Seres Therapeutics Inc (MCRB) 2017 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Second Quarter 2017 Seres Therapeutics Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to introduce your host for today's conference Mr. Carlo Tanzi, Head of Investor Relations and Corporate Communications. Sir, you may begin.

Thank you, Amanda, and good morning, everyone. A press release for the company's second 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. I'd like to remind you that we'll be making forward-looking statements, including on the timing of data for our clinical studies, the design of our clinical studies, whether we are on track in our clinical development plans, any potential approval or registration of our various therapeutic candidates, the objective for SER-109 to meaningfully reduce the risk of recurrence of C. diff infection, the potential for SER-287 to offer a novel, non-immunosuppressive treatment option for ulcerative colitis patients, the timing of accounting for the Nestlé SER-109 Phase III milestone payment. 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. And with that, I'll pass it over to Roger.

Thanks, Carlo, and thank you all for joining us. Seres has continued to make excellent progress in our efforts to develop an entirely new class of therapeutics based on restoring the function of the healthy human microbiome. Seres is focused on developing new therapeutics for serious human diseases, where dysbiosis of the gastrointestinal tract 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 3 therapeutic areas, where compelling clinical and/or preclinical data indicate that the microbiome is important. These include infectious diseases, metabolic diseases and inflammatory and immune diseases, including immuno-oncology.

On today's call, I will provide an update on Seres' substantial recent operational progress, including most notably the start of the first-ever Phase III microbiome drug trial, the SER-109 ECOSPOR III study. SER-109 is a biologically sourced highly purified microbiome therapeutic candidate containing a consortium of about 50 bacterial spore types that represent a significant proportion of the microbiome found in a healthy human gastrointestinal tract.

Our therapeutic objective with SER-109 is to develop a convenient, highly effective and safe product that will meaningfully reduce the risk of recurrence of C. diff infection. The risk of C. diff infection is strongly linked to the use of broad-spectrum antibiotics. Antibiotics are known to cause a dysbiosis of the gastrointestinal microbiome leading to a loss of the normal pathogen resistance provided by healthy gut bacteria.

Ironically, the current standard of care for treating C. diff infection is only using even more antibiotics. While these antibiotics can effectively treat the immediate C. diff infection, these drugs further exacerbate the dysbiosis of the microbiome and result in a higher risk of recurrence of C. diff infection. The goal of SER-109 is to rapidly restore the diversity of the microbiome and reconstitute the normal state of pathogen resistance found in healthy individuals, thereby meaningfully reducing the risk of a future C. diff recurrence. Recurrent C. diff infection continues to be a major public health concern in the U.S. and around the world. In fact, an article published in the Annals of Internal Medicine just last month by [Ma et al] evaluated the recent epidemiology of recurrent C. diff infection in The United States and found that notable increase in the incidents of this infectious disease over a decade further highlighting the need for better therapeutic options in this expanding epidemic.

We believe that SER-109 may represent a dramatic improvement over the limited treatment options available today for these sick and complex patients. Seres has made excellent progress advancing the SER-109 program during the past several months and earlier this summer. We reported a number of positive developments. First, based on our continued productive discussions with the FDA, the agency agreed that our planned trial is a Phase III study. We expect that with persuasive efficacy and safety results from this single study, Seres will be able to file SER-109 for regulatory approval in this orphan disease.

SER-109 has received both breakthrough and orphan drug designations and the FDA continues to demonstrate deep interest in the microbiome as an important emerging therapeutic modality. We have been very pleased with the productive discussions and positive outcomes of our interactions with the FDA, and we look forward to continuing to partner with the agency as we move our deep pipeline forward. This past June, we also announced that we initiated the SER-109 Phase III study, an important milestone for the company and for patients suffering from this infectious disease.

I'd like to spend a few moments reviewing the Phase III ECOSPOR study design. ECOSPOR III is planned to include approximately 320 patients with multiply recurrent C. diff infection, randomized one-to-one between SER-109 and placebo. The robust size of the study was driven primarily by our desire to obtain an adequate safety database that could support product registration with this one pivotal trial.

