Good morning, and welcome to the Evelo Biosciences Second Quarter 2020 Financial and Operating Results Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn it over to Jessica Cotrone of Evelo.

Please proceed..

Thank you, operator. Good morning, everyone. 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 is Simba Gill, Chief Executive Officer; Mark Bodmer, President of R&D and Chief Scientific Officer; and Duncan McHale, Chief Medical Officer, who will review our second quarter 2020 financial results and recent business highlights.

Before we begin, I'd 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 for 2020, the impact of any of our monoclonal microbials and the timing and results of any clinical studies, and the sufficiency of cash to fund operations, 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, 2020, 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 us to review our progress during the second quarter. This is an exciting and important time for us.

We've recently completed our follow-on offering, which provides the capital to advance our programs in inflammation and oncology through the next phases of clinical development, while continuing to invest in our platform and our pipeline.

We expect to generate six clinical readouts within the next 6 to 12 months, including data from our Phase 2 dose-ranging study with EDP1815 in psoriasis, data from the Phase 2 and Phase 2/3 trials of EDP1815 in COVID-19, additional data from the Phase 1/2 trial of EDP1503 in triple-negative breast cancer, and data from 2 Phase 1 trials in atopic dermatitis, with each of EDP1815 and EDP1867.

Our vision is to harness the small intestinal axis, or SINTAX, to develop a new class of medicines that are effective, safe, convenient and affordable.

In both our inflammatory and oncology programs, we have demonstrated that the effects observed in preclinical models translate to humans, showing that we can harness SINTAX to modulate clinically relevant pathways. As you know, in inflammation, we are initially focused on the treatment of individuals with moderate disease.

These people are not generally treated with existing anti-inflammatories such as antibodies or JAK inhibitors because of safety concerns, cost or the inconvenience of injection or infusion. Over 3.5 million people in the U.S. and EU5 alone, have mild to moderate psoriasis or atopic dermatitis.

The numbers globally, including China, are estimated to be at least 5x this level, almost 20 million potential patients globally. This also holds true for broader immune disorders with more than 600 million people around the world living with the conditions such as psoriatic arthritis, rheumatoid arthritis, asthma, allergy and multiple sclerosis.

As you know, resolving inflammation is important not just for the treatment of immune disorders, but also in treating viral infections such as COVID-19.

The Goldilocks effect of EDP1815, we observed pre-clinically in which hyperinflammation is resolved whilst preserving antiviral activity, gives EDP1815 differentiated potential to help COVID-19 patients. Turning to oncology. Our data suggests that EDP1503 is well tolerated and amplifies innate and adaptive immunity to augment tumor killing.

EDP1503 has the potential to provide additional patient benefit in multiple tumors across all stages of cancer from first line to last line. We have a lot going on. And following the $52 million financing that we completed in June, we can execute on our clinical milestones while continuing to explore the potential of SINTAX.

With that, I will now turn the call over to Mark..

Thank you. Simba referred to a Goldilocks effect of EDP1815. In scientific terms, this means being able to resolve inflammation without damaging the immune surveillance needed to protect us from infection of cancer. This is what the body does naturally, but we haven't found any drugs that mimic this natural physiology.

Based on what we've seen pre-clinically and clinically, it seems that the control of inflammation throughout the body by the small intestinal axis may be biology that will enable us to create such medicines. Many important new biologic and small molecule drugs have been created over the last 20 to 30 years.

They all work by extinguishing the mediators of inflammation rather than by inducing processes of resolution, and they have two shared properties. First, they carry attendant risks to immune surveillance; second, they target single pathways of the complex interconnective inflammatory process.

The next frontier in anti-inflammatory therapy will be oral drugs, which resolve this complex process of inflammation in a safe manner. SINTAX medicines may offer a solution by coordinately downregulating multiple inflammatory pathways without suppressing type 1 interferon mechanisms of immune surveillance.

