Q4 2019 Earnings Call
Actual results and corporate update conference call.
This call is being recorded.
At this time, all participants are in listen only mode.
Following the prepared remarks, we will conduct a question answer session.
Instructions will be we provided at that time for you to queue up for questions.
I'll now turn the call over to Kevin Lynn Chief Financial Officer of Arena. Please go ahead.
Good afternoon before before we begin I'd like to remind you that will make forward looking statements that involve risks and uncertainties, including statements about our objectives plans goals strategy expectations beliefs focus regulatory activities R&D programs product candidates and operations and those of our collaborators and might be.
In other states that are not historical facts. These statements are made in the context of the risks and uncertainties that are discussed in our filings with the U.S. Securities and Exchange Commission, which can be found on FCC website at www Dot FTC Dot Gov and include risks related to timing of preclinical and clinical studies, including patient recruitment for clinical trial.
I was which is competitive in challenging to me take longer than we project preclinical and clinical study results in the timing of spectral result, which may not be as expected are sufficient for further development regulatory approval and commercialization, having an outcome regulatory interactions indecision collaboration and licensing activities and the amount allocation.
I can use of RMB overall financial and other resources. Our actual results may differ materially from our forward looking statement now I'd like to turn the call over to on it.
Thanks, Kevin Hi, everyone and thanks for joining our call today.
Today I'll go from corporate imagine an overview of in person will provide highpoint updates and will conclude with a financial review.
Fourth quarter and full year 2019.
And your doesn't like to remain exceptionally strong progress across all sites in the company. We importantly maintained that cadence into 20 twond.
Critically we remain on track with near and mid some operational objectives.
Putting to living up to eight major data read out between 2020 and 21.
Last month, we reviewed our strategic plans it sets the foundation for the future Marina.
We entered the next page of the evolution of the company.
Yeah were too specific and big areas of opportunity first expanding devalue the trademark in traditional indication and second.
Unlocking the value of just vocal arena GE GE poking couple of receptor or GPCR research platform.
Our new strategic footprint ongoing programs, a new initiatives led to a catalyst which provide them from company.
On expanding about even try as much we continued to be better once daily oral agent.
TRASM mods profile offers tremendous promise in the treatment of a broad range of immune mediated inflammatory diseases.
Got it here in Michigan, new programs, both in the area of crude therapeutic focus.
In geography used to be programs, you have kind of thought to salvage either Oh, Yeah me and dermatology phase two program Alipay sure yeah.
Okay.
We expect to initiate bookies problems here in Boston will provide more details in each of these programs later on this call.
To unlock additional value return focus harvesting the broad and diverse of technologies available to us.
As a result of historical two decades, a world class PBC or discovery research batteries.
With the expansion the Beacon discovery collaboration.
As public real establishment and advancement of retail mutual funds.
Well you could really be can discovery represents the next generation all compounds, which may trade spend away, how do you need to do approach and treated.
Project really bought novel in Bellevue targets, and topping and what those are the foundation of long term growth indefinitely.
We know neuroscience represents an opportunity to replicate the strategy we bought the arena.
Half years ago.
Three and half years ago, we rebuilt become remarks to read the potential first and best in class compound.
We reset the financial framework for the company with pivotal transaction and if things continue to make substantial progress a growth across all of our objective.
And now you get to do that again no side.
On the back of multiple clinical and preclinical compound in an emerging platforms I could we do.
Inflammation, we're poised to progress important medicine, and uncover important value for shareholders.
The context I'm incredibly excited that Kevin Lynn has agreed to lead our subsidiary renewal time, Inc. as its president and Chief Executive Officer.
It's all of you know, Kevin if everybody VP and CFO since June of 2016, there's been an integral part of the trying to learn of Needham.
His insights of creative solutions in challenging times and uniquely positioned us for the future, we believe luggage and Kevin skills to advance movie the need to afford to lock the value. We believe that's within this platform.
I'd like to personally take the opportunity to think Kevin.
Well, it's a focal contributions as well as taking this leadership will yeah I mean, when there were.
Joining us as executive Vice President and CFO as moist dr. borys, an accomplished executives a significant financial expertise and will be an exceptional additions walking.
Well he brings over 20 years of experience and biopharmaceutical management, including leading seems Unfinanced Treasury <unk> Investor Relations business development emerging markets.
Right Arena, we held management level positions in several lifetimes come basically how was nine amgen.
Having previously worked with more in the original building Amgen's immunology business I'm confident in our leadership.
Continued scale the company won't be putting in our management resources.
We're thrilled to walk invoice because the reality.
With that all protocol in comparison to provide more detail and updates on our pipeline.
Huh.
Our most advanced programs the global Phase three elevate you see Registrational program, which consist of two key trials elevate you see 52, and all that you see 12 evaluating a TRASM like two milligram in subjects with moderately to severely active ultra quite.
Enrollment in elevate you see 52 was on track and we plan to begin enrollment in L. that you see 12 later this year.
Board to sharing with the three datasets in 2021.
We're pleased to announce that the phase two Oasis trial data were recently published in the prestigious Journal Gastroenterology. We believe these data support across not highly favorable profile compared to other existing and developing therapies and you see.
Turning now to our second G.I. indication Crohns disease.
Earlier this year, we initiated a phase twos reprogramming enrollment is progressing.
This program consists of a phase two dose ranging trial cultivate.
Operationally seamless transition into the base big portion of the program.
Refusing to focus on an operationally seamless phase two three program to afford arena the opportunity to examine the data to cultivate make a real time decision on dose for the pivotal portion of the program.
Publicly released those results at the data catalyst around mid year 2021, I still realize the operational synergy inherent to a seamless transition into the pivotal portion of the program.
Our third G.I. indication it.
In development, it's what I would have TRASM <unk> Senate Bill, it's often drive.
He is a chronic lifelong condition characterized by arrested inflammatory lesions in the topic is causing persist heartburn like chest pain and difficulty swallowing that can lead to buy bread, cystinosis and who didnt action in the thought.
Importantly, there is high patient need asked physician demand for a safe and effective non steroids oral therapy for this disease.
No approved therapy, it's really in the U.S. and that was available X U.S. limited and suboptimal for most patients.
We're excited to be kicking off a base to dose ranging trial later this year, which we expect to be phase three enabling and we believe recent precedent exists for compound in the developed state receiving orphan designation, which could allow a streamline phase three program.
Well look forward to updating you on status. This program as we initiate a phase two work.
Moving now to transmit in Dermatologic diseases. We're currently pursuing development program in a topic dermatitis and I will be sure area.
