Q1 2021 Cymabay Therapeutics Inc Earnings Call
Good day, ladies and gentlemen, and welcome to see him up a first quarter 2020, one 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 up the call for questions. Please be advised.
As of this call will be recorded at the company's request. It is also being webcast live on the Investor section of F. C met phase website at Www Dot Shimon Bay Dot Com now I would like to turn the call over to Mr. Dan Minerals, Vice President of financial as she went back.
Mr. Mental you may begin.
Thank you operator, and good afternoon, everyone I hope you've had a chance to review of the press release, we issued announcing our first quarter 2021 financial results and business update the can.
And access that release on our website under the investors tab.
Joining me on the call today are Suzhou Shah Chief Executive Officer, Dr. Chuck Mcwherter, Chief Scientific Officer, Klara Dickinson, Chief regulatory officer.
<unk> will provide an update on recent progress in the build out of our leadership team to deliver on our value creation strategy. Chuck will discuss an update on our pipeline diversification and I will provide a brief summary of our financials.
Following our prepared remarks will be available for Q&A.
Before we begin I'd like to remind everyone. The statements made during this conference call, including the Q&A session relating to <unk> expected future performance.
Is this prospects events or plans, including clinical plans regulatory approvals and anticipated timelines and data release dates cash runway and planning for commercialization of any future products are forward looking statements as defined under the private Securities Litigation Reform Act of 1095.
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.
Vince are directed to the cautionary statements set forth in today's press release as well as the risk factors set forth on Sema base 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 of Sema day, and any recording of rebroadcast is expressly prohibited without the written consent of Sema day.
At this time I'd like to turn the call over to Joe Joe.
Thank you Dan good afternoon, and thank you for joining us today.
Less than two months ago on our last call. We highlighted the initiation of response, our global Phase III registration study of <unk> for patients with primary biliary cholangitis or PBC.
And the expansion of our clinical pipeline with Mdx 2982, and Seabee O four O six.
This past Monday, and then again earlier today, we announced further significant progress with the strengthening of our executive team with the additions of Louis Stuart as Chief Commercial Officer and Dr. Dennis Kim as Chief Medical Officer.
These seasoned biotech executive come with considerable talent and energy to apply their leadership and experience as we move into a period in which we plan to complete development and regulatory submissions for sell at Alpha begin pre commercial preparations and continue efforts to <unk>.
<unk>, our research and development.
I am extremely pleased to have Dennis Kim joining theme of day as our CMO.
Dennis is a physician scientist trained in endocrinology.
And with significant clinical development and executive experience and an emerging biotech environment that he acquired during substantial 10 years at amylin Orexigen and zapped yet.
Dennis will join the executive team reporting to me and will lead all critical functions, including development clinical operations Biometrics and medical affairs.
His track record fits precisely hema base knee to have him lead a highly motivated and productive clinical function.
That is integrated with research regulatory manufacturing business development and commercial efforts.
I am confident that many of you will learn that Dennis also brings an acumen well suited to articulate the science medicine plans and opportunities of our programs to broad audiences, including medical experts investigators patient groups investors and analysts.
I am equally delighted to welcome Louis Stuart as our Chief commercial officer.
Just a little over two years before sell of Dell parse potential launch. This timing is ideal as we add a recognized commercial leader to implement a thoughtful and efficient bill of both the strategy and an organization.
Lewis comes with deep experience in commercial leadership and product launches in the emerging biotech study.
We were deeply impressed by his knowledge and experience in a variety of situations, including at CV Therapeutics and most recently at my of Theyre, both of which required the self reliant approach of standing up a product launch, but also post launch they ultimately involved integrating marketing and sales efforts.
Into much larger entities.
Drawing upon this exposure to a broad set of practices Lewis will lead all aspects of the commercial function, including marketing and sales.
He will join the senior team reporting to me and will be intimately involved in strategic planning across many functions.
There will be many opportunities to get to know Louis as one of our spokesperson as he moves our commercial plans forward.
I expect many will gain an appreciation for the energy and enthusiasm. He brings that is grounded in his aptitude for a crying knowledge and using critical thinking.
The announcement of these critical C level of higher serves as the capstone to the continued progress we made as discussed in March with the initiation of two studies in patients with PBC the.
The phase III response study and the long term safety assure study.
Our remarks today will be brief mainly reiterating our guidance on timing for these studies, while providing some additional color on study population.
We will also describe progress being made on N b ex 2982, and <unk> four O six our other pipeline projects for which we expect to be able to provide further updates in the second half of 2021 as we seek to bring additional novel treatment alternatives to patient.
We will conclude with key corporate and financial updates.
Completing the development of Philadelphia for patients with PBC remains our top priority.
In the first quarter, we initiated response, a 52 week placebo controlled randomized global phase III registration study evaluating the safety and efficacy of sell at El <unk> in patients with PBC.
Responses intended to enroll 180 patients in of two to one randomization to oral once daily sell Adele part of 10 milligrams or placebo as an add on therapy to patients with an inadequate response or intolerance. The first line first of the deoxycholic acid therapy.
The primary outcome measure is the composite biochemical responder rate after 52 weeks for alkaline phosphatase and bilirubin. The same end point used to register all caliber.
The only approved second line treatment alternative for PBC patients.
