Good morning and welcome to Evelo Biosciences Conference Call to discuss its Second 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 a press release that outlines the topics we plan to discuss today. This release is available at www.evelobio.com under the Investors tab.

Today on our call, Simba Gill, Chief Executive Officer; Mark Plinio, Chief Commercial Officer; and Jonathan Zung, Chief Development Officer will review our recent business highlights and second quarter 2021 financial results.

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 any of our product candidates and the timing and results of any 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 quarter ended June 30, 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 thank you for joining us to review our progress during the second quarter. We wanted to begin by recapping the fundamentals of our platform and the small intestinal axis or SINTAX.

It has long been understood that the gut plays a central role in regulating health, inflammation and immunity throughout the body. Evelo’s focus is discovering how to make medicines that capture the potential of the gut to treat disease and engender good health.

Over the last few years, we have made fundamental discoveries that have confirmed the central governing role of the gut is the biology of SINTAX, the small intestinal axis. This control system for systemic immunity, centered in the gut, can be targeted to make medicines that act as the distance from within the gut without entering the body.

The announcement from Seres last week about the lack of efficacy of SER-287, a microbiome therapeutic in people with ulcerative colitis, has raised questions about the prospects for Evelo’s SINTAX medicines. We want to address this directly and highlight that there is no bearing from Seres’ announcement at all on SINTAX platform or products.

Most importantly, there is no overlap either of mechanism or action or therapeutic intent.

The superficial view that these approaches are somehow linked by having to do with the gut and microbes hides the complete different and scientific principles that from the beginning led us away from complex ecosystem biology of live biotherapeutic products, which seek to replace a disease-causing microbiome with a healthy microbial ecosystem.

The theory’s approach is fundamentally different to Evelo’s focus on SINTAX. Unlike Seres or indeed the broad microbiome field, there is no intent nor actual modification of the microbiome either pre-clinically or clinically with SINTAX medicines.

Evelo’s SINTAX candidates are well-defined, non-life preparations of single strains of microbes and their extracellular vesicles. The mechanism of action is clear.

Their physical structure is recognized by the SINTAX sensing system, cells in the small intestine, which then leads to a triggering of pharmacological signals around the body without the need for the drug to leave the gut. These effects are independent of anything to do with the microbial ecosystem in the colon.

The central point is that Evelo SINTAX product candidates are physical drugs, not live biotherapeutic products. They act directly on target cells with an entirely new mechanism of action that enables systemic efficacy without systemic absorption. From a pharmaceutical and patient value point of view, this is the core advance of SINTAX medicines.

Positive data from 5 cohorts in clinical studies with EDP1815 in over 300 people have shown inflammation-resolving effects across the major types of inflammation, Th1, Th2 and Th17, while consistently observing safety and tolerability of EDP1815 comparable to placebo. These cover psoriasis, atopic dermatitis and human experimental models.

Early phase clinical results were always open to the reasonable question of whether they are robust and reproducible. This is why the emphasis on repeated studies with EDP1815 is so important.

Not just one, but five positive outcomes have shown beyond reasonable doubt that EDP1815 is active in humans and that SINTAX works, as we propose it does, concordant with hundreds of preclinical experiments.

The data are remarkable, revealing a whole new concept in how a naturally-occurring drug can work throughout the body via an external sentry system rather than having to flood the body with foreign substances. Another critical scientific differentiator is where the microbes that underlie SINTAX medicines come from.

The microbes are isolated from mucosal surfaces that line the intestine of human donors, not from stool. This is centrally important as these rare mucosal microbes are the ones that have adapted to interact with and to be recognized by their human host cells. This is where we believe the pharmacology comes from.

They are quite distinct set of microbes from the relatively undifferentiated mass that grows every day to form stool, and they’re also quite distinct in their mechanism of action and pharmacological function. The value of our pipeline of SINTAX medicines rise, in the differences, not the similarities for other microbiome approaches.

Fixed scientific discoveries, which differ from the mainstream microbiome field, have been integrated to create a pipeline of product candidates with the potential to be a significant advance in the development of medicines.

