Q4 2019 Earnings Call
Good day, ladies and gentlemen, and welcome to seem a base fourth quarter and full year 2019 financial results and business update conference call.
This time, all participants are in listen only mode.
Following the formal remarks, well open the call 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 Investor section at the Cymabay website at Www Dot Cymabay Dot com.
No I would like to turn the call over to Mr., Dan men old Vice President Finance at Cymabay. Mr. Mental you May 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 fourth quarter and full year 2019 financial results in business update.
You can access Beverly Center website under the investors tab.
Joining me on the call today are Sujal Shah Chief Executive Officer, Dr., Chuck Mcwhirter, Chief Scientific Officer.
Provide an update on the review of our clinical programs upcoming milestones assessment of strategic pathways and financial position before we open the call for today.
Before we begin I'd like to remind everyone that statements made during this conference call, including the QNX session relating to Cymabays expected future performance business prospects events or plans, including clinical plans and anticipated timelines and data release stage 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 forecast due to many of the impact of many factors.
The company assumes no obligation to update or supplement any forward looking statements whether in the 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 the risk factors set forth in Cymabays quarterly and annual reports filed with the FCC or factors that could cause actual results to differ materially from those anticipated in the forward looking statements.
This conference call is the property of Cymabay and any recording a rebroadcast expressly prohibited without the written consent of seem a bit.
At this time I'd like to turn the call over just suitable.
Good afternoon, and thank you for joining us.
Since we announced the decision to haul development up sell at El Par last November.
We have been focused on two parallel initiative.
And investigation of the unexpected histologic findings identified by the study pathologists in the phase Twob study of salad LPR in Nash.
And in evaluation of potential strategic alternatives for the company.
Before I stepped through our progress with these activities. Let me briefly review the events, leading up to november's decision to halt self help our development.
In 2018, we initiated a randomized double blind placebo controlled.
Most ranging space to be study of cell, Adele par, which enrolled 181 patients with biopsy confirmed Nash.
The primary efficacy outcome was the change from baseline in liver fat content at 12 weeks.
And key secondary measures included evaluation of histological improvement in Nash and fibrosis as assessed by comparing liver biopsies taken at baseline and 52 weeks.
In June 2019, we reported minimal reductions in liver fat, but robust and clinically meaningful reductions in markers of liver inflammation and injury, including Ale T. S. T gamma GT and alkaline phosphatase Ace at 12 weeks.
As the majority of patients in the study had completed 52 weeks of treatment by last November.
The study pathologist began their blinded assessment of the week 52 liver biopsies.
And the plan had been for them to conclude the biopsy review for those remaining patients who are finishing their 52 weeks of treatment sometime in February of this year.
As they read the first batch of slides they identified a subset of patients with an unexpected pattern of histological findings overlaid on Nash pathology.
These findings, which they describe to us as unexpected in Nash pathology were predominantly characterized as an interface hepatitis with or without bile duct injury.
Despite these observations patients enrolled in the study, including those identified by the pathologists as having unexpected histologic findings.
Had either improving or stable levels of biochemical markers of inflammation and liver injury throughout the 52 weeks of treatment, which included a ltd. STD Gamma G. T alkaline phosphatase case total bilirubin direct bilirubin and high sensitivity CRP.
In addition, there were no signals of immune or allergic reaction as reflected by changes any incentive fills or in clinical symptoms of liver injury, nor where there are other changes in markers that can be associated with progressing liver disease, such as platelets are coagulate.
Patient parameters.
No occurrences of liver decompensation or liver related e. cheese.
Were observed for any of these patients.
Importantly, these findings were unanticipated based on our prior clinical and preclinical experiments would sell it LPR.
After consulting with expert liver pathologists, and Hepatologists and with patient safety at the forefront of our minds.
The decision was made to halt development of sell it out par in all indications.
While committing to an in depth review of these findings.
The FDA agreed with this decision while formally placing a clinical hold on cell Adele par development and subsequently provided input on our plans to further investigate the situation.
Our investigation includes three activities intended to confirm and subsequently understand the significance of the findings identified by our study pathologists.
The first is a comprehensive collection and review of data, including patient demographics.
Medical history concomitant medications.
And a broad set of biochemical markers typically elevated in drug induced liver injury.
The second is a blinded independent review of both baseline and end of treatment biopsies.
By several world renowned liver pathologists.
And finally, the third is a formal pathology and clinical Hepatology review panel meeting that we are looking to convene in the middle of the second quarter during which experts will review all information gathered to provide an independent consensus determination of the roll ups.
Philadelphia are in these findings.
These steps will be essential for us to understand the nature and significance of the findings and to have the requisite follow up dialogue with the FDA.
After completing our investigation, we plan to try to meet with the FDA before the end of the second quarter to discuss potential future plans for cell Adele par.