We expect our strategy for differentiation to potentially be significantly strengthened by two key secondary endpoints the rate of normalization of alkaline phosphatase at 52 weeks and the change in pruritus from baseline to six months in patients with moderate to severe pruritus as.
The reflected in a baseline pure riotous numerical rating scale value of four or greater.
As many of you will know the design for response and confidence in the selection of endpoint the significant given the shared population endpoint and the safety and efficacy demonstrated by the spell it out bar of 10 milligram dose in the completed phase III study in hand, which was stopped early.
The results for enhanced were presented in a late breaking presentation at a S. L. D last November.
So the Delphi 10 milligrams achieved a high degree of statistical significance for all three of the same endpoint being used in response after only 12 weeks of treatment.
Our approach in the development program for sell of Dell par is to collect data necessary to characterize the benefit risk of cell Adele part of across the broadest population of patients with PBC.
We have been asked recently about patients with PBC and their underlying stage of disease as it relates to cirrhosis.
Broad categories of increasing severity of fibrosis can be described as non cirrhotic compensated cirrhotic and D compensated cirrhotic.
Within the compensated cirrhotic or sub stages of patients with and without clinically significant portal hypertension.
Clinically significant portal hypertension develop as the fibrotic liver becomes increasingly stiff and is thought to often be a precursor to the compensating liver related events.
Measuring of portal hypertension is an invasive burdensome procedure and so a clinical signature or clinically significant portal hypertension can come from a number of less invasive criteria as recommended in published practice guidelines.
Across two significant studies with the sell adult par enrolling more than 360 patients with PBC.
There were over 50 patients with compensated cirrhosis, some of which were treated for two years or more.
Clinical data from some of these have been highlighted in published abstracts and presentations given at past medical meeting.
Due to the identical eligibility criteria and overlap with clinical sites.
We expect the majority of patients that enroll in response to also be non cirrhotic, but would nonetheless expect somewhere around 15% to 20% to be compensated cirrhotic.
Patients in this population would eventually be in the target population and so it is important that they'd be studied for safety and efficacy.
In this quarter, we continue to make headway with our clinical development program per cell Adele par, including activities for other NDA, enabling drug drug interaction studies and special population studies for patients with renal impairment and PBC patients with hepatic impairment.
Results from the hepatic impairment study in particular, we will provide valuable insights into the exposure and potentially the safety and efficacy of selling the out bar in PBC patients with various degrees of cirrhosis.
In the first quarter. We also initiated a share an open label long term study of <unk> in patients with PBC in order to collect additional safety data to support registration.
We expect sell of Dell parts of half one of the most robust safety databases in PBC patients ever submitted for an NDA.
Our most important focus remains to accelerate site activation screening and randomization in response over the coming quarters.
Our efforts in response with 80 fewer patients are nonetheless on the same scale globally as they were for enhance.
This is being done in an effort to mitigate challenges posed by the pandemic and greater competition for patients.
It remains our goal to enroll the study by the end of the year and we will look to provide additional updates on timeline later this year.
Now, let me turn the call over to our Chief Scientific Officer, Dr. Chuck Mcwherter. The cover updates on our early clinical stage Mdx 2982, and C. D O four O six programs Chuck.
Thanks Suzhou.
I am pleased to announce that the first patient visit has occurred for the phase Iia proof of pharmacology study with MBS 2982, using hypoglycemic insulin implant procedures in patients with type one diabetes the.
The study is being conducted at advent help translational Research Institute.
Orlando, Florida and is fully funded by the Leona am and Harry Helmsley charitable trusts sema.
<unk> seen a day retains all rights can be ex 29 82.
This is a double blind randomized placebo controlled two period crossover study it.
It will examine the effect of mdx 2982 versus placebo to stimulate the release of glucagon under hypoglycemic conditions in type one diabetes.
The endpoints will be maximum glucagon release, an area under the curve from glucagon concentrations.
The study is intended to include about 30 subjects and the investigator believes it will be complete in the second half of this year.
As a brief reminder, <unk>.
<unk> 2982 as of <unk> thousand 19 agonist discovered and developed by seeing the Bay.
It has completed five previous clinical studies, including in pre diabetic and diabetic subjects.
The product concept being investigated for mdx swimming in 92.
As an agent of potentially prevent hypoglycemia in patients with type one diabetes, a significant cause of morbidity and the risks of mortality and individuals with type one diabetes.
Its action is expected to result from the stimulation of glucose regulated released of glucagon.
The counter regulatory hormones insulin.
Which is accretive from pancreatic alpha cells, and which serves to return low blood glucose levels to normal and hypoglycemic conditions.
And recently published studies with isolated human pancreatic islets G. P. <unk> thousand 19 agonists were shown to enhanced glucagon accretion in response to low but not the high glucose levels and further they were able to prevent insulin induced hypoglycemia by increasing glucagon accretion in a rat model.
No.
The translation of these findings to the clinic is being evaluated in this phase Iia proof of pharmacology study.
We continue to progress with the phase one single ascending and multiple ascending dose PK study of CBS. There of course euro six and expect to have results to share later this year.
The objective of this study is to establish its pharmacokinetics safety and maximum tolerated dose in healthy subjects.