Our evidence for not impacting type 1 interferons is preclinical. Following the recently announced results with dexamethasone in the recovery trial in COVID-19 patients, we've been comparing and combining EDP1815 and dexamethasone in preclinical models.

This work's yielded results that have implications for all inflammatory diseases beyond the potential for COVID-19 treatment. EDP1815 and dexamethasone are similarly effective as anti-inflammatories pre-clinically.

However, dexamethasone heavily suppresses Interferon alpha and completely suppresses Interferon beta, the type 1 interferons required for immune surveillance. By contrast, EDP1815 has no effect on these type 1 interferons.

We also noted that combining EDP1815 and low-dose dexamethasone had additive and synergistic effects on various aspects of the inflammatory response. Turning to the complexity of inflammation, EDP1815 leads to the reduction, but not complete suppression of multiple inflammatory cytokines.

This is as important therapeutically as the sparing of type 1 interferons, inflammatory cytokines have many protective roles when presented the right levels at the right time and in the right place. Our evidence for this aspect of EDP1815 is clinical as well as preclinical.

You may recall that we reported reductions in the production of IL-6 and IL-8 ex vivo stimulated blood of patients treated with EDP1815. Excess excursions of these cytokines were prevented, the basal levels were maintained.

I realize this is a complicated story, and where we've learned a great deal in the last few months for the mechanism of action of our SINTAX medicines, both pre-clinically and clinically, these lessons of the science of pharmacology are critically important.

They enable us to explain, more clearly, the potential impact of SINTAX on these new medicines. If we can continue to build on the translation of our preclinical work into clinical studies, we will capture this new frontier of anti-inflammatory medicines, which resolve inflammation without suppressing protective immunity.

I'll now hand over to Duncan for a clinical update..

Thank you, Mark. I'm pleased today to review the recent progress across our inflammation and oncology programs. We have received regulatory and ethics authorization at sites in the U.S., U.K., and EU for our Phase 2 dose-ranging trial for EDP1815 in moderate psoriasis.

We remain on track to initiate the trial in the third quarter of 2020 with interim data expected by mid-2021. As we have stated previously, the study will evaluate 3 doses of EDP1815 versus placebo in approximately 225 individuals, and the primary endpoint will be the mean reduction in PASI score at week 16.

We will also evaluate other clinical measures of disease such as IGA, BSA, IGA x BSA and LSS. The study population includes individuals who are failing topical treatments through to individuals approaching the need for biologic therapy.

As Simba said earlier, we believe EDP1815 could have the activity and tolerability that would potentially make it the first-choice agent across this broad and poorly served group of patients. Now turning to COVID-19. The preclinical and clinical data suggests a clearly differentiated role of EDP1815 in the early treatment setting.

A therapy, which preserves the antiviral response and prevents the development of hyperinflammation and cytokine storm, would potentially be an ideal therapy to be used early in the disease process. The results that Mark described combined with the tolerability observed to date suggest this potential profile for EDP1815.

We are pleased to report that the U.S. FDA recently authorized our IND application for our Phase II COVID-19 trial, and we expect data from this trial in the fourth quarter. For the already approved Phase II/III trial in the U.K.

TACTIC-E, we are working with Addenbrooke's Hospital in Cambridge to bring on new sites globally and continue to expect interim safety data and futility analysis by the year-end.

If the data from these trials are positive, we plan to explore EDP1815 as a potential therapy for other viral-driven inflammatory diseases, such as the pulmonary complications of influenza in which hyperinflammation and cytokine storm also play a key role. So, let me now turn to EDP1503, our product candidate in oncology.

At the ESMO World Congress on Gastrointestinal Cancer Virtual Meeting in July, we presented clinical data from our Phase I/II open-label study of EDP1503 in combination with pembrolizumab in individuals with advanced metastatic microsatellite stable colorectal carcinoma, triple-negative breast cancer and those with multiple tumor types relapsed on prior checkpoint inhibitor treatment.