One, use of single microbes, which are; two, isolated from the mucosa rather than stool; three, they work non-live; four, microbes produce extracellular vesicles, which are pharmacologically active; five, they have direct action on host cells in the gut; and six, putting all of this together, SINTAX enables systemic efficacy and safety of non-absorbed drugs.

So yes, whilst we are working with microbes and the gut, our approach is completely unique. I would like to now turn to one particular feature of the clinical profile. Safety and tolerability are critical parameters for both adults and children with diseases such as psoriasis and atopic dermatitis.

Our products have the potential to have a differentiated profile, given that they are orally-delivered, gut-restricted and systemically-acting. Studies to-date have shown EDP1815 to be well tolerated and with a safety profile comparable to placebo. This is important to clinicians and to the people with these diseases.

A reminder also that inflammatory diseases, including psoriasis and atopic dermatitis are systemic, not local diseases. EDP1815 is designed to treat systemic inflammation. Topical treatments do not treat systemic effects.

We have several additional clinical readouts across atopic dermatitis and psoriasis with EDP1815 and EDP1867, which Jonathan will tell you about. The research and development teams continue to explore ways to enhance and extend the applications of SINTAX medicines.

Of note is the previously announced preclinical data for our first extracellular vesicle product candidate for inflammation, which is on track to enter clinical development next year. EVs have the potential to drive even greater efficacy than seen with our whole microbe programs.

Execution of our vision requires the highest caliber team and I am pleased that we continue to attract tremendous talent to Evelo. We recently appointed Mark Plinio, as well as Chief Commercial Officer.

Mark brings significant sales and marketing leadership to Evelo, including experience launching blockbuster products for inflammatory diseases such as Cosentyx, a biologic which has been approved for the treatment of both psoriasis and arthritic conditions.

I would now like to turn the call over to Mark, who will provide a bit more color on it himself, his role at Evelo and how he will help us enable broad global access of our medicines to benefit the lives of billions of people worldwide.

Mark?.

Thank you, Simba. I am thrilled to be here this morning. I joined Evelo for three main reasons. First, the company’s innovative scientific platform, which I believe has the potential to transform the treatment of inflammatory diseases.

Second, the opportunity to apply this novel science to address areas of immense unmet need, where new oral medicines that are effective, safe, well tolerated and affordable could meaningfully impact the lives of billions of people.

And third, the opportunity to work closely with a phenomenal team with the capabilities and expertise to turn a big vision into reality. Today, I would like to focus on the vast unmet need that we are seeking to address.

As Simba alluded to, there are more than 1 billion people worldwide suffering from classic inflammatory diseases, diseases with which we are all too familiar like psoriasis, atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease.

While each of these diseases presents differently, all are characterized by systemic inflammation and all have a significant negative impact on people’s lives. Our initial clinical programs are focused on demonstrating the impact of SINTAX medicines in the treatment of psoriasis and atopic dermatitis.

People living with psoriasis or atopic dermatitis are underserved by existing options, especially those with mild and moderate disease. Innovation, including oral therapy, primarily has been focused on the moderate to severe population.

Despite such innovation, it is estimated that in the United States, less than 8% of people with psoriasis and less than 2% of people with atopic dermatitis have received these treatments.

Safety, tolerability and high cost are significant barriers to treatment with many people, especially those with mild and moderate disease, opting for marginally effective topical treatment or no treatment at all. Take for example, atopic dermatitis, for which there has been limited innovation and currently, there are no oral therapies available.

People suffering from mild or moderate atopic dermatitis suffer from very painful, itchy skin lesions that are highly visible. They report a significant impact on their quality of life and experience a significant psychosocial burden, which has been shown to be greater than the impact of diabetes, cardiovascular disease and even some cancers.

These people also suffer from a number of other comorbidities, such as asthma and allergies. Despite the high level of suffering, there remains a very large treatment gap for the more than 20 million atopic dermatitis sufferers in the U.S. alone.

Most of these people are treated with topicals that are time-intensive and inconvenient to administer, have low compliance and address only the outwear dermatologic manifestations of disease, leaving the systemic inflammation that characterizes this condition entirely untreated.

