Seres Therapeutics, Inc. (MCRB) Earnings Call Transcript & Summary

Hello, and welcome, everybody. My name is Chris Shibutani. I'm a member of the Goldman Sachs biotech equity research group. Welcome to our 42nd Annual Healthcare Conference, virtual this year, hopefully, live next year. We're very pleased to have Seres Therapeutics join us for the presentation. As you can see from all the panes that we have just about everybody from the C-suite. Nobody is doing any work other than with us for the next hour. So we'll try to make sure we get the most of everybody's time. Joining us, and I have my little cheat sheet here is Eric Shaff, who's the President and CEO; David Arkowitz, who is the recently appointed Chief Financial Officer. David, welcome to this craziness. Lisa von Moltke, who is the Chief Medical Officer; Terri Young, Chief Commercial and Strategic Officer; and Matt Henn, who is the Chief Scientific Officer. Often in the wings, probably biting his nails, worried is Carlo Tanzi from Investor Relations. So we'll give Carlo a quick shout out even though he's not on camera. So 40 minutes here, more than the usual half an hour, but with so many of you, there's a lot to cover.

Eric, I think that during the first quarter call, you talked about all the progress that you're making, and I think there are some pretty clear domains. And maybe you wanted to just begin some of the process of thinking about just introducing the company, the key assets, and then we'll really dig in.

That's great. So good morning, and thanks, Chris, for having us here, and thanks to Goldman for having us here. Appreciate the intro for the team, for Lisa, Terri, Matt, Carlo and now David. I can assure you that even though we are pleased to be here with you, that there are folks that are hard at work back in the office, getting things done. But thrilled to be with you to talk about Seres and talk about the microbiome. And I think it's a great time to do so. A lot of folks that have been following the company know and for those that haven't been following the company, I think it's a good time to start looking that we think that we're at a critically important point with the microbiome as a new modality. And last August, we announced our Phase III ECOSPOR III results for our recurrent C. diff study, our lead asset. And we think that in any new modality, there can be a tipping point, right, where you can say, look, there's conviction that there's a technology, that there's approach, there's a new modality that's here to help patients today, not decades off in the future, but really here today. And we feel like we hit that moment last summer with our Phase III results with ECOSPOR III. And we have an incredible opportunity and responsibility to help patients with recurrent C. diff with innovation that this field really hasn't seen in decades. So we are tremendously invigorated by that, excited by that. We're conscious of the responsibility towards patients in fulfilling our obligation in that dimension. But at the same time, Chris, we are as excited about what's next, right? And we think it's going to be an incredibly important year for us. We've got our Phase IIb study results upcoming, our induction results for our IIb study in SER-287 in ulcerative colitis. We're in the clinic in a study with our follow on the 287 with SER-301. We announced recently that we have gotten clearance from the FDA to begin our study for 155 for patients with GvHD. And we really think that this is just the beginning of the story of the microbiome as a new emerging modality. And we really feel that we're at the front end of it, that we're pioneering this new space, that we've got a set of capabilities and assets that are well positioned to help patients, and we're thrilled to be here to talk to you about it.

Terrific. Thank you. Very comprehensive introduction. A lot of exciting things to talk about, and we're equipped with so many great people to discuss. So I think you had in your script and comments for the first quarter you talked about all the progress that you're making kind of on the clinical, the regulatory, manufacturing and commercial fronts. So I'm sure we'll touch upon all of those. Would start obviously with SER-109, the data last summer, quite spectacular, really was absolute sunshine on the field after a couple of really rough years, right? I think the scientific premise and the work that had been done had been continuing to be explosive, but we really needed that pivotal trial to sort of give visibility into that path towards this becoming an actual commercial product. So again, congratulations on that, but that was still 2020. So now here we are in 2021. And I think everyone's kind of waiting on the open-label extension study, right? We're gathering 300 patients. I got to imagine that there's kind of an interesting learning that is happening throughout the organization as you're enrolling these patients in this study because there is that opportunity with the data in hand to demonstrate, "Hey, folks, this works." And you're enrolling more patients. And you're having an interface and a discussion with patients and with physicians and centers. And this almost kind of has this dress rehearsal component into a commercial launch. So can you talk to what ways you're developing, learning and experience from that? Like whether you're testing yourself to enroll more quickly as a way to increase adoption? Sort of what are we getting from? Because I get the sense that people are just waiting for the 300 patients to enroll, that should be straightforward and you need this for the BLA. But there's layers beneath that, wouldn't you say?