These data provide the first substantiation of our hypothesis that our products can stimulate immune responses via SINTAX to combat tumor growth in humans, in line with our preclinical data. We were particularly encouraged by the results in patients with triple-negative breast cancer.

As you may know, metastatic triple-negative breast cancer is an aggressive disease with very few treatment options. Historically, most patients received cytotoxic chemotherapy in this relapsed setting and with only a 10% to 20% clinical response rate.

The poster presented at ESMO GI included preliminary date on 11 triple-negative breast cancer patients, including eight treated with the high dose of EDP1503 and three with the lower dose. An overall response rate of 25% and a disease control rate of 37.5% were observed across all triple-negative breast cancer patients receiving the high dose.

There were no drug-related grade 4 or grade 5 adverse events, and only four grade 3 events. Suggesting EDP1503 could be an attractive candidate to combine with checkpoint inhibitors and other agents such as cytotoxic chemotherapy or antibody drug conjugates.

Now although the number of treated patients is still small, these data compare favorably to historical studies of anti-PD-1 monotherapy in heavily pretreated patients with triple-negative breast cancer, which have yielded an overall response rate of between 5% and 10%.

These efficacy data are in the range for clinical results observed in newly approved treatment for third line or later metastatic triple-negative breast cancer.

If the current response rate is maintained, then the pleiotropic immunostimulatory actions of EDP1503 will make it an ideal agent to combine with any therapy, which increases neoantigen generation. It has the potential to augment cell death by enhancing the initial inflammatory action in the tumor.

This suggests that the combination of a targeted agent to drive a localized inflammatory action and neoantigen degeneration of tumor sites with an immunostimulatory agent and a checkpoint inhibitor could be an ideal early treatment regimen.

It would maximize the potential for durable clinical responses whilst minimizing the need for broad acting, poorly-tolerated chemotherapeutic regimes.

Based on these data, we're now focused on enrolling additional individuals with triple-negative breast cancer in our ongoing Phase 1/2 trial and expect to report additional data from this cohort in the fourth quarter of 2020. Let me now turn the call back over to Simba..

Thank you, Duncan. I want to conclude with a reminder of the upcoming milestones across our portfolio. Beginning with EDP1815, we expect data from a Phase 2 trial with ruptures in COVID-19 in the fourth quarter of this year 2020. For the Phase 2/3 TACTIC-E trial, we expect interim safety data and futility analysis in the fourth quarter of this year.

We also expect to initiate a Phase 2 trial of EDP1815 in moderate psoriasis in the third quarter of this year with data by mid-2021.

We didn't spend time discussing today the additional trials that we're looking to initiate with EDP1815 in atopic dermatitis, a Phase Ib trial in the fourth quarter of this year, as well as our first non-live product candidate for inflammatory diseases, EDP1867, in atopic dermatitis in the first quarter of 2021.

Data from these trials are expected in the first quarter and mid-2021, respectively. We plan to provide more detail on the unmet need in atopic dermatitis on our third quarter call in October. Finally, we expect to report additional data from our Phase 1/2 clinical trial of EDP1503 in triple-negative breast cancer in the fourth quarter of this year.

Following our follow-on offering in June and the drawdown of an additional $10 million under our existing debt facility in July, we have sufficient capital to support our operations into the third quarter of 2021, beyond four key clinical milestones for each of our ongoing programs, while enabling continued investment in our platform.

Our lead programs, EDP1815 for psoriasis and COVID-19 and EDP1503 for triple-negative breast cancer have shown promising potential in key areas of unmet medical need where the potential unique activity of our product candidates may prove particularly beneficial.

Over the next 6 to 12 months, we expect six clinical readouts, which could further validate our platform, reinforce the predictability of our preclinical models, highlight the potential breadth of SINTAX as a drug target across a broad array of programs and enable the further expansion of our efforts into other indications where we may be able to provide transformative results.