Biologic therapy used in less than 2% of people with atopic dermatitis is not without its own limitations, including administration by injection, the potential for immunosuppression and high cost.

Simply put, there remains a significant need for oral medicines that are effective safe, well tolerated and affordable for the more than 200 million people suffering from atopic dermatitis globally and the more than 50 million people impacted by psoriasis around the globe, which is why we have chosen to focus our initial efforts on improving care for these patients.

This creates a unique opportunity for Evelo to improve care for a significant population of sufferers, especially those with mild to moderate disease who remain underserved.

With our SINTAX-targeted therapies, we have the potential to deliver effective, safe, well-tolerated and affordable oral therapies that treat a number of inflammatory conditions across multiple arms of the immune system. And this is exactly what we intend to do.

I joined Evelo to help fulfill this vision, specifically to create a business model that allows us to translate the tremendous potential of SINTAX into medicines that are affordable and accessible to people worldwide.

As we begin to build the commercial organization, we will challenge the traditional pharma business model in the way people think about drug pricing and in the way technology and other channels are used to provide care and deliver medicines to people suffering from diseases, so that every person who can benefit from a SINTAX-based medicine is able to receive it.

This is core to our vision, and I look forward to the opportunity ahead. We will provide additional details on our commercial strategy as we advance our programs through the clinic and begin preparing for our next steps. Now, over to Jonathan to provide an update on our clinical progress and future milestones..

Thank you, Mark, and good morning, everyone. As Simba shared, during the third quarter, we anticipate readouts from our ongoing EDP1815 Phase 2 and Phase 1b trials in psoriasis.

The Phase 2 trial is evaluating the safety and efficacy of three different doses of EDP1815 versus placebo in individuals with mild and moderate psoriasis following daily dosing for 16 weeks. The trial has been designed to evaluate the efficacy and safety of EDP1815 and to select the appropriate doses for the Phase 3 program.

The trial aims to confirm the safety and tolerability of EDP1815 and to demonstrate and confirm effects on a number of clinical efficacy endpoints in psoriasis. The primary endpoint is the mean percentage change in the Psoriasis Area Severity Index or PASI score at week 16.

Secondary endpoints include a number of physician measures such as PASI 50; PASI 75; body surface area, BSA; and the Physician Global Assessment PGA times BSA, along with different patient-reported outcomes, such as the Dermatology Life Quality Index, DLQI; and the psoriasis symptom inventory or PSI.

In parallel to our Phase 2 trial, we have an ongoing Phase 1b trial in individuals with mild to moderate psoriasis that is evaluating tablet and capsule dosage forms containing a higher concentration of drug.

We will use the totality of the results from the Phase 2 and Phase 1b trials to further understand the potential of EDP1815 in psoriasis and to select an appropriate dosage form for EDP1815 for the next phase of clinical trials.

Moving on to atopic dermatitis, we continue to be very excited about our EDP1815 atopic dermatitis program and will begin the Phase 2 trial this quarter. As a reminder, in our Phase 1b trial in a cohort of people with mild and moderate atopic dermatitis, trial participants were dosed for 56 days with EDP1815 or placebo.

The data showed consistent improvements in percentage change from baseline compared to placebo for three clinical scores, the Eczema Area and Severity Index, EASI; IGA times BSA; and SCORAD.

7 out of 16 or 44% of trial participants treated with EDP1815 achieved an outcome of a 50% or greater improvement from baseline in EASI score, EASI50 by day 70 compared with 0% in the placebo group.

The Phase 2 trial will be a 12-week double-blind, placebo-controlled multiple cohort trial in individuals with mild, moderate or severe atopic dermatitis. This will allow us to more fully understand the potential benefits of EDP1815 across a range of disease severity.

All trial participants who complete the 12-week study will be eligible to enroll into an open-label extension study where they will all receive EDP1815. Approximately 198 participants will be randomized to receive EDP1815 and 66 participants will be randomized to receive the matching placebo.

