Q4 2020 Arena Pharmaceuticals Inc Earnings Call
Good day, everyone and welcome to Arena for my Cuticles Corporate Conference call. This call is being recorded on them.
Now I'll turn the call over to Patrick Malloy, Vice President Investor Relations at Arena. Please go ahead.
Thank you good afternoon, everyone and thank you for joining US today, we hope you had a chance to review the press release, we issued this afternoon announcing our year end 2020 financial results joining me on today's call on Amit Munshi, our President and Chief Executive Officer, and Laurie Stelzer, Our Chief Financial Officer.
Before we begin I'd like to remind you that we'll be making forward looking statements that involve risks and uncertainties about our goals expectations plans beliefs.
There'll be events or future results, including those risks and uncertainties related to our pipeline financial projections 'twenty 'twenty, one financial guidance and the COVID-19, pandemic and its potential impact on our business.
Forward looking statements involve certain assumptions risks and uncertainties that may be beyond our control and could cause actual results to differ materially from these statements. A description of these risks can be found in our earnings press release, and our latest SEC disclosure documents all for.
Looking statements are based on information currently available to arena and we disclaim any obligation to update. These forward looking statements now I'd like to turn the call over to Amit Munshi Amit.
Thanks, Pat and thanks, everyone for joining today, let me go through a couple of key highlights here and then we'll jump right into Q&A.
Today.
We reached another key milestone for the company in dosing our first participant in the phase <unk> voyage trial for <unk> in the treatment of eosinophilic esophagitis. So we're excited about continuing that program and look forward to seeing the results as we go forward.
Earlier this month, we named Garry Neil Dr. Garry Neil as our chairman of the board and added New Walgreen for board of directors continuing our.
Continued expansion as well as enhancement of our governance structures.
In January we completed the elevate UC 52 trial enrollment in ulcerative colitis.
And both the UC 52, and 12 are on track for topline data in Q1, 2022, and we continue to monitor the impact of COVID-19 across all of our studies.
Physically you see 12 and 52.
As we continue those programs in.
In January we also announced the introduction of demand grow our second cardiovascular program.
And back in November we had the atopic derm phase <unk> data readout.
And thinking back on October 20.
Where do you learn that captivate data read out and we expect data from the <unk> Captivate phase <unk> trial.
Domino pain associated with irritable bowel syndrome.
Expect that data this quarter, so with that a quick synopsis, let's move to Q&A.
At this time I would like to remind everyone in order to ask your question you May Press Star then the number one on your telephone keypad.
On that star one on your telephone keypad, we'll pause for just a moment to compile the Q&A roster.
Yeah.
Your first question comes from the line of Alicia Young from Cantor. Your line is open.
Hey, guys. Thanks for taking on too.
My question for happened and congrats on the continued progress of all these program first of all on obviously learn out of what was coming down the Pike I. Just wanted if you could talk a little bit about this abdominal pain score and whether that's something you think could be used on pivotal study or you know what kind of analysis would be needed there and then just.
Picture can you just talk a little bit on what's going on with the crumbs on readout and how we think about you know the probability of potential success. There in light of public thing on the ultra quiet. Thanks.
Sure Hi, Alethia. Thanks, so much for your question on the EPS scale.
On a percentage of patients getting a 30%.
Plateau or 30% of rate in the P. S. Scale is is the phase three endpoint and is included in one of the endpoints in this study so we'll be looking at as with all 50 studies continuous variables things like changing from baseline the EPS compared to placebo as well as categorical changes like percentage of patients getting to 30%.
50 per cent threshold.
And it is the same scale that will share at work here B B.
Used in the phase III trial as far as Crohn's is concerned we're continuing progress on Crohn's. We expect data later this year from the sub study.
As you'll recall, we're setting book two and three milligrams there.
Looking for a dose response and looking for some initial indications of directionality on the dose.
We in in terms of the activity, we know that it was on a mod showed activity in the Crohn's population, we know that drugs that have shown activity in U C tender tend to show activity in Queens and recall that we're taking a higher dose of three milligrams in as well to see if there's some additional efficacy in this population.
Weren't pushing the dose from two milligrams to Melbourne. So again, we're looking at <unk> three milligrams and we look for seeing the data later in the year.
Great. Thank you.
Yeah.
Your next question comes from the line of Marty Auster from Credit Suisse. Your line is open.