Based on our study assumptions, the Phase III study is also highly powered to demonstrate clinical superiority of SER-109 compared to placebo. All Phase III study subjects will be treated with standard of care antibiotics to address the qualifying acute C. diff infection and subjects will then receive either SER-109 or a placebo. The Phase III ECOSPOR III study will evaluate patients for 24 weeks and the primary endpoint will examine the C. diff recurrence rate in subjects who receive SER-109 versus placebo at up to 8 weeks after dosing.

We have demonstrated several important insights from our previous SER-109 development efforts that we are applying to the Phase III study. Diagnosis of recurrent C. diff infection, both at study entry and for primary endpoint analysis will be confirmed by C. diff cytotoxin assays. We believe that the use of cytotoxin testing will ensure the patients entering the study are experiencing a true, active C. diff recurrence. In contrast, our data as well as other published literature indicates that PCR-based diagnostic approaches can erroneously identify some individuals having as a C. diff infection when, in fact, they are only carriers of the C. diff bacteria. The use of cytotoxin assay in the Phase III study is expected to ensure that only appropriate patients enter the study and also that in-study recurrences represent an actual C. diff infection.

A second important design consideration implemented in the Phase III study relates to SER-109 dose. Based on our previous microbiome clinical data sets, we have determined that administration of higher doses of SER-109 result in more rapid and more robust engraftment of SER-109 bacteria. We believe that more rapid restoration of the microbiome following antibiotic therapy is likely to be very important in the competitive race between microbiome restoration and C. diff recurrence. Specifically, clinical data indicate that in the first weeks immediately following a C. diff infection, patients are particularly vulnerable to recurrence. We believe that the rapid reestablishment of the healthy microbiome during this period is critically important to reducing the risk of recurrence and thereby breaking the recurrent cycle that so many patients experience.

We have entitled this, the race to repair. To maximize the rate of restoration of the microbiome, patients in the Phase III Study SER-109 arm will receive a total treatment dose that is approximately tenfold higher than the dose used in the prior Phase II study, and this dose will be administered over 3 consecutive days. Overall, we feel confident that the changes implemented in the Phase III ECOSPOR III study meaningfully increase the trial's probability of success. Expediting the study startup and enrollment to hasten study completion are among the highest priorities for Seres. Since Phase III study initiation, we have made steady progress executing our clinical operations plan. We are leveraging our prior clinical experience and taking numerous measures to speed enrollment. We have been rapidly activating clinical sites across the country, and we already have over 2 dozen active sites. In total, we plan to utilize over 100 clinical sites. We have also had productive discussions with Health Canada regarding our SER-109 Phase III study, and we expect to begin adding Canadian clinical trial sites later this year.

Overall, I am extremely pleased with the progress the company has made during the past year, advancing the SER-109 program. I will now transition to discussing the progress that we've been making in our other microbiome therapeutic candidates beginning with our SER-287 ulcerative colitis program.

In June, we announced that Seres had completed enrollment in our SER-287 Phase Ib study. This Phase Ib multi-dose placebo-controlled study is evaluating SER-287 as an induction therapy in patients with mild-to-moderate ulcerative colitis, who are failing prior non-biologic therapy. The study enrolled 58 patients. We believe there is compelling rationale for evaluating microbiome therapy in ulcerative colitis supported by several published, well-controlled clinical studies using repetitive fecal transplants or FMTs. Collectively, these studies indicate that modification of a microbiome can result in a meaningful clinical response.

While chronic and repetitive treatment with FMT is not likely to be widely adopted, we believe these studies do provide clinical data supporting the concept that modulation of the microbiome can improve ulcerative colitis patient outcomes. The SER-287 Phase Ib study is evaluating 3 treatment arms that include daily or weekly SER-287 administration over the 8-week treatment period as well as the placebo arm. I will note that the repeat dosing used in the SER-287 study differs from the single administration of therapy that we had evaluated in our prior SER-109 studies in C. diff infection.