As a reminder, we are evaluating <unk> 0406, the active metabolite of the prodrug of <unk> will open eight that had previously been studied in diabetes in gout.
CBS 0406 of the <unk> gamma non agonists ligand that attenuates the expression of inflammatory genes.
It has been shown to block innate immune responses through the Nf Kappa B and MLR piece III inflammatory pathways.
And published studies <unk> III caspase, one on IL, one beta where all decreased by <unk> 0406 in response to inflammatory triggers and macrophages.
It was also shown to attenuate the MLR P. Three dependent pathophysiology of goudy inflammation when dosed as the pro drug in a mouse model and also on a phase II clinical study in gout patients.
Based on pharmacokinetic studies in monkeys, we believe the CBS 0406 may have greater exposure potentially greater efficacy than does the prodrug of our whole opening.
Decisions on any future development of our contention on its achieving a favorable profile with respect to safety and exposure.
We believe <unk> 0406 may have utility in various inflammatory diseases and are currently exploring potential opportunities to advance the development pending the results of the ongoing phase one study.
So Joe.
Thank you Chuck although this business update is coming only a few weeks since our last earnings call, we would point to significant news the.
The importance of filling the commercial and clinical leadership roles with Louis Stewart and Dennis Kim its worth emphasizing.
Since the lifting of the hold on sell of del Mar we have aggressively filled out the roster of talent up and down the organization, including leadership at all levels and on our executive management team.
In early April we expanded and strengthened our board as we announced the appointment of Biopharma veteran Tom Wiggans and commercial leader Janet Dorling.
Tom's experience, leading such biopharma companies as their mirror Pep Lynn and kinetics through.
Through development to commercialization makes him a perfect addition to guide seem a day through our next phase of business growth.
He has a distinguished career, both as an operator and director across numerous pharma companies.
Janet knows as well, having been our past chief commercial officer.
This gives her unique insights into sell of Dell parse potential opportunity to significantly advance patient care and PVC.
This coupled with her executive leadership as the commercial executive at two of the most successful biotech companies in the World Gilead and Roche Genentech should enable her strong strategic and operational contributions to the company in the years ahead.
Progress on response of share and other NDA, enabling studies for sell at El <unk> and PVC is being made every day.
The out the company. It is clear that completing the development of sell it out bar for PVC is imperative above all else.
Even so we had important progress with the first patient visit for the Mdx 2982 proof of pharmacology study.
And the phase one study for CBO of four six is nearing completion.
The progress on our portfolio through our people highlighted today is something that we will continue to emphasize.
Finally, before we turn to Q&A I'll ask Dan to provide a brief summary of our financials in the first quarter Dan.
Thank you Sue Joe over.
Over the course of 2020, we successfully managed our overall cash expenditures, while we completed our Nash study investigation obtained the fda's clearance to restart the development of the Philadelphia program and commenced our response and assure of clinical studies and other NDA, enabling studies necessary to complete our late stage development of <unk>.
All of del <unk> in PBC.
Our emphasis on operating efficiencies continued into Q1 of 2021, albeit the balanced against our need to increase our spending appropriately to support our expanding clinical development activities in PBC and other development initiatives.
Overall, we completed the quarter ended March 31, 2021, with cash cash equivalents and short term investments totaling $125 $5 million, which we believe is sufficient to fund our current operating plan, including the execution of the development program for celadon on PBC into mid 2022.
Turning now to a brief review of our operating results net loss for the three months ended March 31, 2021 was $17 6 million.
<unk> 25 per share compared to net loss of $13 $1 million from <unk> 19 per share in the three months ended March 31 2020.
Net loss was higher in the three months ended March 31, 2021 compared to the corresponding period in 2020, primarily due to an increase in operating expenses, including clinical trial in labor related expenses as a result of our continuing efforts to conduct of response for sure and other late stage clinical activities associated.
With our development of Philadelphia on PTC.
As mentioned in our prior updates given the fda's lifting of the clinical hold on the Philadelphia Our program last year in July of 2020, and our subsequent restart of Philadelphia and PVC and further exploration of other clinical development opportunities are cash expenditures are expected to increase in the future as we advance.
Ah restarted clinical development programs and activities.
Finally, I would like to provide you with the brief update on our current operating environment.
Due to the ongoing impact of the global Coronavirus pandemic. We continue the conduct operations remotely for all employees, which is a lot of business activity to continue as seamlessly as possible.
While vaccination progress worldwide in the first quarter of 2020 was encouraging it is still ongoing.
Therefore, we will continue to closely monitor pandemic developments and their associated risks to our business, including our ongoing clinical development of Philadelphia on PBC and we will.
To take actions available to mitigate these risks where possible.
As always all our actions will continue to be guided by our commitment to ensuring the health and safety of our employees as well as patients enrolled in our clinical studies.
No.
As Dan described we continue to be very capital efficient.
Our balance sheet supported the intensive work, we completed in 2020, leading to the restart of clinical development of cell Adele par earlier this year.
Allowed us to both accelerate our activities in PVC.
And expand our pipeline.
And it's also given us an opportunity to add critical resources across the organization.
With cash into mid 2022.
We have not been limited in the execution of our operational objectives.