Hey, Tim Arena.
Yeah.
Hey, Marty.
Yeah, I wonder if I could follow up on on his question on the Crohn's trial, just given that this is sort of a just a uncontrolled just from the 2 million and three milligram dose arms could you comment a little bit in terms of how to think about interpreting that data and what sort of kind of historical placebo responses.
Observed from studies and then also if you had a dose response and success would you think about a future UC study looking at the three milligram dose as well down the road or is that something you think is gonna be a preference for beneficial crops.
Yeah, I I am you know the placebo rates a little bit of a range about 100 point change in TDI 250 point range share.
About 100, 150 point Delta on on top of that is is considered on emission standard.
Those would be what we would be looking for in terms of an aggregate response in this trial and again, we've got analogs from moves on a month open label study.
So we one of the lease for point of comparison in terms of being able to see far if our activity is is comparable or preferential to.
He was on them on.
On the three milligrams. It's interesting. This is the first time, we're taking it into a study participants non non healthy volunteers.
We're also going to be contemplating that dose that's part of the broader atopic Derm study and this will talk more about that as we get through the agency and absolutely. If we start seeing that we're seeing increased efficacy were seeing.
On the safety profile stays consistent as we've seen historically.
With three versus two that we will consider taking free into ulcerative colitis as well over time. So it gives us a lot of flexibility. It also gives clinicians a lot of flexibility in terms of them in terms of treatment. So we think that's going to be important.
Over the long haul.
Got it great. Thanks, Amit.
Your next question comes from the line of Kennan Mackay from RBC capital markets. Your line is open.
Hey, guys, Hey, Amit thanks for hosting the call on.
Taking our questions.
On atopic Derm again would just love to get your ever evolving.
Sense of sort of how this landscape is stretching out as it relates to.
Oracle's and some of the recent JAK inhibitor approvals and maybe how about setting the stage for all the asphalt costs and attract margin. Thank you.
Yeah.
Thanks, Ken and really appreciate it yes, it's the atopic derm market as we know has substantially more moderate to severe patients.
Hey, ulcerative colitis, rheumatoid arthritis and.
We know that despite depictions fantastic success with their own data suggest it only penetrated less than five per cent of the moderate to severe population and as we continue to research and understand physician practice and behavior of what we see is that the advent of oral agents with a with a safety profile similar.
For two of crowds mod.
We are well poised to be earlier used in the atopic derm population, we know that some of the other world classes in development is significant.
Safety issues as we've seen and continue to evolve including.
On increases in cardiac events increase.
Increases in DTE risk and of course, the increases in malignancy, even as compared to the anti TNF. So.
Again, we think and we continue to believe that the positioning of the traveling long term of the atopic derm market is very favorable as a once a day oral.
With Iga scores in line with depiction from our phase two studies with all the caveats of cross trial comparisons and and being able to see.
Our safety profile, but it's again consistent with what we've seen with the crowds on.
On the historically so.
We remain incredibly optimistic about where this product will fit and about the market opportunity and the chance to really impact the deed on these to these patients.
Operator can we go to the next question.
Your next question comes from the line of Joel Beatty from Citi. Your line is open.
Hi, Thanks for taking the question.
The first one is on the three milligram arm of the CRO for the disease trial is there a potential to see any of the lymphopenia discontinuation that we saw in the phase two atopic dermatitis study and then the second question is on the lower ROE NAV readout coming up and.
Ibs pain is there any reason to expect there might be differences in results in Ibs C versus Ibs D.
Hi, Joel Thanks for your question on on.
On the on the Lymphopenia issue as Youll recall.
In about 30 sites in the atopic Derm study we had these discontinuation is primarily at a single site.
A single investigator accounted for a bulk of these patients that had the discontinuation so.
We don't think this is a broader <unk> issue in fact, the cross over 500 clinical sites across all the other programs, we're not seeing any patterns, even consider even remotely consistent with that so.
I'd be careful not to extrapolate too much from.
A single predominantly a single site at the beginning of the Covid Ken.
Pandemic the.
As far as three milligrams, we know that.
They it drives about 12% to 13% additional lymphocyte decreases.
From our healthy volunteer study from our Phase one study and we don't think that will get a disproportionate share of patients into a great for lymphopenia recall that the discontinuation is again predominantly at a single site.