Participants will receive either 1 capsule once daily, 2 capsules once daily or 1 capsule twice daily. The trial will be conducted in North America, the U.S. and Canada, along with Europe. The primary endpoint will be the mean difference between EDP1815 and placebo in the percentage change from baseline in EASI score at week 12.

Secondary endpoints will include a number of investigator IGA and BSA, along with patient reported outcomes, such as the DLQI, itch using the daily Peak Pruritus Numerical Rating Scale and the Patient-Oriented Eczema Measure or POEM.

We anticipate reporting results from this trial in the third quarter of 2022, which will be used to support the dose selection for the Phase 3 atopic dermatitis program. Our Phase 1b trial of EDP1867 in a cohort of individuals with moderate atopic dermatitis is ongoing. Trial participants are being dosed for 56 days with a 14-day follow-up.

We anticipate results from this trial in the fourth quarter of this year. As a reminder, 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.

And moving to EVs, as Simba mentioned at the beginning of this call, EDP2939 is our lead microbial extracellular vesicle product candidate for inflammation. We anticipate initiating a clinical trial in 2022. We will share more about this program next quarter. With that, I will hand it over to Simba..

Thank you, Jonathan. As you heard, we have a number of milestones expected over the next 6 to 12 months. In Q3 of 2021, we expect data from a Phase 2 dose-ranging trial of EDP1815 in psoriasis.

We will also expect data from the Phase 1b trial of EDP1815 in psoriasis in cohorts with tablet and capsule dosage forms containing more concentrated drug, and we will begin the Phase 2 trial of EDP1815 in atopic dermatitis. In Q4 of 2021, we expect interim data from the Phase 1b trial of EDP1867 in atopic dermatitis.

And in 2022, we will initiate clinical development of our first inflammatory extracellular vesicle product candidate, EDP2939. And we expect data from the Phase 2 trial of EDP1815 in atopic dermatitis in the third quarter of 2022. I wanted to conclude by thanking the Evelo team and our partners.

In the midst of the pandemic, we have continued to execute successfully across all areas, including clinical development, manufacturing and supply chain and to advance our research platform and our pipeline. We have continued to grow and to build Evelo capabilities and expertise.

We are now all physically working in our labs and offices and highly focused on delivering on our next sets of data. This has been a particularly hard period, and we are very proud of the results we have produced under the resilience, fortitude and great spirit of our team. I would now like to turn the call over to the operator for questions..

Thank you. [Operator Instructions] Our first question comes from Matthew Harrison with Morgan Stanley. Your line is open..

Great. Good morning. This is Vikram on for Matthew. Two questions from our side.

So first, we were just wondering how you plan to manage the placebo rates in the atopic dermatitis study you expect to start in the third quarter with 1815? And also just wanted to see what sort of safeguards you have in place to kind of manage any impact from the pandemic for the study?.

Hi, Vikram. Good to hear from you. Let me take those in reverse order. So for the pandemic, first of all, as I concluded in my prepared remarks, we’ve already had experience recruiting very successfully through the pandemic, both in atopic dermatitis and psoriasis.

And one of the keys to our historical success we’re applying to the forward plans for atopic dermatitis, which is to have multiple sites in multiple geographies and to be very close to all of those sites and that will obviously mitigate against any potential issues because, obviously, the pandemic has different realities at different times in different geographies.

So we’ve got multiple geographies across the U.S. and across Europe, and we’re very close to all of the relevant sites. Jonathan, who’s leading clinical development for us has obviously taken our capabilities to the next level. So we’re feeling very confident that we will recruit on schedule with the atopic dermatitis.

That’s the first study and then on the second question. On the first, let me hand it over to Jonathan..

Yes. So for the first question in terms of the placebo response, the way we’ve designed the study is the study will have a 2-week lead in on emollients for patients. So the patients, we’ll look at their incoming EASI score. They will be on emollients for 2 weeks.

They will then get another EASI measurement, and then they will be randomized to either active or placebo. So that’s how we are looking to manage that effect..

Great. Understood. And my second question was on the psoriasis program. So just wondering how in the third quarter of this year – I know you mentioned that you are going to have the data from the Phase 2b study and also data from the Phase 1b cohorts for the tablets and capsules.