Alongside the progress of our current pipeline, we've expanded discovery into other disease areas, such as neuroinflammatory disorders, metabolic dysfunction, viral-related inflammatory syndromes and for vaccination. In closing, I'd like to thank the team at Evelo.

Because of their exceptional work, we've been able to continue to deliver on our commitments during the COVID-19 pandemic. We look forward to updating you again soon. And I'd like to now turn the call over to the operator for questions..

Thank you. [Operator Instructions] Our first question or comment comes from the line of Connor Meehan from Morgan Stanley. Your line is open..

Hi, all. This is Connor Meehan on for Matthew. Thanks for taking the question.

So you touched briefly on the response rates of pembro alone, but can you just comment on the initial efficacy for 1503? And I guess, how you intend to evaluate the supplementary effect that, that has above or beyond pembro alone? And then just quickly, what kind of commercial contribution do you see for the COVID program, if successful? Thank you..

I'll let Duncan answer the question on how we're looking at the combination study in terms of the readouts and how we're setting that ongoing TNBC combination clinical study with pembro. Duncan, do you want to take that question? And then hand back to me, and I will answer the question about COVID-19..

Yes. Sure, Meehan, an open-label combination – an open-label cohort of the combination. So really what we are comparing is the objective response rate or overall response rate we see within that cohort with the historical data. So, we're looking really for what would be sort of a significant increase over the sort of historic rate of 5% to 10%.

So here, as we've sort of seen at the minute, a response rate of 25% would suggest that where EDP1503 is doing something more than the pembrolizumab, and the combination is, therefore, better than pembrolizumab alone with all the caveats of historical response.

We're also looking at some of the biomarker data with some of the predictors of pembrolizumab response, and that data would be released at a conference in the upcoming time..

So Connor, hopefully, that was helpful. Let me answer your other question on COVID-19. It's actually an incredibly straightforward question for us, which may or may not be true for other biotech companies.

The reason it's a very straightforward question for us, Connor, as you know, from our outset, we had a very clear vision and purpose for the company, which we've been very public on since we founded the company.

And that vision is to create a new profile of medicine which would be not only effective but also safe, convenient by oral delivery and affordable. We've always been incredibly clear about that point. And our definition of affordable is something that is affordable for all populations globally and all patients at all stages of disease.

That is enabled because of the power of SINTAX, which opens up the possibility to create that profile in a way which is not addressable with other things.

So going back to some of the prepared comments we made, the reason – for example, for the reasons, for example, antibodies aren't used in moderate or earlier stage patients with inflammatory disease linked to the cost, linked to the inconvenience of injections and infusions, as well as potential concerns, as we mentioned, on part, clinicians and some patients around safety and tolerability.

So for us, it's pretty straightforward. We're just going to execute on the vision and the plan we always have, which was to provide medicines for very large patients on an affordable basis. And that's what we're going to do in COVID-19 assuming we're successful..

Understood. Thank you..

Thanks, Connor..

Thank you. Our next question or comment comes from the line of Chris Shibutani from Cowen. Your line is open..

Good morning. This is Pam on for Chris. Thanks for the update.

Can you comment on what you're seeing in the field as you try to get the Phase 2 psoriasis study going in these unprecedented times? What is the status there? And what specific challenges are you encountering?.

Hi Pam, good to hear your voice.

So just to clarify, your question relate to recruitment and that type of issue? Is that what you were referring to with your question, Pam?.

Exactly. Yes. Just [indiscernible]..

Yes. Yes. So we – as we said, are looking to essentially initiate the formal Phase 2 dose-ranging study shortly. We haven't yet started dosing, but we have spent a lot of time together with our CRO, working up sites and looking at dynamics linked to recruitment.

What we've done – Pam, obviously, it's very uncertain times and what we've done in the guidance we're giving, which is to get a result on the interim data by the middle of next year, is to provide conservative guidance, which assumes that it's going to be slower recruitment than we would otherwise normally see.