We believe that attracts a lot has great potential in dermatologic conditions that are T cell media.
Because both indications are de Novo clinical programs I will point out from key reasons, why we believe across the <unk> has the potential to disrupt the immune based inflammatory how could you elaborate process to modify disease progression of these conditions and improve patient symptoms and outcomes.
Let's start first with a topic dermatitis.
80 is a chronic inflammatory skin disease associated with cutaneous hyper reactivity to environmental triggers as often the first step in a progression of systemic allergic disease that kind of food asthma and allergic rhinitis.
The clinical you know type that characterizes eight topic dermatitis is a product that interactions between environment susceptibility gene defective skin barrier function and of course immunological response.
Exposure to environmental Allergan is recognized by dendritic cells in the epidermis, but then traffic to Miss does.
Present antigen and activate seaborne cdeight positive T cells, what's been traffic back to the skin and drive inflammatory tissue injury via satellite expression and recruitment of other immune cells at TRASM on has impact on each step in this pathlogic disease.
Specifically dendritic cell scrapping to lift nokia's reduce which reduces the presentation of antigen to Tito, resulting in reduced activation of those seaport and see deposit itself.
Activated T cell traffic is also directly were due to fewer tito reach the target tissue site of injury and along the way cytokine expression by T. Helper cells is reduced that's the T.H. two and teach one profile Commons a topic dermatitis is lowered and when she reduced expression of the associated cytokine such as out four and five.
And downstream about.
We also note that recruitment of other immune effector cells are reduced such as you said it.
All this has been documented in preclinical assessment for the TRASM up and we're confident in the scientific rationale for Transmode and we're also on track with the ongoing b to B advise trial any type of dermatitis, which is testing one milligram and two milligram of TRASM I compared to placebo among patients with moderate to severe a dee Ann.
[noise] inadequate response to topical steroids, we look forward to sharing these first clinical results in AG later this year.
I'll now turn to our second dermatology program, our Peachtree area.
Hey, good a chronic autoimmune disorders, much activated cdfour and Cdeight positive T cell attack hair follicles, destroying growing here.
Hey, the common disorder affecting one to 2000 and the population.
Causing have off somewhere even all areas of the body, causing major psychosocial stress.
Putting a clear reductions quality of life and tend to wellbeing, social phobia anxiety and depression.
Hi treatments for Alipay sure Suboptimal and there was no single therapy that is sufficient for the majority of patients.
Similar to what I described above the transmode reduces the activation of these seaborne cdeight positive T cell and their traffic into the hair follicles.
Reduction of <unk> Cdeight positive T cell is one of the most widely recognized aspects of the mechanism of action for us when P. modulators.
This year, we will initiate a phase two proof of concept trial in hey, he will be a randomized double blind placebo controlled trial evaluating two milligram of Transmode once daily insider could moderate to severe our fish area as assessed by the severity of allocation tool, one or salt one scale. The score of 54 higher we will know a pocket.
35 patients in the U.S. in Canada, we believe that initial positive data from this trial may translate into breakthrough designation with the FDA, allowing an accelerated based twothree program with attractive development timeline similar to recent precedent.
We look forward to providing additional detail on study design and program development in terms of these plans over the next anymore.
Finishing up now with the rest of the pipeline for a lot out we are pleased with our enrollment progress I look forward to delivering base to be topline data in the second half of year, you not yet hey.
And finally with regard to our cardiovascular asset if people when eight which is targeting acute heart failure, we have initiated phase one.
And granted fast track designation from the FDA, we expect phase one data later this year, which would be followed by a phase two proof of concept trial that will read out in 2021.
With that I'd like to turn the call over to Kevin to review our financial results Kevin.
Next question I'll now provide a brief review of our fourth quarter and full year 2019 financial results here well more detailed results are discussed in our press release from earlier today and in our 10-K, which will be filed this week for the fourth quarter claim Nike revenues totaled 3 million, primarily consisting of 5 million of development milestone wrap.
And you from Everest offset by a reduction of estimated future royalties from Belviq sale.
In terms of cost research and development expenses totaled 74.6 million in Q4, including 7 million related to noncash share based compensation DNA expenses totaled 22.2 million of which 6.3 million west share based comp net loss for the quarter was 88.3 million or.
Dollar 76 per share on a basic per share basis.
For the full year 2019 result revenues totaled 806 million, primarily consisting of 800 million revenue from the United Therapeutics upfront payment in terms of call research and development expenses totaled 231.5 million, including 27 million related to non cash.
Share based compensation DNA expenses totaled 77.6 million of which 25.7 million where share based comp income tax provision was 110.3 million as a result of utilizing the deferred tax assets that were recorded in the fourth quarter of 2018 net income for the year was.
397.6 million or $7, a 99 per share on a basic per share basis. At December 31, 2019 cash cash equivalents and investment was approximately 1.1 billion and approximately 50.2 million shares of Alina common stock outstanding.
In terms of guidance, we had approximately 70 million of cash burn in the fourth quarter of 2019, excluding onetime items, we anticipate Q1 2020 burn excluding onetime items to be approximately 95 million.
And increasing their after quarter by quarter in a high single digits to low double digits as we continue to ramp up enrollment and scale manufacturing Quinn farm and nonclinical towards the potential India and bring online additional clinical trials as outlined by process.
Finally, I'd like to thank the entire rina team and broader ecosystem supporting the company, including our shareholders, who have ahead and I have had the privilege of working with over the past three years, it's been a phenomenally rewarding experience and it's on the pointed out I look forward to running the arena playbook, a second time going forward I mean, usually ask about the opportunity to control.
And you to build value for patients the community and our shareholders on it.
Thanks, Kevin.
As we continue on our path to deliver important medicines to patients remain focused on making significant progress across all aspects of the company and delivering on a call all the major deliverables and build a world class company.
Our emphasis on execution in terms of we remain on track.
With all the major catalyst one company and we look forward to sharing are exciting milestones in 2020 years in.
Including the upcoming initiation.
Hey study.
Do you see Twoku studies and delivering important phase two data later in the year for <unk>, you need topic them and the lower and had an idea.
As a final note I want to picked up in the thing Kevin first continued leadership and welcome lowering could be arena thing.
Over the next couple of quarters, we're excited to share more on our progress on arena numerous huh.
I will now turn call over the operator begin acuity session operator.
Ladies and gentlemen, do you feel like that's good question. Please press Star then one.
True moves yourself into Q, you May press the pound keep our first question comes from Jason Butler of JMP Securities. Your line is open.