In addition to studying dosing regimens, the SER-287 study will also evaluate the impact of vancomycin antibiotic treatment prior to administration of SER-287. Vancomycin pretreatment will test the hypothesis that reducing gastrointestinal bacterial levels prior to SER-287 administration may support more robust microbiome therapeutic candidate engraftment. The SER-287 studies primary endpoints focus on evaluating safety, tolerability and pharmacodynamics as measured by microbiome changes. We hope to observe a favorable safety and tolerability profile with a normalization of the microbiome and increased microbiome diversity in study subjects following administration of SER-287. In addition, the study will also evaluate a number of exploratory efficacy measures, including changes in various biomarkers and total Mayo scores. The Mayo score includes 4 components and results in a 0 to 12 scale with 12 being the most severe. The components of the Mayo score include stool frequency, rectal bleeding, a physician's global assessment and endoscopic evaluation. All endoscopies in the SER-287 study are being centrally read to minimize site-to-site variability. With enrollment of the SER-287 study now complete, we continue to look forward to top line SER-287 study results in the second half of this year.

Our objective with SER-287 is to develop an effective orally administered therapeutic option, which is not immunosuppressive. There are over 700,000 ulcerative colitis patients in the U.S. and although some patients needs are partially addressed by available therapies, drugs in current use typically result in a clinical response in less than half of patients during induction therapy. Furthermore, only about a half of those patients will maintain a clinical response when using maintenance therapy.

Coupled with the sub-optimal efficacy of currently available therapies, there is a substantial opportunity to improve upon the safety profile associated with later line ulcerative colitis therapies. Many of these products carry serious safety risks, including immunosuppression, opportunistic infections and certain kinds of cancer. Seres has 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 particularly notable as it is the first-ever clinical trial to evaluate a human synthetic multi-strain microbiome therapeutic candidate. SER-262 is manufactured using bacteria grown in anaerobic production fermenters in a process that does not require human donor material. This manufacturing is accomplished in Seres state-of-the-art facility, which we believe is field-leading. SER-262 contains a consortium of 12 bacterial strains in spore form rationally selected from Seres' field-leading proprietary library containing over 14,000 bacterial strains.

We expect the future of microbiome therapeutics to increasingly move towards design synthetically fermented approaches, and we believe the SER-262 program is an important landmark for both Seres and the microbiome field. The SER-262 Phase Ib trial is a first-in-human 24-week randomized placebo-controlled dose escalation study in patients who have experienced a first episode of C. diff infection. The SER-262 Phase Ib study design initially included dose-escalating patient cohorts evaluating single administrations of SER-262 doses ranging from 10 to the 4th to 10 to the 8th spores. Based on our learnings from the SER-109 Phase II root cause analysis, we had decided to expand the SER-262 study to include additional cohorts with SER-262 administered over multiple days and at higher doses. Each patient cohort arm includes 10 treated patients into placebo patients. In this first-in-human dose ranging Phase Ib study, we are evaluating firstly safety and tolerability of this synthetic microbiome drug candidate and then pharmacokinetics and pharmacodynamics as measured by microbiome changes, plus clinical efficacy trends in some cohorts to inform those levels to be used in a larger Phase II trial in the future.

We anticipate obtaining a 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 disease, metabolic disease, liver disease and immuno-oncology. In parallel with our SER-287 development efforts, we are actively working to advance SER-301, our follow-on design synthetic microbiome therapeutic candidate for inflammatory bowel disease, including, but not limited to, ulcerative colitis.

We have made excellent progress in expanding our internal preclinical immunology capabilities. Our R&D group now has developed multiple animal models that recapitulate aspects of the biology and the pathology related to ulcerative colitis in humans. We are using these model systems to evaluate the immunological and therapeutic effects of treatment with various compositions of bacterial consortia and importantly, our results demonstrate that these model systems are responsive to the composition of the microbiome.

Going forward, we plan to use our robust preclinical capabilities data from our academic collaborations as well as the pending SER-287 clinical data to inform the final composition of the components of the SER-301 therapeutic candidate. We have also continued to make substantial progress advancing the SER-155 preclinical program. SER-155 is a synthetically fermented designed bacterial consortium that is being developed to reduce bacterial infection risk and graft-versus-host disease in immune-compromised patients receiving either solid organ or hematopoietic stem cell transplants.

