Seres Therapeutics Inc (MCRB) 2017 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Third Quarter 2017 Seres Therapeutics, Inc. Earnings Conference Call. (Operator Instructions) As a reminder, this call is being recorded and will be available on the Seres Therapeutics website.

I would now like to turn the call over to Dr. Carlo Tanzi, Head of Investor Relations.

Thank you, and good morning. A press release with the company's third quarter 2017 financial results and a progress update became available at 7:00 a.m. Eastern Time this morning and can be found on the Investors & Media section of the company's website. We've also posted slides on our website that will accompany the information discussed in our prepared remarks. I'd like to remind you that we will be making forward-looking statements relating to the timing of data for and progress of our clinical studies, the potential approval or registration of our various therapeutic candidates, the potential for SER-287 to offer a novel non-immunosuppressive treatment option for ulcerative colitis patients, our development plans for our other product candidates, the promise and potential impact of microbiome therapeutics and the value of the SER-287 study results for the development of SER-301. Actual results may differ materially. Additionally, these statements are subject to certain risks and uncertainties, which are discussed under the Risk Factors section of our recent SEC filings. Any forward-looking statements made on today's call represent our views as of today only. We may update these statements in the future, but we disclaim any obligation to do so.

On today's call, I'm joined by Dr. Roger Pomerantz, Seres' President, CEO and Chairman; and Eric Shaff, Chief Financial Officer. Our Chief Scientific Officer, Dr. David Cook, will also be available during the question-and-answer portion of the call. Before I pass the call to Roger, I'd like to mention we'll be participating in a number of upcoming investor conferences later this month, including Stifel on the 14th in New York, Piper Jaffray on the 29th also in New York and the Evercore ISI Conference in Boston on November 30. I'll now pass the call to Roger.

Thanks, Carlo, and thank you all for joining us. Seres has made excellent progress in our efforts to advance our microbiome pipeline. Seres is focused on developing new therapeutics for serious human diseases, where dysbiosis of the gastrointestinal microbiome is thought to play a central role. We believe that microbiome therapeutics have the potential to address multiple disease states, and our R&D efforts target therapeutic areas where compelling clinical and/or preclinical data indicate that the microbiome is important, such as infectious diseases, metabolic diseases and inflammatory and immune diseases, including immuno-oncology.

On today's call, I will provide an update on Seres' substantial progress advancing our pipeline, including most notably, the positive data we obtained with SER-287. So let's begin with SER-287. SER-287 is an orally administered, biologically sourced drug candidate comprised of a wide array of species of natural commensal bacteria in spore form that reside in the healthy human gastrointestinal tract. Our advanced manufacturing processes isolates and purifies the spore fraction from human donor material. These hardy bacterial spores are metabolically inactive until they reach the germination conditions of the colon where they transform into a physiologically active state. Both preclinical and clinical studies have indicated that fecal microbiota transplants, or FMTs, would benefit ulcerative colitis patients. Repetitive fecal microbiota transplants have been evaluated in at least 4 randomized placebo-controlled studies of patients with ulcerative colitis and clinical efficacy was demonstrated. This shows that modulation of the microbiome can lead to clinical remission and provide strong clinical evidence supporting the role of the microbiome in ulcerative colitis. Last month, we announced positive results from the SER-287 Phase Ib study, a randomized double-blinded, placebo-controlled multiple dose trial in 58 subjects with active mild-to-moderate ulcerative colitis who were failing their standard therapy.

As seen on Slide 4, subjects were assigned to 1 of 3 SER-287 treatment arms or a placebo arm. The SER-287 arms included a daily dosing arm with vancomycin pretreatment, a weekly dosing arm and a weekly dosing arm with vancomycin pretreatment. The study's endpoints are listed on Slide 5. Total modified Mayo scores were collected in all study subjects at a pretreatment baseline at the end of treatment. The Mayo score is evaluated based on measures of stool frequency, rectal bleeding, a physician's global assessment and endoscopic evaluation. In order to maximize the objectivity of the endoscopic evaluation, all endoscopy recordings were assessed by a blinded central reader.