Let me ask Chuck to provide you with some further updates Chuck.
Thank you so Joel.
Decisions last November were based on a review of the first 86 end of treatment liver biopsies read by our study pathologists.
Since then the review has been completed for all 152 patients with end of treatment biopsies.
Across subjects with or without these unexpected histological findings all of the standard laboratory markers, usually associated with drug induced liver injury, including allergic and auto immune reactions, either improved or were stable.
This encompasses liver test, including Ale T. S T gamma GT alkaline phosphatase pace in total bilirubin again, all independent of whether or not there were unexpected findings.
Further patients with unexpected findings did not display any pattern of clinical symptoms medical findings or liver related adverse events.
Liver test that 52 weeks, there were 1935, 41, and 40 evaluable patients in the placebo 10, 20, and 50 milligrams sell it LPR groups respectively.
The corresponding percent reductions from baseline that week 52 in a L. T were.
Plus 1.1, minus 29.1, minus 41.9, and minus 41.3% respectively.
Similarly for a S T relative reductions at week 52 were minus 0.5 minus 19.7, minus 25 and minus 16.6% for placebo 10, 20 in 50 milligrams sell Adele par.
Finally, corresponding decreases in gamma G T or minus 0.6 minus 29 minus 46.1 at minus 35% for these groups respectively.
The effects at week 52 in the parameters I've mentioned as well as an alkaline phosphatase pays and total bilirubin resemble the results we reported at week 12 last June.
We've also begun to analyze additional biomarkers and today, we have yet to see any changes on treatment that might explain the histology identified by our study pathologists.
The completion of the end of treatment review allows us now to share the key secondary histological endpoints in the study.
The two most important endpoints are those that have been used as phase three endpoints, namely the proportion of responders and each treatment group, having either one Nash resolution defined by a ballooning score of zero and a lot better inflammation score of zero or one with no worsening fibrosis stage or two.
The improvement of fibrosis by one or more stage with no worsening and Nash.
Hi to 181 patients enrolled in the study there were 152 with paired biopsies that entry and end of treatment.
I'll remind you that the study a randomized subjects into for treatment groups of 10, 20, and 50 milligrams sell at a par and placebo and a two to two to two to one ratio.
The number of patients with paired biopsies in the placebo 10, 20, and 50 milligrams sell Odell part groups were 25, 39, 42 and 46, respectively.
The percent responders with resolution of Nash with no worsening in fibrosis were.
810.3, 19, and 26.1% in the placebo 10, 20, and 50 milligrams sell Adele part groups respectively.
The corresponding rates for at least a one stage are more improvement in fibrosis with no worsening in Nash, where 20, 23.1, 23.8 and 37% the percentages of patients meeting both endpoints were eight 5.1 11.9.
And 19.6% for the placebo 10, 20 in 50 milligrams sell adult part groups.
We believe the completion of the additional biomarker analysis in parallel with the ongoing blinded in independent reviews of liver biopsies will provide a detailed picture of our patient population in this study the independent pathology review will include an accepted pathology, scoring framework known as the is shock.
Modified H AI, scoring system to quantitatively characterize features of histology, president and our patient population both at baseline and end of treatment.
Among these features includes the scoring for the presence and severity of interface hepatitis, which is not quantified in the existing framework for scoring Nash pathology.
The entire clinical picture of our patient population at baseline and end of treatment will be central to the expert panel review, we look forward to convening then the second quarter, and which outcome. We believe will allow for properly informed dialogue with FDA regarding sell Adele part development now, let me turn it back to Sue Joel.
She Chuck.
Elements of our investigative analysis have been discussed with the FDA.
Based on what we have learned today, we believe it is not only prudent but that we have an obligation to see this process through to its completion on behalf of all our stakeholders, including patients regulators and our shareholders.
I'll remind you that in addition to the data we have shared with you today from our study of sell at El par in Nash, we have presented celadon pars phase two data in PBC patients at major medical meetings over the past few years, highlighting its efficacy safety and Tolerability in this patient.
Population.
In parallel to our investigative activities, we have been focused on a comprehensive evaluation of all strategic alternatives to maximize shareholder value.
Including a liquidation a sale a merger asset acquisitions or potentially continuing clinical development of sell it alkar based on additional discussions with the FDA.
While we remain committed to completing the investigation. We believe this evaluation is prudent in order to make decisions expeditiously once we gain clarity on the potential path forward for sell it LPR.
In other words, we are keeping all potential doors open at this stage.
Since our announcement last November we have also been focused on a series of cost cutting measures to minimize expenses and conserve capital.
I'll turn it over to Dan to provide you with an overview of our actions.
And review fourth quarter, and full year 2019 financials Dan.
Thank you Sergio.
