Arena Pharmaceuticals Inc (ARNA) Q4 2020 Earnings Call Transcript

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Arena Pharmaceuticals Inc (ARNA)
Q4 2020 Earnings Call
Feb 23, 2021, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day everyone, and welcome to Arena Pharmaceuticals Corporate Conference Call. This call is being recorded. I will now turn the call over to Patrick Malloy, Vice President, Investor Relations at Arena. Please go ahead.

Patrick Malloy -- Vice President, Investor Relations & Corporate Communications

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 are Amit Munshi, our President and Chief Executive Officer and Laurie Stelzer, our Chief Financial Officer.

Before we begin, I would like to remind you that we'll be making forward-looking statements that involve risks and uncertainties about our goals, expectations, plans, beliefs, timing of events or future results, including those risks and uncertainties related to our pipeline, financial projections, 2021 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 forward-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?

Amit Munshi -- President & Chief Executive Officer

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 2b VOYAGE trial for etrasimod in the treatment of eosinophilic esophagitis and we're excited about continuing that program and we look forward to seeing the results as we go forward.

Earlier this month, we named Dr. Garry Neil as our Chairman of the Board and added Nawal Ouzren to our Board of Directors continuing our continued expansion as well as enhancement of our governance structures at Arena. 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, but specifically UC 12 and 52 as we continue in those programs.

In January we also announced the introduction of temanogrel, our second cardiovascular program and back in November we had the atopic derm Phase 2b data readout and thinking back to October 20, we had olorinab CAPTIVATE data readout and we expect data from the olorinab CAPTIVATE Phase 2b trial in abdominal pain associated with irritable bowel syndrome, we expect that data this quarter.

So with that quick synopsis let's move to Q&A.

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from the line of Alethia Young from Cantor. Your line is open.

Alethia Young -- Cantor Fitzgerald -- Analyst

Hey guys, thanks for taking, two of my questions I have and congrats on the continued progress to the ELEVATE program. First one obviously olorinab, which is coming down the pipe, I just wanted to talk a little bit about this abdominal pain for and is that's something that you think these and several study or what kind of analysis will be needed there?

And then just big picture, can you just talk a little bit about what's going on with the current readout and how we think about the probability of potential success there in light of what we've seen in ulcerative colitis? Thanks.

Amit Munshi -- President & Chief Executive Officer

Sure, hi Alethia, thanks so much for your questions. On the AEPS scale a percentage of patients hitting the 30% plateau or 30% rate in the AEPS scale is the basically endpoint and is included in one of the endpoints in this study. So we'll be looking at Phase 2 studies continues very well seems like change in from baseline AEPS compared to placebo as were categorical changes like percentage of patients getting to a 30% and 50% threshold and it is the same scale that will show that will care [Phonetic] be used in the Phase 3 trial.

As far as Crohn's is concerned, we are continuing progress on Crohn's. We expect data later this year from the sub study. As you'll recall, we're starting from 2 mg and 3 mg there looking for dose response and looking for some initial indications of directionality on the dose. We, in terms of the activity, we know that ozanimod showed activity in the Crohn's population. We know that drugs have shown activity and UC trying to show activity in Crohn's, and recall that we are taking a higher dose of 3 mg and as well to see if there is some additional efficacy in this population that might warrant pushing the dose from 2 mg to 3 mg. So again, we're looking at 2 and 3 mg and we look forward to seeing the data later in the year.

Alethia Young -- Cantor Fitzgerald -- Analyst

Great, thank you.

Amit Munshi -- President & Chief Executive Officer

Thank you.

Operator

Your next question comes from the line of Marty Auster from Credit Suisse. Your line is open.

Martin Auster -- Credit Suisse -- Analyst

Hey team Arena, how are you doing?

Amit Munshi -- President & Chief Executive Officer

Good, hey Marty.

Martin Auster -- Credit Suisse -- Analyst

Hey, you know I wanted to follow up on Alethia's question on the Crohn's trial, just given that this is sort of just uncontrolled just with the 2 mg and 3 mg 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 you've observed in Crohn's studies?

And then also if you had dose response and success would you think about a future UC study looking at the 3 mg dose as well down the road or is that something you think is going to be preferential beneficial in Crohn's?