Well, so let me ask Lisa to comment. Chris, I think it's the safety dimension of things is the place to start, right? So the FDA had said to us that they were looking for at least 300 subjects on what was the winning dose, the higher dose of the Phase III. We had about 1/3 of those patients at the time that we read the release -- the August 10 release. And we've made great progress since then. I think in our last earnings call, we guided that we expect to finish enrollment in Q3, and then we'll have a 6-month follow-up. Maybe Lisa can comment further on the phase -- on the open-label study and our expectations around it.

Yes. So as you said, the data are out there. The data have generated a lot of excitement. So we've got a lot of interest, and it's a great opportunity not only to get the drug to a lot of patients, but to continue to educate, right, on what the therapy is, how it needs to be used, what its place in the treatment paradigm is. And we're really thrilled with the response to the therapy.

You talked about how the enrollment criteria -- you got the FDA to kind of agree during this phase to expand that a little bit. I think if you look at the enrollment criteria for the Phase III ECOSPOR trial, it was for a second recurrence and beyond. And I think you talked about being able to enroll patients with a first recurrence. And that may seem like a nuance, but The Street is very keen on thinking about the ultimate TAM and how the label is going to look and who's going to qualify. Walk us through a little bit about how that's going? Are you seeing the ability to enroll those patients? What might be their contribution to the total population at the end of the day from this open label study?

So in an amendment, we had asked the FDA to allow us to improve first recurrent subjects, and they allowed that, right? And for us, it opens up, of course, the patient population for the open-label, but it also is a data point that we find encouraging as it relates to how they may be thinking about the label. Of course, the label will be determined at the end of the BLA process in negotiation with the FDA. But we're encouraged. Maybe I can ask Lisa to comment just medically on how we think about first recurrent versus multiple recurrent.

Yes. I think we've been pretty clear that from a medical standpoint, that we think that the dividing line really is between primary and recurrent, so that there's really -- by the time you get the first recurrent, second recurrent, they're all indications of a dysbiotic state. So that's why we believe that medically it makes sense to include these patients, and we are seeing them. They're not as common as the later lines, but we're seeing them.

Is your hit rate as good? Or is it better to be able to enroll those patients? Sort of what's the mindset of the patient who is having a first recurrence?

I don't think we can really say yet. I mean we're in the throes of it, right? So well obviously, we -- as you see patients who are further down the line, they've had just more experience with the horrors of C. diff. That's not to say that you don't see first recurrences that have had it with the continuous diarrhea also.

And is there a difference in sort of like the treatment setting? Where is the patient by the time you're trying to get them to enroll if they're first recurrence versus a latter recurrence? Is there more of an inpatient-outpatient divide? Maybe just comment about the sort of the clinical backdrop that you're seeing these patients in?

Yes. We will be able to comment. We can't -- I don't think it will be -- it would be premature right now for me to try to give a sense. We're in the throes of it.

Okay. But if I had to just sort of make a reasonable guess, first recurrent patients, typically, by the time they're contemplating, doing something more interventional rather than just the generic antibiotics. These are patients who were hospitalized in general? Is this -- are you thinking about the interface that the therapy is being introduced is on an outpatient basis, inpatient, 50-50?

Well, I can speak to what we saw in our trial. I don't know if Terri wants to -- yes. I mean, we had an awful lot of outpatients -- patients who start as outpatients. In fact, that was the predominance that we saw in our Phase III study. What can happen is during the throes of the C. diff infection, they may have to enter the hospital briefly. And that just depends on how significant the diarrhea is. So I don't know if Terri wants to speak more to what we would expect.

Sure. So I'll speak to the part of your question, Chris, where you asked where SER-109 would be primarily administered, and that is in the outpatient setting. And the reason why is because the way the disease works, right. These patients are very sick with the C. diff spores producing the vegetative bacteria, almost like little factories. And that sents them into the hospital, but vancomycin will kill off that vegetative bacteria pretty quickly. And so the hospital's incentive is to discharge that patient as quickly as possible, right? And so they finish the vancomycin and then start SER-109, and the role of SER-109 really being to shut down that factory before it can reopen, right?