The development of SER-155 is supported by published clinical data, demonstrating that hematopoietic stem cell transplant patients, who have a more diverse healthier microbiome have far better clinical outcomes as compared to patients with dysbiotic microbiomes. In this study, the patients with higher diversity microbiomes experience lower rates of mortality due to infection and graft-versus-host disease. We are developing SER-155 in conjunction with our collaborators at Memorial Sloan Kettering. I look forward to providing further updates on this very exciting program in the coming months.

I would like to transition and now mention that Dr. Willard Dere, a highly distinguished industry professional, recently joined Seres' Board of Directors. Will is a first-class physician scientist, who brings more than 2 decades of scientific, clinical and strategic biopharmaceutical experience, including a tenure for over a decade as Amgen's Chief Medical Officer. He has led the development of drugs in diverse therapeutic areas. I am extremely pleased that Will has joined the board and I would like to take this opportunity to warmly welcome him. 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 $28 million for the second quarter of 2017 as compared to a net loss of $27.9 million for the same period in 2016. The second quarter net loss was driven primarily by clinical and development expenses, personnel expenses and ongoing development of the company's microbiome therapeutics platform. The second quarter net loss figure was inclusive of $3 million in recognized revenue associated with the company's collaboration with Nestlé Health Science.

Research and development expenses for the second quarter were $23.1 million as compared to $22.2 million for the same period in 2016. R&D expense in Q2 was primarily related to Seres' microbiome therapeutics platform, the clinical development of SER-109, SER-262 and SER-287 as well as the company's SER-301 and SER-155 preclinical programs. General and administrative expenses for the second quarter were $8.4 million as compared to $9 million for the same period in the prior year. G&A expense was primarily driven by headcount, professional fees and facilities costs.

The decrease in cash balance during the quarter was $27 million. Seres ended the second quarter with approximately $175.2 million in cash, cash equivalents and investments. This cash balance does not include the previously disclosed $20 million milestone payment from Nestlé Health Science associated with the start of the SER-109 Phase III study. We expect to account for the receipt of this payment in the third quarter of 2017.

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

This has been an important period for Seres where the company meaningfully advanced its pipeline with the completion of the SER-287 Phase Ib study enrollment, continued execution of the SER-262 Phase Ib trial and most notably the start of the SER-109 Phase III study. With SER-109 now in a registrational study, Seres is now a late-stage development biopharmaceutical company and the fully differentiated leader in the microbiome field. I am very pleased with the progress Seres has made as we continue to develop this new field of medicine and grow towards becoming a commercial stage organization. Thank you for your continued interest in Seres. We look forward to keeping you updated on our continued progress.

Amanda, let's open the line up for questions.

(Operator Instructions) Our first question comes from the line of Terence Flynn of Goldman Sachs.

This is Cameron on for Terence. Maybe a 3-part question on SER-287. So first, can you remind us where in the treatment of IBD you're hoping to position the drug? Then second, can you remind us what we should be thinking as clinically meaningful when we do see the data later this year? And then finally, are you still confident in the dosing regimen in light of the prior Phase II ECOSPOR results?

Those are 3 great questions. So thank you for them. First, as some of you may remember, but I'll remind everyone, SER-287 is being placed in the scale of ulcerative colitis patients, where patients have failed first-line therapy. Remember, those are patients who have gotten 5-ASA plus/minus steroid boluses. We think this is a very important part of the compendium of patients that are not doing well on standard of care. Firstly, as I said before, almost half of these patients will fail first-line therapy and/or cannot be maintained in maintenance. If you look at what their options are when that happens now is they have to go into immunosuppressive drugs, including expensive and dangerous monoclonals. We think that this is the spot both for patient care and commercially, where an oral easy-to-take non-immunosuppressive drug would be highly important in the armamentarium of the future. We want to keep everyone out of immunosuppressive drugs and we expect this drug to not be immunosuppressive. Number two, you asked about what results would be meaningful to us. Obviously, we're looking at safety and tolerability first, because this is a Ib trial. Number two, we are looking at effects on the microbiome, that is our PK/PD in these drugs. And then obviously, we'll look at the exploratory endpoints where we -- as I said, are looking at Mayo Clinic scores, we're looking at endoscopic findings both before and after treatment, and we'll look at a variety of biomarkers. So that's how we will think about success of this drug and how we would move it forward. I believe that the third point was dose. We are -- we did, obviously, look and make changes in the SER-262 trial, but did not make 287 changes based on our learnings from the root cause analysis of 109, but that's a good question. I will remind you that the people who are getting this drug are, as I said in the script, get it on a daily or a weekly basis. The people on the daily basis are getting 50x or more of what we gave to patients in the Phase II 109 trial for a totally different indication of C. diff. So we're comfortable that this is a large continuous dose that can be given safely and easily, chose by how rapidly we completed the study. So we don't plan and didn't think that there needed to be a change in the 287 trial. Hope that helps.