Amit Munshi -- President & Chief Executive Officer

Yes, I -- the placebo rates have a little bit of a range about 100 point [indecipherable] to a 150 point range, seeing about 100 to 150 point delta on top of that is considered a remission standard. So those will be what we will be looking for in terms of an aggregate response in this trial. And again, we've got analogues from ozanimod the open label study, so we will have at least a point of comparison in terms of being at least to see if our activity is comparable or preferential to ozanimod. The 3 mg it is interesting, this is the first time we're taking it into study participants non-healthy volunteers. We're also going to be contemplating that dose as part of the broader atopic derm study and we'll talk more about that as we get through the agency. And absolutely, if we start seeing that we're seeing increased efficacy, we're seeing the safety profile space consistent as we've seen historically with 3 versus 2 then we'll consider taking 3 into ulcerative colitis as well over time. So, I guess there is a lot of flexibility and also gives clinicians a lot of flexibility in terms of treatment. So we think that's going to be important over the long haul.

Martin Auster -- Credit Suisse -- Analyst

Got it, great. Thanks Amit.

Operator

Your next question comes from the line of Kennen MacKay from RBC Capital Markets. Your line is open.

Kennen MacKay -- RBC Capital Markets -- Analyst

Hey guys, hey Amit, thanks for hosting the call and taking our questions. May be on atopic derm again, we'd just love to get your ever evolving trends and sort of how this landscape is shaking out as it relates to orals and some of the recent JAK inhibitor approvals and maybe how that's setting the stage for the S1P cost and attractive margin? Thank you.

Amit Munshi -- President & Chief Executive Officer

Thanks Ken, and I really appreciate it. Yes, it's -- the atopic derm market as we know has substantially more moderate-to-severe patients than say ulcerative colitis or rheumatoid arthritis. And we know that despite the picture of fantastic success with the wrong data suggested only penetrated less than 5% of the moderate-to-severe population.

And as we continue to research and understand physician practice and behavior, what we see is that the aggregate oral agents with a safety profile similar to etrasimod are well poised to be earlier used in the atopic derm population. We know that some of the other oral classes in development have significant safety issues as we've seen and has continued to evolve including increases in cardiac events, increases in DTE [Phonetic] risk and of course increases in malignancy even as compared to the anti-TNFs.

So again, we think and we continue to believe that the positioning of etrasimod long term in the atopic derm market is very favorable as a once a day oral with IGA scores in line with depiction from our Phase 2 studies will all the caveats of cross trial comparison and be able to see a safety profile that's again consistent with what we seen with etrasimod historically. So, we remain incredibly optimistic about where this product will fit and about the market opportunity and chance that to really impact the deal for these cases.

Patrick Malloy -- Vice President, Investor Relations & Corporate Communications

Operator, can we do to the next question?

Operator

Your next question comes from the line of Joel Beatty from Citi. Your line is open.

Joel Beatty -- Citi Investment Research -- Analyst

Hi, thanks for taking the questions. The first one is on the 3 mg arm of the Crohn's disease trial, is there a potential to see any of the lymphopenia discontinuations that we saw in the Phase 2 atopic dermatitis study? And then the second question is on the -- a load of readout coming up in IBS pain. Is there any reason to expect there might be differences in results in IBS-C versus IBS-D?

Amit Munshi -- President & Chief Executive Officer

Hi Joel, thanks for your question. On the lymphopenia issue as you'll recall, at about 30 sites in the atopic derm study we had these discontinuations primarily at a single site, a single investigator accounted for a bulk of these patients there had been discontinuation. So we don't think this is a broader etrasimod issue. In fact across over 500 clinical sites across all the other programs we're not seeing any patterns even remotely consistent with that. So, I'd be careful not to extrapolate too much from predominantly a single site that at the beginning of the COVID pandemic.

As far as 3 mg, we know that it drives about 12% to 13% additional lymphocyte decreases from our healthy volunteers study, from our Phase 1 study and we don't think that will get disproportion of patients into a grade for lymphopenia recall that the discontinuations again predominate a single site, were at a grade 3 lymphopenia which was a protocol violation. So again, we're not seeing grade 4 lymphopenias at 2 mg and with a nominal change in lymphocyte reductions from 2 mg to 3 mg we don't expect to see much there either. So again, we can see in our healthy volunteer study and we don't expect to see this as a systematic issue across the trials.

And sorry Joel, could you repeat your second question please?