Following the decision to placed in Philadelphia, Our program on Hall management implemented a cost containment and restructuring program during the fourth quarter in order to reduce our operating expenses and associated cash burn.
Specifically, we froze hiring significantly scaled back future procurement plans.
Reduced our workforce by more than 60% and scale down or canceled many of our existing contracts for goods and services.
As a result of these actions we recorded a $5.1 million restructuring charge during the fourth quarter, which includes $2.9 million of employee severance cost point $9 million of noncash stock based compensation expense associated with the acceleration of stock options of certain terminated employees and.
$1.3 million of charges associated with the termination of certain contract manufacturing agreements.
Of the total 5.1 million in restructuring charges $3.3 million of these charges are expected to be settled in cash.
We paid out point 1 million in Q4, and the remainder is expected to be paid out over the course of fiscal 2020.
I will now briefly turn to review of other elements of our Q4 and full year financial result.
Research and development expense for the three in 12 months ended December 31st 29 team was $20.9 million and $83.8 million respectively.
As compared to R&D expense of $16.4 million and $58.1 million for the same periods in 2018.
Prior to the decision to halt developmental Philadelphia are in November 2019.
Research and development expense for the three in 12 months ended December 30, Onest, 2019 was $20.9 million and $83.8 million respectively.
This compared to R&D expense was $16.4 million and $58.1 million for the same periods in 2018.
Turning to the decision to halt development Astellas LPR in November 2019 research and development expense in the fourth quarter and 12 months ended 2019 was generally higher than in 2018 due to expanding clinical trial activities related to our Ptcs phase III clinical trial or PSC phase two clinical trial and other.
Okay and da enabling studies.
General and administrative expense for the three in 12 months ended December 31st 2019 was $4.5 million and $19.2 million, respectively, compared to $4.2 million and $14.4 million for the same periods in 2018.
Prior to the decision to haul development of sellers LPR June expense in the fourth quarter and 12 months ended 2019 was higher than in 2018, as a result of higher labor costs and other administrative expenses necessary to support our expanding development activities.
Overall, our net loss for the three and 12 months ended December 31st 2019 was $29.4 million or 43 cents per diluted share and $102.8 million or $1.53 cents per diluted share respectively.
This compares to net loss of $19.4 million were 32 cents per diluted share and $72.5 million or one dollar and 26 cents per diluted share for the three in 12 months ended December 31st 2018.
The increase in net loss for the fourth quarter and full year 2019 compared to the prior year periods was primarily due to increases in our operating expenses, including our restructuring charges as discussed earlier.
Finally, I'd like to share with you our current cash position the outlook for planned activities in 2020, and the expected impact of those activities on our operating expenses and our cash burn.
At December 31st 29 team, we had $190.9 million in cash cash equivalents and short term investments on hand, compared to 178.7 million at December 31st 2018.
As noted earlier in 2020 management intends to focus on concluding its investigation of the clinical observations seen in Nash patients and completing a review of strategic options.
In addition management will work to complete ongoing clinical study close out and monitoring activities.
These activities involve a number of key efforts, including caring for and monitoring Nash patients with histological observations recovering investigational drug product.
Conducting early termination visits with patients performing investigator site monitoring and close out visits.
And quality reviewing analyzing and reporting on clinical trial data accumulated to date.
Consistent with amounts previously provided in our recent letter to our shareholders. We continue to estimate our overall cash burn will be between $30 million and $50 million for the first half of 2020.
Of this total we expect between $20 million and $35 million will be used to fund the clinical study close out patient monitoring and sell it up our investigation activities previously mentioned.
Let me now turn the call back to surgical for final remarks Suzhou.
Thank you Dan.
I hope this update has been helpful.
I want to reiterate that we believe we are engaged in the most sensible and reasonable path forward at this time.
There's still much to be learned in the first half of this year in our ongoing investigation that we believe will provide clarity on the situation and potential path forward.
The best course of action given what we know about sell it LPR is to continue to evaluate our clinical findings. While also in parallel ensuring that we are thoroughly assessing strategic alternatives.
Well in our view.
It is too soon to commit to any specific strategic option.
We will certainly not be caught unprepared in the event. This emerges as the best way to maximize shareholder value.
Before opening up the call for questions I'd like to remind everyone that the purpose of today's call has been to provide updates on our corporate activities and our fourth quarter and full year financial results.
In order to ensure the ongoing investigation involving blinded independent reviews of patient biopsies is not influenced in any way, we will be limited with what we can share in detail on this activity beyond what we have discussed thus far today.
Operator.
Thank you we will now begin the question and answer session to join the question Q You May Press Star then one on your telephone keypad, you'll hear a tone acknowledging your request. If you are using a speakerphone. Please pick up your handset before pressing any Keith.
Withdraw your question. Please press Star then too.
