Evelo Biosciences Inc (EVLO) 2021 Q1 法說會逐字稿

Good morning, and welcome to Evelo Biosciences' conference call to discuss the first quarter 2021 financial results and business highlights. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

At this time, I'd like to turn the call over to Jessica Cotrone of Evelo. Please proceed.

Thank you. This morning, we issued the press release that outlines the topics we plan to discuss today. This release is available at www.evelobio.com under the Investors' tab. Today in our call, we have Simba Gill, Chief Executive Officer; Mark Bodmer, President of R&D and Chief Scientific Officer; and Jonathan Zung, Chief Development Officer.

Before we begin, I would like to remind everyone that statements made during this conference call that do not relate to matters of historical facts, including statements about our objectives and anticipated clinical milestones, the impact of our product candidates and the timing and results of our clinical studies should be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. Actual results could differ materially from those indicated by the forward-looking statements due to the impact of many factors. Participants are directed to the risk factors set forth in Evelo's quarterly report on Form 10-Q for the 3 months ended March 31, 2021, and the company's other filings with the Securities and Exchange Commission. Any forward-looking statements made today speak only to Evelo's operations as of today. Evelo disclaims any duty to provide updates to its forward-looking statements even if subsequent events cause the company's views to change.

It is now my pleasure to pass the call over to Simba.

Thank you, Jessica. Good morning, everyone, and thanks for joining. 2021 is a pivotal year for us, and we've begun the year with continued strong execution. Together with our partners, we have successfully progressed our research and clinical plans despite the COVID-19 pandemic. And because of this, we remain on track to deliver multiple clinical readouts across psoriasis, atopic dermatitis and COVID-19 over the next few months. We also continue to advance our extracellular vesicle product candidates in oncology and inflammatory disease.

Mark's team in research and development continue to explore, enhance and expand the applications of SINTAX-based medicines, and he will give you an overall view of our drug platform in a moment. We have expanded Evelo's leadership appointing Luca Scavo as Chief Financial Officer. Luca starts with us on June 1. And Julie McHugh to our Board of Directors, effective immediately. Both Luca and Julie have deep and successful track records in building global organizations and commercializing blockbuster products across a wide array of indications.

We also announced a strategic collaboration with Abdul Latif Jameel Health to develop and commercialize EDP1815 in the Middle East, Turkey and Africa. The collaboration combines Evelo's leadership in biotech innovation and Abdul Latif Jameel's regional presence, reputation and expertise with the goal of accelerating the delivery of effective, affordable medicines to people in these high-growth markets. As we look forward, we continue to make strong progress in executing on our clinical strategy and plans, and Jonathan will tell you more about this later in the call.

With that, I will pass the call over to Mark.

Thank you, Simba. Over the last 18 months, a series of clinical and preclinical results have advanced our understanding of the small intestinal axis, SINTAX. Building Evelo's platform and portfolio started 5 years ago with a vision and strategy, which has remained constant. We proposed a way to make a new type of medicines, that are both innovative and affordable, and that are convenient to take orally and are safe and well tolerated.

This profile is quite different to other innovative medicines. The science enabling this is a novel way to control inflammation from within the gut, the gut restricted drugs that have effects throughout the body. The key to understanding our medicines is to look at the gut and the profound control exerted by the gut’s connections throughout the body. The question was how to make effective medicines to take advantage of this biology.

We realized that single microbes could be selected from the gut that behave like conventional drugs with desirable therapeutic effects. We can now also select extracellular vesicles for the same purpose. In preclinical studies, product candidates have properties and the profile that is differentiated from current types of drugs, hence, the claim that they have transformational potential to benefit the health and lives of so many people.