Could you just walk us through how those different datasets are going to kind of come together to help you formulate your plans for the Phase 3 study?.

Yes. So let me say one overarching comment and then again, I will hand over to Jonathan to give you a bit more detail. So we will release all of the data together. That’s the way all the data is coming together. We expect late third quarter we will be ready to do that.

So just to repeat the question for everybody else’s benefit, Vikram, because I think it’s important. We’ll release the Phase 2 data together with the Phase 1b data looking at increased concentration in tablets and capsules.

And then Jonathan, any additional comments?.

Sure. So as we think about the Phase 2 trial, we will be looking at the three cohorts, which are evaluating different dosing regimens and looking at those in terms of PASI 50 PASI 75 responses, along with patient reported outcomes, will guide us in terms of next steps around dose selection and how we move forward..

Great. Thank you..

Thank you. And our next question comes from Kristen Kluska with Cantor Fitzgerald. Your line is open..

Hi everybody. This is Rick on for Kristen. I just have a couple of questions for you this morning.

First of all, when you are looking to – in the Phase 2 atopic dermatitis trial, when you are looking to move into now these mild, moderate and severe, different severities, how are you thinking about maybe targeting specific percentages of patients to fall into these categories? Is that something you are looking at? And how are you thinking about baseline inclusion and exclusion criteria based on what you observed in the Phase 1b trial?.

Good questions. So, in terms of that study, we are looking to enroll and we have got plans in place to maintain the percentages. So, we will probably enroll about 65% of the participants in the moderate and then 10% to 15% each in the mild and severe. So, that will give us a good range of patients that we are studying..

And Rick, one important point, which is embedded in your question, we anticipate the potential for EDP1815 to have meaningful activity across all three groups, mild, moderate and severe, as we think forward to the ultimate goal of the program..

Thank you.

And maybe just one more, how did the increased concentration preliminary work that you have been doing in the psoriasis side as well as the ongoing study of cohorts kind of influenced the design of the trial design, relative to the different capsule combinations?.

Hasn’t had any impact in that the way we think about the overarching clinical development plan is to get that data now. So, that’s part of the data that we will release at the end of third quarter. And then that will inform on what we do in the next wave of studies.

So, the goal of the existing clinical trials, as Jonathan was saying, is to determine optimum dose and optimum formulation and concentration. And we will get that data from the ongoing studies in psoriasis. And then that will inform on what we do next..

Okay. Thank you all very much..

Thank you. Our next question comes from Chris Howerton with Jefferies. Your line is open..

Great. Thank you very much for taking the question. Obviously, I am really excited for all the data readouts that you have coming up. So, I guess maybe I feel like maybe we could get a little more information on the totality of the readout with respect to psoriasis.

In the third quarter, I think, Jonathan, you certainly address the feature of the different dosing cohorts within the Phase 2. But the part that I feel was not answered was the idea of the two different formulations. And then I think the other concept as well as in terms of kind of the dosing frequency.

So, how does that fit into the comments that Simba made at the beginning with respect to how this therapeutic modality works and certainly some of the features relative to some of the ecological approaches that are out there?.

Sure. So, the Phase 2 study is designed to basically demonstrate the efficacy of 1815.

As you think about the Phase 1b studies, the two studies that we are looking at, the cohorts of tablets and capsules, that’s to really understand the performance of each of those dosage forms in the psoriasis patient population that we would then use to inform future studies, whether there is a switch between capsules and tablets.

So, that’s a pretty straightforward approach that we are looking at. Then that would inform us as we think about our Phase 3 program, next steps post the Phase 2, which dosage form we would bring forward, whether it’s the capsule or the tablet..

And Chris, just to expand on that a little bit to the reference [Technical Difficulty]..

Simba, we lost you..

You may continue..

Okay. Great. Well, I – so this is Chris Howerton.

I was – I guess I am wondering, Jonathan, if we can just understand maybe is it simple as the different formulations have different efficiencies with respect to GNC activities or is there a putative clinical benefit of one or either of the different formulations? And I guess the added and implicit question on top of that is that, obviously, we are going to learn a lot of information from the specific Phase 2b study in psoriasis.