As we look to the future we are grateful for the level of support we're getting from investors interested in continuing to see us achieve our long term strategic goal and we believe we have access to multiple potential sources of capital.
All of which may be non dilutive.
As we approach the halfway point of 2021, we.
We eagerly look forward to sharing our progress with you on the second half of the year.
We're now happy to take questions on.
Operator.
Thank you if he would like to ask a question. Please press star one on your telephone keypad.
The confirmation tone will indicate your line is in the question queue. You May press star two if he would like to remove your question from the queue and from participants using speaker equipment and may be necessary to pick up of your handset before pressing the star of Ts.
Our first question is from Yasmin Rahimi with Piper Sandler. Please proceed.
Hi team. Thank you so much for sharing all of the update on the two questions for you maybe the first one of timeline relate it on.
Can you just maybe provide some color of the you're still planning to be on track on enrollment completion for him and of this year to ensure topline data from late 2022 early 'twenty three and then I have of regulatory question.
Yes. Thank you for the question you asked I mean, we continue to make significant progress every day all of this effectively is counted by country approvals followed by site activation screening and randomization. So.
As we've discussed a bit in the past.
With respect of response, we anchor on the very significant experience of the global clinical study enhance where we had randomized 265 patients in just under a year. So our objective remains.
To enroll response by the end of this year.
We're still in that early part of the curve, where things continue to accelerate significantly as we get more sites activated and I think we've discussed also mean that there's no question the global pandemic.
Is a factor is a headwind as there's greater competition for patients today than when we were on a rolling enhance.
But our efforts for a response are on the same scale as we execute it for enhanced despite looking to target a randomization of 80 fewer patients. So fundamentally our strategy remains for the global significant effort to offset those headwinds and I think it will be important for us as we continue to.
See this progress we're making every day to reassess on a quarterly basis as of now it remains our goal, yes mean to get this study completed by the end of the year and that would effectively put us in a position of having topline data by the end of 2022 of very early 2023.
Thank you Sue and thank you for highlighting that you are actually doing the hepatic impairment study as well as the day.
On the two of your study of 50 patient set of compensate it way you know I.
I think I've seen clean safety I, just want to understand do you think that that data as well as the result from the hepatic impairment would be sufficient.
You the the ultimate label would allow you to dose compensate of patients with portal hypertension or do you think the FDA stance at this moment at the.
No therapy at this point should be given to the patient populations. If you could just drill down a little bit more that would be helpful for us.
Yes, certainly as mean I think as we've discussed previously in our in our prior phase II as well as the enhance study.
We have had patients that have been well compensated cirrhotic, some actually with portal hypertension. So this is an area on which we continue to further investigate it is an area that we expect to continue collecting both safety as well as the efficacy data in the population and I think this question.
We will continue to be answered by the data sets themselves and perhaps I'll invite Chuck to speak more specifically around what we've learned thus far and what's important for us to evaluate as we go forward.
Yes sure of and thank you for the question guys.
As Susan said we.
Across all of our studies, we've enrolled more than 360 subjects with PBC in roughly about 15% to 20%.
<unk>.
Have cirrhosis.
We did find patients that we enrolled that had clinically significant portal hypertension.
And of compensated cirrhotic patient reflects the higher risk for liver related or decompensation events.
Yes.
Back on these could be things like liver bleeds the societies are encephalopathy.
The medical complications that come cells require invasive intervention and reflect the increasing likelihood for poor prognosis. So the ability to deliver efficacy in that population. There is an unmet need there.
On the evidence supporting the of hypertension measuring portal hypertension is an invasive procedure and so.
Evidence for it can come from a variety of ways using laboratory findings are non invasive.
Imaging and this could be things like low platelet counts are typical of the routine ultrasound can detect an enlarged spleen and there are some other.
The imaging methods that can detect evidence of portal hypertension without actually having to go through.
The complicated procedures. So we do have some data there.
2019.
<unk>, we had a poster I think thats still available on our website, we did a small PK sub study in patients with PBC.
And we found that there was the reasonably comparable exposure. So there was not a real large difference just about a twofold increase in steady state of exposures.
And as you can see in the baseline demographics, you can detect that many of these patients had evidence of portal hypertension.
So we will as <unk> said, we will continue to expand study of this important population.
We so far feel.
Like the experience has been favorable but.
As always this is something that we have a responsibility to confirm with our both response study and Theyre ensure study.
Thank you so much checking on one last question that we've been getting from clients is.
The pause we have spoken with strategic partnership on the Philadelphia or in Nash, but maybe what would be helpful to understand this inc.
Are the strategic players who are interested in Nash maybe the same players are interested in.
And having a therapy that such a solid the alpine PBC can you just comment on on on that to that to the extent of your Canada would be helpful for us. Thank you.
Yes, sure, yes happy to address that I think as you're quite aware of Nash and PBC, although both are chronic inflammatory liver diseases.
In the one case you have of highly prevalent disease for which there are no current treatments with respect to Nash.
Think some growing level of questions around regulatory hurdles as well as profiles for agents that have been studied to date in that setting.
PBC is an area of high unmet need as well and although there are two approved treatments there are significant unmet needs for PBC patients.
Very straightforward of regulatory pathway of course in the setting of PBC in an area in which we have significant data that we believe continues to derisk sell at El <unk>.