Next question.

Your next question comes from the line of Chris Shibutani of Cowen.

On the SER-109 Phase III study, it's obviously helpful to know that, that is a Phase III study. We're trying to get a sense for when we can expect enrollment to be complete? I appreciated the update on some of the initial progress, but can you help us a little bit with metrics or timelines for completion of enrollment?

Yes. No, it's a great question. We -- nothing is more important to Seres than moving with alacrity, but in a careful way in this trial. As I said, we've just gotten started trial. We're opening up large numbers of sites in this international trial, both in the U.S. and Canada. And we have learnings that we expect to increase our enrollment and moving patients through these trials and screening them. It's really early for me to make a prognostication. I like to see a slope or a curve over several months before we see, especially with sites still opening and less than a quarter of our large trial sites up and running. So I would say give me -- give us a little more time to see what the slope looks like, so we can say something meaningful. But again, with our learnings from Phase II, with the sites that we had in Phase II that are now being opened in Phase III, we expect to have the best chance to move with all due speed, but care in this trial.

What do you think is the rate-limiting process as far as new sites in particular?

No, it's just getting them up and running. We've had amazing interest from sites. Everybody wants this drug for obvious reasons. And so we don't think that there is anything that's slowing it down. It's just we have over 2 dozen sites open already. We're moving forward. As I said, we're going to get Canadians sites later in this year. We don't see a block at this point.

Our next question comes from the line of Joseph Schwartz of Leerink Partners.

This is Dae Gon actually dialing in for Joe. So thanks for the update today. So just 2 quick ones from me. You mentioned the alignment with now the initiation of the Phase III ECOSPOR III study, FDA has been really interested in getting this across the goal line. But can you just comment on where you are with regards to the EMA or some of the other worldwide agencies, where there might be a little more taking a different stance in terms of microbiome therapeutics? And then on the second one, I just wanted to get a sense of how the community of the physicians have been evolving their sort of grasp of the microbiome therapeutics? And how that might be impacting positively or negatively to the -- getting the sites up and running?

Yes. You know that's both 2 great questions. So thank you for that. So when you think about how other regulatory agencies are looking at it, as I've said, we've had great interactions with Health Canada. We see no blocks there. They are similar to the FDA, very excited about trying to move this drug forward to patients. We have talked to the EU, where they have told us in initial discussions last year, that 109 sourced in The United States could be used in Europe, which makes sense because the microbiome is virtually the same. And where we've accelerated with our partners, Nestlé, going to EMEA to move this product forward. As I've said in previous calls, we don't want big separation internationally between the patients and the markets in the U.S. and Canada and in the European Union. And as we've said in a press release, Nestlé and Seres are working to accelerate going into Europe based on our very positive results with the FDA. Your second question is how physicians are looking at the microbiome and that's a great question, because this is a totally new field in medicine. And physicians being one, are usually conservative. But I think what we've seen is something different in the microbiome. People are -- it's well known in the physician communities especially in ID and GI, which are primary call points for this disease, everyone is excited about it because of the lack of safety signals that have been seen in our drugs, people look at it with a different light than a new field in small molecules or genetic diseases. And we have seen not only no pushback, but the physicians, again, all want a microbiome drug and that's what's helping us open up sites in the 109 trial.