But how can we better understand whether or not, let’s say, the tablet formulation would enhance those results? What would be the information to help you make that determination? [Technical Difficulty].

Again, at this time, please stand by. Again at this time, we are experiencing technical difficulties. Please stand by. We will resume momentarily. And you may resume..

Hi. This is Simba. We got disconnected for some reason. So, I am not sure what happened there, but hopefully, everybody knows. Chris, I am not sure where we lost or where you lost us, actually..

Yes. Can you hear me now, Simba? Are we….

Yes..

Hi. I am fantastic. Yes. So, I think you cut off right where I think you were about to address how that may or may not relate to your comments with respect to the different ecological approaches.

And then I actually pressed on the point just like – while I have the podium is that the – I guess, I would love a little more information, Jonathan, with respect to the actual tablets and capsules.

Is it as simple as that each of the different formulations has different GNC efficiencies, and that’s really the focus of understanding that or is there a putative clinical benefit of one or either of the formulations with respect to either the concentration or the dosing frequency?.

Okay. So thanks, Chris. So, just on the fundamental question which really centers on the mind, the platform the key point is, as I said in my prepared remarks, there is no linkage for ecosystem-based approaches. So, the intention here is not to colonize the microbial ecosystem.

The goal is to make sure there is as much exposure as possible to active pharmacological agents at the right place for the right period of time. And that’s what the different things that we are looking at across the Phase 2 and the Phase 1b are focused on.

So, the core point is that the platform is based upon recognition of structural motifs on the microbes or the extracellular vesicle. And so we need to get enough and an optimized demand of the microbial extracellular vesicle to the target cells in the small intestinal axis.

And the different things we are looking at are aimed at investigating those differences.

Jonathan, maybe to expand on that in terms of the second part of the question?.

Yes. In terms of the second part of the question, I mean we are evaluating the tablets and capsules to understand if there is a difference between them in terms of the delivery of the drug in the psoriasis patients.

And then obviously, we would use the data from those two cohorts to then determine next steps if one formulation is superior to the other..

Okay, great. Thank you so much for taking the questions. And obviously, like I said, look forward to the coming months..

Thank you. Our next question comes from Matthew Luchini with BMO Capital. Your line is open..

Hi, good morning and thanks for taking the questions and thank you for the update. So, first, on the atopic dermatitis study, it seems like the – how should we interpret the inclusion of severe AD patients? In the past, the company has sort of really emphasized the strategic focus on mild to moderate disease.

Just wondering if this is the prelude to perhaps pushing into more severe patients in this indication? And related on atopic dermatitis, can you just remind us where you see the potential advantages of 1867 relative to 1815? I recognize it’s a different microbe.

But at the end of the day, is this an efficacy story? Is it perhaps potential for better concentration and thus lower dosing? If everything works out, where does – how do these two product profiles kind of shape up relative to one another?.

Hi, Matt. I will answer the first question, and I will let Mark Bodmer answer the question about 1867. So first of all, just to reemphasize the unmet need for patients with atopic dermatitis. There are about 20 million patients in the U.S. alone with atopic dermatitis and hundreds of millions of patients around the world.

The major area for a patient unmet need is in patients with moderate to mild disease, where there are no oral, safe, well-tolerated, affordable and effective drugs available. So, it’s a massive area of unmet need. And SINTAX-based medicines are uniquely positioned to solve that, and that’s exactly the profile that we expect.

And we will know soon over the next year or so in atopic dermatitis that we expect to see in.

If we get that profile, again of confirming safety tolerability, obviously, we have something that is oral-convenient, and if we can generate the efficacy, and obviously, we will make sure, to Mark Bodmer’s comments, that we are delivering on an affordable basis. We expect we will have BT treatment for that huge population.

In severe disease, to your question, we believe we will have the possibility of important impact. Even in the severe patient population in atopic dermatitis, there is unmet need, and there is plenty of room improved drugs. And yes, we are keen to explore what we might be able to do there as well.