Joel Beatty -- Citi Investment Research -- Analyst

Yes, thanks for those details. And then the other question was on olorinab and any differences to expect from IBS-C versus IBS-D?

Amit Munshi -- President & Chief Executive Officer

Yes, so IBS-D has historically been on the AEPS scale and where you see placebo just at about 1 point change across all the major programs, somewhere in that range. On the IBS-C setting you see something in the 0.5 to 0.8 change compared to placement in the IBS-D. So you do see what seems to be directionally slightly more difficult to treat populations. So, we'll see how the data plays out. I think the big difference is most of the other programs that have been tried in the pain setting have predominantly been used to impact motility and then the pain is a secondary component. Here pain is the primary component. It is the number one reason these patient fear gastroenterologists accounts for 70% of gastroenterology that this has to do with abdominal pain.

So thinking about pain first here, we think will result in slightly different approach as opposed to thinking about the motility benefits first and then pain secondarily. But we'll see that when we see the data. But we do expect those patient populations to be different. They have reacted differently in previous clinical programs.

Joel Beatty -- Citi Investment Research -- Analyst

Great, thank you.

Amit Munshi -- President & Chief Executive Officer

Thanks, Joel.

Operator

Your next question comes from the line of Yatin Suneja from Guggenheim Partners. Your line is open.

Yatin Suneja -- Guggenheim Securities, LLC -- Analyst

Hey guys, thank you for talking my questions, two from me. First on the CR formulation can you give us an update where you are with regard to the AD study are you going to take CR formulation in AD? And then on olorinab side, I think in the Phase 2a there was not a clear dose response, but there was a very nice PK dependent response after each dose. So just trying to get a sense of what level of receptor occupancy you need to achieve at what dose you think you could achieve that effect in this bigger study? Thank you.

Amit Munshi -- President & Chief Executive Officer

Thanks, Yat, and thanks for the questions. On the CR we're continuing our work on the CR formulation, manufacturing stability, additional studies that have to get done. As we've said previously, we expect to bridge into the atopic derm study. It will not be ready for the beginning of the atopic derm study, but we'll be able to bridge into the Phase 3 and that's our current plan and working assumptions and as we're working toward it. On the olorinab Phase 2a study, we knew that the 25 mg arm achieved sufficient receptor coverage and then for safety we took up 200 mg arm and we didn't see a difference in 25 and 100 as you pointed out. For the Phase 2b we took one dose below the 25 and one dose 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 that was the idea coming out of the Phase 2a study.

Yatin Suneja -- Guggenheim Securities, LLC -- Analyst

Got it, thank you.

Amit Munshi -- President & Chief Executive Officer

Thanks.

Operator

Your next question comes from the line of Joseph Springer from Needham and Company. Your line is open.

Joseph Stringer -- Joseph Stringer -- Analyst

Hi guys, thanks for taking our questions and congrats on the progress. So the Phase 2 alopecia readout later this year, can you help kind of frame expectations around the date of readout and what's considered a clinically meaningful SALT score and perhaps tie that into the responder analysis on the secondary endpoints? Thanks.

Amit Munshi -- President & Chief Executive Officer

Sure yes. So as you know, there are different types of alopecia areata and you move toward universalis and totalis and different types of alopecia. So we'll be, it will be mixed bag of patients in this small Phase 2a exploratory trial. We'll be looking for a 20%, 30% 40% improvement and we think those are meaningful improvements on the overall SALT scores across these different patient populations. Again, the objective of the Phase 2a and from Phase 2b program and helped us understand which patients are more likely to respond and have a benefit with etrasimod.

So, that's kind of what we'll be looking at. Again categorically percentage of patients that achieve SALT 50 would be a meaningful or SALT 30 would be a meaningful result. Now, just like we did with the Phase 2a study on olorinab, let's be cautious in over interpreting small Phase 2a studies. They're designed to really help us inform the next clinical step in the program, and help us identify the right patients to move forward with.

So again, we think the biology is extremely intriguing. We know that CD4/CD8 positive lymphocytes or cytotoxic follicular hair fall level we know they traveled there on the S1P1 gradient which is [indecipherable] and so we can clearly see that we're -- it's an on target mechanism and now we'd like to see a clinical response across different subsets of these patients, so we can begin to educate ourselves on where to go forward on our Phase 2b program. So excited to see that data and again, we'll be looking for changing that SALT score, compared to placebo and it will differ by the subsets of patients we'll be looking at.

