly upon successful top line data, we believe there's opportunities for us to continue.

To execute and fund the next stage of development to create value around a variety of different alternatives again, we look at financing strategy long term is being inclusive of potential partnership strategy and various non dilutive sources of capital as well as a host of other vehicles that we've deployed in the past as well so we feel as though.

We have quite a few levers to pull as we continue to move forward, but current guidance around cash running through the end of next year is not predicated upon ultimately N D. A post NDA filing approval and launch we certainly would look to file the NDA as quickly as possible post topline data all of that of course is already embedded in our projections.

Great. Thanks for the color.

Yeah.

Thank you. Our next question comes from the line of Kristen <unk> with Cantor Fitzgerald. Please proceed with your question.

Hi, everyone. This is Rick on for Christian. Thank you for taking our question. We've just called one here in a paper that we recently saw published in frontiers in immunology researchers looked at the role of hepatic CD eight T cells in a mouse model of PBC identifying two distinct subsets of T cells with high cytokine production.

<unk> and greater proliferation potential respectively, given the potential role for cell at Dell par in inflammation and fibrosis. How are you thinking about its potential role in interacting with resident immune cells in the liver and how that could be associated with PVC pathogenesis. Thank you.

Thank you for that question.

As Chuck to give some comments here Chuck.

Yeah, I just wanted to make sure I was off of mute. So thank you for that question and I think you know that is of that.

Uh huh.

The publication that you cited is one of a number that have looked at with increasing interest in the roles of.

Various immune cells, whether they'd be a T cells or NK cells.

And the like in an autoimmune liver diseases.

The short answer to your question is what were intrigued by it but we haven't yet developed any data that really indicates to us that we've established one way or another whether it is or is not a role. We did do a study that we presented an abstract.

At a recent meeting where we looked at its effect in immune mediated fibrosis.

Model, where we saw that Philadelphia part did.

Kris both liver and renal fibrosis, so that may be one indication that there may be something there, but it's a it's the question of a liver immunology is one that's.

Currently are continuing to advance.

And I think that's something that we'll just have to understand going forward, but it is an area that is interesting.

Okay. Thank you very much.

Thank you. Our next question comes from the line of Matt Young men Fannie with B Riley Securities. Please proceed with your question.

Oh, Hi, this is all for my own. Thank you all for taking our questions.

As you know clothes are nearing enrollment completion do you have a sense, how what portion of all of the patients have a biopsy taken.

Yeah. Thank you for that question. So of course in a blinded fashion, we are able to see how many patients have in fact volunteered for biopsy I think when we talked a little bit in the past.

The fact that biopsy and this study is still voluntary for patients they're not required to have a baseline and then a 52 week paired liver biopsy.

We're of course encouraging patients to do so we're required to share a subset of those with the agency and so it is a number we're able to track and once again, we're confident in our ability to deliver on what our agreement has been with the agency we've talked a little bit about the fact that in the past in our enhanced phase III study about 16% of patients actually volunteered.

For that baseline biopsy and our agreement with the agency is something that we think is certainly something we can accomplish in the context of response as well.

Got it. Thank you for the additional counter and one more question from US can you remind us of how your regulatory path you might it be different than those in the U S and what about other territories and how does that inform your BD transactions you might be evaluating right now.

Yeah. It's a good question, we certainly believe based on what we've seen historically in the setting of PBC and precedents as well as our guidelines and in Europe .

As well as the U S that response, we believe will allow us to register cell. It ALP are both in the U S and in Europe , So from a regulatory perspective.

Again, we believe that the primary endpoint in response will allow us to register in both geographies.

I think when you think a little bit about other territory territories again, the dataset. We think is supportive the endpoints. We thank our supportive clearly there are some geographies Japan as an example, where you have to have at least some sets of data to demonstrate PK and potential in that population. So there could be additional work clearly in geographies.

Like Japan, and China as well so theres. Some specifics you know outside of just U S and Europe , but fundamentally we think this dataset from response.

We will really support registration and a host of geographies outside the U S.

Thank you for the additional color that'll be all.

Thank you.

Thank you. Our final question comes from the line of Thomas Smith with SBB Securities. Please proceed with your question.

Hi, everyone. This is Mike on for Tom Thanks for taking our question.

So you talked a little bit about expanding the addressable population in PBC just looking at the U S market. It seems like sales have started to slow down pretty meaningfully.

I think that this is a market that should see a pretty meaningful growth from now until the time that you get to market.