Hi, Thanks for taking questions I'm, just a couple on the Dermatologic indications can just first of all talk about how you think about the commercial infrastructure and how you would build out the commercial infrastructure a focused on derm and then can you talk briefly about how you think about the the payer landscape recipe show.
Thanks.
Sure. Thanks, Jason.
In in selecting a couple of questions from goes back to actually why we select specific indications and how we select them and it really starts with following the biology and exclude the detail and then we proceed to build a whole school animal models and work with world experts in the state.
To make sure we're having gotten the bike path in each one of these indications an important part we really think about the commercial aspects you you're talking about today, well kind of working on the fusion concentric circles on the commercial side, we're extremely excited but how would you like GE high, especially indication where a company.
You know, we must position can overtime no they look within infrastructure commercialized.
We know that the various going to become increasingly competitive we think that's actually real positive tremendous unmet need and we caught a few patients lots and lots of acquisitions.
Well, we think about the payer landscape difficult I think whats apparel landscape, where they symbol indication in isolation.
Payers will you wont routinely reimbursed products.
Most of them indication from inside the broad range of indications provides the strategic advantage.
And then getting payer access compared to competitive product. So we think that's gonna be really critical and you see the anti TNF space for example, again, having a broad range of indication.
Hi, this plays a very substantial and getting to access we think that's one of the advantages to too much graduate level person.
Okay, Great very helpful and let me just a add my congratulations to both Kevin on Lori on their their new roles.
Thanks, Thanks, Jason.
Our next question comes from a least young of Cantor Fitzgerald. Your line is open.
Hi, This is and I'm sure you can't just wondering if you could provide any additional color on the rationale behind carving out the working or a science and now kind of at least early stage on what strategic like study that separation give you and then just given the history of S. One key as a target mass is there any interest not disease area, specifically or any existing work that you feel you can leverage more broadly.
No.
Sure. So <unk>, let me take a part of this not Kevin comment on.
I'm not national news that he may have some thoughts on.
Hi idea of carbon yourself into a separate entity is in actually multiple components. One is we're still a growing involving company coming off a pretty massive.
He said of the company back in 2016, so with all the phase three in phase two programs. We have ongoing it's important to that if we're going to person team.
Certain products I know its launch phase.
The we want to have some focus on it and no better way to keep whole comes into play <unk> leadership team around the compound. So that's that's sort of point number one point number two was while in the near term as we progress. These compounds I mean, it's got the financial Wherewithal to progress then there will be a point in time, which I guess.
Capital would be required in this allows us to when capital into the neuroscience portfolio and then actually even eventually spin it out and the complete Standalone enterprise. So it creates a tremendous amount of flexibility from a company overtime I think that that's really important but that's a secondary to really this idea of creating in card.
Okay.
These compounds.
It's really fascinating if you kind of we wind back in 2016, well we had a couple of compound that come out of phase one to one certainly page to and we were able to really build around us and this is a very similar situation. We've got we comp outside of clinical or preclinical stage Oh, He's got an underlying.
Platform and Michael will inflammation and it doesn't look too dissimilar than the leap two arena kind of mid 2016, and I think that's one of the reasons I think Kevin is the perfect person. So someone that's been a price on BMS question, we're not gonna give him for a lot of detail I mean vacation Jeff.
Lot of wants to be done on these top out I will tell you that we have shied away spoken for me MSP simply because of the competitive.
Landscaping M.S. as well, yes, pending patent expiry, the multiple compounds and that's been so let me apologize deployment has anything additional pad well. The dollar you said it very well I would just say if you look at the indications currently for the S. One piece. The vast majority are in that space and so we're excited about the potential of.
And that's one p. going and being focused on that as part of neuro.
Great Thanks, and my congratulations as well.
Thank you.
Our next question comes from Martin Auster of Credit Suisse. Your line is open.
Yeah, Hi, this is Thomas on for Marty wanted to quickly touch on the phase two readouts expected in the back half of the year, So a lot and I b S paying and attracts them out and a topic there.
Can you guys kind of frame what a positive result would look like on primary endpoints and these trials and then I'm curious if you've set a specific far for what you would need to see that moved these four programs for the phase three thanks.
Sure. So you know it's always important remember that the bars for a lot of things are not just efficacy everyone focused.
Simple efficacy end point, but it's the is the risk benefit of compounds as well see if the taken take that into a wall convenience of compounds into space into into place. So all these things kind of work together in terms of having a competitive commercially viable product I'll provide some some top level than them personally conducting.
In a little bit more detail on let me talk a little more Nab a in the IBX basins, you know on a placebo Justin correction on the P. upscale most products have about a one point change you'll recall from our phase <unk> study with all the caveat. The small open label, how we saw about afford outlay exceeding a four and a half.
Point change on the P.F. scale.
So well north of that one point delta that you've seen a placebo Justin situation and so what do you know we'd be looking to be.
Well most of that one point people just collection, we think that creates a compound that can work across idea. He indeed and has a husband safend callable profile, assuming that's what happens out of the study and we think that's commercially viable product. So Watson look at the totality of the data we've got it.
Well, that's my market research and Allison good sense of hobbies. My first of all I would point out one other important thing all the other ideas pain programs that are out there programs that have.
Pain on label would be developed there all the idea category and call, we're enrolling but I'd be a C and D. Patients. So there's also some water couldn't concluding to Florida. So let me pause now worn out and see person I think the that and then I'll.
A discussion topic, yeah, maybe just two quick points. In addition to the 0.6 change from baseline, which again was not people corrected.
But the additional endpoint or way of looking at the results that gives us a lot of competence, even though a small and no secret control is that the categorical endpoint of clinical response, which is the ft defines as at least a 30% reduction in pain score from baseline was met by 100% of.
Patients all patients at week eight met that definition and so to us that he is well I can't tell you today with a placebo corrected a delta is likely to be because we don't have the.
The placebo from that study.
If it's highly unlikely that that the majority of our result, even is due to a placebo response, given the categorical change we've seen in other placebo controlled studies.
People you pain studies tends to be around 30% of that kind of categorical response, and so to see 100% in this albeit small data that was really encouraging and then just second they'll say is very clear that there is a high level of unmet need.
In this space with patients related desiring, giving them some good desperate for pain relief and so as long as we can demonstrate that theres something here in terms of efficacy and that it's a safe and tolerated product, which we fully believe it is how we think there's something really attractive here.
So switching gears to the topic during question as you know, there's like a broad range of placebo corrected delta on easy 75 across <unk> across all the compound biological world amusement topic. There there's lot of patient heterogeneity like this is one area where.
We did by no pun intended soon as caution on comparing crossed trial just because of the patient populations. This tend to be.
More hydrogen that there's more heterogeneity days.