Three paradigms were challenged to make this new type of medicine. Firstly, immunology. That there is a control system for systemic immunity centered in the gut. This is not widely appreciated or understood. Second, pharmacology. That this control system can be targeted to make medicines that act at a distance from within the gut without entering the body. Thirdly, the microbiome. That there is an alternative way to think about making medicines based on the microbiome by selecting elements of the microbiota which can have direct pharmacological effects and work in non-live, non-colonizing forms. The ultimate expression of this are the discoveries about the pharmacology of extracellular vesicles. These are 3 big claims to make which are all supported by data that you've seen emerging piece by piece, initially preclinical and now clinical.

Let's recap the clinical picture of EDP1815. Five studies have shown anti-inflammatory effects with EDP1815, 2 cohorts of people with psoriasis, a cohort with atopic dermatitis to 2 groups of human volunteers in an experimental inflammation model. Each of these alone was a small study. Collectively, they show a consistency of effect, proof that a non-live single strain of bacteria can act at a distance from within the gut to control systemic inflammation. The 3 paradigms in immunology, pharmacology and the microbiome have been effectively challenged.

The range of clinical information that's been studied Th1, Th2 and Th17 pathways supports the Goldilocks effect, so called broad resolution of inflammation without over immunosuppression. And around 300 patients have taken EDP1815 for between 4 and 16 weeks in several diseases including hospitalized patients with COVID-19, and EDP1815 continues to be well tolerated. EDP 1815 is a unique asset in the pharma world. It has an increasing probability of success to become a major medicine. A year ago, it seemed a possible outcome, the data now suggests that it's a likely one.

Two more things are worth reflecting on. First, a reminder of extensive range of preclinical data. EDP1815 has been compared with the best standard of care drugs in mouse models of all 3 major forms of inflammation, where it's been shown to have clinical activity, Th1, Th2 and Th17. In every case, EDP1815 and other emerging drug candidates in our pipeline are comparable to, for instance, tofacitinib, fingolimod and dexamethasone. These are amongst the most potent, small molecule anti-inflammatories, all of which are effective, but dose limited by toxicity, which does not appear to be an issue for EDP1815.

It's hard to see any of these classes of drugs being used routinely across the full spectrum of inflammatory disease severity. EDP1815 and EDP1867 also compare favorably to mass equivalents of anti-IL-17 and anti-IL-4 biologics. Again, it's hard to see these in routine use and very large numbers of patients given their costs and route of administration. These are remarkable broad and consistent effects of EDP1815, one drug that potentially can match all of these comparators with safety, convenience and affordability.

Finally, new data has been generated about how our SINTAX drugs work. The mechanisms by which a gut restricted medicine can have systemic effects. We've identified the biological exchange mechanism, the contact point where immune cells in the gut would see our drugs transfer information to immune cells in the periphery, which have the therapeutic effect. This exchange takes place in the lymph nodes of the gut, which are the place where the gut and peripheral immunity meet. The ability of the immune cells to traffic through those lymph nodes that link the gut to the rest of the body can be blocked by administering antibodies to receptors that are required for the cellular trafficking.

When this is done in combination with EDP1815, then EDP1815 does not exert its effects in the periphery. This inhibition has also been shown for EDP1867, the second anti-inflammatory microbe that has just started in the clinic and for EDP2939, the anti-inflammatory EV. It's a general property of anti-inflammatory SINTAX medicines. This is a formal proof of mechanism, which explains this new pharmacology. It's the linchpin to understanding that there’s a defined system and cellular basis for this newly discovered biology. This has all come a long way quickly improving what initially seemed an unreasonable idea.

Simba and I have early history together from the mid-1980s in some of the very first therapeutic antibody projects. Conventional wisdom was that antibodies could not possibly be drugs. They would work. They would be tolerated. They couldn't be made at scale. We know how that turned out. [With lymphoma] experience to build the Evelo platform for EDP1815 and all of the other candidate products in our pipeline for inflammation and oncology. Continuing research investment in formulation and extracellular vesicles will allow us to maximize their effects in patients. Continuing investment in manufacturing at scale and low cost of goods will enable us to make these new medicines widely available and affordable.

Now over to Jonathan.