When you asked specifically about strategics I think there are certainly some who are focused in the liver space and both large unmet need areas and highly prevalent diseases like Nash.
As well as an interest in areas like PBC. Although there are also some that are more specifically focused on rare and orphan diseases versus others that really are predominantly focused on the.
Disease like Nash, so it's a bit of a bifurcation, yes, I think they are quite of few players that are solely focused in the area of Nash and then there are some that have a more holistic approach to treating patients with liver disease.
Thank you to Tom and thank you Chuck.
Yes. Thank you.
Our next question is from the Steve seed House with Raymond James. Please proceed.
Yes, Hi. This is the two more of on income on for Steve The at home.
Just wanted to clarify it sounds like you haven't started dosing in your phase III response study. So if you just kind of clarified that and on also in terms of the recruitment and the response study. So when you see 11 sites are up in the U S. On one side is up in Italy. So as this current split driven more by COVID-19 or is it more of a competition because.
The thing done so just trying to read out around the same time you are.
Yeah. Good question. So first of all responses has initiated so we are in fact screening and randomized in patients in that study. So randomization has in fact begun in response.
To address your question around the sites that are updated on calling trials dot Gov of course, we try to update those as frequently as we possibly can there not seamless in terms of timelines to getting that up that information uploaded but you know our approach is one in which we are really leveraging the experience that we have.
Again for enhance.
That was the study for which we had actually activated sites in 20 plus countries around the world of course in the U S.
Given where we are with vaccinations and the number is relative to the coronavirus pandemic, there's a real opportunity here.
To accelerate site Activations approvals here on site Activations and begin screening and randomization most predominantly in the U S.
And then when we look at countries in Europe. These are things that we do really largely in parallel. So what you see is a reflection on Clinton trials is simply where we've been able to accelerate the approval processes from IRB and ethics committees in some cases those take longer timelines, just depending on the country, but I'd.
<unk> say that the process internally here is one in which we try to parallel as many of those country and site Activations as we possibly can of.
Of course, they don't all happen instantaneously. It is a process in which we expect these.
These to continue to accelerate through the rest of this quarter and beyond.
Okay. Thank you so Joe and then also in the past.
In the past I think.
You talked about getting encouraging patients to get a baseline biopsy.
The response, just like you did on enhance and quick could you remind us what proportion of patients in the task of baseline biopsies and the that's sort of your goal of her response.
Yes, it's a good question. So we had about 15% of patients randomized in enhanced the agreed to a baseline biopsy once again and that study those patients would not have had a second biopsy until perhaps two to three years into the long term study.
And so as we've discussed in the past the change here with respect to response as the patients that do volunteer to have a baseline biopsy. We will have a second biopsy of 52 weeks as an additional safety assessment and although it's voluntary for patients as to whether or not the <unk>.
To get a biopsy in the study it is required for us to have a subset of patients of course for an additional safety assessment at the time of NDA submission. We've had a very open dialogue with the agency around this threshold based on the 15% we achieved in enhance of course, our goal is to us.
<unk> something greater.
But we made a proposal to the agency that they accepted based on our significant level of experience here. This was not prescriptive. It was a very constructive dialogue I would simply say.
And we're confident that we can meet the requirement that set forth for us here.
Okay, great. Thank you.
Thank you.
Our next question is from Patrick does all with the latest high capital. Please proceed.
Hi, Thanks for taking the questions.
Just on the response trial enrolls and Theres a bit of downtime of ahead of data just curious if you have any further position on the K will offer its plan to keep the community engaged during this time on I know it's early considering you just brought on Louis as Chief commercial officer, but what pre commercialization efforts.
I guess, one more of those efforts begin to ramp and what those look like.
Yes. Thank you for the question Patrick.
We're like minded by the way with with the suggestion on your question, we've actually already begun some of the work around market research on pre commercial efforts of Louis as of.
Of course come on board of this week and really hit the ground running it is absolutely our goal to continue to communicate our strategy and our pre commercial planning and commercial plans ultimately.
I'd simply say this Patrick I think as Lewis gets integrated to the team here internally and the work that's already been done and continues to effectively help us think about the commercial strategy for <unk> going forward.
We will in fact look to have an investor day in the second half of the year, perhaps even to one that I would envision being centered around sell Adele <unk> for PBC anchored around some of the opportunities we think with respect to commercial opportunity for solid L par and perhaps even lifecycle management going forward.
And then potentially of second that's more centered around the earlier stage pipeline with respect to Mdx $29 82, and <unk> of course, our goal is to make sure that there's a meaningful amount of update on information for us to share, but I would absolutely envision us doing that in the second half of this year.
Got it that's helpful and I know you've talked about primary sclerosing cholangitis before.
Would love to hear how you're currently thinking about potential of Philadelphia or on the syndication and kind of ultimately just how youre thinking about a go or no go decision of pursuing this indication at the moment.
Yes, no. Another another good question Patrick look I think fundamentally there is no question of our mind that that the opportunity for sale of Dell par in PBC is of central focus and one for which as we've discussed if we execute appropriately we have an opportunity not just to be preferred second line treatment alternative of choice.
But potentially to connect collect data sets that really start to expand the overall addressable patient population of potentially in a very significant way and so we continue to remain highly focused on that objective. We do believe based on the profile of cell of Dell par in PBC.