Having said that, at the moment, the situation we anticipate is going to be okay. And certainly, as we look across all of the sites, we're working through, which, to be clear are global, as you know, so we've got multiple sites across different countries in Europe, multiple sites across different regions in the U.S.

And if we look at those in total, we're confident we're going to be able to recruit, Pam. We have mitigated some of the risk that is obvious in the current environment by increasing the number of sites. And you'll remember that we also actually increased the size of the study, just to give us more flexibility from that perspective as well.

So, we've taken steps to have more sites to help with the recruitment, we're being conservative in our guidance. And as much as one can predict anything right now, we're confident we're going to be able to hit the guidance we've given and potentially could even beat it.

Practically, we're not able to comment, Pam, on what are we living with in terms of recruitment right now because we're not actively recruiting right now, but we have done the field work. And we and our CRO, as I said, believe that we're going to be able to continue to recruit depending on the region. And so obviously, we're trying to open up sites.

We're aiming to open up sites in multiple geographies to, again mitigate against what might happen with a given spike at any given moment in time. I hope that's helpful, Pam..

It's very helpful.

If I can ask a follow-up on 1867, can you remind us of what properties you think make it likely that 1867 will be more successful in atopic dermatitis than 1815 or others like 1066?.

Yes. I'll say a couple of things, and I'll let Mark get into the science. Just one clarifier, the way we think about all our programs in inflammation is that they are working on multiple different cytokine pathways, are pleiotropic and that leads to the inflammation resolution that Mark discussed in the prepared marks, and I suspect he'll expand on.

And each microbe is different in terms of which pathways each microbe is impacting. They're all leading to inflammation resolution. We look at atopic dermatitis as a model system for HPs broadly, just to be clear.

So, it's atopic dermatitis as an attractive indication in terms of fundamental unmet need for moderate diseases and beyond, but it's also a model for broader HPs, including asthma, food allergy, et cetera. I'll let Mark answer the question from a more fundamental scientific perspective..

Yes. So, the attractions of EDP1867 are not – in terms of the pharmacology, not specifically related to atopic dermatitis. So, it is very effective. We're productively effective in preclinical models, but actually that's proved for quite a variety of preclinical models.

And what's interesting in the comparison with EDP1815 is that they have slightly different propensities and abilities to inhibit in the different systems. So, they both have the broad inflammation resolution capacity. So they're not – this is not like – don't think of these like antibodies.

These are not targeting specific pathways, but they're targeting overlapping pathways. So, we're looking at optimizing the translational pharmacology, if you like, from what we're seeing pre-clinically and into what we're seeing clinically.

The other aspect of this is actually thinking of these things as drugs in terms of pharmaceutic properties and ADME properties and the rest. EDP1867 is a very different organism to EDP1815. It was isolated in the different part of gut, has different microbiological properties, it has different sensitivities to bile acid and acid.

It was also selected for its particular ability to not only withstand, but actually to have its activity improved by gamma radiation. And as we said early on, when we talked about EDP1815, it's our first deliberately non-live or nonviable product, which we think is a big step in the field.

And as you're aware, Pam, often, what we're doing gets confused with microbiome activities. And – so it was a way of formalizing the fact that there's no microbiome effect. These are directly acting agents that are skipping the whole microbiomecology component and acting directly on host cells in the small intestine.

So the strategy was to – this is a new field. So it's – we are exploring the range of pharmacology and the range of microbiological and pharmaceutic properties. And the distinctions would complement the overlaps between 1815 and 1867. I think we – give us the range we need to go forward.

And actually, we're going to continue to do that, both to explore the range of different types of agents that can be used as different chemotypes in classical drug terms, as well as using them to expand the range of disease indications that we can get into, capturing Simba's comments about getting the broad potential of SINTAX in different products around the different indications.

So, the specific question of whether EDP1867 will be better or worse than EDP1815 in atopic dermatitis, that's a clinical question.