Thank you, Mark, and good morning, everyone. As Simba shared, we'll have readouts from several clinical studies in the second half of this year. We remain on track to report top line data for the full cohort of study participants in our Phase II dose ranging trial in psoriasis in the third quarter. As a reminder, this is a 16-week trial evaluating 3 doses of EDP1815 in capsules versus placebo in approximately 225 patients with mild to moderate psoriasis. The primary endpoint is the mean percentage change in PASI score at 16 weeks.

Secondary endpoints include a number of physician and patient reported outcomes across different measures of clinical efficacy. Our Phase Ib trial evaluating tablet and capsule dosage forms using the higher concentration of EDP1815 drug substance is underway in 3 cohorts of patients, 2 with capsules and one with tablets. The purpose of these 3 cohorts is to select the most appropriate doses form, either capsule or tablet for our Phase III programs. Initial results from these 3 cohorts are anticipated in the third quarter along with data from the Phase II psoriasis study together this information will position us to go forward into Phase III trials with an optimized dose and dosage form of EDP1815.

Moving on to EDP1815 in atopic dermatitis. We're planning to initiate the Phase II atopic dermatitis trial in the third quarter of this year. This will be a double-blind, placebo-controlled trial in participants with mild, moderate and severe atopic dermatitis. The trial we've conducted in North America and Europe. Our Phase Ib trial of EDP1867, evaluating safety and tolerability in healthy volunteers and patients with moderate atopic dermatitis is ongoing and progressing according to schedule.

Dosing in the healthy volunteers is underway and we will begin dosing of participants with moderate atopic dermatitis later this quarter.

The moderate atopic dermatitis cohort will be dosed daily for 56 days with a 14-day follow-up. We will report results from this study in the fourth quarter. Just a reminder that EDP1867 is from a different genus to EDP1815 and has been rendered non-live by gamma irradiation. EDP1867 has demonstrated robust anti-inflammatory activity in preclinical models of Th2 biology. By testing it in patients with atopic dermatitis, we will learn about its potential in treating Th2 mediated diseases.

Our 2 COVID studies are ongoing. The first study TACTIC-E is a randomized parallel arm open label adaptive platform Phase II-III trial of potential disease modifying therapies in patients with COVID-19 related diseases. It is sponsored by Cambridge University Hospitals in the U.K. with joint funding and drug supply by Evelo and AstraZeneca. The planned review of interim data after the first 90 subjects enrolled, including 30 subjects treated with EDP1815, was conducted by the Independent Data Monitoring Committee in accordance with the protocol. No safety issues for EDP1815 were identified. The trial has therefore proceeded with continued recruitment. The next review of safety and efficacy data will be after approximately 125 subjects have been enrolled into the EDP1815 arm.

The primary outcome measure is the incidence of any one of death, invasive mechanical ventilation, ECMO, cardiovascular organ support or renal failure. We've recently opened additional sites in Mexico, Brazil and India, where hospitalizations continue to increase in order to increase enrollment. The second COVID study is being conducted at Rutgers Robert Wood Johnson University Hospital. This study has evaluated EDP1815 in adult patients newly hospitalized and on oxygen due to the COVID-19 infection. Patients are equally randomized to receive EDP1815 plus standard of care or placebo, plus standard of care for 14 days. The primary outcome is change from baseline to the lowest ratio peripheral blood oxygen saturation, for fraction of Inspired oxygen measured up to day 14.

Secondary outcome measures include overall survival, WHO COVID ordinal scale score, duration of hospital stay, duration of oxygen therapy and time to clinical improvement. While we continue to recruit patients in both trials during the quarter due to the increase in vaccination rates and the lowered number of patients hospitalized with COVID-19, we expect both trials will take longer than originally planned. Because we do not know when we will be able to report data from these trials, we will no longer provide guidance on timing for data readouts for either trial.

Now I'll hand it back to Simba for closing remarks.

Thank you, Jonathan. We are at an exciting inflection point for Evelo, and have a catalyst rich few months ahead of us with multiple clinical readouts as we head towards later stage development. I would like to conclude by thanking the team at Evelo and our partners. Passion and commitment makes all of this possible. With that I will now open the call for questions.