Once again to join the question could you. Please press Star then one now.
Our first question comes from Yasmina remaining of Roth capital partners.
Hi tax hike to Joe. Thank you for an additional color I'm just two quick questions for you. The first one is.
Are you able to give us a little bit more color in regards to the numbers I see a typical lesions between placebo teladoc par.
Between placebo.
Treatment arm at the beginning and at the end up the treatment can you give or if you can get back can you just walk us through exactly how initially the biopsy sample to our Rad.
Dick.
Did the pathologist hop back in reading.
At end of treatment basically where that baseline.
Samples, we ranked at the time, so just kind of the logistics of how all that occurred could be very helpful. Fraud. Thank you.
Yes. Thank you for the question he has made I can.
Highlight some of these details and certainly as Chuck to jump in but anything that I Miss you're absolutely correct at some point in time, we will share all the details with respect to the into one of these unexpected finding that ended treatment, but as as I mentioned earlier.
Part of the key for US is to get through an independent blinded assessment of both baseline and end of treatment biopsies by several well known and world renowned pathologists.
With a tremendous amount of experience in Nash to confirm as well as ultimately have some.
Our interpretation as to the significance of these findings that we want share them, Jeff yet until we get through that investigation. We think it's incredibly important for us to maintain the integrity of that element of the an investigation, particularly as we take it to the panel review and ultimately to the to the agency.
With respect to the Nash biopsy ratings, we had a single pathologists do all the screening biopsy we.
And we had that same pathologist any second both well known and experienced pathologists and mass read the ended treatment biopsy.
At this point in time, we've not had those specific pathologist, we read any of either the end of treatment or baseline biopsies that is in particular, the key activity being conducted by several independent pathologist at this point in time.
Thank you Sidral for that color. That's helpful are you.
I mean, I'm certain they're only a handful of very well known pathologist are you comfortable to share with that.
How many total pathologist are part of this consortium of re reading and looking at the sample.
Yes, again here, we have several folks that will mentioned once this is actually completed I think again in the interest of maintaining their independent review, we'd prefer to do so as we share the results of their analysis, which we will of course do I think as we've mentioned as I mentioned in the prepared remarks our plan.
As to in fact have this review completed and conduct.
Panel review meeting with these expert pathologists, along with our study pathologist and clinical experts.
In the same room effectively to add some interpretation of the results of the investigation.
Sometime in the middle of the second quarter with the goal of ultimately taking out interpretation and the results and any conclusion back to the agency before the end of Q2. So we'll do that Yasmeen, but again I think it's really important for us to just let those individual get through their independent review.
Thank you and the best of luck tests, you guys, you're digging deeper into that.
Thank you.
Our next question comes from Elie moral of Cantor Fitzgerald.
Hey, guys. Thanks, so much for for taking the questions.
I guess in terms of the range of outcomes from that independent investigation could you sort of walk us through sort of the range of scenarios.
And then in terms of potential future next steps for Saldazo par on you mentioned that your plans to meet with the FDA discussed that I guess, how do the findings you've seen so far maybe.
Impact or shape, how you're looking at you know what indication.
You would be discussing this AD and you know if this is different sort of prior to that and I guess, what that says about the role.
Potentially be different and each indication and then I guess, Jeff in terms of you know you're obviously digging incredibly deep into 15 I. Just you know I guess what have you may be uncovered so far as you begin to the safety of ads that might have giving you more comfort sort of everywhere around the safety profile. Thanks.
Yes. Thanks, Kelly. This is Chuck I think I'm, you know, you're probably going to hear a recurrent theme here as I think but just just to give you a sense.
Because the way that we're approaching this is a completely independent arm's length.
Expert panel review that includes not only the upside of pathologists.
But experts and.
Drug induced liver injury experts and got a clinical hepatology, including Nash as well, let's call a static liver disease since we've been developing sell adult par there as well.
Other regulatory experts.
And then participation by.
Individuals who have been involved in this study, but the panel itself will be individuals who have not had not any association with the company or.
Or with the study to be completely arm's length it'll be.
You know the minutes LP.
Questions it'll popi posed to the to the panel and you know we think it's vital that whatever we determined can really.
You know help inform the agency and regulatory decisions.
So in light of that I don't think that I really want to speak to the range of options I think everything is possible.
We do feel that.
The determination of the panel if they if they make a consensus view that.
No it's appropriate to consider based upon their cuts out causality and risk group had a toxicity that sell adult part.
Could be contemplated for development that will be the recommendation if on the other hand, they have concerns that will be shared with the agency as well.
We think that kind of taking this very rigorous.
Hi, its based independent review is the level that would be required for the agency to make a really strong and comfortable decision.
If thats what happens for solid out part of move forward, so and that and that lied I don't think I want to comment really any on any specifics about.