As of Cola static disease that there is of course promise potentially for the potential of sell at El <unk> in the setting of PSC.
There's no question patients with PSC are more heterogeneous.
Often with more advanced fibrosis, often with biliary strictures complications also including comorbidity with with inflammatory bowel disease. So it is a more complex patient population and our approach here Patrick is really to think about two things. One just the early focus for us to make sure that we get respond.
<unk> enrolled as quickly as possible the.
The most near term Derisked opportunity and then two to really reconvene with a set of experts in the setting of PSC, where we're continuing to learn more and more about the disease and about treatment alternatives and then really put together the right development program in the setting of PSC and communicate that when our plans of our ifs.
<unk> set and were ready to act behind it but it remains an area of focus it is an area that we recognize as high unmet need and when we step forward into PSC, we wanted to do so with a really meaningful.
And focused development program, that's going to generate the kind of dataset to really inform our path forward.
I appreciate the congrats on all of the progress.
Thank you.
Our next question is from my Ant Man Tommy with B Riley Securities. Please proceed.
Thank you so much for taking my questions wood on for my.
On timing I was curious how does the caliber.
The label update read through to some of the Dell for.
Well I think again, perhaps I'll invite Chuck to talk more specifically about what we know today of course, we only know what's been made publicly available.
By intercepts to date, and we don't yet have the revised label of course for medical the gas suggest yet we recognize that very likely as the intercept has articulated that there could be further restrictions, particularly for patients with compensated cirrhosis and clinically significant.
Perhaps.
The portal hypertension.
As we've discussed this is of patient population for which we have collected some data.
In addition to having a sense of the efficacy.
Is comparable in the pit and the subset of patients we studied thus far.
With compensated cirrhosis as it is with those that are non cirrhotic. We also see comparable safety to date in the subset of patients, we think that could be potentially of significant differentiator, but theres much more data for us to of course collect.
But perhaps again here I'll pause and see Chuck if you'd like to add any additional color.
Alright, I think thats, a pretty good summary.
Just to reiterate it is really important.
Your study of broad population of PBC patients.
Would typically expect that if your.
Safe and effective at the <unk>.
Population use study will be the label that you received.
But even beyond that there's the potential for patients who are treated once the drug is marketed.
For those patients to progress and if they progress.
Into advanced disease that hasn't been studied that's the problem. So you do have to study those patients even if youre not seeking.
And the indication.
But for US I think right now the.
The inclusion of the eligibility criteria really has been non cirrhotic in compensated cirrhotic patients with PBC. We have included some patients with clinically significant portal hypertension.
And if we can confirm the.
Benefits for safety and efficacy of the potential path forward for us to have that to be the indicated population, but we will we'll have to wait and see what response tells us.
Thank you so much and then one second question on.
Could you provide any update on how you were thinking of the next steps in Nash.
Yeah sure look I think our strategy is really consistent with what we've outlined in prior calls with our focus on PBC.
The plan fundamentally based on the data set of Nash is to have conversations with other strategics, who particularly have assets that can complement the effects. We've seen with <unk> just as a reminder, we saw significant effects in fact on reducing fibrosis and.
Our phase <unk> study, although the study wasn't designed to show statistical significance. There, we did see meaningful effects, 37% of patients at our 50 milligram dose group with a one point or greater improvement in fibrosis of no worsening of Nash versus 20% on placebo. The overall profile of <unk> and anti inflammatory.
And now with these data showing the anti fibrotic effects, we think could be quite complementary.
To target that otherwise can either cause weight loss or a more significant reduction in total liver fat.
And so these are things that we've talked about we continue to talk about with other strategics also very important that any path forward brings with it a partnership with significant resources today, we do believe that the most.
Fruitful and Derisk the opportunity for US is to continue to conserve our capital for what is a very near term significant opportunity. We believe in PBC first and foremost.
And so we've articulated that we will not carry forward once again in Nash solely on our own again without a partner with significant resources and the right complementary asset. So those conversations are ongoing they continue of course theyre never done until they're fully completed but we do think sell at El par has a promising profile here.
We will continue to carry on those conversations.
Thank you so much and thank you for taking my questions and congratulations on all your efforts.
Thank you.
Our next question is from Jay Olson with Oppenheimer. Please proceed.
Oh, Hey, this is Matt on for Jay.
For taking our question.
So we were wondering the CBO score of six P.
P per gamma.
Wondering if the compounds has any CNS penetrant <unk> and the that's something Youre looking at in the Phase one study.
And then also which potential indications I know, it's early but at the moment could you potentially envisioned.
Pursuing ultimately with that asset that would be great. Thank you.
Yes. Thank you for the question this is Chuck.
I would say fundamentally that we have not seen we don't believe that this would be of drug that would potentially be targeted towards the CNS indications.
We do think this pathway the on RPC pathway, we recognize has got a lot of attention.
With respect to north of the generation, but that wouldn't be our focus in terms of of what we might focus on I will say that we're very excited based upon the clinical validation of the target and.
And a lot of emerging science, and inflammatory driven diseases, including ones that drive.
Fibrosis, we're not really ready quite yet to give any specific guidance.