Operator

Next question comes from the line of Jason Gerberry from Bank of America. Your line is open.

Unidentified Participant

Oh hi, good afternoon. This is [indecipherable] for Jason. Thanks for taking our questions. Two questions, first one on Crohn's. Maybe just to follow on your expectations, I think people are inherently going to do cross cultural [Phonetic] comparison versus ozanimod Phase 2 data, which is also an open label. Can you talk about your expectation, you are looking for something comparable to ozanimod or are you looking for something potentially better in the, from Phase 2 readout?

And then second question on etrasimod controlled release, if you do end up seeing a stronger signal with this 3 mg, would you be able to formulate the CR formulation for both the 2 mg and the 3 mg dose? Thanks.

Amit Munshi -- President & Chief Executive Officer

Suchi [Phonetic] thanks for your questions. On the Crohn's given the broad range of inherent advantages we have over etrasimod from faster onset, the faster offset, and no titration schedule to seeing single digit heart rate changes, but the absence of the 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 Crohn's study being able to see an effect that's commensurate with those ozanimod would be a great outcome for us. Naturally with 2 and 3 mg, we'd like to see potentially 3 mg show an increase of 2 mg and we will see a dose response. So, I think if we saw those things. I think we can call that a very successful win in that program.

The CR formulation, absolutely we're starting with the 2 mg, but once we're at that place where we can begin to confidently replicate what we saw in the original studies into actual tablets and into human clinical studies taking that from 2 to 3 mg is definitely in the plan. And again, we want to see that 2 and 3 mg dose response in the Crohn's before we make that call. There's no point in spending a bunch of money making a 3 mg CR formulation if we're at some kind of plateau effect between 2 and 3 mg.

So, we're going to let the data lead us there. Again, we'll be looking at 3 milligrams not only in Crohn's, but potentially in our atopic derm work as well and as a consequence will have multiple data points in which to inform, whether we take the CR to 3 mg, but it is actually feasible. There's nothing technically not feasible about doing that.

Unidentified Participant

Got it, thank you.

Operator

Your next question comes from the line of Joseph Schwartz from SVB Leerink. Your line is open.

Joseph Schwartz -- SVB Leerink -- Analyst

All right, thanks very much. A couple of questions on the ELEVATE studies. I believe you've said that the baseline characteristics in these studies are fairly similar to those who you enrolled in OASIS with maybe a slight skew toward 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 experience patients who might be more motivated. Can you speak to that apparent paradox and maybe talk about the sites that have enrolled the most patients and how they might compare to those who were involved in OASIS in terms of anything like geography, experience with IBD trials or any other aspects that might influence the results?

Amit Munshi -- President & Chief Executive Officer

Sure thanks, Joe. The baseline characteristics we haven't disclosed as being similar to OASIS. What we've disclosed is that the inclusion criteria were similar to OASIS and had been across most of the Phase 2 trials 2 and 3 trials done in the contemporary patient population. The only baseline characteristics which we provided is this, 70/30 kind of range and as you'll note ozanimod had about the same, albeit 6 or 12 months before us.

So, pandemic notwithstanding, when you run programs, small Phase 2 programs which are predominantly U.S., maybe some European sites, Western and Eastern European sites, and you get to what we saw which is a 60/40 split 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 ozanimod might end up with the exact same split we did.

So, we don't think that's much of a paradox. 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 UC patients have never received a biological and advanced therapy. So that's pretty consistent with what we think the contemporary market looks like in that 65% to 70% range. We think that's consistent.

In terms of site selection, there is just a handful of sites around the world, handful is probably the wrong word there, but there is a finite subset of sites around the world that can effectively run these studies. And one of the challenges has been historically that everyone's in the same sites, we're in the same study. So we're really pleased to be able to be in those sites, experienced sites around the world using CROs and have conducted many of the other Phase 3 investigations in the ulcerative colitis space, and still be able to maintain enrollment timelines. As you know, the endoscopies are locally conducted, but centrally read. And that's a critical quality assurance metric across all of these programs

So we feel good about the site selection. We feel good about the inclusion criteria, half of 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 a pretty contemporary patient population that's again supported by the market research we've conducted over the last couple of years.