How this might play out I think that for those on the call I think what you can take comfort in this just.
You know the commitment to the quality the integrity thoroughness. So that when the results are made available thats. The we feel the best that could be done and I think thats appropriate floor for patients.
People have invested in the study investigators.
Regulators as well and of course importantly, our shareholders that be we ultimately hold responsibility to.
Because this is where you know them up the most valuable you'd be created for them.
Yeah, Let me maybe I'll just add as you asked a bit of a question around our level of confidence I think Chuck expressed it well we're still in the midst of this investigation, but as we discussed today as we've collected additional biomarkers that are typically elevated.
When we see drug induced liver injury. The fact that we've not yet seen any specific signal.
Across a host of biochemical markers not just those we reported back in November but additional biomarkers that have been collected and continue to be collected.
It really guide that to making sure that we have a full some understanding of the patient population in our study.
Not just at end of treatment, but also at baseline we shared effect on histology endpoints today as well I think some of what we hypothesized around the anti inflammatory benefits that sell Adele par have translated to the histology endpoints we reported today.
So the robust decreases and liver enzymes, LT ASP gamma GT and alkaline phosphatase case that we've seen at 12 weeks.
The maintained through 52 week and with respect to at least improvements in fibrosis without worsening of Nash and Nash resolution without worsening of fibrosis I think we see again these.
Key effects of cell Adele par translating into benefits on histology for a portion of patient. So it's a complete picture of what we continue to learn that really focuses.
And on making sure that we complete this investigation in its entirety and maintain and integrity and independents to that investigation at the same time.
Thanks, so much better color.
Yes.
Our next question comes from Steve seed House of Raymond James.
Thank you thanks.
Thank you guys were reporting the data from the end of treatment Histology assessment I just want to commend you for continuing to.
Look into the results and share those with the community.
It was remarkable to see that the Nash endpoints as you just mentioned fibrosis and Nash resolution resolution how to dose response signal afterall.
Which obviously is correlated with deliveries on changes and inversely correlated with liver fat so.
Two questions, we'll try to keep up the ones that hopefully wouldnt compromise the ongoing blinded investigation in the first one is just how are the patients doing that had to the interface hepatitis a view.
I have there been any clinical correlates or problems for these patients subsequent to the finding.
Yeah. So thanks for the question you know today third there haven't been any further complications reported.
Of course.
Well you make remain engaged with investigators and we continue we haven't place.
Plans and a protocol to continue to follow patients are.
We do to have a recommendation for a repeat biopsy for those subjects in particular, who had finding that would occur six months after the but the last dose of the drug and so that process remains ongoing I don't have anything to report now it's just it's still still in progress but today.
No news is good news I would say.
Okay. Thank you and do you have an opinion yet on the the findings mechanism specific related to people are delta or molecule specific.
Something that you could remove from the pharmacology by improving the molecule what retaining what looks to be efficacy.
So I think the whole point of the independent review is just to figure out what what did happen. So I think I don't want to go to the next step about what was the cause until we understand what was cost.
So I'm just going to defer an answer to that I will mention that you know in and all of our preclinical work in multiple obese mouse.
Nash models, we hadn't seen any findings like this so the mechanism of itself is still.
It's still not in our and our my mind anyway, yet yeah lengths. So we'll just have to wait until the independent review is is completed and then I think that will be appropriate for the.
The panel to to make any.
Any comments or recommendations to us on an additional follow up.
Okay.
The Gulf phrase this next on a little bit.
Differently. The are you able to given the design of the study are you able to exclude.
The possibility that this could be a drug drug interaction, that's causing the signal or is that one possibility that could be concluded from University division.
Well I think you come back to some of the remarks, we've made at this point in time as we look at things like medical history concomitant medication.
Other underlying conditions, we've we've yet to see any pattern in fact.
These factors related to patients with unexpected finding that end of treatment.
So again, where we are today is in a position where this independent reviews, specifically will head the most light around any significance with respect to these findings any potential causality, but also provide a much more in depth picture around the specific unexpected findings.
End of treatment.
Given the fact that this independent review will include.
Scoring systems that are use that are not part of the typical Nash scoring system. So as Chad mentioned.
He shops modify histology activity index or ha high has several different components that are scored and quantified including.
Features such as interface hepatitis.
That is cellular and a CRO see a number of different things that are not typically quantified if you will in Nash other than called out.
To the degree that a study pathologist see something unusual on toward so I think the in depth methodology and framework that we're using here with respect to that pathologists involved in the investigation is one in which will give us that a tremendous amount of additional information with respect to our study population.
Okay. Thank you lot last one for me, it's I find it hard to believe.
You would observe this like that this is a mash specific finally, but maybe it is obviously the investigation and cover that.