Two prespecified intent-to-treat statistical methods were used to analyze SER-287 Phase Ib efficacy outcomes. These are illustrated on Slide 6. The first method analyzed all observed data and the second analyzed missing data counted as failure. Analyses from each approach demonstrated that SER-287 administration resulted in a dose-dependent improvement of both clinical remission rates and endoscopic scores. The highest efficacy was observed in the vancomycin pretreatment daily SER-287 arm of the study.

As seen on Slide 7, based on an intent-to-treat observed data analysis in this arm, 40% or 6 of 15 patients reached remission, while only 10% or 1 of 10 patients achieved this endpoint in the placebo group. The single placebo patient who achieved remission actually had a flare during the study and received steroids, a protocol violation. However, because this patient was in clinical remission at the end of the study, the prespecified observed data approach counted the patient as a remission, even though they violated protocol.

Now moving to Slide 8. Under the other prespecified method, missing data counted as failure. Again, 40% or 6 of 15 subjects reached clinical remission but now compared to 0%, 0 of 11 in the placebo group. Even in this rather modestly sized initial study, this result was statistically significant with a p-value of 0.0237. In addition to the clinical remission endpoint, we also showed -- we also saw compelling treatment effects of a similar magnitude on direct endoscopic measures in both statistical analyses. I also wanted to discuss the clinical response data observed in the study. We observed high clinical response placebo rates that were not differentiated from the rates in the 287 treatment arms. Based on the drawbacks of clinical response endpoint, the FDA's latest regulatory guidance from August 2016 now recommends the use of clinical remission, and not clinical response, as the primary endpoint in all registrational studies for UC. Clinical response is a subjective endpoint and prone to high variability. As such, high placebo rates in clinical response have been clearly demonstrated in several previous Phase II trials in UC with drugs using diverse mechanisms of action. We believe that response rates are very difficult to interpret in ulcerative colitis clinical studies, particularly when interpreting data from any modestly sized study.

Now as part of the FDA's most recent guidance, modifications were made to the definition of clinical remission. These can be seen on Slide 9. The new FDA guidance requires that for clinical remission to be achieved, a subject must have a 0 score on both rectal bleeding and stool frequency Mayo subscores, and a 0 or 1 on the endoscopy subscore. Because this FDA new guidance was implemented after the SER-287 study was initiated, the statistical analyses defined in our protocol were based on the prior standards. We have, however, also analyzed our study results based on definition of clinical remission included in the new FDA guidance. These results can be seen on Slides 10 and 11. When analyzed under the new FDA guidance, the SER-287 study efficacy results remain highly compelling. Indeed, the level of statistical significance associated with endoscopic improvement endpoint for the SER-287 daily arm is increased when our data is analyzed per the new FDA guidance defining clinical remission. This improvement is seen when the data are analyzed with both the observed case analyses and the missing data counted as failure analyses. Interestingly, in the missing data counted as failure analyses using the new FDA guidance, both the clinical remission rates and the endoscopic improvement rates were statistically significant in the SER-287 daily arm. As previously mentioned, clinical response is not defined nor recommended as a primary endpoint under the new FDA guidance.

Now moving on to SER-287 safety. The SER-287 safety and tolerability profile was very favorable. Results demonstrated no imbalance in adverse events in the SER-287 treated patients as compared to the placebo arm, and there were no drug-related serious adverse events associated with SER-287. Now interestingly, we also observed that SER-287 subjects in the daily dosing arm experienced fewer GI related adverse events than those treated with placebo. And we believe this represents an additional independent line of evidence pointing to a beneficial SER-287 impact on disease activity. If you are interested in additional information, I would point you to the detailed study results slides that are available on our website.