(Operator Instructions) And our first question comes from Roger Song with Jefferies.

Can you guys hear me?

Yes, loud and clear, Roger.

The first question is related to 1815 Phase II atopic dermatitis. Understanding you are planning to initiate a trial in the third quarter. I'm just curious, what are the steps to prepare the initiation and specifically, what are the expected endpoints potentially different from the current approved drug in the mild to moderate patient population, which we know are mostly topical?

Thanks, Roger. I appreciate the questions, Roger. So let me say a few words and I'll let Jonathan expand on the endpoint. So in terms of steps, as you know, we brought Jonathan on board is our Chief Development Officer. It feels like a lifetime and it feels like yesterday as well. And Jonathan's just been a fantastic addition to the leadership team and on Jonathan's leadership, we've really built out clinical development capabilities together with our CRO partners. So we're very well prepared already in terms of blocking and tackling late to the Phase II in terms of site identification, et cetera.

So all of the fundamental operational things are very much in hand. Obviously, the other key thing is drug supply and everything around tech ops and manufacturing. Chun Zhang, Head of Tech Ops, for us is a magician and is constantly able to deliver what we need and again we're very much in a great position. So I think we're -- would just moving forward on plan and should be in a great position to start in that context.

For your second question in terms of what are the endpoints and what are we looking for, I'll let Jonathan talk to some of the technical points of that, but just to frame the unmet need and the market situation. As you suggested Roger, atopic dermatitis essentially moderate and mild patients has no meaningful oral safe drugs.

And so patients are limited to using topicals. You've heard us talk Paul, Roger about the fact that whilst topicals have a role, and we expect always will have a role in treating patients with moderate and milder forms of dermatological disease. There is a huge desire on the product patients and clinicians to have oral therapies. As you know, Roger, you see the benefit of oral therapies on the psoriasis side in moderate disease, where it has just rocketed to a multi-billion dollar product, just because it's intuitive.

Obviously, patients want an oral tablet or capsule versus having to lather creams on to their bodies every day. So it's a wide-open space. The last meaningful topicals get approved was crisaborole, Eucrisa. And we certainly expect to have a very competitive product versus your Eucrisa or crisaborole or indeed any of the other topicals. But the point is, what will be the key oral, safe, effective and affordable medicines in the atopic dermatitis space. So we're very excited about that, Roger and really see a very clear path for us having the key defining oral product in the whole atopic dermatitis space. I'll let Jonathan pick up on the technical points about the endpoint.

Sure. Thanks, Tim. And Roger, in terms of the endpoints, we're looking at the conventional endpoints. We'll be looking at change in EZ change in IG, we'll look at IGA and BSA. And then in addition, we'll be measuring a slew of patients and physician reported outcomes, including POEM, DLQI, SCORAD, things of that nature. So we'll be able to fully understand 1815.

Okay. Great. Okay. And maybe just my -- another question is for your -- you have 2 EV product candidates, 2339 and 19018 (sic) [2939 and 1908]. Knowing you will start an -- potentially start a clinical next year. So just curious to what are the steps into the IND filing, and given these are EV product versus the single strain, and live one and replicating products, what are the key differences versus the current pipeline products?

Yes, so let me answer your specific questions in a moment, Roger. If you just bear with me, I'm very happy you're raised EV, our extracellular vesicle program. So I just want to recap that aspect of what we're doing, because it's something we're incredibly excited about. So just to re-summarize I know you understand this, Roger, but I suspect others on the call may not. So EVs naturally produce microbial extracellular vesicles, which we have discovered can be delivered orally to drive very potent responses in oncology at the level that goes far beyond what we and others in academia and even other companies have seen in terms of oral delivery in oncology.