We're at a great free Lymphopenia, which one is the protocol violation so.
Again, we're not seeing grateful Olympic Lymphopenia for two milligrams and with a nominal change in it.
And look at transactions from two to three milligrams moving we expect to see.
See much there either so again, we didn't see it in our in a healthy volunteer study and we don't expect to see.
This is a systemic issue.
Systematic issue across trials.
I'm sorry, Joe could you repeat your second question. Please.
Yeah. Thanks for those details and then the other question is on all over and add on any differences that spectrum Ibs C. But there's obviously.
Yeah, So I I Ibs D has historically been tougher to treat on the EPS scale and you know.
Whereas you see plus.
Placebo adjusted about a one point change across all the major program somewhere in that range.
On the Ibs D setting you see something in the 0.5.
2.8 change.
Compared to placebo on the Ibs D. So you do see.
Which seems to be directionally, a slightly more difficult to treat population. So we'll see how the data plays out.
I think the big difference is most of the other programs had been tried in the pain setting.
Have predominantly been.
<unk> used it to impact the volatility.
And then the pain as a secondary component here pain is the primary component. It is the number one reason these patients see a gastroenterologist accounts for 70% of gastroenterology that just have to deal with abdominal pain. So.
So thinking about teen first here.
We think will result in slightly different approaches as opposed to thinking about the mortality benefits first and then teen secondary but we'll see that one when we see the data, but we do expect those those patient populations to.
To be different.
Do you have reacted differently in previous clinical programs.
Great. Thank you.
Thanks Al.
Your next question comes from the line of Yadkin Sunday Ha from Guggenheim Partners. Your line is open.
Hey, guys. Thank you for taking my question two for me first on the CR formulation can you maybe give us an update where you are.
With regard to the a day study or are you going to take the CR formulation in.
A D and then on a layer on that side of thing in the phase two a there was not.
Not a clear dose response, but was a very nicely kept dependent response after each dose so just trying to.
Get a sense of you know.
What level of receptor occupancy you need to achieve at what do you think you could achieve that effect in this a bigger study. Thank you.
Thanks, Jeff and thanks for the questions on the CR will continue my work on the CR formulation.
Manufacturing stability additional studies that have to get done.
As we've said previously we expect the bridge into the atopic Derm study will not be ready for the beginning of the atopic Derm study, but we will be able to bridge into the phase III and that's our that's our current plan on working assumptions and that's what we're working toward him on the on.
On the Allure net phase Iia study.
We knew that the 25 milligram arm.
<unk> achieved sufficient receptor coverage and then for safety, we took a 200 milligram arm.
And we didn't see a difference between 25 and 100 is as you pointed out for.
For the phase two b we.
Took one dose below that 25, and one day above so we really do hope to see a little bit of a dose response.
And again that 25 was sort of the anchor for receptor coverage. So again, we'll see that data when we see that data.
But the but that was the idea coming out of the phase Iia study.
Got it thank you.
Thanks.
Your next question comes from the line of Joseph Stringer from Needham and company. Your line is open.
Hi, guys. Thanks for taking our questions and congrats on the progress.
For the phase two alopecia Readouts later this year can you help kind of frame expectations around the data readout on what's considered.
Clinically meaningful salt score.
Perhaps tie that into the responder analysis on the secondary endpoints.
Sure Yeah. So so.
<unk>.
As you know there's different types of alopecia on reorder.
And you move toward a universality until palace in different types of alopecia. So we will be if you give me a mixed bag of patients from the small phase Iia exploratory trial, we'll be looking for a 2030, 40% improvement. We think those are meaningful improvement on the overall salt scores.
Losses from patient population again, the objective of the phase II <unk> and former <unk> program and help us understand which patients are more likely to respond and have a benefit with <unk>.
So that's kind of what we'll be looking at again categorically percentage of patients who achieve a sub 50 would be a meaningful or salt 30 would be a meaningful result.
No just like we did with the phase Iia study on worn out.
Let's be cautious on over interpreting small phase Iia studies.
They're designed to really help us inform the next clinical step on the program.
And help us identify the right patients to move forward with them.
Again, we think the biology is extremely intriguing we know that CD for CDA positive T lymphocytes for cytotoxic follicular hair follicle level, we know they traveled there on the EPS when people.
Mediant, we can stand for.
And so we can we can clearly see that we're on target.