For example, I B D. Having said that we think we can deliver a week. If we can build more product in the range of these existing deltas and we're doing that was a one something wrong, how we would the safety profile.
He.
And the problems month to date.
I've been listening I think we have no leading.
I don't know program I think we have a program here that can make a substantial.
Substantial difference in any topic done at the market landscape evolves.
Note that the some of the other competing products that are being developed in conjunction never have serious liabilities, including a black box warnings or malignancy and I'm sure as you talk to dermatologists I'll tell you Moser wasn't very difficult for some time just to get their head around those are not liabilities normally.
I expect couldn't be at one PM category. So we think there's a real competitive profile handbook enough capacity.
[laughter] God I think the only thing I'll add is that just to.
Highlight again that be efficacy bar for an oral compare to a biologic may well be different we know with Tesla for example does quite well.
And does not have the efficacy response in psoriasis had seen by some of the biologics. So other tilbury viable compounds. So we'll see we get we're very excited about the how that half, though physiology of a topic dermatitis lines up but the mechanism of action for TRASM odd.
And we've been through a litany of preclinical results that that are a positive in terms of but directionally, giving us some confidence and some indirect clinical evidence through other programs that we have initiated in the past pyoderma gangrenosum and qualitative anecdotal examples of skin manifestation.
Related to you see in a waste program, all of which well not a direct clinical evidence in the public dermatitis gives us a high degree of confidence in what this drug can do in that disease state.
Great Thanks and congrats.
Thank you.
Our next question comes from Kennen Mackay of RBC capital markets. Your line is open.
Hi, This is 10, new for Kennen, Oh first I'd like to add our congrats to both Kevin in all around the new appointments.
So first question is can help us understand how you and the team are thinking about the all come off the two north trial, which now has a top line do you mean this year as a potential raised through to ask them on its own phase three trial, a we'd also be interesting what he and the team are focused on within that child beyond the top line success or failure.
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Great Great question, and how could it go through that.
One of the challenges as I think everybody is aware.
If you look at the Touchtone study from Santa Monica.
And subsequent publications posters abstracts et cetera.
Ever see.
We analysis of that NATO onto read domain.
Mayo score rectal bleeding of zero and as you know that is the ft declined and point and is in the true north standpoint in their phase three trial. So one of the things that very difficult in answering that question is.
We don't have clarity from their phase two to phase three now.
Smaller companies don't get a Catholic that actually showing the phase three data I'm sorry, the phase two data to be domain names score.
We showed a 25 26 point delta or 31% of patients.
In remission at week 12 under three domain mail score. So in terms of read through I think the better question is what's the read through from our phase two to often we there we've got absolute clarity we understand effect size you know our data inside and out we know that the more quantitative you get the battery TRASM odd lots and that's a that's a that's all.
Really great place for us to be as a company coming back to Truenorth.
There's a couple of key variable outside of the.
I don't mean versus four domain and again, we've not seen there are three domain, so difficult to understand powering assumption, but for many perspective, if you want to the long.
Run the math you'd see that the study. This study is is.
His overpowered and it's very well powered I'll say and so we don't have plenty of powered to detect a very small difference in the three domain I think that's indicative of what they might have soon I'm the only domain.
Post talk analysis again, we haven't seen it but just making I guess secondarily, we know that they are looking for a disproportionate amount of patients who have not received the biologics. So naive patients again to create more effect size. So the combination of those two things I think one.
Turning to keep in mind, we're we're addressing a completely different than we know that from our phase three study in patients were 40% to patients failed and anti TNF on integrating which is essentially very contemporary patient population in key markets will choose to commercialize over time.
We did very well, but exercise on for domain in a very robust effects I was on three domain.
I think that's moving forward to keep in mind as we think about a week two from two north to anything in the future. So.
As far as we're concerned I think I have more on it TRASM aren't any read through from Murphy to the phase three and were we're optimistic that a that though the drug will perform.
You know difficult to tell when there are simply because it just not just to have not been is this closer with their clinical data.
Okay, great. Thank you along for the color I saw our next question it sounds like a topic terms. So several publications suggests a pretty clean coal F.I.T. seen do smartdose for a topic term <unk> rapid cadences tornado dishes.
Leave some differences immunologic responses like 54 assay anyway shows first a few maybe.
Can you talk at all about south of the other preclinical work. They have you had down around Etrasimod Inc. a topic term ahead of them I stayed up like later this year. Thank you.
Yeah, Hi, this is person so we've.
Conducted a variety of dermatitis models across a variety of species focusing on different aspects of that.
Immunologic cycle that I described so [laughter] and look there are a lot of similarities related to these.
Immune based inflammatory responses, so ulcerative colitis atopic dermatitis, yeah, we.
They're not identical for sure, but they have general similarities in terms of something triggers the immune response that is an energetic could be an auto energenic could be an environment Atlanta engine and the case of you see an AG for example.
Felt that a breakdown in epic field barrier function I do the G. I tracked where the skin.
Secondly leads to the introduction of some form of antigen that has to get picked up by an antigen presenting cells and presented to lymph nodes.
Activate the corporate immune cells and in this case, we're talking about crazy. If he says he reports because as Keith said, a scanner dendritic skins, though I would also have longer himself.
Or that initial agent that begins and then continues to propagate.
The immune response, and so they have to pick up that antigen and traffic to lift that we've demonstrated in these preclinical models very directly examining dendritic cells that there is a reduction in the cell trafficking of needs to the left that so there's less added and to be presented because of dendritic cells are not getting there that means that there is.
Activation of T cells in the left that would also demonstrated that directly.
And then for any T., so that Mike activated it is less likely to get out of them of note and traffic back to the tissue site.
Where are the antigen wasn't countered with injury is base.
That's also been demonstrated that component the T cell trafficking, some liver tissue.
To the tissue of origin or injury, that's been the most well documented I would say a mechanistic aspect to absolutely modulators generally, but again dendritic cells cytokine expression activation within within the lymph node itself are all impacted by.
S&P signaling in addition, I just to kind of a final point on this there's even aspects that don't have to do with sell trafficking or cytokine expression that S&P a receptors have a role in interest cellular inside the cell signaling of the S. One p. one receptor subtype of.
Phillip pay cell to cell junction at the epic Delia level and the endothelial level and that's a good thing and the fact that attracts about only hit S&P, one and does not get asked one piece too as an example, which does the opposite it actually widened cell to cell or loosens cell to cell junction.
The good thing and we think it helps to maintain a tighter subscale junction that the skin and at the old endothelial beds, which oh can beneficially impact efficacy and safety respectively.