Yeah. It's a great question and you know we talked you talked a little bit about sales starting to plateau, and I presume youre, referring to a vertical like asset and when you think about sell adult bar. We think there are a number of key opportunities first of all in those patients who are clearly incomplete responders to first line.

Met with early Deoxycholate acid.

There is a need for greater efficacy not just in reducing cholestasis inflammation, but really starting to normalize biochemical response in patients. So that's one thing we think sell at El Pas is quite differentiated from from even a vertical like asset. When you look at separate of course separate datasets not head to head data, but we think that.

Alone demonstrates an opportunity for us to have significant.

Both opportunity just in second line treatment, we think the Tolerability is another key element of that when we think about persistency and adherence to treatment alternatives.

We know that a better call it asset can potentially cause or worsen pruritus in patients with PBC and so when we look at some of the data sets with a vertical like asset clearly that impacts.

They're there opportunity in the market and we think sell Adele part can be quite differentiated.

A greater level of adherence and we talk a bit about just tolerability, but clearly actually having a been a potential benefit on pure writers and reducing edge I think patients would argue is actually an efficacy outcome for them.

And so those are some of the core elements of the Philadelphia profile, along potentially with safety.

We've seen a couple of label revisions for our vertical like asset, particularly in more advanced population. We've shared some data sets in compensated cirrhotic with and even with that with portal hypertension and without portal hypertension.

And so there's much more work for us to do here, but clearly here once again, an opportunity to treat the spectrum of disease in the spectrum of the population. We think is yet a third potential differentiator.

That that would support a much more a growing opportunity say for sell it upfront just a second line treatment setting I think with that profile certainly we have a tremendous amount of excitement and confidence around potentially expanding market opportunity. There's a tremendous amount of data being generated now around the benefit of <unk>.

Adding patients earlier.

With treatments that get them fully to biochemical normalization. So again no patients that might otherwise wait for a second line treatment opportunities to treat them earlier in.

An improved potential outcomes for patients. We think these are some of the things that can lead to overall expansion of the addressable patient population. So we're excited to continue to explore that.

And to continue to see where our data sets would potentially support that growth.

Got it that's very helpful. Thanks.

Thank you.

Thank you. Our next question is a follow up from me ink, maintaining with B Riley Securities. Please proceed with your question.

Thank you one more question from US is since last fall, we our peers, but how fast route days half slightly you'll have it all you guys are.

So we on a longer range, how are you anticipating that to shape the narrative for wassa, what's the expectation should be for response and we know.

How more severe patients included thank you.

I appreciate the question. So I you know I presume, you're referring to the ongoing development of LSA burner in patients with PBC, where we did hear the sponsor referred to completing screening last month, our projection is with a run in period that usually goes beyond screening that that study could potentially.

We enroll here in the coming weeks, if not towards the end of this month.

You know I think fundamentally we're focused on what we can control obviously, we're putting every effort to getting response enrolled as quickly as possible, but I will importantly, say that you know in addition to just response the assured dataset, we think gives us a tremendous amount of potential data supporting not just <unk>.

Dizzy, but also safety in this population we think this program will still yet to be much more extensive than even the development program for L. A fibrin or in the setting of PBC. These.

These are some of the things that I think will be quite important as we ultimately see the dataset from.

From these two programs currently in phase III.

We've also had the benefit of effectively targeting a number of patients empowering response, not just for the primary and key secondary endpoint around around biochemical response and normalization of biochemical response, but also around treating pruritus that's.

Something that we think we're advantaged around given our prior data set so I think at the end of the day, our push is to get the study enrolled as quickly as we can.

But it's also to have the most extensive expansive quality dataset and we think the latter is something that will certainly position Philadelphia are quite well against other potential treatment alternatives.

Oh, great. Thank you for taking our questions.

I appreciate it thank you.

There are no further questions at this time I'd like to turn the conference back over to Mr. Shaw for any closing remarks.

I appreciate it so you know once again as we approach the second half of the year, we expect to provide multiple updates at major medical meetings.

And investor conferences through the remainder of this year.

Against the backdrop of what has been a very challenging biotech market. We are grounded by the strength of our existing data and ongoing late stage development that we believe highlight a significant opportunity for sell at alpine PVC.

We believe we are well positioned with a strong balance sheet and a highly derisked differentiated lead program.

To capitalize on creating significant value.

We look forward to completing enrollment in the coming months ahead and speaking to you all once again soon.

Thank you. This concludes today's teleconference. You may disconnect. Your lines at this time. Thank you for your participation and have a wonderful day.

Okay.

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