You've obviously treated a lot of PBC patients with this drugs. So can you just from minus have you ever during the development of sold over in PBC assessed biopsies in those patients post treatment and if so.
You quantify that how many biopsies.
Yeah sure I'll, maybe I can answer that question. So as we discussed in the path.
Biopsy is not part of medical practice in PBC, it's not necessary and facts to diagnose to the disease, that's not part of.
Michael studies, either in our enhanced phase three study we did offer patients.
The opportunity to volunteer to have a baseline biopsy. The intention in that study would have been that at some subsequent time point as patients rolled into a long term extension.
We would have the opportunity to take a second biopsy, perhaps that for example, three or time point to see if theres any benefit overall and histology or any change in histology. So it's not really been part of our clinical development, it's not part of medical practice within the setting in PBC. However to provide you with an update.
November's call, we have had approximately doesn't patients for which treating physicians elected to have biopsies taken.
We don't have baseline biopsies for all of these patients. However, we do know that based on assessment by those physicians and or.
Biologists within those centers. They described the histology as being consistent with PBC.
So we've not yet seen anything that anyone's identified to us in our study populations with respect to PVC that appears atypical.
Okay very helpful. Thank you guys for taking the questions.
Sure. Thank you see.
Our next question comes from Jay Olson of Oppenheimer.
Hi, Thanks for taking the questions.
Is there any biological explanation, even if it were hypothetical that would support a causal rule.
So with L. par for interface hepatitis and is it possible that this is potentially harmless finding since it didnt seem to be correlated with any liver injuries or adverse events.
Yeah, I would say at this point.
In a long alliance I'm not aware of any expectation that did.
Our delta agonists and sell adult par in particular would have a relationship to interface per se and I would say that at this point again, one of the things that we're seeking to understand is really characterize.
The entire study population you know very independent way both both on treatment.
As well as comparison to placebo and and compared to to baseline.
So.
I think thats, that's really the bottom line is where we didnt expect this.
We've never seen it before typically drugs that have been associated with drug induced.
Auto immune liver disease or hard daily.
Features that include interface hepatitis.
Almost always have some clinical corollary like.
Elevated a LTM asap.
Day would typically have more advanced necrosis.
Drug induced liver injury is often associated with that sometimes elevated bilirubin, but also clinical symptoms to you.
After and expect to see.
John This just color during may be flight pain.
And if theres an allergic component you often would see for example, a drug crash or eosinophilia and so none of those features.
We are found in this study was solid l. par and that's that's one of the reasons why weve.
We've done we've initiated such a thorough investigation around how long a broad.
Range of characteristics not only the clinical picture the laboratory picture, but also the histopathology picture and bringing expertise with experience in all aspects of this and using the CEO graded staging system for the pathology is key we think for four sorted.
And this out.
Okay. Thank you for that.
And then.
Maybe if you could talk about it.
These phase Twob study results could support it a pivotal trial is that if the if you were too.
I agree to remove the clinical hold on silver so part development.
Do you think these results would support a pivotal trial or do you think you'd need to conduct another phase Twob study in Nash.
That's a good question Jay I think it's a bit premature for us to speculate on what else would be required I will say again, when we look at the changes in liver enzymes across both LT at Ti as well as gamma GTN al Phos, where we.
What we would have otherwise expected to see that the anti inflammatory benefits of sell at El far in fact have translated at 52 week to improvements in histology that we think are actually quite meaningful.
These results are preliminary and so the statistics are not included in our in our press release, but if you just look across other agents that have been studied in Nash today I think we are quite pleased at what we believed to be really the benefits of sell at El part in this population in fact appear to have.
Translated so.
I'm unsure about what the next pads forward would be but again I think our primary focus.
As to learn more about what's occurred here and have the potential opportunity to think about pads forward for cell Adele par really in any indication of course, our most advanced indication was PBC. So that is a priority.
I'd simply say at today, we're pleased with what we've seen with respect to efficacy I think futuresteps at this point are unknown.
Okay, great. Thank you very much.
Yes.
Our next question comes from Ed Arce of H.C. Wainwright Enco.
Sorry about that.
Hi, Chuck and Seadrill, Thanks for taking my questions.
And thanks for all the extra detail and analysis that you provided today, it's been very helpful.
So I have to sort of major questions.
First is.
You clearly you've taken some some effort to a really really detail and delineate all of the clinical findings to date. So below par you mentioned, how the the more them dozen or so biochemical markers all are improving or state.
So there is no signs of potential duly there's no signs of immunological signals or platelets are calculation factors no liver related fees.
[music].
So in light of all of that Ah first question really isn't I think was kind of danced around that a bit here on the call is.
Is it possible that.
One of the key determinants from this panel, but I would I guess would happen in may or June.
One of the terms determinants is that the atypical findings.