Oh, Thank you lot for on a science details here Oh, sorry last question, it's about arena neuroscience. So I believe we try and scientific community I seem someone makes two ways. The sounds just to ask one p. may be more involved D. A dramatic bringing drain.
Well I stare might maybe more involved with Alzheimer's disease. So how how's the team thinking about dies or do you have any plans to more directly it's hard to seven mighty any of those newer indications. Thank you yeah, it's a bit early breast and discuss specific compounds in indications well in the process of showing up critical pieces animal.
All information as well as intellectual property and.
Well be doing so I'm on the future earnings call and.
Kevin building up his organization team critical piece was an intellectual property you need to get filed minimal work needs to get completed and then well come back and talking about the specifically, we're you know as you're pointing out there's a tremendous amount of interest in GPCR targets broadly in the middle sized space.
And having both clinical and preclinical compound and in underlying platform really gives us.
Gives us a portfolio that's.
Amends rate are comparable to.
Companies in a one to 2 billion dollar market cap space that are already public and that's a that's a really exciting place for often we're we're looking forward to sharing that information with you.
I should point in time.
Okay. Thank you.
Our next question comes from Jason Gerberry of Bank of America. Your line is open.
Oh, Hi, good afternoon, and good evening, everyone thought this as she on for Jason Thanks for taking up questions.
I guess first one maybe for Preston, though maybe I'm at.
And TV is really doing pretty well in a you see space just curious on your thought off given that ask one p. an entire brand has some stuff overlapping functioning immune sour trafficking. How important do you think it is to demonstrate a trough in my efficacy in patients pretreated with Ti vo thick enough.
A couple of follow off top of that.
So we had some of those patients not a phase two study.
We're not exclusion into excluding Integrio pretreated patients and I think we and Oh, we always said publicly we did see an effect a in patients were between them and then tell me at some point understand and having a very slow to act.
And we've demonstrated separation in both rectal bleeding frequency as early as two weeks. So tough month dusting have activity beyond just T cell migrations patents talking about in clinic selectivity and cell to cell junction. This is not just simply T cell sports I think that's important remember the second important part numbers that we.
Think about these diseases in compartments because.
Training in our medical.
Landscape is anything in Oregon based screening, but all of these auto immune disease have tremendous overlap you talking from overlaps with I'll be sharing data you have begun over last will also quite us and so are you really talking about her systemic autoimmune conditions with some.
Third biology, with primary organ manifestation, and and drugs or got specific actually can't address the systemic manifestation. So I think that's also sort of important room or 65%.
I b patients have extra investment manifestations Antonio not likely do a heck of a lot was essentially a person who want to build I think you covered it.
Awesome. So I guess, you know space too when I look gets hot off the M. Roman baseline affecting being roughly 10% gift for tech on entry on into the L. or entire Grand and you know and city you I think right now it's about maybe 30% plus up the market.
Yeah in the U.S. right now just say it doesn't sound like that you know to post control I may be different makes up and Ti Vo Burgess TNF into phase three is going to have any it's going to be a factor as we said I think about how face to efficacies trusts lineup of the phase three.
Yeah, I think you I think you have that completely misunderstood so 22% of the market share. So don't confuse market share with patient opportunity my and what patients getting into trials marketshare as percentage of patients were treated with certain products right you would not compare market share.
Steroids, you'd say still would have a 90% market share in in IBT, So <unk> using market share to figure out what the actual underlying baseline waiting for clinical trials.
Is completely erroneous, what you really need to look at as a percentage of patients and how they fit between biologic treated and untreated and if you look at all the epidemiology and you look at all the extensive market research that we shared with you what you'll see is approximately 60% moderate to severe patients.
In the United States have never been treated with a biologic and of those that have 50% or not in remission. That's the more important metric that gives you a among a good sense of how that flows and all that group that's been treated with the biologics you could say over 22% or on have you know that's actually.
Every small number of 22% a 40% and some portion percentages those are not information that's a much better way to apply that market share number its a wrong just apply that cost me a whole inclusion criteria, that's probably not how it actually works.
And perhaps not just follow up I think in another part of your question was just around what what our expectations in terms of phase three compared to phase two in terms of background therapy or history of therapy biologic failure for example.
And I think I think what I'd say, we're not.
We're not really concerned about the different types of cnf versus in Civeo. For example in terms of biologic failure coming into our study and we take a good amount of confidence from the fact that our based to proportions.
Are likely to be pretty similar to what we see in phase three at least with the risk with respect to.
Prior biologic failure versus naive so in our based you'll waste. This trial, we had oh, 40% of patients with prior.
Logic exposure, so 60% not your name where naive had not seen prior biologic and that's actually right in line with what I'm just said in terms of the market, we see the patients with moderate to severe disease, you see today, 60% doesn't have not seen a biologic and so we don't anticipate a large differences.
Terms of what we've already experienced conveys to compared to phase three and I would I would say that other programs.
If they if they had a.
Much lower biologic exposure in phase two you would expect things to be different for them in phase three because phase III always tends to more accurately reflect the market.
So again I, just I'll summarize by saying midstream lead cost since making the leap from marketshare.
We should never have 22% to patient inclusion because that's actually not hallmark and breaks out when people talk about market share as market share relative to just the biologic segment I'm not relative to the entirety of the marketplace.
Got it and maybe one last question from me on cross or can you elaborate on maybe walk us through to seamless transition from the phase two p. attitude of phase three trial I, maybe it would help you know if you can walk us through okay. You follow the patients through 14 weeks in the face.
To be that's gonna be data Unblinding, that's gonna be at time tie a gap time that you need to analyze data data are you talking about that potentially you can try assertion patients from face to face straight from the induction straight to maintain and so how might or might not the blinding and the time off data analysis.
May or may not affect that process. Thanks, Yeah, I think your misunderstanding does the concept of seamless maybe a question talk about there. So what we're talking about is operationally things versus essentially sema. So.
And if we're actually seeing less often people mean by a phase two three program as it is that patients in phase two actually can serve as part of the pivotal for phase three we're not doing that if we were to do that we would not sponsors typically don't have access to that information.
And for example, does those decisions would be made usually by an independent committee and how we're electing not to do that because we want to see the data have access make around a decision on those and then move forward and that also enables especially publish the phase two data, which we think is a nice catalyst in.
2021.
What we are meaning by this is we will keep enrolling patients into a program. While we have locked why we're locking the amount of data the amount of patient data that's required to make the dose decision.
Makes a decision rapidly we can do that and and then flip the switch so that subsequent patients enrolled into the phase three program.