Mechanism and now we'd like to see a clinical response across the different different subsets of these patients. So we can begin to educate ourselves on where to go forward on a phase <unk> program.
So excited to see that data and again, we'll be looking for a change and thats all score compared to placebo and differ by the subsets of patients we'll be looking.
Okay.
Next question comes from the line of Jason Gere vary from Bank of America. Your line is open.
Oh, Hi, good afternoon, there and this is chi on for Jason Thanks for taking our questions.
Two questions first one on cross maybe just to follow on your expectation I think people are inherent on he cannot do cross trial comparison for US is always Panama phase III data, which is also on the open label can you talk about your expectation you're looking for something comparable to Osama model or are you looking at something potentially.
And the cross sales to read out and then second question on each crossing border control with lease it.
If you do end up seeing a stronger thinking on what day three milligram.
Would you be able to formulate the CR formulation for both the tumor like right now for two months three months.
Thanks.
Okay. Thanks, Thanks for your questions on on the Crohn's.
Given the broad range of inherent.
Vantages payable over ozona margin faster onset to faster offset to no titration schedule.
To seeing single digit heart rate changes with the absence of other titration schedule not to mention the metabolite issue and the drug drug interaction issue advantages that we have.
We think at least for this first crooned study being able to see an effect that's commensurate with those on them what would be a great outcome for us.
Naturally with two and three milligrams, we'd like POC potentially three milligram show an increase of two milligrams.
And we will see it goes for smiles. So I think if we sell those things.
We can call that a very successful win.
In that program for the CR formulation, absolutely, we're starting with the two milligram, but once once we're at that place where we can begin to confidently.
Replicate what we saw on the original studies into actual tablets and into human clinical studies, taking that from two to three milligrams.
Is definitely in the plan and again, we want to see that two and three milligram dose response in the Crohn's.
Before we make that call because there's no point in spending a bunch of money me Q3 milligrams CR formulation.
If for some kind of plateau effect between two to three milligrams. So well then let the data lead us there.
Again, we'll be looking at three milligrams not only improves the potentially in atopic derm work as well.
As a consequence, we will have multiple data points in which to inform whether we take the CRM between programs, but it's absolutely feasible, there's nothing technically not feasible would like for like that.
Yeah.
Got it thank you.
Yeah.
Your next question comes from the line of Joseph Schwartz from SBB Leerink. Your line is open.
Alright, thanks, very much a couple of questions on the elevate studies I believe you said that the baseline characteristics and these studies are fairly similar to those who you enrolled in a way for us with maybe a slight skew towards more biologic naive patients.
This strikes me as a bit counterintuitive since biologics have gained more share over time and I would think that the pandemic would tend to select for more severe treatment experienced patients who might be more motivated.
Can you speak to the apparent paradox, and maybe talk about the sites that have enrolled for most patients and how they might compare to those who are involved in a way for us in.
In terms of anything like geography experienced with IBD trials any other aspects that might influence the results.
Sure. Thanks, Joe.
The baseline characteristics, we haven't disclosed as being similar who basis. What we've disclosed is that the inclusion criteria were similar to a system had been across most of the phase III trials two in free trials are done in the contemporary patient population the only baseline characteristics. Once we provided is this.
70 30.
Yeah.
Kind of rage, and as you'll note ozona Mod had about the same.
Albeit you know six to 12 months before us so.
<unk> notwithstanding.
When you run programs small phase II programs, which are predominantly U S. Maybe some European sites western Eastern European sites.
And you get to what we saw which was a 60 40 split and and then when you go more global you get to closer to 70, 30 split and that's consistent across all the programs that we've seen so again was on it might end up with the exact same split we did so we don't think that's much of a paradox or our data that we've shared for the last couple of years, we've run this.
Study a couple of times does suggest that.
Even in major markets two out of three moderate to severe you shouldn't you see patients.
Have never received a biological net dance therapy, so that that's pretty consistent with what we think the the contemporary market looks like is the net 65% to 70% range. We think that's consistent.
In terms of site selection.
There is just a handful of sites around the world.
Haynesville try the wrong word, but there is a finite subset of sites around the world that can effectively run these studies and.
And one of the challenges has been historically that everyone's in the same sites for study. So we're really pleased to be able to be in those sites the experienced sites around the world using.
Using C O Roes that are conducted.