Joseph Schwartz -- SVB Leerink -- Analyst

Okay, great. That's really helpful, thanks. And then, I know you continue to monitor the impact of potential resurgence in this pandemic. So I was just wondering if you could give us an updated assessment of how it's impacted data collection so far in terms of any color commentary around discontinuations or the transition of patients from the induction to the maintenance phase of your seamless study?

Amit Munshi -- President & Chief Executive Officer

Yes, I think all we've shared publicly is that the discontinuation rates, interruptions, and all the other pre-planned parameters that we track on an ongoing basis, all of those metrics are below our pre-planned statistical expectations. So for example, discontinuations and interruptions are well below our pre-planned statistical expectations. Patients moving from 12 to the longer studies, patients kind of moving forward, again those are at or above our pre-planned statistical expectations across the board. So we're monitoring this incredibly carefully in terms of study conducted from day one was our primary area of worry and we've got, we're watching as we have been since the beginning of the pandemic, every patient, every site, every country, every day.

Joseph Schwartz -- SVB Leerink -- Analyst

Thanks again, keep up the good work.

Amit Munshi -- President & Chief Executive Officer

Thanks Joe, I appreciate it.

Operator

Your next question comes from the line of Jessica Fye from JPMorgan. Your line is open.

Unidentified Participant

Hi guys, this is Danielle for Jessica Fye, thanks for taking your questions. In this scenario where you see no greater than 2 point placebo corrective signal on APS in one group, either IBS-C or IBS-D. What does it mean in terms of your plans to advance the program forward, would you still take the product in both populations?

Amit Munshi -- President & Chief Executive Officer

Yes, it depends on what we see in the IBS-D right? Like I said, the bar is much lower in the IBS-D setting. Most products are well below 1 point corrected change, the placebo corrected change. So seeing something worth of 1 in the D space is very remarkable, seeing something more at the 1.5 and in the C space is quite substantial. So, again they both, I mean the previous question was asked around the same area which is the threshold is a little different, mostly. So, let's take a look at the data and make a judgment call about, where we go next and how we evaluate the program, since it's premature until we see the data to be able to really understand where we go next. We can hypothesize around, is 1 good, is 1.5 good, but again the barn, we can say unequivocally the barn IBS-D is much lower. And so it doesn't have to be two across the board.

Unidentified Participant

Okay. Thank you.

Amit Munshi -- President & Chief Executive Officer

Yes, thanks, Danielle.

Operator

Your next question comes from the line of Patrick Trucchio from H.C. Wainwright. Your line is open.

Patrick Trucchio -- H.C. Wainwright -- Analyst

Thanks, good afternoon. First, can you give us an update on the status of the GLADIATOR study, were the mild to moderate UC and how this trial is overall, how important this trial is overall in positioning of etrasimod in what's becoming increasingly competitive UC market?

Amit Munshi -- President & Chief Executive Officer

I really appreciate it. Great question on GLADIATOR and thanks for bringing it up. It's one of our favorite topics. The GLADIATOR program as you'll recall was designed to be more of a modern patient population. Patients who might not otherwise qualify for ELEVATE 12 or 52. And so the GLADIATOR program is up and running site to be initiated. We will continue to provide progress updates. As you know, we don't provide enrollment updates, but we'll continue to provide broad progress updates on the program.

It has being run at an overlap subset of the sites that are running 12 and 52, so as the 52 study moves over to 12, and the 12 study continues to enroll and patients don't qualify for 12, 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 despite the broad penetration of biologics, two out of three moderate-to-severe patients still haven't received an advanced therapy and they tend to be more on the moderate population.

So they're not captured in the clinical studies. These are patients with significant risk of bleeding still frequency. They have active ulceration on endoscopy, but not severe enough to actually qualify for the clinical study. So those are the patients that we'd be going after with GLADIATOR. The market essentially doubles, with a 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 desire to make etrasimod the standard of care and also the colitis.

Patrick Trucchio -- H.C. Wainwright -- Analyst

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 therapeutic area of focus and potential collaboration, specifically with the three areas of GI, derm and cardio building out. I'm wondering if there's a preference on which of these areas make sense to keep within Arena's control versus collaborating on, and how we should think about potential commercial collaborations of various compounds in development.