And we don't have the answer to that question yet, but the broad question of having really striking pharmacology in preclinical models, which is overlapping, but divergent in some of the models just gives us the breadth to go after the clinical range that we're after..

Thank you..

Thanks, Pam..

Thank you. Our next question or comment comes from the line of Matthew Luchini from BMO. Your line is open..

Hi. This is [Jen] on for Matthew, and thanks for taking our question and congrats on the progress. Two from me.

So could you – how are you guys thinking about the long-term commercial outlook for COVID treatment? Could you guys point to any benchmarks that you think are appropriate, including remdisivir from a pricing perspective? And how are you guys thinking about the cost? And I have a follow-up after that..

Hi [Jen] thanks for the questions. And thanks for the comment on progress. Just actually to just comment on your – [thank you for our] progress.

Mark and I were actually just reviewing the formal press release a few days ago, and your comment is well made because of the progress we've made over the last 6 to 12 months is pretty remarkable, back to the fundamental point that we now are expecting 6 important clinical readouts over the next 6 to 12 months. So, thank you for that.

On the COVID question, I partly answered it in my response to Connor's question. So what we've always said, just to repeat on that one is that we want to deliver medicines, which help very large patient populations globally and at all stages of disease, with effective, safe, convenient and very importantly, affordable medicine.

So our goal has always been to price on an affordable basis so it links to each market's ability to pay the relevant drug. We're in a very fortunate position because of the nature of the product to essentially be able to add scale, manufacture much more cost effectively than an antibody or at the extreme, a cell therapy.

And that gives us lots of pricing flexibility. We're not commenting beyond that. But you can be confident that we will price on an affordable basis, which would allow the drug to be accessible for very large patient populations around the world, assuming that we drive efficacy, and we're not commenting beyond that at this stage..

Understood.

And can this trial be a pivotal trial, if not – is there any gating factors for moving on to Phase III?.

For the COVID trial?.

Yes..

So the U.K. trial – so we have two COVID trials. The U.K. TACTIC-E trial, it's called, which is a Phase 2/3 trial. And then in the U.S., we just got approval for a Phase 2 trial. So, if I take them in that order, the U.K.

study is structured to reveal whether or not we are making a fundamental difference linked to progression of the disease and linked to mortality.

And so obviously, we need to generate the data, but it is quite conceivable, but if we were to generate positive data through that study, we'd be able to look for some form of an accelerated approval, in a best case, without having to do any additional studies. We obviously have to generate the data.

We have to have the discussions with regulatory agencies. But the trial, as I said, is still up very deliberately as a Phase 2/3 study. The U.S. study is a Phase 2 study. So, assuming that's positive, we'll go into an expanded Phase 3. And they're both set up to allow rapid progression to [aide in] the U.K. situation, potential rapid approval.

Obviously, again, we're in an uncertain world in terms of how regulatory agencies will look at data in an effort to try and accelerate approval given the need that we all have, but that's basically a summary of the situation..

Got it. That’s helpful. Thank you..

Thanks..

Thank you. [Operator Instructions] Our next question or comment comes from the line of Chris Howerton from Jefferies. Your line is open..

Great. Thanks so much for taking the questions. I guess for me, Simba, just a couple of questions.

First of all, with respect to the cash runway, does that take any considerations for CMC scale up or any other activities that might be required in the back-end to move quickly towards some of these near-term commercial opportunities we're describing? And then the second question I have would be thinking about the strategy within oncology more broadly, we've obviously had some announcements this morning with respect to KEYTRUDA working in triple-negative breast cancer.

And then, of course, Metamatics antibody-drug conjugate, so maybe just help us understand your vision in terms of how your product might fit within that evolving landscape? Thanks for taking the questions..

Hi, Chris. Thanks for the questions, Chris. So, on the first one, we've already implemented a number of measures to put us in a position to provide product for COVID-19 patients over the course of next year sufficient for 10 million to 15 million patients with what we have already essentially lined up.