Oh, the histological findings are either a.
Hey, false or meaningless signal.
Or be it the findings were actually real but somehow not caused by citadel par.
And then I have a follow.
Yeah, I think it's a good question Ed look I think yes, you've asked the million dollar question and as what we believe the investigation is really geared to answer I think if I did the two scenarios you identified it would most likely be the latter potentially if theres a path to move.
Forward that in fact, it wasnt something caused by sell Adele par as opposed to not being there at end of treatment.
And again I think the framework that we're using to assess both end of treatment and baseline biopsies that goes beyond what is typically done.
In Nash is solid you review isn't factor framework that will give us a much more clear understanding of the patient population even at baseline.
So we're incredibly focused on making sure that the review happens in a fulsome independent fashion and and executing all the way through panel Review Committee to the agency is in fact.
The key priority within the company.
Okay, great. Thank you.
Second part sort of related to this depending of course on the outcome of this panels are.
Oh work.
You have these preliminary topline results from the study.
Most of the patients had had parallel biopsies and obviously as you noted the statistics here are still pending so we don't have anything in terms of stat sick, but seems fairly clear to me that at least in the 50 make dose.
It's likely to end up being stat Sig.
Perhaps across all three of these.
You know acceptable surrogate endpoints in Nash and so our given.
This pretty.
Fairly possible positive findings your preliminarily.
Given.
That you could find that sold out par.
May not have been a direct causes is how would you see going forward with this data once you've gotten final determination.
I guess what are the next steps.
With the drug once you've gotten the final determination from the panel and the final.
Efficacy results Wits statistics.
Well I think you yeah, we agree with you add with respect to the interpretation of the efficacy data in the study.
I'll simply say again here, we're focused on getting through the independent review and engaging the agency in dialogue.
That'll that'll tend to be pending the results of this independent review if in fact.
We come out of the panel review meeting with an ability to argue around lifting the clinical hold for cell Adele par not just in PBC, where we were most furthest advance, but also in Nash and really in other indications.
Then I think we go back to the strategy. We ultimately had in hand, we know that within the setting a PBC with the strong set of phase two data.
There's a clear unmet need in that population.
With respect to Nash, we've always also felt theres a clear unmet medical need here in this data in fact is encouraging from our perspective I think with respect to Nash, we've always felt that strategies to develop treatment alternatives would involve studying various agents in combination I think these data could potentially be supportive of.
That but I don't want to put the car before before the horse so to speak I think the key element for us is to maintain the focus on the investigation.
Yeah, I don't want it to minimize the the path ahead of us to get through the investigation and pending the results engage the the agency and further dialogue.
Okay, Great clearly there are some encouraging signs here and I just want to.
Take a moment to congratulate you on your thorough diligence here in the work that you've done so far regardless of the outcome.
We appreciate it thank you and thanks for this apart.
Our next question comes from Derek our children of Stifel.
Hey, great. Thanks, guys. This benefit Derek Thanks for taking my call I'm.
Sorry, if I Miss this but did you give the reason for why the second biopsies only done in 152 out of the 180.
Oh patients thanks.
Yeah. Thanks. This is Chuck it's the usual, we had about 83% to 84%.
Of subjects, who had an end to treatment biopsy, that's a pretty.
Common range or number I would say for a phase to be paired biopsies study of 52 week study.
Some of this was related to typical reasons for early terminations or lost a follow up.
And sometimes patients don't want to have the second biopsy and again, we did in November.
Terminate the study early and so then that was also another another impact that patients just decided to pay were.
Not interested in going to going throughput. So I think in my perspective, a you know 80, 384%. It's a pretty good number I think that that really doesn't raise any red flags from from our from our perspective.
Okay.
Thanks for the infill guys appreciate it.
Thank you.
Our next question comes from Joel Beatty of Citi.
Hi, Thanks for taking the questions. The first one is on the data table that in the press release that shows that the statistics are pending final analysis.
Could you share what remaining.
You did that needs to be done that for a final analysis compared to what's shown is there any potential for the numbers shown there to change.
Yeah. Thanks. Thanks for the question Joel That's you know, it's just about an abundance of caution and being very true to the.
To the good clinical practice a process. The so the database is not yet locked so we're in the process as you know the final cleaning quality control all the typical types of things that need to move us towards a good.
Clinical study report and so once all that's understood and recognize then statistical analysis can be done according to the to the pre specified plan and that we didn't want to.
I have to have to.
Modify that later the results are preliminary so they have.
So while there could be some adjustment, but I wouldn't think that it would be any if anything changed it wouldn't be anything that you would consider significant to the overall interpretation really really shouldn't change at all.
Great. Thanks, and then one other question on PVC could you remind us how close the trial was to completion and the amount of data that you collected for patients.