Amit Munshi -- President & Chief Executive Officer

Yes, that's a great question too. I would say that one of the things advantages we have is that, this is a staggered build. UC comes first, then we start entering into dermatology, with some additional GI indications coming after that, including Crohn's and EoE; and then, we enter cardiology into Phase 3. So not all these programs are running at the same pace, they are the cardiovascular indications are just initiating Phase 2 now. So, they will be in Phase 3 in total where a lot of phase three these other indications. So it's not a fair assumption to make, that we're going to have to make portfolio choices today. We'll definitely be in a situation, we'll have to make portfolio choices in the future, potentially, and if things go as we hope and anticipate then building out cardiovascular, we think will be an important leg of the stool long term. So it gives us an important consideration in terms of the five to 10-year footprint of the company, and that's beyond the scope of most of the investors you guys talk to, but we're thinking in that time horizon about how to build a company and if you really want to build a company having single assets that have binary outcomes or are not the right way to go.

You want to have a broad and diverse portfolio, you want to be in multiple therapeutic areas, where you think there's provocative unmet medical need, where you think you've got key competitive advantages, and that you can actually execute by yourself and we think we can execute each of these therapeutic areas by ourselves and that's a big consideration before we go into an area.

As you know, we licensed out our PAH asset to United Therapeutics, that's a highly specialized area and United Therapeutics has incredible skills and breadth and scope of knowledge, with that physician community and that patient population and we felt that product was better in the hands of a partner. We recently spun out our Arena Neuroscience, now called Longboard Therapeutics [Phonetic] and Longboard Biopharmaceuticals [Phonetic] and that's again a therapeutic area that we chose not to be into directly. And we thought it required a different level of focus and we were able to spin that out. So we've continued 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.

Patrick Trucchio -- H.C. Wainwright -- Analyst

Yes, that's helpful. Thank you very much.

Amit Munshi -- President & Chief Executive Officer

Yes, thanks Pat.

Operator

Your next question comes from the line of Chris Howerton from Jefferies. Your line is open.

Chris Howerton -- Jefferies -- Analyst

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? And then the second question, I was actually just reviewing your transcript from the JPMorgan 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 if you could give us a couple of highlights from that report this year?

Amit Munshi -- President & Chief Executive Officer

Sure. So, let me take me take the ESG and then I will hand it out to Laurie to talk about cash runway. On the ESG side, we issued a 2020 ESG report last year and so feel free to peruse 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 are Long shareholders. We have a considerable amount of European shareholders and we take their concerns very seriously.

So we started on this process two years ago, in terms of understanding what it means for a smaller company like ourselves to be highly engaged and active in managing our broader footprint, our environmental, social and governance footprint. And we've made critical improvements based on that feedback between 2020 and 2021. We'll be issuing our 2021 report later this year.

So you'll be able to read a second report. So we're extremely excited by that. We have set the governance up to the board, we are always side up to the board level. We've got an internal executive level sponsorship on this. 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 and we think that's important for building a sustainable vibrant company.

Laurie, do you want to take the cash runway question?

Laurie Stelzer -- Executive Vice President & Chief Financial Officer

Sure, sure, absolutely. Yes, so we ended the year with $1.1 billion in cash. We landed our operating burn as we had predicted at about $353 million. We haven't guided yet for 2021, but as you can imagine, our expenses are continuing to grow. We are in a number of Phase 3 programs and we're looking out to the planning of the AD program as well as progressing the pipeline. So it's a more complicated picture than just a straight calc on cash burn, but certainly we have cash to get us to that commercialization point.

Chris Howerton -- Jefferies -- Analyst

Okay, all right. Well, like I said, I think most of the questions have been asked already. I really appreciate you taking them. And Amit, for what it's worth, I think you're building a great company and the ESG report, I look forward to reviewing it and seeing just that.

Amit Munshi -- President & Chief Executive Officer

Cool, welcome your feedback. Thanks so much.

Operator

Your next question comes from the line of David Hoang from SMBC. Your line is open.

David Hoang -- SMBC -- Analyst

Hey, guys, thanks for taking the question and fitting me in. Just had a couple. A lot obviously has been addressed by the prior questions, but maybe a follow up on the UC GLADIATOR study. Yes, I mean, you talked about whether this could be a registrational in terms of putting forth an approval in the mild-to-moderate population. And then on timing there, do you think that you might be first to market given there are a few Phase 2 oral assets, also looking at the mild-to-moderate space?