But I think it would it would suffice it to say that for us it starts with the scientific rationale.
On the medical need is there of medical need here do we believe that it would be differentiated.
The development possibility is on a regulatory pathway is it feasible to accrue patients and do a trial and the capital efficient way that because of meaningful result, and then of course, there's always the business case, we have to understand the market what the.
The unmet need is but the existing therapies, if any and if there are any emerging therapies. So that we have of full.
The full view of the landscape before we make a decision so I think as the.
We've alluded to before we think that once we have the phase one data in hand, and we've completed some of our diligence around making the selection from.
Honestly quite a number of opportunities that fit what I've. Just described we will be able to communicate that in the latter half of this year.
Okay got it that's really helpful. Thank you.
And then we were.
Just curious if you could please remind us actually the <unk>.
<unk> the IP exploration on so they'll per really appreciate that thanks.
Yeah, absolutely so sell of Dell par has composition of matter to the 2026.
The lysine salt for them, which is the only firm that's being developed carries to 2026 and that's without the potential for an additional five year of patent term extension.
Importantly in the setting of PBC. So again, so on the composition of matter could in theory be taken the 2031. There are use patents already issued as well for solid L. Par on the settings of coal the static diseases PBC PSC.
As well as in Nash and Apple those all go to 2035, and then also we have orphan drug designation in the U S and in Europe. So the exclusivity associated with orphan drug designation exists for Philadelphia on the setting of PBC as well.
Okay awesome. Thank you so much congrats on all of the progress and thanks again for taking the questions.
Thank you.
Our next question is from Ed Arce with H C. Wainwright. Please proceed.
Hi, Thanks for taking my questions and congrats on the on the recent progress including.
The feeling of your executive team.
Oh.
Some of the questions I had already been asked.
And answered, but I did have a couple of related to N. Bx 29 82.
You had mentioned the.
Your your goal is to enroll 30 subjects.
The.
The the investigator of who's doing this by.
By the second half of this year and.
The primary endpoint of maximum glucagon release.
My two questions around this program.
Our.
Where does the endpoint fit in in sort of the.
Regulatory pathway, how how well defined.
And validated is there.
A pathway for <unk>.
This specific indication and then related to that is what exactly does the.
Uh huh.
Landscape for this indication look like and where would you potentially see of fitting in.
If indeed, there are others already on the market.
I'd be happy to take that question of thank you very very interesting and important question just to emphasize that the study that we started as a proof of pharmacology studies. So.
Yes.
You've alluded to it's not actually directly of that but you would expect to the regulatory endpoint. The first thing that we're trying to establish is that we can affect the increase in glucagon secretion in response to the hyperglycemia clamps low low low sugar low blood sugar.
Conditions that will be benchmark. The study includes both type one diabetics.
In healthy volunteers, we will be able to benchmark the responses that we see.
In the diabetics versus what we see in the healthy volunteers and we also do include continuous glucose monitoring in the study. So we will look to be able to examine the effects on restoring glucose levels as well.
So that's an important aspect to it in terms of the product concept. There is no. There is no product on the market right now thats of preventative.
The hypoglycemia.
So the challenge for the type one diabetic who's using the insulin.
To try to control of their blood glucose there always are concerned.
Potential risks of inducing the insulin induced hypoglycemia.
Especially as you know type one diabetes could be something the emerges and.
And childhood or adolescence. So you have families that are concerned about.
About their children.
Hypoglycemic episodes can happen not internally overnight, while you sleep.
So there wouldn't be any anybody around to help deal with the situation now theyre typically dealt with for example, just by taking glucose by mouth.
Glucose pills and there are marketed rescue therapies.
Glucagon sublingual glucagon.
On pumps that are being developed as well, but these are all just rescue they don't actually deal with the.
Of the unmet need of having a preventative really providing.
The patient and their families with the confidence that they no longer have to be concerned.
By low blood glucose.
The day.
Basically can be more intentional about using their insulin appropriately to get better glucose control.
I think in terms of regulatory endpoints I would just say that.
This would be of first so that would of course have to come through first developing the concept of conversations with the experts regulatory interactions.
But in our mind in early <unk>.
<unk> it would really be about preventing.
Either moderate or severe episodes of hypoglycemia.
So those have clinical definition of various levels of glucose glucose concentrations define those and you could use continuous glucose monitors as the way to make the measurements to evaluate the endpoints.
That's very helpful.
Thank you for that.
So just as a follow up how would you envision moving forward on taking over from the pulp.
Were you to see.
Significantly positive effects here that would lead you to choose to want to move forward with this asset.
Well I think we would take the approach that we always take which is.
The engage with external experts and.
<unk>.
Develop a deeper understanding of the indication the patient need.
The <unk>.
Clinical development.
As well as what we would understand to be the regulatory environment. So that would require specific regulatory interactions to help define and then of course.
Importantly, youre not going to make significant investments without doing a deeper dive.
The full analysis on the business case, what is the commercial opportunity like and then finally, we'd have to evaluate what's the strategic fit with seam of bay at the time.
Where does that word of our other assets lie.
Our aspirations, but because of the company want to become an EBIT.
We took the decision assuming all of those things lined up.
What's the best for the asset what's the best value, we can create deliver both the patient center of course ultimately to shareholders. So we would have we would take that all in and I think make an objective assessment, let's say it was extremely positive.