Okay. And then while I have you as well, we're thinking about -- and with, Lisa, the pivotal trial took a look at what the efficacy profile was like at 8 weeks. And then you followed up later last fall with the 24-week data. So -- and that showed that there was very good durability of the benefit that you saw. So when we think about an individual patient, should we think that this is kind of more of a one-and-done kind of treatment once they have this? I mean recurrences are just so common with this condition, right? I don't believe there's a reason why someone wouldn't be able to -- let's say, they received the therapy, still had issues, they could try it again. But from a modeling perspective standpoint, when we're thinking about the number of patients who are out there, if someone gets the treatment, is that kind of it for them? I mean, certainly, it's not a chronic disease. Hopefully, you're trying to solve that. So maybe you can help us understand how we should think about how many times a given patient who goes on therapy would actually get treated.

Lisa, do you want to start and then -- yes, and then maybe Matt can comment afterwards scientifically.

Yes. Just from a medical standpoint, as you said, our data indicates that most patients are durable -- their response is durable. If someone were to get another treatment of antibiotics that cause disruption, there's no reason why they couldn't have a restoration again with 109. I mean that makes perfect medical sense.

Yes. Chris, I mean, just keep in mind, our drug is designed to restructure the microbiome of someone who has C. diff and is susceptible to C. difficile infection. So our whole goal is, of course, to increase the diversity of commensal bacteria that has been lost often in these patients and then as well bring onboard the back train our drug that changed that metabolic landscape in the gut to be unfavorable to C. difficile growth. So -- and our data has shown that we get a durable engraftment of the bacteria. They stay there after we cease dosing. But certainly, if over time we saw a waning or a senescence and a shift in the microbiome back, for some reason, say someone went on another antibiotic, as Lisa says, there's no reason why we wouldn't be able to retreat them with SER-109. And I think the core pharmacological concepts of the drug would hold.

Great. And then if I go back to the Phase II, which then became the Phase III and how the protocol revised. One important aspect of that was selecting patients, the diagnostic criteria, right, finding evidence of the toxin that's in place. And I think what's happened in the real world is that there is some different degrees of adoption of methodologies for selecting patients. And that had been back a couple of years ago, when you talked about revising the Phase III, a process that was evolving and becoming more and more what people were looking for, toxin. Where are we right now in the real world in terms of how this disease is being diagnosed? And should we be thinking that there's anything specific to the label language that might require some degree of specific diagnostic mode be used to identify patients so that they could be treated?

So Chris, in the Phase II to the Phase III, you may remember, we made 2 -- I think 2 major classes of investments. One was on the dose that we used. The second was, as you mentioned, the diagnosis. We felt that the adjustments made to the diagnosis would give us the most interpretable data set. But maybe Lisa can comment on our perception of real-world practice and how that manifest itself as it relates to the drug.

Sure. So C. diff remains a clinical diagnosis. The diagnostic test that's used is part -- just part of the clinical diagnosis and depends a lot on what tools are available in a particular setting, what agreements there are between institutions in terms of when a test can even be ordered. So just suffice it to say, it's a whole package picture that's presented in terms of making that diagnosis. And we continue to see that everybody is concerned about over-diagnosis and making sure that you're not including people who have post infectious, irritable bowel or just are in a carriage state. That just -- all that does is result in more antibiotics being thrown around. So you see all sorts of ways that people are going at trying to make sure they're getting a true positive.

Right. So you established that in the Phase III trial you require that there'll be evidence of the toxin present. What percentage roughly do you think of the U.S. practitioners are using that methodology now in terms of establishing a diagnosis of C. diff? Is that 1/3, 1/2, 2/3?

I think most are using some kind of an algorithm. And I can tell you, I've now seen -- I'm seeing algorithms from all over the country and whether it is a PCR reflexing then to a toxin or some other test or a combination of GDH reflexing to a PCR, I see very little in the way of actual only PCR in terms of what we're seeing. Now you can see in some published reports that PCR is the most common, is the easiest. But you see on most lab readouts that they're encouraging, if not requiring multiple steps to be in play, whether they're clinical steps or other diagnostic steps.

Including testing specifically to the platform?

Yes. Absolutely. Yes. The issue with toxin is not as sensitive, so that one has to backfill with either another test or clinical acumen.

Will you guys be involved with sort of maybe influencing a recipe or a paradigm, if there are so many different protocols that are out there? And I think when you think back to the treatment options, it reflects some of that, right, very disparate, some things that have been around forever. This represents a new paradigm in some respects. And so are you planning on being able to play a role in constructing sort of the new paradigm or some protocol so that it becomes a little bit more formulaic and standardized?