Amit Munshi -- President & Chief Executive Officer

Yes. So is this by itself a pivotal study? That's a conversation we'll have to have with the agency. No one has generated a broad data set here. We've seen smaller studies generate some anecdotal information I'll call it, but in terms of running a large scale, multi-center global clinical investigation in the same scale and scope as ELEVATE, no one has done that. So we think we've got at least the opportunity to have this be a single pivotal and question is we will need a second pivotal, if we were going to make it a registration trial. I think more importantly, we spent a lot of time with the peer community. We've probably had about two dozen meetings with key peers around the country.

We've taken their input into the design of the GLADIATOR program and that's been a big driver of generating this information. Not only does it double the eligible population in this space, but it begins to create a provocative case for the payers to have a preferred position for etrasimod. So we think it's important from multiple points of view. And I don't see anybody else running large scale global Phase 3 equivalent type trials, like we are running with GLADIATOR. So I think we are at or near the forefront of exploring this population.

David Hoang -- SMBC -- Analyst

Okay, great. And then I just wanted to touch on the cardiovascular assets. I know the readouts are still a little ways off, but we're just wondering if you would be able to maybe preview, the design and endpoints for APD418, as well as the new asset, temanogrel?

Amit Munshi -- President & Chief Executive Officer

Sure, so temanogrel both have Fast Track designation, and we're moving both into Phase 2. Just to recap, temanogrel, we're taking the microvascular obstruction, we'll be looking at a subset of patients, we'll be looking at patients, and we'll be looking at actual resistances as measured quantitatively, distal to the site of the occlusion and in those patients. And so, that's really design of the study. It will be an international cath lab. And then similarly, in the APD418 space, those will also be in an international cath lab, with this quantitative set of metrics as we can possibly develop in that setting.

Again, we're trying to look for real clear measures there of cardiac output and ejection fraction, and no change in hemodynamics. So we'll be able to do that again in a controlled setting. So both those studies are really designed as 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 are in the '22 timeframe?

David Hoang -- SMBC -- Analyst

Okay, thanks so much for taking the questions and congrats on the continued progress.

Amit Munshi -- President & Chief Executive Officer

Yes, thank you so much.

Operator

Your next question comes from the line of Prakhar Agrawal from Jones trading. Your line is open.

Prakhar Agrawal -- Jones trading -- Analyst

Hi, thanks for taking my questions and congrats on all the progress. I had a couple on EoE, what doses are you testing in the Phase 2 ADVISE trial? And what's the bar for success for etrasimod here in terms of reduction in eosinophilic count, relative to what has been shown by some of the injectables such as Dupixent? Thank you.

Amit Munshi -- President & Chief Executive Officer

Yes, thanks. So we'd love to see efficacy in the same range. Biologically, from what we've done animal experiments we don't see any reason that etrasimod would be substantially worse than the biologics? And with the advantage of it once a day overall we think that's quite meaningful. And of course eosinophilic esophagitis opens up the door to other eosinophilic GI conditions for us to explore over time. So we think it's incredibly exciting and supported by the biology we have done to date. And we'll be exploring 1 mg and 2 mg in etrasimod study. And there is a Phase 2b study. So it should yield sufficient amount of information to be able to move forward into a registration trial from there?

Operator

Your next question comes from the line of Jim Birchenough from Wells Fargo Securities. Your line is open.

Unidentified Participant

Hi, thanks for taking our questions. This is Yananjiu [Phonetic] on for Jim. So first, the question on the ELEVATE 52 trial design, this trial has a treat through design. And it's different from the typical induction, then rerandomization then maintenance type of UC trial design. So I was just wondering, because with the typical historian or traditional design, they typically add more patients at the rerandomization step, just to make up for the loss of non-responders.

And certainly, by definition, their maintenance sections, maintenance phase of the study starts with all patients being responders. And how, with your Treat-through design, I was 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? Thanks.

Amit Munshi -- President & Chief Executive Officer

Yes, thanks. The reason we did the Treat-through design after consultation with both U.S. and European regulatory authorities, is that it more closely mimics real life, right? In the real in the real world you don't start rerandomizing responders and seeing drop offs and adding more patients and over enriching your population for your maintenances. Patients who do well on the drug stay on the drug for an extended period of time. It's also important to remember the historical context, the Treat-through re randomization dichotomy really goes back to the early biologics that had a different dose for induction versus maintenance.