And the study will provide initial data that what gives us a sense as to how much impact can we have in that severe patient population. So, that’s that. I will let Mark Bodmer answer the question on 1867..

Hi Matt, it’s Mark here. I am going to also, in a – first of all, a strategic way and then a specific way about EDP1867 and 1815.

The claim that we made at the outset to the aspiration to make single strains of non-live, now we see the mucosally-derived microbial preparations and their extracellular vesicles, which acted directly in the gut on the sensory system that had pharmacological effects, was a fairly substantial claim to be able to do something with the new type of medicines, total immune modality that hadn’t been made before.

We never assumed that the first drug we picked would necessarily have the benefit. So, any more than you would if you were starting again with small molecules or antibodies or gene therapy or whatever, modality.

So, our strategy from the outset was to pick multiple microbes and work out experimentally and clinically what the best pharmaco falls or pharmaceutical types were going to be. We actually got pretty lucky with EDP1815, getting a lot of positive data going in. But we are not an EDP1815 company. We are a SINTAX medicine company.

So, the breadth of the biology and the pharmaco and pharmaceutical structure of the drugs was important. So, EDP1867 flows into that. As by the way, do the extracellular vesicles. EDP1867 is another mucosally-derived microbe, derived from a different part of the microbe. It’s taxonomically distinct.

And it has been repeatedly robust in the preclinical studies. I am not going to make particular comparisons to EDP1815 on that, because I don’t want to answer the question because I can’t, about which is better, if you like. They are both good, but EDP1867 has been very robust in preclinical studies.

The other thing which is emerging, we haven’t talked much about this publicly, is that various of these microbial preparations and actually their cognate extracellular vesicles appear to have in common, this broad inflammation resolving pharmacology, apparently without immunosuppressive effects or other types of side effects or differences in the details of the molecular-targeted mechanisms of action.

That is very interesting because if we can get diversity of induction of the effects for common broad-spectrum inflammation resolution activity, that puts this whole platform into a very powerful position. So, just a sum now, there is two characteristics.

One is the strategy, how do we make these medicines, what are the best ones they are going to be, and then those specific characteristics of EDP1867 in comparison with EDP1815.

And we see them as being very complementary in the clinic and will just broaden the base of what we are able to – dosing clinically as we think about diseases beyond dermatological..

Okay. Thanks. And then just really quickly on psoriasis.

Given that you are going to have a bunch of data all being presented at the same time later in this quarter, how much of the kind of go-forward strategy do you expect to be able to communicate concurrent with data or do you see that as being something that you will have to work out after? And if so, at what point would you expect to be able to communicate?.

We expect we will be able to give meaningful guidance on the go-forward strategy. So, the idea is that we do a meaningful analysis of the data across the three cohorts, and that should guide on what we do next in a very clear way, and that’s what we would expect to announce..

Okay, great. Thank you. Thanks for taking my questions..

Thanks very much..

Thank you. Our next question comes from Gobind Singh with JMP Securities. Your line is open..

Hi. Thanks for taking the questions.

So, just thinking about the 16 efficacy measurements like PASI 50 that are coming in the Phase 2 psoriasis readout, can we take a step back and discuss a little bit about what efficacy measurements, how they evolve maybe from week 6 or week 8 to week 16? And maybe you could help us apply to what was previously shown with 1815? I think it was week 6, to help us get an idea of how to kind of set expectations for the upcoming readout? And then one follow-up question if you don’t mind..

Yes. Hi Gobind. So on the first question, let me just start by reminding everybody about the unmet need and what we are targeting. And I know you know this scope, but I think it is important again to kind of ground everybody.

So first of all, psoriasis also has a massive patient population, about 9 million people in the U.S., tens of millions of people globally. Only about 8% of those patients receive innovative treatments today. In a similar way to atopic dermatitis, the majority of patients with moderate and mild psoriasis are unhappy with current treatments.

With the important things, again, being first of all safety and tolerability, that is something that is extremely important to patients and to the physicians treating them. There are no well-tolerated oral drugs that are used in that moderate to mild population right now today. Obviously, being oral-convenient is much preferable to the injection.