Many of the other phase III investigations in the ulcerative colitis phase and still be able to maintain enrollment timelines.
The as you know the Endoscopies are on.
On locally conducted with centrally read and that's a critical quality assurance metrics.
Across all of these programs so we.
We feel good about the site selection, we feel good about the.
Inclusion criteria you have for the studies and we sort of let it kind of play out the way it was going to play out we didn't try to enrich for more naive patients for example.
And I think what we're seeing is Rudy contemporary patient population that's again.
Sorted by the market research, we've conducted over the last day.
Mhm, Okay, great. That's really helpful. Thanks, and then I know you continue to monitor the impact of a potential resurgence on this pandemic. So I was just wondering if you could give us an updated assessment on how its impacted data collection so far.
In terms of any colored commentary around discontinuation or.
On the transition of patients from the induction to the maintenance phase of your seamless study.
Yeah, I think all we've shared publicly is that the discontinuation rates Inc.
<unk> and.
And all the other pre planned for.
Parameters that we track on an ongoing basis all of those metrics are.
Below our pre planned statistical expectations. So for example, just continuations interruptions are well below our pre planned statistical expectations.
Patients moving from 12 T, though to the longer studies patients kind of moving forward again those are.
Or or above our pre planned statistical expectations across the board. So more monitoring this incredibly carefully in terms of study conduct that from day, one was our primary.
Are you worried.
And.
We've got a we're watching as we have been since the beginning of the pandemic every patient every site every country.
Every day.
Thanks, again and keep up the good work.
I appreciate it.
Your next question comes from the line of Jessica Fey from J P. Morgan Your line is open.
Hi, guys. This is Daniel for Jessica Fye, Thanks for taking our questions.
On in this scenario for you see no greater than two point placebo corrected for technology.
On EPS and been one group either Ibs C Ibs.
Ibs D on what.
Does it mean in terms of your plans for advanced the program to forward. What are you still take the product in both populations.
Yeah. It depends on what we see in the Ibs D right that like I said the bar is much lower in the Ibs D setting.
Most products are well below one point corrected change the placebo corrected change.
And.
So seeing something north of 1 million in the in the D. Space is very remarkable seemed something north of one on a half and in the DC space is quite.
Substantial so they again they both.
This question was asked for in the same area, which is the thresholds are little different flows team. So.
Let's let's take a look at the data on them, we make a judgment call about where we go next.
And how we value program.
It's premature until we see the data to be able to really understand.
Where we go next we can hypothesize around there's one good one and half two but again the bonds, we can say unequivocally the bar in Ibs D.
Much lower.
And so.
So it doesn't have to be true across the board.
Alright, thank you.
Thanks, Tony.
Your next question comes from the line of Patrick <unk> from H C. Wainwright. Your line is open.
Thanks. Good afternoon first can you give us an update on the status of the Gladiator studying what the trial might in mild to moderate you see on how this trial is overall how important. This trial is overall on positioning of a trough margin, what's becoming increasingly competitive UC market.
Hi, Bert really appreciate it.
Great question on Gladiator and thanks for bringing it up its one of our favorite topics.
On the the Gladiator program as you'll recall was designed to treat more of the moderate patient population.
Patients who might not otherwise qualify for <unk> 12, or 52, and so the Gladiator program is up and running sites should be initiated we will continue to provide progress updates as you know we don't provide enrollment updates, but will continue to provide broad progress updates on the program.
It is being run at an overlap subset of the sites that are running for 52, so as as the 52 study.
Moves over to 12, and 12 study continues to enroll and patients don't qualify for 12 of those patients will be self selecting into the Gladiator program.
The reason this is important comes back to something I mentioned, a few minutes ago, which is the.
Despite the.
The broad penetration of biologics two out of three.
Moderate to severe patients.
Still havent received an advanced therapy and they tend to be more on the moderate population. So theyre not captured in the clinical studies.
These are patients with significant rectal bleeding stool frequency they have active alt.
<unk> on endoscopy, but not severe enough to actually qualify for the clinical study.
Those are the patients that we'd be going after with gladiator.
The feed the market essentially doubles with the successful Gladiator outcome, and we think that's very significant and being at the forefront of addressing these patients we think.
Makes this landmark study very important to our long term.
On desire to make it RASM on a standard of care in ulcerative colitis.