With with the appropriate does and so we'll talk more as we I mean this this is clearly going to happen as we get closer to seeing a database lock for the phase two portion and so as we get closer to that would just at the beginning stages of phase two now in Crohns disease will be more disclosed publicly about exactly how.
We're doing that but the entire premises don't shut sites off because there's always an S shaped curve a ramp up period to get sites activated get them up and running we would like that machinery to stay high so to speak stay active keeping rolling and so I will be we'll talk more about those plans as we look forward.
This is very helpful. Thanks, so much thank you.
Our next question comes from Jessica five JP Morgan Your line is open.
Hey, guys. Good afternoon. Thanks for taking my question as it relates to a topic term well have dermatologist expressed to you.
In terms of bar they want to see for safety in that setting both in adults and in the adolescent and pediatric setting.
Yes, let me comment on what we've seen in market research persons been a participant in lot of the advisory board phone call.
I'll be the play by play much color here.
Well, we see from market research into more is definitely higher for safety you need topic term than it is in I'd be dermatologist and just more cautious across the board. The first dose monitoring component is a little bit big big of a barrier for dermatologist and good Friday deeper.
Patients.
However, when you put that in the contracts of the JAK inhibitors.
As my profile tends to do much better. So if you if you do a standalone profile for and TRASM odd ellipses certain set of responses.
If you put in side by side, because the Jackson, they've had more time to sort of acclimate.
Intellectual lead to the idea of JAK inhibitors me talking to them and then you put aside by tied to the tax and then they tend to Oh, well Oh wait a minute you don't have all the other stuff and and tend to be more receptive to.
A couple of hours in office in terms of having a monitor patients again, that's the kind of a worst case scenario that we present in the market research, but having a patient setting the chair for a couple of our and monitor Vitals you described it in the right way doesn't turn out to be a huge hurdle and then when you describe it in the context of Jack.
Neighbors actually looks better so that's from home Martin resource perspective, do you want to lump sum.
Just a comment to say that.
You know as you mentioned monitoring with first dose, which we know is.
The topic in terms of S&P modulators. We're encouraged you talked about this before we're encouraged that FDA is clearly signal that it's not a class label.
That they take each individual a compound at it and its face value in terms of the data that are shown and that's why you see supporting that as an example, as our label that does not have first does monitoring for the majority patients as long as they don't have a pre existing credit conditions that would would lead to a greater need for monitoring.
And so that's obviously what we're.
The direction where huh.
Designing the program to address and we know that attracts a lot of definitely modulators has the lowest intrinsic potential to clause first dose delay in heart rate or Amy conduction delay.
And we know this because of our phase one and phase two data and the fact that led us to the ability to not appetite for its all the other programs out there compounds out there take rate.
Element that amount spent a lot, but it's not etcetera and the TRASM does not need to because it hasn't listen to the potential. So we are working to translate that known.
Difference and make sure that I label reflects our compound or not classic.
Okay, great and to confirm our <unk> are you establishing that by doing first just wondering in your clinical trials.
Oh, yes.
And it all overcrowding first as monitoring and and then demonstrating why that would not be needed in the commercial setting in the marketplace setting of but you have to collect the data to be able to be able to show that.
Okay, Great and second question kind of related to the phase two a topic drama data later this year curious for your plane connection or any biomarkers in that study on the effect of the transmission on the underlying immune cells and what if any read through we could expect to learn from.
That type of biomarker information as it relates to efficacy in other settings.
Including the G. I think.
Yes, I you know specific things you're thinking about here are you looking at no for example tissue biopsies and looking at histology or something else yeah exactly.
Okay. So then but tissue biopsies mythology line.
Yeah, well will in terms of the overall development will have a plan to do that obviously and you take a look at this we've done a bit of that and how are you see programs tend to degrade and any more of that.
In phase three is a subset analyses et cetera. So the short answer is yes, but we don't necessarily I would have I would say for the for this disease specifically.
Have a there's not a clear there's still a lot of understanding that the molding around the pathophysiology and which biomarkers are best.
Let's take here, we specifically as an example, well people tend to focus on his NFL why because that's the way you know that's the name of it the way that that's because patients who had.
Who were thought to have refractory GERD didn't respond to PPI is eventually got scope and on histology.
With that pathologist seems to me instead of Bill that's great, but there's also a lot of T cells. He forced to be positive T cells dendritic cells, there as Matt. So there's a whole so no no you. In addition to the here said it fills it isn't just the Senate bills that are causing damage and so.
Pretty good for E. Lee the the.
Information that is leading us to understanding what biomarkers are the best to look at is still I would say an evolving field.
Thank you.
Thanks, Jeff.
Our next question comes from Joseph Schwartz of STB Leerink. Your line is open.
Great. Thanks, very much and congratulations on all the progress as well.
First of all on the sees a three you see program I was wondering if I know you're not going to the entertaining any real time enrollment updates just qualitatively given your.
Experience that went well and space to know what kinds of things are you doing in order to.
Ensure that the execution is a smoother than as rapid as possible.
In order to.
Make sure that the network or you know produces a timely in high quality data.
Sure you are you you're specifically talking about the ongoing you see a program.
Yeah, exactly I'm, you know, obviously competitive space right now.
Just wondering what kinds of things you're doing in and out of house.
Yes, really clear of you see it grows very competitive space and so.
It's not uncommon to hit that have sponsors announce their 12 month to month delay that cetera. We are very pleased that we are on track and so again as you pointed out we don't give weekly enrollment updates one of the key factor a key triggers that will get people good to get clarity is.
When we started talking about enrollment and you see 12, which we anticipate to be later this year because we're using the same global network of 450 to 500 sites for both you see 52 in 12, and obviously because it is longer study, we want to complete whereas the majority complete that enrollment prior to tick.
You know you see 12, so we'll talk about that more over time, but that will be a key indicator in terms of the types of things. We're doing there's a short answer we're treating the launch of a trial like the launch of a drug it's a cross functional.
Endeavor, where sites are your customers, we are establishing a field teams of clinically trained individuals both one team to interact with Oh physician investigators P. eyes.
And another 2 million interacts with a study coordinators nurses and additional staff.
To make sure that the sponsor arena owns the relationship at the site and make sure that we're doing everything we can.
They have things be fluid and and productive.
And listen to them as much as we're asking them to do things another factor is focusing on referrals.
As I mentioned.
60% of patients with moderate to severe chronic you see lobby have not seen a biologic so that means a lot of patients.
Who have moderate to severe disease or not coming on a biologic yet if you go to trial sites. So often say hey, all of our patients enrolled in studies well why is that because those sites are typically used and they what are they dropped patients from their own clinic roster and that of course is limited maybe they do some advertising but that's.