That's where I'm going is if you get to a point we're off to yea agrees to lift the clinical holds a you know you know what could that data support you know kind of because its court approval could as a part of doing another trial, whereas the trial data.
Yeah, Great question, I mean, we agree with the sentiment pitcher, which you're alluding to there. So the study was completely enrolled we had to.
A full enrollment across 25 countries more than 150 sites and in fact that we had significant numbers of subjects.
Through treatment through a more and more than six months of treatment and many even through through nine months. So we believe that well it's unlikely that trial by itself would be a registration trial. It would be a very significant data set that could support be used as part of the consideration for.
Or regulatory decision.
In particular, I'll, just remind you that.
The primary endpoint in that study as a composite looking at call a static markers.
Pasco Tase below 1.67, with at least a 15% reduction and alkaline phosphatase from baseline and an ability rubin in the normal range.
Usually at 12 months, but by six months Theres very little difference between historically, what you see in studies between six and 12 months.
Again.
Another.
Key secondary endpoint was normalization of alkaline phosphatase pays looking at that at six months I think would be very informative and then importantly improvement in prior to us and that was a six month endpoint and so we think we would have a very full placebo controlled data set that would.
That would would speak to that so.
Just to round out the answer to your question Accordingly in terms of our clinical wrap up we're taking measures to make sure that we collected data to date is clean we close it out that we can get.
Clinical study report that could be used in the event that that we were to go back into PBC with a registration study and that would be I think enormously valuable lot of clinical experience there coupled with our very large open label Phase two study, which was also a 12 months study.
In which we've extended we have a lot of patients pass more than 50 patients past two years a treatment even some patients with three years of treatment with with good results. So far in terms of efficacy tolerability and the appearance at least of safety.
Great. Thank you.
Thank you.
Our next question comes from Manic mentality of B. Riley FBR.
Hi, this is way or somebody else. Thanks for taking my questions. The first I thought the quick several quick quite a quick ones. The first will be on the Nash study.
Could you let us know.
So what the so they'll part doses level was that would it be and well you ever to approach the of three analysis.
I'm sorry, Lee can you.
Mentioned the first part of your question again can you repeat that.
Just just still what those sits level where the.
The study.
So we studied three different doses of cell Adele par in the Nash study 10, 20, and 50 milligrams. If your question is more related to patients with unexpected findings again at this point in time, we think it's important not to disclose those specific details as we have several.
Independent pathologists reviewing again, both baseline and end of treatment biopsies and so not to influence their independent review, we'll share that subsequent to the completion of the investigation.
Thank you and also.
How about the proceeds three analysis are you going to do any.
Analysis on that.
Thanks, There is that the study had a very extensive and rich.
Set of assessments, including noninvasive imaging MRT incorrect to T. One.
We have some fiber scan data, we do have some some other biomarker data, including fibrosis markers. Those those will be shared at some point I think you know the entirety of the results of this study like all our studies our plan would be too to bring them to.
For external review it like a medical conference and eventually to publish the results but.
We're not yet ready to too.
To make that disclosure until we get everything wrapped up.
Great. Thanks, and then could you let us know assays to Nash study how to allow the patient to remain on the baseline treatments such as DLP and looked at lower in treatment et cetera, or if there was a washout period, excluding and the background treatment.
Yes, so they weren't they were non GLP. One so quick ones were not not a lot per the per the protocol, but.
Obviously these subjects have.
Many different kinds of co morbidities, including hypercholesterolemia diabetes, all those kinds of things and they were allowed.
As a.
Appropriate.
Therapies for their underlying.
Conditions and then they would go be limited in terms of what types of adjustments that could be making during this study.
Okay and my last question will be a follow up on the PBC study.
Could you maybe oh.
Give us more color on the status with the PBC phase three data assets is there any time mindful about what the available for this may or June investigator meeting.
So good question that I think so weve terminated the study as we previously announced last December.
The database lock and cleaning it is yet to be completed and again as Chuck mentioned, we want to maintain those timelines in the integrity that data.
We don't believe that data.
Take dealers needed for the panel review.
Thank you would be certainly helpful data for us this year should should we be successful at some point finding a path forward result, alpine PBC would be I think in our intention useful to share regardless with respect to just the overall update to the medical community but.
Not something in the near time.
Okay, great. Thank you.
Thank you.
This concludes the question and answer session I would like to turn the conference back over to Mr. Shah for closing remarks.
Thank you once again, everyone for joining us on the call today as we've noted we're working diligently and expeditiously across each of our parallel work streams.
We're incredibly mindful of all of our stakeholders in these efforts, including patients regulators and shareholders.
And we look forward to providing further updates as the work progressive Thank you.
This concludes today's conference call you may disconnect. Your lines. Thank you for participating and have a pleasant day.
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