That's helpful. And then just kind of a bigger picture question, how should we be thinking about the strategy going forward with regard to a therapeutic area of focus on potential collaborations specifically with the three areas of Gi and derm and cardio building out I'm wondering if there's a preference on which of these areas makes sense to keep for them.
On arenas control versus collaborating on.
How we should think about potential commercial collaborations with various compounds in development.
Yeah, that's a great question too.
I would say that one of the things advantages. We have is this is a staggered build.
You see comes first and we started entering it for dermatology.
Some additional Gi indications coming after that including Crohn's and Eo.
And then and then we enter cardiology into phase III. So you know not.
Not all of these programs are running at the same pace. The cardiovascular indications are just initiating phase two now so there they will be in phase three until we're a lot of phase III in these other indications so.
It's it's not a fair assumption.
Assumption to make that we're going to have to make portfolio choices today.
We'll definitely be in the situation, we will have to make portfolio choices in the future potentially.
And if things go as we hope and anticipate.
And then building on cardiovascular we think will be an important leg of the stool long term.
So it gives us a.
An important consideration in terms of the from the.
10 year footprint of the company and I know that's beyond the scope of most.
Most of the investors you guys talked to but we're thinking in that time horizon about how to build the company and.
If you really want to build a company having single assets that have binary outcomes are not the right way to go and do you want to have a broad and diverse portfolio you want to be in multiple therapeutic areas, we think theres provocative unmet medical need.
What do you think you've got key competitive advantages and a net you can actually execute by yourself and we think we can execute each of these therapeutic areas.
Ourselves on and that's a big consideration before we go into an area.
As you know we licensed out our ph asset to United Therapeutics, a highly specialized area.
And United Therapeutics has his incredible skills and breadth and scope of knowledge with that physician community in that patient population. We felt good that product was better in the hands of a partner.
We recently spun on our arena neuroscience, now called Longboard Therapeutics, and longboard back from cynical and.
And that's again, a therapeutic area that we.
We chose not to be into directly and we thought it required a different level of focus and we will just from that out. So we continue to make prudent pipeline decisions and prudent prioritization decisions and holding on to the things that we think we can execute.
Over the mid to long term, so that's really been the strategy.
Yeah. That's helpful. Thank you very much.
Thanks for that.
Your next question comes from the line of Chris Howerton from Jefferies. Your line is open.
Hey, there thanks for taking the questions.
I mean, frankly, I think most of them have been asked at this point, but.
Maybe just a couple from me one would be obviously, you're in a great cash position, but what is your view of cash runway and kind of does this get us to the point of ulcerative colitis commercialization.
I and then the second question I was actually just for reviewing your transcript from the J P. Morgan Conference earlier this year and you were kind of talking about your ESG report.
I must admit I haven't had a chance to review that so I was just curious maybe Amit if you could give us a couple of highlights from that reported this year.
Sure. So let me take the ESG and then I'll hand that bill already talked about cash runway on the ESG side, we issued a 2020 ESG report last year and so feel free to.
For proves that we took a lot of pride in going through the audit process internally.
We had multiple conversations at the board level in terms of the importance of ESG long term.
Many of our shareholders as you know or.
Our long shareholders will consume on European shareholders, when we take their concerns very seriously.
So we started on this process two years ago.
In terms of understanding what it means.
Sure.
For a smaller company like ourselves to be highly engaged enacted in in managing our AR.
Broader for environmental.
Environmental social and governance footprint and we've made critical improvements based on that feedback between 'twenty and 'twenty, one will be issuing our 2021 report.
Later later this year so.
Well it will be you'll be able to read a second report so.
So we're extremely excited by that we have.
This is governance up to the border oversight at the board level.
We've got internal executive level sponsorship on this and.
And again, we're constantly trying to make sure we're improving who we are as a company and what our footprint is long term loans. We think that's important for building a sustainable vibrant company.
Or did you want to take the cash runway question.
Sure sure absolutely.
So we ended the year with $1 1 billion in cash.
Landed our operating burn as we had predicted about $353 million.
We haven't guided yet for 2021, but you know as you can imagine our expenses are continuing to grow. We we are in a number of phase III programs and we're looking out cash.
And the planning of the ATM program.
It's progressing the pipeline.
So it's yes, it's a more.
It's a more complicated picture than just that.
<unk> calc on cash burn, but certainly we have cash.