We continue to look forward to additional important data from the SER-287 Phase Ib study, including detailed microbiome analyses, histology and other biomarkers in the coming months. We believe these data could provide further insights into SER-287's mechanism of action and could help inform future 287 development efforts and the development on -- of follow-on products, including our fully synthetic SER-301 program.

Overall, we were very pleased with the SER-287 Phase Ib results. Our objective with SER-287 is to develop a highly effective, orally administered therapeutic option which is importantly not immunosuppressive. Ulcerative colitis is a highly debilitating condition that is often refractory to all available treatments. There is a high need for new mechanistic approaches, and it is our hope that SER-287 will provide an entirely novel mechanistic approach. We are now considering a development plan that maximizes SER-287. We intend to meet with the FDA to determine the optimal next steps for development once we obtain the remaining study data.

Now moving to our SER-109 program Phase III for patients with multiply recurrent C. diff infection. We have continued to make progress adding clinical sites and actively enrolling patients. We also recently obtained clinical trial application clearance from Health Canada and expect to have Canadian clinical active sites in the coming weeks. To remind you, SER-109 has received both Breakthrough and Orphan Drug designations in the U.S. and the FDA has demonstrated a deep interest in the microbiome as an important emerging therapeutic modality. Based on our discussions with the FDA, we expect that with persuasive efficacy and safety results from this single Phase III study, Seres would be able to file SER-109 for regulatory approval.

Seres had also continued to make progress driving the SER-262 Phase Ib study forward in patients with primary C. diff infection. The SER-262 study is notable that it is the first-ever clinical trial to evaluate a rationally designed, multi-strain fermentation-generated microbiome therapeutic candidate. In this first-in-human dose-ranging Phase Ib study, we are evaluating primarily safety and tolerability of SER-262 and also pharmacokinetics and pharmacodynamics as measured by microbiome changes. We will also evaluate clinical efficacy trends across the dose cohorts. We anticipate obtaining SER-262 Phase Ib top line study results in early 2018.

In addition to our 3 clinical stage programs, we continue to make progress in our earlier stage R&D efforts, including those in inflammatory diseases, metabolic diseases, liver diseases and immuno-oncology. Seres has just been awarded a grant of up to $5.6 million from CARB-X that will support the advancement of our preclinical SER-155 program. CARB-X is a public-private partnership devoted to advancing novel antibacterial therapeutic approaches. We are developing SER-155, a rationally designed bacterial composition, to reduce rates of both serious infections as well as graft-versus-host disease in patients who receive either allogeneic stem cell or solid organ transplantation. The rational -- the rationale supporting SER-155 is based on clinical data showing that patients with healthier, more diverse gastrointestinal microbiomes have better outcomes than those with more dysbiotic microbiomes. We will continue to finalize the composition of SER-155. And with the support of CARB-X funds, we intend to move this program into a clinical study.

I'll now pass the call to Eric to review our recent financial performance.

Thanks, Roger, and good morning, everyone. Seres reported a net loss of $6.9 million for the third quarter of 2017 as compared to a net loss of $18.7 million for the same period in 2016. The third quarter net loss was driven primarily by clinical and development expenses, personnel expenses and ongoing development of the company's microbiome therapeutics platform. The third quarter net loss figure was inclusive of $23 million in recognized revenue associated with our collaboration with Nestlé Health Science. Please note that the $23 million revenue figure included a development milestone of $20 million associated with the initiation of Seres ECOSPOR III Phase III clinical study. Research and development expenses for the third quarter were $22.2 million as compared to $24.1 million for the same period in 2016. R&D expense was primarily related to Seres' microbiome therapeutics platform, clinical development of SER-109, SER-262 and SER-287 as well as the company's SER-301, SER-155 and immuno-oncology preclinical programs.

General and administrative expenses for the third quarter were $8.1 million as compared to $8 million for the same period in the prior year. G&A expenses were primarily due to headcount, professional fees and facility costs. The decrease in cash balance during the quarter was $3.9 million with operating costs for the quarter partially offset by the $20 million milestone from Nestlé Health Science. Seres ended the third quarter with approximately $171.3 million in cash, cash equivalents and investments.