And again, affordability really matters. So, the efficacy is very important as well. The feedback we are getting from continuous discussion with physicians and with patients is we need to show that we have something plus or minus that is at a PASI 50 level or better.

But if we do that together with the safety and tolerability, we have an important medicine that will make a big difference for patients. And so that’s what we are aiming at. To your specific question on what happens at 6 weeks, etcetera, the original Phase 1b study was a four-week study.

And what one typically sees with drugs to treat psoriasis is it takes at least 16 weeks to see plateau effect. And it can go longer than that if you look at other drugs that have been used in this area.

So, the expectation that we have, and we have always communicated if you look at historical drugs that have been in use with psoriasis populations, is that extended duration of therapy should lead to deepening responses and potentially a broader population of responders as well. And it’s partly due to the fact it takes time for the skin to heal.

There is a variety of other things, but we expect extended duration will lead to deeper effects and stronger effects..

Great. And then for the Phase 2 atopic dermatitis trial that’s coming up. I just want to dig a little bit more into the moderate to severe population.

Maybe just particularly thinking about the strategy with the patients that may be also on dupi, can you – is that still the case, there will be some things like this? And how might you be controlling? If so, the patients that are on dupi alone, for example, in the placebo arm versus the combination.

Is there any kind of control in that, I guess, about 40% or so are going to be moderate and in the 10% to 15% in the severe, how is that asset….

Yes, let me give it to Jonathan..

So Gobind, for this study, no patients will be on dupi. So, they will be – they are excluded from the study. So, we are looking at patients that are not on biologics, haven’t been on another trial for a period of time. So, these will be patients that have active disease.

And again, as you think about the population, about 65% of that study will be in the moderate. And then we will also be studying the extremes, meaning the mild patient population and the severe population, to better understand the full potential of 1815 across the mild, the moderate and the severe..

Gobind, one other point I should have mentioned as reflecting just again in terms of duration of response, duration of treatment versus response rate. So, the other key thing, obviously we are looking at is patient reported outcomes. So, we will be looking at those. And again, those should improve over time.

But I just wanted to emphasize the importance of those patient-reported outcomes as well. So, looking at things in an integrated manner, including sleep, itch, overall patient integrated feeling, PASI and so on are important as well..

Great. Thank you for that..

[Operator Instructions] Our next question comes from Joe Thome with Cowen. Your line is open..

Good morning and thank you for taking my questions. A couple on the atopic dermatitis study. I know it was just mentioned that patients cannot be on dupilumab at the same time during the study.

But are all the patients that are going to be enrolled biologic naive? So, could they have failed dupilumab previously? And then if you could just all us to know sort of what is the dose on a capsule basis compared to what we saw in the Phase 1b? Is it the same dose, you are just giving it more frequently? And then last question on the trial design.

There is a BID dosing arm. Maybe what data led you to think that maybe the two times a day dosing, may be more a beneficial indication? Thanks..

Yes. So, in terms of the study design, I will take the BID first, so as we think about it, we have not tested the drug in the QV versus BID. So, we want to understand the full breadth of potentially dosing twice a day. As you think about the concentrations in the study, we will be using the more concentrated material.

So, we will be dosing one cohort with one capsule a day, another cohort with two capsules a day. And then that final cohort will be BID, one capsule in the morning and the afternoon. The material is more concentrated. So, if you think about that Phase 1b study, we were dosing 10 capsules.

In this particular study, we will get to equivalent numbers using the current dosage form and dosing regimen..

Great.

And then on the – are these all biologic naive patients that will be entering the third of your baseline?.

They will be about biologic-naive participants, yes..

Okay, great. Thank you..

And at this time, I am showing no further questions. I would like to turn the call back over to Simba Gill for any closing comments..

Thanks very much, everybody. This obviously, as you have heard from some of the questions, a very exciting time for us with lots of clinical data readouts coming up, building on very positive multiple clinical cohorts that we have shown historically.

So, I appreciate your continued interest in Evelo, and we will keep you very updated over the next couple of months and beyond. Thanks very much, everyone..

This concludes today’s conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day..