And given that we're taking forward our first EVs we absolutely are moving more towards the clinic, again I'll come back to the specific actions and things that need to happen in order to allow that in a moment, Roger. But our anticipation is that we have a real potential to have again the key foundational in orally delivered immune activating agent in the oncology world. And as you know Roger, there's 3 core pillars to the school of modern I-O therapy. Checkpoints have done a great job removing the brakes, that's largely solved.

Obviously, there's a range of new products including TRODELVY, which are doing important things in terms of increasing exposure of neo-antigen and antigen to the immune system. But the piece we haven't solved as a broad field, is how do we activate immune system in the most optimal way. People use the analogy of cars, so you can take the break off the car, and the car's still not going to go anywhere if you don't have fuel in the car and you don't hit the accelerator.

And so that's really the key missing piece in our view in immuno-oncology. How do we make sure the immune system is optimally activated? And the preclinical data that we presented at SITC in November, is quite remarkable. We are seeing results preclinically and relevant in vivo models, where we're activating systemic immunity at a level which is as strong as the best products that people have seen historically. But those other products delivered intratumorally and/or systemically and they typically come with significant side effects, tolerability issues. The results are in line with the type of things that people became very excited about with STING agonist, for example, a few years ago.

So the reasons why EV is more potent Mark may perhaps touch on later. But fundamentally, because they're so small, they're about 1,000th size of a microbe, they can penetrate through the mucus layer to get to the surface of the small intestinal wall much more efficiently with microbes. And given that, that allows them to be recognized much more efficiently, we believe than microbes. So that could well also in inflammation translate to even more potent activity than we've seen with 1815 or any of the other things we've worked on preclinically, and we don't know how far that could go. In the best case we could maybe get antibody like activity with EVs and inflammation, which obviously, Roger would be beyond transformative. So we're very excited about EVs. We'll get the data next year almost in inflammation and we'll go into the clinic, we expect with confidence in inflammation and in oncology. The steps are very much in line with what we just talked about, in atopic dermatitis.

As your question suggests that the challenge is to manufacture something which is never being manufactured for pharmaceutical use before. The fundamental first part of the process, is still to ferment and produce microbes, and then form the microbes. Essentially we have a process which is production of microbial extracellular vesicles and then those microbials extracellular vesicles are essentially through filtration isolated and then again converted in a very similar way to drug substance with the end product being a tablet or capsule containing the microbial extracellular vesicles. China again has tech ops as you've always done, it's done a great job on developing the microbial extracellular vesicle manufacturing process with the partners that tech transfer and scale up is underway.

We're already at a place where we're very confident that there is not going to be any unpredicted issues there and we to have to scale up and do the relevant tech transfer. It will take a little bit of time, Roger. So that's what we're going through right now, but it's already well underway. And then we obviously have to go through regulatory interactions and so on. Again, that's all anticipated for later this year. We're not anticipating any fundamental changes.

Again, these are very much linked to the microbes. We've already talked with regulators and other about it. So those are the fundamental on EVs. Hopefully that answered your question.

No, that's very helpful. Thanks for the answer and very informative background information. I believe it's very beneficial for the audience. Thank you for taking the question and then congrats for the program.

Thanks a lot, Roger.

Our next question comes from Matthew Luchini with BMO Capital.

Congrats on the progress. First, I guess in the context of 1815 in the upcoming psoriasis data. We're not -- you've spoken a lot over the past several months about Otezla as kind of being the best comp, but now we're in a post -- we've got the TYK2 data. Just wondering if you could share your views -- your latest view, latest thinking on the competitive landscape. And if you still view Otezla as the best or most relevant benchmark when that Phase IIb data comes out. And if so, why? And then I have a couple of follow-ups after that.

Yes. Good to hear your voice. So yes is the answer to your question and let me explain why. I mean, yes, we see Otezla as the key benchmark. Fundamentally, as you know, Matt, the psoriasis space is segmented from a conceptual perspective into terms of mild, moderate and severe patients. And we have always said, as an entry point, we want to tap into the moderate and milder forms of psoriasis, and then we’d expand over time into use in maintenance, potentially in more severe patients, potentially there’s even standalone use there and we’d expand in the other direction to very mild patients.