I'll now pass the call back over to Roger.

This has been a period of important progress for Seres where the company meaningfully advanced its pipeline, obtained promising SER-287 Phase Ib study results, continued execution of the SER-109 and SER-262 studies and had exciting progress in our earlier stage R&D efforts, including advancing our initial -- our initiatives in immuno-oncology. I now want to provide some additional perspective on the SER-287 data. We believe these data are encouraging both as a future -- as a potential future ulcerative colitis therapy, but also more broadly for the microbiome field. Our SER-287 data provides the first-ever clinical results demonstrating the potential for microbiome therapeutics in chronic inflammatory diseases. We believe that these data sets provide additional support for the broad potential for microbiome therapeutics as a novel treatment modality with the capability of this new therapeutic approach to impact many areas of medicine. Of note, the ability of microbiome compositions to modulate immune responses in the colon, which is the body's largest reservoir for immune cells, including regulatory T cells, demonstrates the promise for microbiome drugs to not only interdict in autoimmune diseases, such as ulcerative colitis, but also potentially to alter the efficacy of immune checkpoint inhibitors that target specific T-cell subsets in cancer, in essence, in immuno-oncology. We are particularly interested in immuno-oncology as a therapeutic area. The rationale to further evaluate microbiome therapeutics development related to immuno-oncology comes from multiple published studies that provide preclinical and clinical evidence demonstrating that the composition of bacteria in the gastrointestinal microbiome may impact response to checkpoint inhibitor therapy. Also, as I mentioned, we believe our SER-287 data provides further clinical evidence for the ability of the microbiome to impact the immune system.

I will also mention landmark research published just last week in the Journal Science by Jennifer Wargo and colleagues from MD Anderson that further elucidates a specific microbiome bacterial signature that may influence the checkpoint inhibitor response observed in metastatic melanoma patients. Interestingly, this research also demonstrated that the favorable microbiome properties found in checkpoint inhibitor responder patients is able to be transferred to mice. We believe these data provide further support for the design of microbiome therapeutic consortia to augment the clinical benefit of cancer immunotherapy.

Please stay tuned for the additional news across our pipeline, including in immuno-oncology.

Operator, let's open up the lines for questions.

(Operator Instructions) Our first question comes from John Newman of Canaccord.

So Roger, I'm just curious, I know that you will be meeting with the agency to discuss the results of the 287 study. But I'm just curious as to what you're thinking at this point in terms of trial design there going forward? Are there specific groups of patients that you'd like to focus more on going forward? And are there other endpoints that you might like to look at?

Yes, so -- thanks for the question. It's a good one. Obviously, with this very good data, we have a lot of possibilities for what are the next trial or trials. Let me just say that the first thing we want to do is meet with the FDA and the next trial will likely be in a similar group of patients. There may be some changes, but we want to move this drug with some alacrity forward rather than just broaden it out into various agents -- various patient groups early on. That does not mean we don't see a huge future for this drug moving into earlier stage patients, later stage patients, even Crohn's disease. We are highly interested in pediatric patients, which is an orphan potential indication and that, as I've said before, we will discuss with the agency. But going forward, moving this drug, which we think, will be safe non-immunosuppressive into patients who are failing standard of care, which is what this patient group is, that's what's so important. I don't -- I think that was missed by some people. We are not just treating mild-to-moderate patients. We're treating mild-to-moderate patients, who are failing standard of care. And when they fail standard of care, they end up in immunosuppressive drugs, including, but not limited to, monoclonal agents against TNF and other mediators. We think that if we can keep patients out of the group of agents that lead to immunosuppression, and I might add, are very expensive, we think this is a sweet spot, both medically, most importantly, for the patients, and economically when you think about what pricing could be. So we will move this drug forward. We think there's a number of places it could go. We will though stay focused on this patient population of failing patients, as we move the drug forward. But again, I never like to put words in the FDA's mouth. And we'll wait until we talk to them. Obviously, we are very glad that the agency has also made this disease much more objective to study. And therefore, you get objective endpoint, such as clinical remission and endoscopy. We think this is not only for SER-287, but for all drugs being designed in ulcerative colitis, a real step forward.