So what you had to do is, you had to induce a remission in the case of Infliximab at a higher dose 5 to 10 mg/kg and then reduced down to 3 mg/kg. And that's why that study design originally came to bear. You're right, it does require to maintain the same powering requires more patients. You have more drop offs and you have about a six to nine months delay in the middle as patients get rerandomized.

So the treating design is just more efficient all the way around. We can achieve the same powering with a smaller subset of patients with less dropouts and importantly, not lose six to nine months in the middle. So it's a more streamlined trial design. And 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 looks like in terms of maintenance and we think that's going to be a competitive advantage.

Unidentified Participant

Got it, that's very helpful. And then a couple of questions on the AD side of the AD program. Obviously, at 1 mg you have a like a 30%, lymphocyte reduction, and two mg, maybe you might have, you know, a 13% incremental reduction. And this is a first in class study for the S1 key mechanism in AD. Is it surprising for you that 1 mg or 30% lymphocyte reduction on average didn't result in an 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 you want to explore higher doses, while you increase the dose and trying to maintain the same efficacy profile, does it make sense to have kind of a personalized dozing, guided by the peripheral lymphocytes reduction? Thanks

Amit Munshi -- President & Chief Executive Officer

Yes. So let me start with a debunking a preconceived notion. Lymphocyte reductions are 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 Keratinocytes. So to over fixate on lymphocyte counts is incorrect, just in general. And it's something that just is something we continue to spend time educating investors on. We know from historical analysis that lymphocyte counts across all trials, all drugs in the same category really only account for about 50% of the effect size.

So there's multimodal activity, for example, S1P1 plays a critical role in cell-to-cell junctional barriers and being able to close. Cell-to-cell junctional proteins and we know S1PQ of target activities we've seen with competitive products, open cell-to-cell junctional protein. So it's important to remember that just focusing on lymphocyte counts by themselves is probably over reading a PD marker in terms of what's going on.

We also know that different therapeutic areas require different doses across all the different trials. The most recent data with the JAK inhibitors, for example, use a threefold higher dose for the ulcerative colitis trial than they did in their rheumatology trials. Abrocitinib, for example is 7 and 15 mg and now they are up to 45 mg and they push those high doses in the AD trials as well. So there's a broad range of dosing based on the indications you go after. And your points a great one, which is yes, we're the first ones to go into atopic derma the S1P modulator. And the key, one of the key lessons learned is, we probably need to have more drug on board in the dermatologic settings, specifically atopic derm as we think about these indications, and that's nothing new. We know that different indications, different autoimmune conditions, we have two different doses with different drugs. And that's been consistent going all the way back to the early anti-TNF dose.

Unidentified Participant

Got it, very helpful. Thank you.

Amit Munshi -- President & Chief Executive Officer

Thank you.

Operator

There are no more questions at this time, turning the call back over to Mr. Amit Munshi, President and CEO.

Amit Munshi -- President & Chief Executive Officer

Great. Hey, thanks everybody, for joining our call today. I hope everyone is staying safe. 2020 was a difficult year; I just want to really call out our team, at Arena for their focus and their resiliency and the energy to get things done. It was a Herculean effort and we continue to drive that momentum forward into 2021. We look forward to staying in touch with everybody as we continue to drive on the key catalysts over the next 12 months. So, thanks, again. And look forward to talking soon.

Operator

[Operator Closing Remarks]

Duration: 51 minutes

Call participants:

Patrick Malloy -- Vice President, Investor Relations & Corporate Communications

Amit Munshi -- President & Chief Executive Officer

Laurie Stelzer -- Executive Vice President & Chief Financial Officer

Alethia Young -- Cantor Fitzgerald -- Analyst

Martin Auster -- Credit Suisse -- Analyst

Kennen MacKay -- RBC Capital Markets -- Analyst

Joel Beatty -- Citi Investment Research -- Analyst

Yatin Suneja -- Guggenheim Securities, LLC -- Analyst

Joseph Stringer -- Joseph Stringer -- Analyst

Unidentified Participant

Joseph Schwartz -- SVB Leerink -- Analyst

Patrick Trucchio -- H.C. Wainwright -- Analyst

Chris Howerton -- Jefferies -- Analyst

David Hoang -- SMBC -- Analyst

Prakhar Agrawal -- Jones trading -- Analyst

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