I think our data are going to speak for themselves. And in fact, we are in the process of getting some more of that diagnostic data out. And I think then the leaders in both the ID field and the GI field will run with that data.

Okay.

And Chris, maybe just to follow-on on that. I think maybe somewhere in your question was where FDA may land on this, and we don't speak for the FDA. But the FDA has historically not been in the business of prescribing how medicine is practiced as it relates to test and methodologies. So we don't expect that to be a constraint for us as we move forward.

Right. Perfect segue. So an Advisory Committee is expected. I think you talked about that during the last earnings call, which isn't surprising to anybody or shouldn't be given the novelty of the therapeutic approach. They're going to gather a bunch of people, probably based, and won’t be so expensive. What are they going to talk about? Help us understand, to some extent, prepare the potential list of questions. I mean, what's your sense for how we should be thinking about that?

Lisa?

Yes. No, I think you've said it right there. It's a novel modality. People want to understand what the drug is actually comprised of, how is it made, what's the effect on the body, how do we -- how can we tell where it is and where it isn't. And I think it's going to be largely an education process.

Okay. As opposed to anything controversial because speaking of controversy, the FDA themselves had certainly highlighted concerns about FMT, fecal microbiota transplant, going back now a couple of years, kind of a doctor's alert, a gathering of folks from industry and experts as well. I think this is now almost 2 years ago, about 1.5 years ago. So the FDA has certainly been aware of the issues in terms of the overall backdrop there. So it will be interesting to see how this is juxtaposed. How this is made? So Matt, let's turn to you. Everything in the world seems to be on short supply, whether it's chips to make automobiles or just components, et cetera. Give us some confidence in terms of your manufacturing process, your supply chain, that when it's time for the curtain to go up that you're going to feel as if you're ready to have commercial scale product available with the kind of consistency, et cetera, that's going to be what would be called for?

Well, Chris, maybe I can start and then ask Matt to comment on some of the least asked questions. And you brought up the idea of safety, which I think is also something that we should talk about. But just maybe a little bit of context. When the company was founded, the folks that really constructed the company, I think, had some vision that in a new modality, controlling manufacturing allows you to really control your own destiny, right? And there was an element of that. There also is probably an element of practicality in the sense that we deal with bacterial spores. Most conventional biopharma networks and plants, when you talk about bacterial spores, they want you to get those spores as far away from the plants as humanly possible. So there is some element of vision and practicality that catalyzed the company really cultivating, investing and creating capabilities in the fashion along the way, which we think are not commoditized, that maybe are underappreciated and certainly are strategic capabilities and assets for us. So in terms of what we control, there's elements of our supply chain in our manufacturing process, which are less commoditized that we outsource, there's elements that are more commoditized that we work with. But we really think that manufacturing is a critical asset. And you brought up the question around safety that the FDA had been focused on historically around specifically the use of FMT in recurrent C. diff. And maybe I can ask Matt to comment a little bit more comprehensively on that.

Sure. So Chris, just a quick point on our manufacturing, material, supply chain, et cetera. I mean, as Eric said, we're in a position and continue to scale that and sit in a good spot and as well, which we didn't touch on, is all the identity, purity, potency, assays, et cetera, that are required for product release. And of course, we've been engaged with the agency for quite some time around those various different specifications, et cetera, and feel we're in a strong position to move the product forward into a commercial setting. With respect to the safety itself, as Eric pointed out, really SER-109 was designed with safety in mind from inception. And really from the ground up, the drug itself is designed to contain the active bacteria and not all the other components of school that you will find in an FMT or an FMT product. And really, we do that by actively fractionating and purifying the bacterial spores. And there are several advantages to that. One, of course, is that you have the active bacteria. Number two, in terms of dosing, of course, you can be -- this is a live biotherapeutic. So once it's dosed, and it's in the body, the body is being used in a sense as a bioreactor. And of course, that has important advantages in terms of scale of manufacturing, et cetera. And then lastly and most importantly, is that this manufacturing process and numerous steps in it inactivate various viruses, vegetative bacteria, fungi, et cetera. And we have done rigorous product testing to demonstrate that inactivation across a broad range of pathogens. And we get the question a lot of times of, well, can't donor screening accomplish that? And the answer is no, not alone, right? Donor screening can help on the front end, but we have certainly seen that the inactivation steps that we've introduced into the manufacturing process specifically knocks back various different pathogens that could squeak through on a donor screening, and particularly in the context of emerging pathogens, right? SARS-CoV-2 is a perfect example. Look at our recent global pandemic. There were no diagnostic tests for SARS-CoV-2. So -- and people didn't even know the virus existed for a period of time. And the FMT -- the FDA put out an alert, right, around concerns around the transmission of COVID. We have data in hand that shows that our manufacturing process actually inactivates coronaviruses like SARS-CoV-2, providing that key layer of safety in addition to what could be achieved with something like donor screening alone.