Generally about it but we got 100 miles are those site. How many clinics are there that are not trial sites that have these patients and why those patients not enrolling well they don't know about the study.
They and then maybe issues related to physicians being concerned about sending their patient elsewhere.
And so there's ways to deal with that and we're actually.
Putting forth additional field teams that don't develop relationships with outlined clinics to let people know raise awareness of the study et cetera. So I just looked blip with two things there I'll say, we'd have a whole host depending we actually have a separate team that brings cross functional folks together, it's not just about clinical development or clinical operations results from both.
All medical Affairs would take a lot of a commercial insights as well I know table to think about this in a cross functional way, we understand the pressure and we think creatively and many people on the team of the history of doing this and other endeavors and again I'm just very pleased to be able to say that we're on track.
That's very helpful. Thank you and then maybe one on a worn out in addition to being perhaps a better aegion. It seems like selecting the right kind of pain was key to success in phase two I. So I was wondering you know what.
What have you done do get comfortable that idea, Spain etiology is analogous to I B D pain.
You know when you made that pivot.
Yeah, that's a great there's a great question.
Preclinically the way you develop a an animal model of high B.S., which is essentially hyper sensitive colon.
You basically introduce an inflammatory insult initiate Ivy D. As it were and then removed inflammatory insult and wait for the finished the died down and you're left with a hyper sensitive colon.
And specifically in our phase two a proof of concept trial, we didn't take active acute flare crowns, we took quiescent problems. They specifically did not have a lot of macro inflammation.
The disease was.
The quiet and yet they had daily abdominal pain. So they had a hyper sensitive colon and so that mix, what we did clinically with with what we know about the the preclinical the way you develop the animal models.
In addition to the fact that the literature is clear that phebe two receptors are up regulated in both IBT and I V S and that inflammation exists at a tissue level in Ibps, which I think is important in terms of upregulating cbtwo receptor and making it very important in terms of diminishing.
Sensory a fair nerve fiber firing so all of that leads us to have confidence in in the IB S. approach and another kind of additional helpful.
Aspect to this is a clear unmet need in the space and there's lots patients out there and so again enrollment is clearly on track.
That makes sense, thanks for all the color.
I'm sure.
Our next question comes from Joel Beatty of Citi. Your line is open.
Hi, Thanks for taking my questions. The first one is on or learn Bernab can you talk about the trial design comparing the previous phase two and the ongoing phase to be.
Similarities or differences.
Put into context, how likely the previously strong efficacy results are likely to be replicated and the ongoing trial.
Yeah. So the most important a difference and which is was just the topic of the last question is that the two a proof of concept study was in a different disease state he was quiescent crohns.
In patients, who still have daily abdominal pain, and so that is there sort of you really could have different than ive. Yes. Now I just gave all of the reasons why we think the pathophysiology and the development of a hyper sensitive Colin is actually similar between that quiescent crumbs and I'd S state and.
The the documented upregulation of the Cbtwo receptor and roll that plays in reducing the pain fibers from fire essentially a particularly when you've got some inflammation in the system and we know that I'd be asset of tissue level does have that inflammation. So with all of those caveats I'll also say that the overall.
Design is the same it's a 12 week treatment period and I'm the.
The only difference is we've got placebo.
Which is important of course, and we have three doses, so where it's a full on TV dose ranging study that should be phase three enabling.
Great. Thanks, one other question so any thoughts on Belviq being pulled from the market recently, you know any implications for arena beyond the small amount of royalty revenues on that you're gonna be sitting from that.
Yeah. So let me take the first part which is just the royalties you know we're expecting to see lower royalty revenue going forward and we had an offset to our revenue in Q4, which had to do with the.
Estimated value of the potential royalties in the ex U.S. jurisdictions, we had to recognize the future value of that when we sold certain IP and rights to belviq outside of the U.S. in our re negotiated agreement with he signed 26 team I'm. So.
Yeah, we've now reduced to that projected sales value to zero outside of the U.S. and we'll see what the sales look like going forward.
And their impact on the wealthy.
Joe This is on the which party you're talking about again [laughter].
Huh.
Just kidding.
Oh, we answer your questions. All you have in other parts of that question.
Sure that's good thank you.
Thank you.
Our next question comes from Alan Carr of Needham and company. Your line is open.
Hi, Thanks for taking my questions.
[music].
So almost done with Belviq, I guess, but not quite alright. So I wanted to ask you about 418, what can you give us an update on the.
On your and your long term strategy, there, which help to accomplish in phase two assuming.
Phase one is clean and then Kevin can you over burn again for 2020.
Assume that's mostly a TRASM on but with.
The big clinical program, but to what extend this is any of this derived from they knew entity arena neuroscience. Thanks.
Sure.
This is on the mood music the broader strategic question on for women. So an additional four when they actually do you have some additional clinical stage.
Cardiovascular compounds and closing those over time.
You know you believe when thinking about this right now is just.
Let's just make sure that all hypothesis.
But this compound can improve kodak output would that change in human dynamics in this patient and.
Beginning this incredible unmet need out there for these patients and once we can prove that we'll figure out what's the strategy is in love the strategy for cardiovascular disease, and we talked about this before is only going to relate to where the rest of the company's at that time.
There's a crowd amount at the time what are the capital markets look like at the time worse quantum I was personally. So there's so many variables that are sort of someone all control and most outside our control the intended weather.
It would be something creative with the cardiovascular portfolio or whether we choose to be developing I I will tell you we're incredibly excited about.
The program, Oh, we formally and and we believe that program to make that.
I'm patients.
Chris will talk a little bit more about the we haven't disclosed phase two study design in a lot of he tells the story there's somebody specifically, we'll talk about them can.
Because it's been done we've made it public we're happy to talk about yeah, and I just said at what would it be looking for clearly would be mechanistic.
The information so typically and in become sit in heart failure that would have to do it cardiac output and that those kinds of measures so not a none and outcomes.
Just a assessment necessarily I'll also say that in terms of longer development. So pivotal phase three programs and these are not 10 or 20000 patient outcome studies, you know looking at mace endpoints over years.
And to get you considered a heart failure is very often a 30 day assessments.
Under a variety of of ways to go about this the FDA is very willing.
To sit down and discussed with the sponsor in the space because of the tremendous unmet need the lack of appropriate medical therapies at this time and so it's a it's a nice set up to be able to bring a completely novel ml a.
Forward as a beta three antagonist.
Just got a great story around why why and work and so we're excited about it but.