In the true moderate patients, obviously, the line between mild, moderate and severe are somewhat artificial. But true moderate patient population, which is millions of patients in the U.S. alone, we do not believe, in general, will be the target of TYK2 actually, and we don't believe there'll be significant uptake there. And the main reasons for that are, again, these are millions of patients. Ongoing question marks around the safety of JAKs and that includes TYK2s, the potential for black box warnings, et cetera. We don't know what's going to, obviously, be defined by regulators. But what we do know and everybody knows there's a history of serious side effects and safety and tolerability issues with the broad class. Dermatologists are extremely conservative in their prescribing practices. There's another situation where we're treating patients. You've got late stage cancer. And so safety and tolerability is absolutely key.

And that's also true for the patient. So we'll see what happens with TYK2, but we don't see them as a core competitor. We think they're going to be used primarily in the more severe moderate patients and in severe patients as opposed to the broad moderate class. So that then leaves us with Otezla as still the key oral drug. Otezla, by the way, still also is used, despite the fact that it's already clearly on the path to being multibillion dollar drug. It's only used in a small fraction of patients with moderate psoriasis.

So 2 things. We do think Otezla is the benchmark. It's established and has tolerability issues, depending on which numbers you look at around 10% and 20% of patients of serious GI tolerability issues with Otezla. But it's reasonably safe in the mind of dermatologists and patients and they're used to using it at some level right now. So we do think Otezla is the benchmark. But what I'd point out is the same comment I made about the TYK2s. Otezla has a tiny fraction of the moderate psoriasis patient population. That's true in the U.S. and it's even more true as one goes globally.

And as you know, Matt, one of my favorite points is we'll soon be 10 billion people on the planet of which only a tiny percentage will be in the U.S., and our strategy has always been to develop, manufacture and distribute to patients on a global basis. And we're able to do that, we believe, as we go forward because we can also produce on a very affordable basis and that's part of our anticipated pricing model. So we expect we're going to get dramatically higher uptake from a volume perspective than Otezla has done. So I wouldn't think of us as taking share away from Otezla. I think about it as creating a massive new market where there's huge unmet need for oral.

Okay. Great. That’s helpful. And on the Phase Ib, the formulation study, I guess, what do you expect to communicate and also in kind of what forum, meaning press release or medical conference for that data? And what in particular do you want us to be focusing on?

Yes. For the Phase Ib, as I expect, we'll release it through a press release, Matt. We'll probably release it as a combined integrated set of data because those Phase Ibs, as Jonathan mentioned, in an integrated manner aimed at helping us to find what's the best formulation, what's the best concentration, together with the Phase II, what is the best dose as we anticipate in moving towards Phase III studies. And so what we want to do is just look at all the different things across those parameter through the Phase Ib data together with the Phase II data. And so we expect we'll report it out, certainly the Phase Ibs in an integrated manner so that we can clearly communicate to everybody why we're choosing whatever it is we're choosing or moving forward towards Phase III type studies.

Great. And one last one before I get back in the queue. So with 1867 in atopic derm, you've got the Phase Ib come in 4Q. Assuming success there, just how should we be thinking about the development strategy between 1867 and 1815, specifically in atopic derm, given that obviously 1815 will be just starting at Phase II and in the third quarter. So I guess what's the sort of mid to long-term plan for these 2 products?

Yes, it's going to be data driven, Matt. We sometimes talk internally about the fact that a lot of people will sometimes ask us, what you do is they both look great? And the short answer is, we say, fantastic, what a wonderful position to be in. So we have to look at the data, Matt, and there's lots of different ways in which we can develop to the degree that both look good or one of them looks good, the other looks very good in atopic dermatitis. There's lots of different directions it can go, and we'll make that decision driven by the data. The one thing I'd emphasize, is that -- again, you know this, Matt, from our historical conversations, but we chose atopic dermatitis and psoriasis from our earlier strategic work as the key initial indications in inflammation for a number of reasons.