Yes. No, I think you highlighted that during the call as well. That whole notion that screening works as long as you have a diagnostic assay and you know what you're looking for. But in the absence of that then a more holistic approach certainly is differentiated. Let's turn further to the commercial side and think about pricing a little bit. And Terri, I think one of the things that you like to help frame the discussion is you draw analogies to other therapeutic classes. But there's quite a range when I think you look at Street estimates in terms of how people are thinking about what the pricing and the cost of this therapy can be. Help sort of rank for me how you're thinking about what considerations are, kind of really important. Obviously, there's the patient, the physician, but the payer component of it? You talked about doing primary research and haven't yet shared some of that. But what's the latest as we sit here now approaching mid-June? And what you're willing to share? How you're thinking about pricing?

Sure. Well, I think the bottom line is that we have time, right, before we launch to determine the final price, and we'll take that time certainly. But what I'll also tell you is that coming out of the remarkable ECOSPOR III data last summer, I did embark on a series of tests with payers because as ambitious as the Seres team was prior to me joining the company and getting the data, they weren't as ambitious as to actually test the profile that we got, which was quite tremendous. So as you might expect, given the clinical value of the product, right, and the high unmet need and lack of innovation in the category that Eric referenced earlier, payers recognize this. They're really receptive to a product that can more effectively treat these difficult to manage patients and prevent recurrences that involve additional hospitalizations and antibiotic use that run, on average, $34,000 a year per patient. They indicated willingness to pay for innovation. And in fact, in recent testing, I think you referenced this at a high level, but I'll double-click on it. The payer thinks SER-109 are very high-value rating and, in fact, in the same neighborhood of some life-saving hepatitis C medications. So we were quite pleased with that. And I guess, I would say, in closing, we have a very strong value proposition, right, underpinned by a tremendous clinical profile and a high unmet patient need and costly health care system outcomes, if you will. So our goal is to determine the right price that provides the right level of patient access, but also returns value for the innovation that we're bringing.

Great. I'll turn to David here and talk about your pen is going to have to sign off on some budgeting. Two levels, obviously, in the operating expense side and the marketing stuff. How much money you're going to give to Terri? And maybe you probably have become increasingly familiar with what your partners over at Nestlé Life (sic) [ Health ] Sciences can bring to bear. But David, help us understand how you're thinking what the level of investment that's going to be required in the commercialization? And when we should expect that cadence of investment to really begin to step up?

Yes. Thanks, Chris. Look, I think that's all in front of us, right? I think we're going to ensure from a commercialization standpoint that we're appropriately resourcing SER-109 to ensure success as our -- as the first microbiome product that will be commercialized. So again, I think a lot of good work has gone into helping to understand what will be needed. That will continue. And as I said, we're going to ensure that we're appropriately resourcing things on a go-forward basis.

Most people are not going to...

And maybe I can -- sorry, Chris, I'll just add too. I agree 100% with David's comments, and maybe I can just add to them, which is we have been focused for some time on some of the longer lead time, critical longer lead time items that we think put us in the best position to be successful. So whether it's payer research or -- and some of the data from that research we've included in our corporate deck, which is available for people to review. Branding analysis, we've hired, trained and begun to deploy a group of MSLs. We think that medical education is critically important in this field, enhancing our supply chain and capability and capacity to produce product. All of these things together are things that we've been working on for some time, and we're focused on serving patients and creating value and following the Phase III results. We were able to support the company financially in a position, which allows us to move forward aggressively in those dimensions.

And sorry, maybe if I could just also jump in. I mean, after 5 days with the company and a lot of discussions, we've got the right people around the table -- around this table and the rest of the organization to really think through this in the best possible, optimal way for both SER-109 and for the company overall. So I've been tremendously impressed with that.