And the initial investments linked to that have already been made, to answer your question. Chris, obviously, until we have approval, we're not going to pull the trigger on the spend, but we have everything ready, allows to provide, as I said, product for 10 million to 15 million patients. So that's already factored in.

If we were to get an approval, which, to the previous question, could be on an accelerated basis and could be earlier next year then that first wave of supply is lined up. Going beyond that 10 million to 15 million patients, we've not yet made the relevant investments, but obviously, ready to do that quickly if we were to get that positive result.

So, that's where we are in terms of scale up preparedness. And we give that very quickly, given that none of us knew that COVID was going to be what it's become until around March, April of this year. So, on your question on recent data, linked to KEYTRUDA and TNBC immunomedics product to delve in TNBC and how we see ourselves fitting in that space.

We think there's very nice complementarity between the different approaches. So, it's a simplistic summary level. As you know, Chris, checkpoint inhibitors, whether it's KEYTRUDA or any of the others, are essentially removing the brake that is applied to the immune system by the tumor. One would anticipate that, that is often going to be required.

The antibody-drug conjugate immunomedics products, various others and other approaches are looking at essentially increasing neoantigen generation and/or exposure.

And we come in as a very nice third complement where we're activating and amplifying the relevant parts of the immune response, which were actually needed to kill the tumor and needed to recognize the tumor antigen basically.

And that's what we have reported on pre-clinically, as you know, Chris, in terms of seeing increased infiltration and activation of the relevant T cell populations and K cell populations, macrophage populations, as well as increased levels in the tumor microenvironment of relevant chemokine and upregulation of MHC Class I.

So, all of that is going to be very complementary with antibody blood conjugates, which were impacting neoantigens, and all checkpoint inhibitors, which are removing the brake. So hence, Duncan's comment that we can see a very nice opportunity as we go forward.

To actually be the foundation to which other things can be added from first-line therapy to last-line because, again, we've got the fundamental benefit that all our products have are being oral, safe and well tolerated in oncology on a relative basis. And also, again, the affordability point down back to the COVID-19 question.

So that means that we, given the properties I've just described could establish ourselves as a foundation from early-stage to late-stage patients to which other things will be added. And that's a pretty unusual position. And I appreciate the question, Chris, because a lot of people don't actually fully appreciate that.

That's always been a strategic intent. Hopefully, that was a helpful answer, Chris..

Yes. Perhaps I could just ask a slight clarification. So, I think in terms of the rationale and the overall mechanism, completely understand and, in fact, agree, but I guess, maybe help us understand what that clinical development path looks like.

What would be an initial setting in which you would anticipate a potential approval? And how would the label expansion move to kind of meet this vision that you're describing right now?.

Sure.

Duncan, do you want to take that question?.

Yes. Yes. I mean I think because you've sort of seen the initial studies at the minute are demonstrating that we've got clear sort of antitumor activity. This particular one is in a single open label.

So, with pembrolizumab, it's likely as we move forward, that we would do a similar sort of study, but a blinded study just to prove that you have evidence of antitumor effect in monotherapy.

And I think once we've got that, then I think we will look at the actual sort of set of treatments and treatment options that the patients have within triple-negative breast cancer and start to work with partners about positioning EDP1503 in combination, sort of with the rationale that Simba was talking about, sort of as an early type therapy in that sort of space would be what our strategy was, but the next steps would be to demonstrate I think, clearly, in a blinded study, the sort of the activity of the agent on its own before we then go into the combination setting..

Got it. Okay, well thank you so much for taking the questions and hope all of you are well. Thanks..

Thanks, Chris..

Thank you. I'm showing no additional questions in the queue at this time. I'd like to turn the conference back over to Dr. Gill for any closing remarks..

So, just wanted to thank everybody for the continued commitment to Evelo and for following us. Appreciate it, and look forward to staying in close contact with all of you and keep you updated on our progress in what is going to be a very busy 6 to 12 months. Thank you very much..

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day. Stay safe..