Our next question comes from Mark Breidenbach of Oppenheimer.

So Roger, if you're likely to proceed with daily dosing strategy for SER-287 in ulcerative colitis, could you maybe just comment on the need for vancomycin pretreatment? I'm wondering if the bugs really need even a graft or if it's possible they're exerting beneficial effect, while they're simply transiting through the gut?

Another really great question. And we think that, first of all, the hypothesis of, whether it's due to transit or engraftment or both, will help us and -- we will be helped in that understanding when we have the microbiome data and some of the biomarkers that are coming forward. We believe that this is a clear important effect. The mechanism of action could be either or both of what you're describing. We think we'll be able to understand it better as we get the microbiome data. Obviously, we'll go to the FDA once we have that all in hand so that we not only know what is a really nice clinical effect but why it happened. That being said, when you think about something like vancomycin, as we said before, the vancomycin was put in simply because there was anecdotes in the literature in FMT and some preclinical data, not something that we were able to really reproduce in our laboratories. But since vancomycin, given orally, is very safe and only for 6 days as a pretreatment, we decided to study it in the best organism for microbiome experiments, which are humans. As you might have seen by the data, when you look at the weekly dosing, there didn't seem to be a difference with vancomycin. But obviously, we will make sure that, that is not or is the case. And again, I don't like to design the trial before talking to the FDA. But clearly, we would like to know, for sure, whether vancomycin is needed. I actually don't think it is but it's important to be absolutely clear as we move a drug or a drug combination forward in these patients. So we'll look at it carefully and discussions with the FDA, expect us to be able to sort it out. And I -- just looking at the data, as it's put together, if you are Bayesian with pre-test probability, you'd say that vanco probably isn't necessary, but we'll make sure of that.

Okay. That's helpful. Second question, if I may, on the therapeutic study, where, of course, looking forward to the top line results of this placebo-controlled trial. Given that FMT really isn't widely used in primary CEA recurrence, can you just remind us how you settled on the current trial size? How many doses of SER-262 are being tested in the trial? And how the maximum dose of 262 compares to the dose of 109 that has been used in ECOSPOR III?

Yes, so that's a really great question. So yes, We're still on track. And my guidance still holds of early '18. Remember, first of all, what this is. Some -- we've seen some publications from different groups about a first synthetic drug. SER-262 is the first fermented synthetic drug ever given to patients, ever given to humans. And that's important to note. The other two, 287 and 109, since we have the only drugs in the space are both biologically sourced, because this is a synthetic made totally in anaerobic fermenters, obviously, we did, with the FDA, put together a trial in Ib that was different from 287 as a first-in-man ascending dose looking at safety and efficacy for this first synthetic microbiome drug. We also are highly interested in whether the -- this engrafts and what the engraftment and diversity looks like in the microbiome. Again, this is the first time a synthetic was used. So you look for safety, you look for PK/PD, which, in this cases, effects on the microbiome. And then you setup like any ascending dose trial, you see safety in different cohorts and you see microbiome in the general case PK/PD in each of the cohorts. And then you look for efficacy trends. Obviously, the cohorts are really small, but are there to give us an idea on what the trends may be because what you try to do is use a typical first-in-man study to inform what the likely doses will be in a much larger Phase II trial. So we'll look for that. As we've said before, the dosing regimen, which went from 10^4 to 10^7 has been increased and has gotten some cohorts with multiple dosing, not only because of the data and learnings we had in the root cause analysis in 109. We're moving those forward. We haven't said exactly how high we're going, but we're comfortable with the extensions to an area with multiple dosing as well as higher dosing that will give us significant information as we think about what Phase II might look like.