Perhaps this would fit well with seeing the base future plans or perhaps we would come to a determination.
Based upon gaining further understanding.
There might be other entities, who are maybe more fully invested at the moment and type one diabetes, who could make more of it than we could.
Okay very good that's very helpful. Chuck Thanks for your perspective.
Our next question is from a sea of young with Cantor Fitzgerald. Please proceed.
Hey, guys. Thanks for taking my question and congrats on the progress on two questions from me. One can you talk a little bit about alternate financing since I think you mentioned there were potential from non dilutive options just wanted to get your thoughts on that.
And then as it relates to of.
The thick.
Can you have you specified what might be from interesting other programs to go after and I apologize one more of just one.
What are the what are the plans on thoughts around next generation Philadelphia Index.
Yeah sure. Thanks for the question of the way it yes, I'll start off with the first and maybe ask Chuck to comment again on all four of six here I think fundamentally we've had I would say proud of adding a long track record of successfully financing seem a day with really quality investors.
And as we have continued to share datasets that Derisk Philadelphia, we believe in the setting of PBC. We continue to see significant interest from investors around the various different sources of capital given how derisked, Philadelphia or is having phase III dataset, albeit from a study that was terminated early.
We also think that there are avenues and potential structures available that are in fact, non dilutive typically avenues and structures that would be available for assets that are either approved or approaching approval.
So fundamentally I would simply say that from our perspective, we always think about capitalizing the companies to the best of our ability on behalf of our existing stakeholders and shareholders and we think of evaluating various alternatives inclusive of some of these that are non dilutive.
As prudent on.
Behalf of our stakeholders in fact, we're confident that we can do the right thing for the company at the right time.
Chuck do you want to talk a little bit more about CB of $4 six I think of late again theres much of.
What will likely discuss around path forward that will come after we conclude the phase one clinical study, but I don't know if theres anything more you wanted to say about MLR P. Three overall.
Just that I think that it's very evident even a cursory look in the literature, we will reveal many many different opportunities.
<unk> drives.
Formation, which then is linked for example, the fibrosis.
I think our focus is.
The company that's really.
Dealt into rare diseases, whether it be in the liver or related therapeutic areas I think of Chase Islands, you think of the Gi tract.
Some others you could you could easily think of makes a lot of sense.
So I think that's the kind of thing that you should think of we're not going to pursue really large say primary care.
Indications that really just don't fit with the the.
On the kind of company that we are and want to be in terms of.
The capital efficiency.
At this point in time, there is a number of ideas that we have that we just really can't comment on yet.
Mainly because they're not certain but also we have some IP considerations that we.
We are currently actively involved in working on.
And the.
To your last question of late there with respect to sell Adele par on opportunities to continue to invest in the future.
Yes, I think when we look at our datasets, thus far we're incredibly encouraged by the potential differentiation around alpine phosphatase normalization of.
Thanks on alleviating the symptoms of <unk>, which have not been shown with even the first line treatment alternatives for PBC patients today.
Nothing approved for treating cole of static etch and pruritus in PBC patients.
These are some of the things that we are largely anchoring around there are patients, whose alkaline phosphatase remain elevated above the upper limits of normal and while classically they've not been defined as second line treatment.
Patients.
We're alkaline phosphatase and stay above 167 times, the upper limit of normal they remain at a high risk of disease progression.
So having an agent that is both effective as well as safe and well tolerated.
For that particular patient population is another potential avenue for growing the addressable patient population of <unk>. These are some of the areas in particular.
That we're intrigued.
Terms of potentially investigating as we as we move the program forward to completion.
Alright, great. Thank you very much guys.
Thank you.
And our final question is from Jared <unk> with Stifel. Please proceed.
Yes.
Hey, Thanks, guys. This is Ben <unk> on for Derik. Thanks for squeezing us in most of the mine have been asked and sorry, if I missed this but just on 292.
Have you guys given any thoughts on how youre going to present the data from the phase III safety right, whether it's a matter of the conference or just the sheer PR any thoughts there would be great. Thanks.
Yes.
Yeah.
Yeah go ahead go ahead Chuck.
I'm sure we're going to say the same thing it's always been on our approach to present our data.
At the appropriate scientific or medical claims so of course, we're partnered in this case with.
With an investigator and we would need to align with them, but I think thats actually the.
Intent and the objective of the Helmsley Foundation is to create new science that speaks to a potential avenue that could meet an unmet need for type one diabetics. So.
I feel confident that thats. The route that we would go when we get the results we will seek to share them.
Okay.
Okay. Thanks.
Thank you.
We have reached the end of our question and answer session I would like to turn the conference back over to management for closing remarks.
Thank you operator, and thank you all for joining us again today we.
We spent the majority of our time in Q1 on re initiating our global studies for <unk> in PBC.
And thus far in the second quarter, we've made further progress with this key primary focus.
The continued to advance two promising early pipeline programs as you've heard today, we've made significant additions across the organization with experienced leaders.
And down our teams we look forward to sharing significant updates with you as our activities accelerate in the months ahead. Thank you.
Thank you. This does conclude today's conference you may disconnect. Your lines at this time and thank you for your participation.
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