To get us on to.
To that to that commercialization plan.
Okay.
Well like I said I think most questions have been asked already I. Appreciate you taking them and Amit for what it's worth I think you're building a great company in the end the ESG report I look forward to reviewing and seeing just that.
Welcome your feedback thanks, so much.
Your next question comes from the line of David Wong from S. MVC. Your line is open.
Hey, guys. Thanks for taking the question on fitting me in just had a couple a lot obviously hasn't been addressed by the prior questions but.
Maybe a follow up on the UC Gladiators study.
Have you talked about whether this could be a registrational in terms of.
Putting forth for approval in the mild moderate population and then on you on timing. There do you think that you might you might be first to market.
Given there are a few phase II oral assets also looking at the mild moderate space.
Yeah. So so.
Is this by itself a pivotal study that's a conversation we have with the agency no one's generated a broad data set here we've seen smaller studies.
Generates from anecdotal information I'll call it but in terms of running a large scale multi center glue.
Global clinical investigation in the same scale and scope is as elevate no one's done that so we we think we've got at least the opportunity to have this be a single pivotal and questions. We would need a second pivotal if we were going to be taking a registrational trial I think more importantly.
We spent a lot of time with the payer community, we probably had about two dozen meetings with key.
Key payers round around the country, we've taken the input into the design of the Gladiator program.
And that's been a big driver of.
Generating this information on not only does the double the the eligible population in the space, but it <unk>.
Begin to create a provocative case for the payers.
They have a preferred position for travelling motto. So we think it's important for for multiple points of view and and.
I don't see anybody else running large scale global phase III equivalent type trials like we already with Gladiator. So I think we are.
At or near the forefront of exploring it.
Explain this population.
Okay, Great and then I just want to touch on the cardiovascular assets I know the Readouts are still a little ways off but was just wondering if you would be able to maybe pre view.
Design and endpoints for for HDD for 2018, as well as the new assets to manage ROE.
Sure. So Glenn both have fast track designation and we're moving into phase two.
Just to recap demand grow we're taking on micro basketball section will be looking at a subset of patients we'll be looking for patients and we've been looking at actual resistance is measured.
<unk> just talked to the site of the.
The occlusion and in.
In those patients and so that's that's really designed the study it will be an international Cath lab and then similarly in the Apd for one space. Those will also be an interventional cath lab, what says quantitative a set of metrics as we can possibly develop in that setting again, we're trying to look for gross.
Real clear measures there of cardiac output and ejection fraction no change in hemodynamics, So we'll be able to do that again.
Control settings for both of those studies are really designed and.
It's very important proof of concept studies.
To begin to inform.
And work with the agency on where to go next in terms of a Registrational program.
And both of those data readouts on the 22 timeframe.
Okay. Thanks, so much for taking the questions and congrats on any progress yes.
Yeah. Thank you so much.
Your next question comes from the line of for car Agarwal from Jones trading your line is open.
Hi, Thanks for taking my questions on congrats on the other progress I had a couple on E. L E.
On what doses are you testing in the phase two wife's trial.
And what's the bar for success for entrusting them on her in terms of production is on a per account realm.
To what has been shown by some other injectables such as top excellent. Thank you.
Yeah. Thanks, So we'd love to see efficacy from the same range.
Biologically from what we've done in animal experiments, we don't see any reason that <unk> would be substantially worse than the biologics.
And with the advantage of a once a day oral we think that's quite meaningful and of course, it's significant.
On the focus off day. This opens up the door to other eosinophilic Gi conditions for us to explore over time. So we think it's we think it's incredibly exciting.
And supported by.
The biology, we have done to date, and we will be exploring one and two milligrams in net voyage study and that is a phase <unk> study.
So should yield a sufficient amount of information to be able to move forward into a.
For Registrational trial from there.
Your next question comes from the line of Jim Burke enough from Wells Fargo Securities. Your line is open.
Hi, Thanks for taking our questions. This is <unk> on for.
For Jim So.
First of all a question on the elevate 52 trial design.
This trial has a treat through.
And it's different from the typical induction then re randomization then maintenance type.
You will see.
On trial design.
I was just wondering because with the typical historic traditional design. They typically add more patient at the re randomization step just for makeup for the roster for non responders.
And certainly by definition there.
Maintenance sections maintenance phase of the study starts with all patients being on.