Okay. So we will get those specifics with the top line data next year?

Absolutely.

Our next question comes from Joseph Schwartz of Leerink Partners.

I actually have two. So first of all, I was hoping you could talk some more about the analyses that you'll be doing on the 287 data, and what you hope to learn from these, and when we will see those results?

So obviously, as I said -- and it's a good question, let me just be clear about it. We have a number of serum stool and urine biomarkers, both for the microbiome as well as immunologically. We do have biopsy results that are being finished and read both before and after therapy. And of course, we have the kinetics of microbiome both during and after the 8-week trial. We think that that's important, as I said, not just for mechanism of action but to further complement it. We're looking in the future and maybe the next trial to also have maintenance, not just induction, pyrrhic victory if you induce and then have to not have a maintenance regimen. How we come up with what is a good guidepost for how you might study maintenance will be by looking at flares after the 8 weeks, when they are no longer are on our drug as well as looking for any changes in the microbiome or degradation in microbiome changes after the daily treatment is stopped. So we think that these are going to be important, not just for mechanism of action and understanding on a deep way immunologically and microbiomically how the drug, but also will be very important practically as we think about what is the reasonable maintenance regimen. Is it once a week? Is it once every 2 weeks? Is it once a month? We will get data, again, both from the microbiome and flares. We're following these patients out to 26 weeks. What we'll get -- that data will be coming out in the next number of months. We do want to do it in compendium, but we will bring it to The Street and not wait for a clinic -- a medical conference as rapidly as we can.

Okay. Great. And then on the 109 program, I was just wondering if you could give us any insight as to how the screen failure rate has been running in the Phase III, given your ROMA criteria is more rigorous than what was used in the previous program?

Yes, I haven't -- we haven't said exactly what the screen failure rate is. And I don't want to put a number on it yet because we're still seeing as it ramps up. But I can say, we've not been surprised.

Our next question comes from Bill Tanner of Cantor Fitzgerald.

I had a couple of questions, just back on the 109 in, a couple other calls going on today, so I apologize if it's been addressed. Is there any rough time frame as to when you think that further we should expect potentially some data from the study that you're currently enrolling? Or is it really too early there to try to comment on that?

Yes, I think, it's too early. We want to see the slope of the curve of enrollment. Remember, we're just opening Canadian sites. This is an international trial. We've gotten Health Canada totally on our side and that will continue to ramp up. I can tell you that there will be no interim analysis. We obviously, have a DSMB. And as you remember from the previous 109 study, there has been no safety AEs, so we don't want to comment on this one. But we think, we have several hundred patients under this drugs now and haven't seen any AEs. But obviously, we have an active thoughtful DSMB. I would give us a little more time before we can comment, but we were very happy to have Health Canada and the Canadian sites. They actually are very active and interested in the microbiome.

Got it. And then you mentioned that the -- if the data were persuasive, that they might form the basis for an approval. And I don't know, if it's an unfair question maybe to ask you, if there is a definition for persuasive, if it's in the eye of the beholder? Or is it the understanding that there's maybe a minimal treatment effect?

We are not hoping for a minimal treatment effect. We're thinking not only for statistical significance, but medical clinical significance. There is a difference there. Let me use as an example a drug that I helped develop, which is the Merck monoclonals to the cytotoxin of C. diff. As you remember, there were 2 enormous Phase IIIs for that in all of recurrent C. diff 900, patients and 1,200 patients. And one of the Phase IIIs failed. It did not have statistical significance. The second one just made statistical significance. And the difference between active and placebo was 11%. Let me say that again, 11%. And the drug was approved. We think that, that shows that there is a real urgency at the agency and in the community to get drugs in this space for patients who are sick and dying of the disease. We are not hoping for a de minimis effect, but it shows how important this is. And again, we're hoping for a statistical significance and clinical significance. Give us time, we'll get there.