One is the point that I made late to your original question, which is the majority of patients who have moderate disease in psoriasis and atopic dermatitis do not take oral medicines today. That's true in the U.S. Again, it's even more true globally. So it's just a massive unmet need. So that was one reason. The second was, as we've demonstrated rapid path to clinical readouts and very informative clinical readouts. And you can literally see improvements in lesions -- you can straightforward things to look at. And then a rapid path for approval from about the stage we're at now. It's very rapid, predictable and we've got positive Phase II data. It's hard to -- you can see in the situation where we're not likely to get approval. So all of those things are particularly attractive. But the other reasons we went into psoriasis and atopic dermatitis that they are rapid ways to readout on the different types of T-cell driven inflammation, meaning cutting across Th17, Th1 Th2 together with the experimental model of inflammation, human delayed type hypersensitivity model we looked at.

So across atopic dermatitis, psoriasis and that human experimental model, we get insight into those different types of inflammatory disease. And again, depending on the data we generate, we can make decisions about where do we want to push one product versus another. But don't think about it in terms of just atopic dermatitis and psoriasis, Matt. As you know, we expect our product will have broad utility across all inflammatory diseases and indeed disease which have inflammation as a core underlying driver. So it's many different directions, in which we can go, and we'd love to have 2 products that are looking great. And as I said, it will be data driven.

Our next question comes from Matthew Harrison with Morgan Stanley.

I guess there are 2 from me. Just one question on COVID. Could you just maybe comment on what the statistical bar is at the 125 patient interim? I realize given the questions around enrollment, it's going to be hard to say when we might get that, but I'm just wondering what that is. And then I guess the second question is on some of the questions you've already gotten on psoriasis. And I guess the real question here is, you've talked about looking at Otezla, you've talked about TYK2 obviously in terms of the data. I guess maybe just a very specific question in terms of what do you think is the right cross trial comparison that people are going to look at? I realize there's issues with that but people are clearly going to do it. So maybe you could just give us your view on what you think is the right comparison as we think about the various data sets that are out there.

Yes. Thanks, Matt. So let me take the questions in reverse order. I'll let Jonathan take the COVID question in a moment. But on the comparisons of what people should be looking at, as you know, Matt, the AAD was last weekend. There was new data presented on Otezla in mild and moderate. And let me just lead with that, because interestingly, there wasn't any data presented on PASI scores. One can read whatever one wants to in that context. But that would be the normal thing that, what we'll be looking for is, what's the difference in PASI versus placebo.

In the latest data on a Otezla, they haven't reported out from that, which is interesting. But that would be one thing to look at. The other is PGA, where increasingly I think people are very focused on what percentage of patients have a zero, one with clear or nearly clear skin. And then the last is into the key indicator is I think increasing focus on patient reported outcomes and things like DQLI which integrates ETCH scores as well as CEIP scores. And I think those are the parameters and I think it's looking at those 3 different parameters and in an integrated way together obviously with the safety and tolerability, Matt.

And as I said, what -- we're intrigued with the fact that there hasn't been a readout on PASI from the latest Otezla data. There is a readout on PGA. So I think that would potentially put a little bit more emphasis on PGA. But we'll measure both. There is historical readout on Otezla in the Phase II, but we don't have it in the Phase III yet, I don't know if they'll release any more data soon. And then there has been readout on DLQI which people are used to looking at. So I think those will be the 3 major blocks. There's a series of additional things that people measure as you know when we'll measure as strong is that all of those different things. But it's going to be those 3 main blocks. Is that helpful answer?

Yes.

And then, Jonathan. Do you want to answer the COVID question?

Yes, I think that is the only thing I would add there and we're happy to take it offline to talk with you. I mean that the TACTIC-E study is being run in the U.K.. In terms of the full type of analysis we'll be looking at, it's the data that I mentioned early on in terms of progression rate, mortality, things of that nature. But we can go into that with you offline, if you want to know a little bit more about the statistics behind that.