I think it's quite an adventure that you're about to embark on. And so from that standpoint, figuring out what the best approach is feels as if it's going to be kind of learning as you go to a certain extent. So we certainly wish you well with all of those things. I do, with 10 minutes left, want to make sure we're touching on 287. It's the next catalyst. It's the next opportunity. You talk about top line data midyear. And then I think it's "additional mechanistic results" later in second half of '21. If I'm preparing what we're thinking about what data we're actually going to see top line, can you help us help frame that? I know you do have -- we'll put a little shout out to the upcoming KOL event that you have, which will help remind people about the disease context. But in particular, what's coming up with the top line data?

So thank you for the shout out. June 21 is the date, just to remind everybody. Hope everyone attends and tunes in. So we expect to release preliminary induction top line results in mid-2021, Chris. And I think you've seen from us in the past, our practice has been to be particularly rigorous in terms of the amount of data that we release, the quality of data we release. In terms of mechanistic data to the question, remember that we continue to feel -- we have felt historically that the microbiome analysis is hugely important to not only the program that we're focused on but the platform in general. It was our microbiome insights that really allowed us to guide the journey for SER-109 from the Phase II to Phase III and the readout for the Phase III, which was positive. We are precluded from working on that microbiome analysis until we unblind the top line results. So we can't start that work until the clinical data is released, and then we start the microbiome analysis. So as we have in the past with other programs, you'll likely see that microbiome analysis lagged by a couple of months, a few months. So that's the plan. And that's what we intend to release and the cadence that we tend to release it.

So ECO-RESET, I think, the end was a little over 200, 203 patients or something. I think in the fourth quarter last year announced that you were fully enrolled. So the top line result, the patient population will be that full end of those 200 patients. And then perhaps when you say preliminary look at induction, there's the regulatory requirement like the Mayo 3 component scoring system, et cetera, which has become the blueprint for how you get drugs approved in UC, right? So should we be thinking about it in terms of each of those components for all 200 of those patients?

Sure. Lisa, do you want to comment?

So we will have the remission determination. And of course, going with that or that each component that goes into that, so we will have that data to be able to look at, yes.

Okay. And then how should we expect the comparison of placebo nontreated group to behave in this milder patient population? I think a lot of us are more accustomed to looking at the moderate-to-severe patient populations from biologic studies, from some of the advanced orals, et cetera. What would be the expectation for how you think the placebo group will perform across these criteria?

Sure. So -- sorry. Go ahead, Lisa. We get the question. In the 1b results, we saw a tremendous signal. We saw 0% remission in placebo, but I think we get the question fairly often as to do we expect to see that again? And maybe Lisa can handle that one.

Yes. We don't expect to see 0. We are hoping that it will stay low. However, we are using a centrally red blinded endoscopy score as part of the Mayo. So the more objective stuff you have in there, the better your likelihood of controlling the placebo. You said -- you pointed out that there's not much data in the mild-to-moderate space to benchmark against. You can look at some of the aggregate net analyses where they look at -- it's around 6% to 9%, knowing that the trials were run a little differently. So that range would not surprise us.

Got it. And then with the 2 treatment arms, there is a difference in regimen. One of the arms has the same dose throughout. Another has after 2 weeks a step down. What should we hypothesize would be the difference in the kind of results you may see -- may not see. But I mean, with the initial leaning the -- we may see a stronger efficacy profile with the same dose or we may see a better safety profile with a step down dose. Those will be my preliminary hypotheses, but help me understand what yours are to have decided when you're sitting around the table, yes, let's do 2 treatment arms?

Well, Chris, I think it's -- we haven't gotten in the business of predicting what we'll see in each dose. Maybe it's helpful to just talk about why we...

Yes, just the hypothesis.

Studied the step down dose. And then we could -- yes, from there. So maybe I'll start and I'll ask Matt to comment. So look, 287 chronic therapy, 700,000 UC patients in the U.S., certainly more globally. We are optimistic, and we saw a really interesting signal in the 1b study. If we're successful in the IIb study, it's a lot of bacteria to deliver, right? So as we think about the supply chain, plenty of precedent of procuring and processing raw biological materials into therapeutics, whether it's blood fractionation or [ heparin cremerin ]. So we think we can do it, certainly. But if we are able to treat patients with that step down dose, it provides a significant relief on the supply chain itself. And maybe I can ask Matt to comment on the idea behind it, the justification for why we're testing it, and we can go from there.