Okay. And, I guess, the last question on 155. You mentioned the reduction in GvHD and a reduction in infection. I mean, is that contemplate -- are you contemplating that those -- one of those or both of those or something like that might be endpoint for approval?

Yes, this is really important. And I'm going to ask my Chief Scientific Officer, David Cook, who really lead the charge on getting the CARB-X grant to make some comments. But I would just say, these are the patients that I used to see when I was in practice. They're the sickest patients in the hospital, the hematopoietic stem-cell transplants, they're the most expensive patients in the hospital. And they don't die of their tumors. They die of two things, bacteremia and graft-versus-host disease. If we can change those two parameters by its very nature, you will change mortality. That's what you saw in the 2 trials. There are several trials, but the best ones from our colleagues at Sloan Kettering and at MD Anderson, where if people had a non-dysbiotic microbiome, they were less likely to not only have graft versus host and bacteremias, but it changed all-cause mortality. We would be aspirational. We're still preclinical but we think CARB-X saw this, as I do, as something that's very compelling and changing some of the sickest patients and the most frustrating patients to treat until now. David, maybe a few points?

Sure. First of all, I think, the data from Memorial Sloan Kettering is very compelling in terms of the association between the microbiome and these bad outcomes, infections and graft-versus-host disease. Importantly, what Eric Pamer and his group have shown is that infection is often preceded by domination of the gut by these multidrug-resistant organisms, like vancomycin-resistant enterococci or carbapenem-resistant Klebsiella. So the notion is if you can actually create a healthy microbiome, you're going to have fewer infections simply because you're going to decrease the burden in the gut. Secondarily, Marcel van den Brink and his group have shown in animal models you can prevent graft-versus-host disease by the proper set of organisms that actually reeducate the immune system in a way that leads to tolerance as opposed to activation. So we think there's good scientific data beyond the overall survival, as it gives us clues as to how to design SER-155, and that was the data that CARB-X looked at and thought that this was the program worth funding.

Thanks, David.

Our next question comes from Vernon Bernardino of Seaport Global.

I just had one question about the path forward for SER-287 and in particular the guidance that how it dovetails with current therapies and the guidance that the FDA provided. Do you anticipate that two things, you'll need to conduct a study in patients that are naive that have not been exposed to biologics, and then after that will also need to do another study that in 1 arm has biologics or rather both arms [seem] biologic as just then to determine the additive effect or any change in response when you add the 287?

Yes, so I love these clinical trial design questions. I think when you have compelling early data, you just have so many things you can do. You have to be able to whittle it down on what is the most important to move the drug forward. There will be a lot of life cycle management trials, I would say, with a drug like this. But your point is well taken. Remember, this is add-on therapy. These patients who are failing their therapy did not have the change. This was added on. And very few of them had monoclonal -- had ever had monoclonals. I don't like to put, as I keep saying, words in the agency's mouth until we talk to them. They are great colleagues of us and have worked very closely with us. Trials in the future will likely be add-on, I would say. What it would be add-on to would be something we will talk about. We would like to have a path as tractable and is clean to approval before we diversify. That being said, as I said before, we're very interested in pediatrics where those patients, as you may know, get very sick. We don't want to put them on immunosuppression. Safety and tolerability is the coin of the realm in pediatric disease. And we think a drug like this, that's oral, easy to take and, most importantly, does not have safety issues associated with it at all is perfect for pediatrics and, again, I'll remind you, is an orphan indication potential. So those are the things that we'll talk about, I think, in the first meeting with the FDA. But I wouldn't -- I don't want to say that we're going to do everything but nothing well. We want to keep it focused and tractable with a path to patients and approval. We're very excited about this.

Operator, why don't we end it there?

There are no further questions.

All right. Just -- this is Roger. I would just like to thank everyone on the call for your thoughtful questions. I also want to thank all the listeners for your continued interest in Seres. Please reach out to us if there are any additional questions. Thank you.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.