Our next question comes from Joe Thome with Cowen and Company.

First one on the atopic dermatitis data for 1815. Now that you've had some time to sit with these results, and I understand there is not a huge patient population here, but is there anything that you've been able to tease out in terms of those that may be have a more robust response versus those that don't? And any implications that has to the enrollment criteria for the Phase II? And then the Phase II is going to have a small proportion of severe patients, I think if I remember. How are you thinking about potential background therapies in that study?

So again, I'll let Jonathan answer the question about details into background therapy and so on. On your first point, Joe, in terms of teasing out additional information, we obviously continue to look at individual patient data exactly as you're suggesting and we'll always look to see if there are learnings, but I think fundamentally it's too small a number of patients to lead to any shift in terms of thinking. We do absolutely look at the individual patient data and see if there are directional things that one might interpret, it's something we talk about a lot. But there's nothing given the small size of the study that we see as you're changing anything we thought of before. And then, Jonathan, do you want to talk about background therapy that we're anticipating in the Phase II in atopic dermatitis?

Sure. So for the Phase II atopic dermatitis study in terms of background therapy, participants in that study will be on emollients. So we'll have a 2-week lead-in on emollients where we'll have all the participants take to 2 weeks. We'll re-screen them and then enter them into the trial. So we'll all be on the background of emollients that we're looking at. And as you mentioned, we'll be exploring mild, moderate and the severe population.

Great. And maybe just one more, just because pruritus and obviously, ETCH scores are important for atopic dermatitis. You did indicate there was benefit in the Phase I. Can you just give us little bit more information there in terms of how robust the itch response was in those patients? And once they were off therapy we saw some well-maintained responses on easy and other measures. Was the pruritus measure maintained as well?

So we've reported out one as much as we're going to say, Joe, so we reported out on the DLQI score and [POEM] as complete scores, and within those they've got ETCH and pruritus related sub scores within them. And there was a clear separation. Again for numbers scores though it's too early, which is why we're doing the Phase II to over interpret. But we're very encouraged by what we saw and there's no more detail than what we've reported out on right now.

I'm not showing any further questions at this time. I would now like to turn the call back over to Simba Gill for closing remarks.

Thanks very much. So a couple of things. So as I said at the beginning of the call, this is just an incredibly exciting time for us. And as Mark described in his opening remarks, a few years into this journey, we are extremely encouraged by the data clinically and preclinically that we've generated with 1815. We've now seen positive data in 5 separate cohorts of patients that's consistent with the very striking data we've seen preclinically in multiple models of inflammation, where again to repeat 1 month's score points of seeing preclinical results consistently as good as best-in-class anti-inflammatories in multiple different models. And we've now also got a much better understanding of the mechanism of action as the cellular level.

As you put all of that together and with confidence, we as leaders of Evelo believe we're now in a position where we've confirmed data driven the existence of the small intestinal axis. I'm a neurologist by training, somewhat ancient immunologist by training nowadays. And even today, very, very few immunologists, I suspect very few Nobel prize winners is my standard statement on that in immunology are aware of the existence of the small intestinal axis. That's just a remarkable thing that we're uncovered, some fundamentals of governing human systemic biology.

But what's really exciting is we've essentially demonstrated now clinically that we can harness that newly uncovered area of small intestinal axis to drive clinical signals. So we're just looking through optimizing that in the way that one always does for classic drug development. Great to have Jonathan join us, great to be expanding the team more broadly. But Mark mentioned that he and I go way back to the very early days of antibodies, and what we've done to date has been much, much faster than what took -- what was required in the antibody world, which we're delighted about. And we're going to have ups and downs always that way in drug development, but we're really well positioned to get there in a very big and transformative way.

So I just wanted to emphasize how it is incredibly exciting inflection point and we're into 2021 with a lot of confidence. And then as always wanted to thank our investors and our great analysts for the coverage and the interest and support. And no other comments from me. Thank you very much.

This concludes today's conference call. Thank you for participating. You may now disconnect.