Responders and.
With your treat through design.
I'm wondering how does that impact the powering of the study for the 52 week endpoint, because obviously you didn't add any new patients and there are patients who don't respond from the outset of the study okay. Thanks.
Yes. Thanks.
The reason we did the treat through design after consultation with both the U S. On European regulatory authorities is a close more closely mimics real life right and the real in the real World you don't start re Randomize, Inc, responders and seeing drop offs and adding more patients on over enriching your population for your maintenance those patients who do well on that.
Drug stay on the drug for an extended period of time. It's also important to remember the historical context that treat to re randomization.
Dichotomy really goes back to the early biologics that has a different dose for induction versus maintenance. So what you had to do as you get that in.
A remission at Inc.
In the case of Infliximab at a higher dose five to 10 Meg per kg, and then reduced and the three mix per gig and and that's why that study design originally came to bear.
You're right. It does it does require.
To maintain the same path.
<unk> requires more patients you have more drop offs and you have about a six to nine month delay in the middle as patients get randomized.
So the treat through design is just more efficient all the way around we can achieve the same powering with a smaller subset of patients for less dropouts and.
And and importantly.
Not lose six to nine months and momentum.
It's a more streamline trial design and from.
From from our conversations with the agency and working through the statistical plan, we're able to accomplish more with less and.
I think that's really important it also gives physicians a much more clear picture of what the real world. It looks like in terms of maintenance and we think that's going to be a competitive advantage.
Got it that's very helpful. And then a couple of questions on the AP.
Side for.
A D program.
Obviously at one Nick you have a like a 30% lymphocyte reduction and.
To make it you might have.
13% incremental reduction.
And this is a first in class.
Study for the <unk> mechanism.
P.
Is it.
Surprising for you that when Nick or 30% no per se reduction on average didn't result in efficacy signal.
Kind of a step function response.
If you may.
And then also as you increase the dose I think you have talked about that you want to explore higher doses.
Well you increase the dose and trying to maintain the same efficacy profile does it makes sense.
To have a kind of a personalized dosing guided by the peripheral lymphocyte reduction thanks.
Yeah, So let me start with the <unk>.
Debunking, a preconceived notion limp.
Lymphocyte reductions.
Not a sole PD marker for this drug the drug has.
It has multiple modes of action, including we know activity against other cell types like dendritic cells and keratin sites.
So the over fixate on lymphocyte counts.
Is incorrect just in general and it's something that just is something we continue to spend time in educating investors on.
We know from historical on.
Analysis that lymphocyte counts across all trials.
All drugs on the same category really only account for about 50 per cent of the effect size. So theres multimodal activity for example, less one P. One plays a critical role in social junctional barriers and being able to close so some junctional proteins and we know that's one P to off target activities, we've seen on competitive products open sales.
Junctional protein so.
It's.
It is important to remember that just focusing on lymphocyte counts by themselves.
Is is probably over reading.
PD marker in terms of what's going on.
We also know that different therapeutic areas quite a different doses.
Across all the different trials for the most recent data.
With the JAK inhibition of example use a threefold higher dose.
For the ulcerative colitis trial than they did in their rheumatology trousers.
For Sydney for example, seven and 15 milligrams and other up to 45 milligrams and they push those high doses in the <unk>.
On a day trials as well so there's a broad range of dosing based on the indications you go after.
And your Point's a great one which is yes, we're the first ones to go into atopic derm with an S. One P modulator and he wanted to key lessons learned is we probably need to have more drug on board in the in the dermatological settings, specifically atopic derm.
As we think about these indications and that's nothing new we know that different.
Indications different autoimmune conditions react to different doses with different drugs and that's been consistent going all the way back to the early anti TNF piece.
Got it very helpful. Thank you.
Thank you.
There are no more questions at this time, turning the call back over to Mr. Amit Munshi, Inc, President and CEO.
Great Hey, thanks, everybody for joining our call today hope everyone's staying safe.
On the.
2020 was a difficult year I just wanted to really call out our team at arena for their focus on their resiliency and the energy to get things done.
It was a it was a herculean effort and we continue to drive that momentum forward into 2021, and we look forward to staying in touch with everybody as we continue to drive on that key catalysts over the next 12 months. So thanks again and look forward to talking soon.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
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Okay.
Sure.
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And on <unk>.
Yes.
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