Sure. So Chris, as you know, we spend a lot of time looking at how the microbiome changes in our patients through time, what are the metabolic implications of that, and how durably do the bacteria that we get on-board in the gastrointestinal tract stay there and as well as how durable are those various downstream metabolic changes, et cetera, that are tied to various disease-relevant pathways. And so our work from the Phase Ib really demonstrated that even after dosing patients and ceasing dosing at 8 weeks that there was a durable response in the microbiome after -- 4 weeks after. But more importantly, what informed that step down dose is that we saw the kinetics and magnitude of engraftment in that daily dosing arm where we saw the largest number of clinical remissions max out around 2 weeks after dosing and then remain very durable even, as I said, beyond. And so it was really armed with that information that we decided to evaluate whether we could step the dose down with a lens towards potential manufacturing advantages on the downstream. So I think our drugs have had a placebo-like safety profile across our clinical portfolio. And so we don't anticipate that we would observe some difference in the safety profile of patients who were at the dose of the Phase I versus the step down. It's more about the drug pharmacokinetics and potential downstream advantages with respect to basically the amount of drug that needs to be supplied.

Got it. And then I'll squeeze in one on 301 here. Phase Ib is ongoing. We're not supposed to, but we will make cross-trial comparisons to compare the 301 data with 287. So can you at least warn us in what ways you think that will be appropriate or maybe warn us against ways that will be especially inappropriate? Is there something very different about the patient selection criteria, about the structure of the Ib that would really make us put on a different lens when we look at 301's 1b data when we see that versus 287?

Maybe Matt can comment scientifically, and Lisa can comment from the clinical side.

Lisa, do you want to go?

Sure. I'll start. So I think there's nothing wildly different with regard to the trial design. They're both in mild to moderate. The 301 does allow naïve patients. But I think the biggest thing is that it's just -- it's a different drug, right? It's a different therapeutic entity, and maybe Matt can explain.

Yes. So look, Chris, as you know, we've been building really a research engine at the company for just over 9 years now, right, which really allows us to dig deep into understanding which bacteria are the bacteria that are interacting with host cells and tissues in the places of disease relevance. And really across our clinical portfolio, we've continued to learn about which specific bacteria do that really well, which do it sort of well, which don't do it at all and as well as sort of then how that plays out in terms of host -- what the host does. And we've done that both looking in human subjects, but then really using the power of our strain library and all the nonclinical assays that we've developed over the years to really get from just association in humans to then actually proving causality. And really, what SER-301 represents is an optimization of the bacteria in the drug for the bacteria that we have identified using our collective knowledge across our clinical portfolio to be particularly important. So as an example, we have learned in our clinical portfolio about bacteria that engraft early versus those that engraft late, and that can be different in different patient populations. So that kind of information is designed into the SER-301 composition to make sure that we get the right bacteria on at the right time and the right patient populations. The drug is designed to decrease pro-inflammatory bacteria that lead to inflammation at the epithelium. It's designed to repair that epithelium. And so there's bacteria in there that we have identified are particularly optimal at driving those kinds of signals. So what I think we see with 301 is really a concept of a first-in-class of 287, followed on by a best-in-class in the context of 301, so that type of drug development modality. And if things work out as expected, we might expect SER-301 to be optimized for certain pharmacological properties. Importantly, we've incorporated data, again, I just want to emphasize this, from across our portfolio, not just the 287 Phase Ib trial as well as all of our translational preclinical work, all of which is advanced substantially since we brought 287 in the clinic. So we're really leveraging all of that collective knowledge into the design of 301 and further as well into the design of our drugs like SER-155 and others.

Right. Okay. We didn't get to touch on SER-155, but we'll have other conversations, which you'll have to promise me. So we're into a little bit of overtime, but I have to ask one last question. So what is this Zoom backdrop that you guys have? It kind of has this [ Matisse ] meets the Flintstones. Where did this come from? What is this image?

I don't know if it's more [ Matisse ] or more Flintstones but Matt as the scientific leader of this company maybe is best positioned to comment on the design of the backdrop.

I don't -- I'll tell you the following. All I know is it always makes my head look weird. So I don't know. No. This is an image of various cells that a fan of the company put together for us and then as well put some nice color overlays into it. So it's a mix of biology with some interpretation on graphic design. So yes.

Excellent. Hashtag fan art, we're all for it.

Yes.

Okay. Thank you, team Seres Therapeutics. We appreciate you joining us. And we look forward to keeping in touch, and everybody see you on June 21 for the company's analyst meeting discussing 287. Thanks very much.

Thanks very much, Chris. We appreciate it. Thank you. Bye.