As point, we'll have to see how I know how the the landscape evolves and what we end up wanting to do with its as we understand it's true potential when we conducted phase two trial.
And then how I think you had a question around burn going board. When we filed the 10-K later this week, you'll see that the vast majority of our external all clinical and preclinical spend which is disclosed in the K was around the transmark.
And our anticipation is that that will be the case in 2020 as well it'll be the vast majority of the spend will be a round of trials might not around other things like neuro or CNS RCB or some of these programs Oh and I think it's important.
Qualitative need to understand when we move programs in the phase three.
Margins indications with.
Diesel or agency requirements, when including foreign talks long term talks we start thinking about men battery backup manufacturing.
We began over a year ago thinking about global supply chain, well for the corner virus machine and being able to dissolve backup a manufacturing sites and making sure. The stockpile starting materials. This was no early on online so well just give you a quick smattering.
All the different programs that.
[laughter] doesn't really see that are required between now and I'm file Navy and it's interesting you always time this issue ever comes up as when there's a deficiency.
Response letter so we're taking a a very.
Aggressive stance in the sense that we want initial work this phone though.
We're extremely optimistic about the compound there's a lot of work to be done we want to make sure. We get the work done a high quality fashion, so that when the phase three data reads out there are no gaps to to move forward on Monday may find them and then sort of where you don't see under the under the water on kind of model.
Is really critical mass so.
That's just something to keep in mind quoted.
It Kevin you said high single digit to low double digit million increase each quarter is it does that would.
And then it's a percentage increase per quarter percent increase okay, so about which translates to about the same yeah.
And remember a lot about as enrollment dependent so really difficult. It's just sort of <unk> you know do a direct line. So.
Enrollment.
So fast as the burn and that should be a good thing.
Great. Thanks for taking my questions.
Thanks.
Our next question comes from Patrick True show, a fair number capital your line is open.
Thanks. Good afternoon, just a few follow ups regarding a Lauren I'm just first keep Charles if we see a positive outcome.
In the phase two trial in the second half a year.
Could you move directly into pivotal trials, I see and I'd, just be or additional phase two trial be necessary and then to what extent secondly to what extent would the upcoming phase two data from M.D. 7246, which is the extended release when I go tide inappropriate benchmark for learn happen.
And then finally or separately can you elaborate further on the unmet need in this area our patient.
<unk> I'm, sorry for being prescribed opioid for their visceral pain or.
Is there a significant difference between the unmet need between the subtype.
I do you see in the and then just around the pay your piece I mean.
What work or can you frame for us what work that you've done around this but suggests the payers would reimburse for an additional treatment on top of prescription medications that are already being use for various.
Oh, yes CMP.
Sure. So let me start with appear on the unmet need and then Huston personally can take the clinical question and the ER.
The question on <unk> change one way from an appetite.
If we look at.
The idea landscape.
Almost 80% of patients.
Independent would gross Iran report recurring continues to Domino pain. This 27 million ideas patients in United States in T C D in Mexico.
The third.
And just by contrast that that that's a market size. That's no roughly 10 X. Nike landscape. So it's a very hard market from a from a patient perspective, and the bulk of patients who ideas C and D. I really am over the counter need.
Over the young kids are agents to a really good job on on relief on constipation regarding yet.
But they don't do a great job on these domino team when you're down we'll pay them credits. So this is just an ongoing.
Conversation around.
Management of payments.
Five person of idea.
Asia. So just think about that given the size and Martin I just described.
Yes.
And that's a pretty striking number and you know you imagine some of those are ideas you patients will then kicking opioids for pinches absolutely confounding.
It's that team that's been.
The notices for these patients for a long time has really patient focus groups and talk to payers.
Remains one of your opinion diminished from the use of opioid consistently.
The thing that deemed a lot of traction naturally these aren't policy would price that.
In oncology type pricing or and that's type pricing a product even possible price.
To be adjunctive in a broad indication on top of the existing.
Products and even further.
The constitution overtime. So it's kinda, how we think about it from a market opportunity perspective, when we take it it's really wide open space well cool about.
Sure. So the first the first question was movement from the Phase two study and I have yes into phase three for both.
Or what are the plant drive yet and I believe so it's pretty clear five yes. This is the current phase two study a phase three enabling so we'll look at the data obviously like dose selection discuss with the agency make sure. We're at which we are doing on an ongoing basis make sure. Our phase three planning is appropriate and go execute that so that's the plan there.
Now for I'd be D. When we see results that are positive and I've, yes, a willing to go sit down with the Sta and and agree on an appropriate.
Wait to introduce or NAV as I guess, you would call adjunctive therapy and in this setting because as we know it's not necessarily disease modifying it's about pain relief and so that will require some additional conversation with the agency there's not a great you know history.
Precedent in this space and so thats why we need to take some time to have those conversations gave us. The I would anticipate then conducting an appropriate phase two trial and then moving into phase three if all goes well and then I think your other question, we just want appetite in the or the extended release formulation and the work that they're doing there so.
You know, what we'll need to see I know that in part the hope is that a that compound with would be the modification could potentially be use more broadly than constipation, we'll have to see that's true or not.
But obviously when appetite itself is is isolated advocacy and then in terms of its ability as a pain agents.
In addition to them agility will lead to understand that as well, but the data that that.
We can see publicly with the original one appetite at that I mentioned this earlier in the call suggests a one point difference placebo controlled difference the overall change from baseline was 1.9.
But 0.9 of that was related to was essentially placebo effect and so that's that's it at least set some kind of a hurdle or bar for US we saw in our small uncontrolled study as we mentioned earlier that delta of 4.6 without placebo seem to indicate that in the considered.
Nation, but that leaves me to believes that.
We have a an agent that can have a demonstrable effect.
But in fact, we need to confirm that in a placebo controlled study, which we're doing now and we'll just have to see how this plays out but we're very confident that we can use galore and have a cross Ivy at sea Ivy its D and mixed and that's the breakdown there's about a third third at a third of the population C.D. and mix and so.
Instead of focusing on one segment, we can essentially go across the entire I get spectrum and pain is the one unifying aspect in I've, yes. So people talk a lot about motility and that's true as Amin just mentioned you can often control that with over the counter agents. The one unifying aspect is pain and that.
For the unmet need really is.
That's helpful. Thank you very much.
There are no further questions like to turn the call back over to admit munshi for any closing remarks.
Great. Thank you thanks, everyone for joining us today, we look forward to continue to update you as the year goes on we've got a lot of really important incredible opportunities ahead of us and we appreciate all your support thanks, everyone.
Ladies and gentlemen, this does conclude today's conference you may now disconnect everyone have a great day.
[music].