Great. If I can just squeeze in one more, it's more of a personal curiosity. So, I guess, looking at some of the mice studies, we see that the diet or the chao has a serious impact on the microbiome composition. So I was wondering is the protocol for the ECOSPOR III, including some kind of a diet restriction protocol to make sure your standardizing any kind of dietary effects on the microbiome?

Yes, so that's a great question. I will point out that one of the reasons we use both animal models as well as human models is there is clear differences in studying a human microbiome in a rodent and in the normal background, which is a human. But you are exactly right, chao effects it. There hasn't been great data that diet affects the microbiome greatly in human. There's a little data. Most of those though are in chronic diseases. We think one of the things that's important when you think of 109 is the complexity of C. diff, this acute alien pathogen is very different than if you were thinking of treating patients with diabetes and obesity and thinking about how the food might have an impact on the microbiome. I think the question is good. I'm not sure it's going to be totally relevant when you deal with acute infectious diseases.

Our next question comes from the line of Bill Tanner of Cantor Fitzgerald.

I had a couple of them. One on 109 and you talked about the C. diff cytotoxin test. Could you just maybe describe a little bit better, I mean, if this is quantitative? If it's qualitative? Is there a threshold? Or will there be a possibility that patients would be stratified by the severity of the disease as it relates to the level of the toxin?

Yes. So let's deal with that first and foremost. So again, as I said before, toxin testing was the way C. diff was diagnosed back in the old days when I trained in medicine. And at that time, it was a CPE test, the cytopathic effect on cell lines. It was very sort of Louis Pasteur-ish. Over that time period, since then that approach has died down as ELISA assays, first, second and third and now fourth generation ELISAs that makes cytotoxin detection of the protein itself almost as sensitive and specific as PCR in many studies. So this is not going to be -- this is going to be done in a central lab. It's going to not be a quantitative assay. You're either positive or negative for cytotoxin. It's not like some people have tried to push up and down PCR. We expect this to be a very important part of who gets into the trial as I said and who gets out of the trial, meaning that is diagnosed with a recurrence on the trial. We think this is making a C. diff objective again. And we've done everything we can to make sure that this approach is most important in making the diagnosis yes or no, not in gradations to active true C. diff infection.

Okay. That make sense. And then as it relates to 287 and UC just -- you mentioned, obviously, that the patients have been treated with repetitive FMT and it sounds like there's going to be a repetitive aspect to 287. And I'm just curious, one is the underlying biology that makes repetitive treatment important perhaps irrespective of the source. And then it's a hard question to answer, I guess, is there any contemplation that perhaps 287 could enhance the engraftment or reduce the repetitive requirement?

So again, 2 great questions. Let me point out that when we deal with C. diff, although it is an inflammatory colitis when the C. diff is active, when you treat people for recurrence, you have a healing, less immunologically active, less inflamed colon. That's different from ulcerative colitis, from Crohn's, from several other diseases, where you have ongoing continuous regenerating inflammation. The data would suggest, because of that reason, that's why repetitively hitting the microbiome to get further engraftment to keep turning down the immune tone in this case an ulcerative colitis, not only made sense empirically, but was shown in animal models, in our hands and others and in fecal transplant trials. I think it's the difference in the pathogenesis of the disease, the diseases that make the repetition important here. And when you think about whether 287 could decrease the repetitive need for engraftment, we thought about that. If we move forward to Phase II, we would think about a maintenance therapy in that trial. In maintenance, the use of this drug may decrease the need from -- for repetition, not that it would be one-and-done, but you might be able to expand it greater than once-a-day or greater than once-a-week or greater than once-a-month. So we think that's the place where you might see a change in the dynamics of treatment.

And maybe just as a follow-on to that, I mean, is there anything in the preclinical animal model literature that would suggest that there may be some either GI or otherwise immuno-modulation as it relates to the microbiome?

Yes, that's how we think this works. The data in our hands and others has shown that in ulcerative colitis, there's increased immune tone in the colon and the T regulatory cells are damped down. What we know is that a normal microbiome, especially from clostridiales, will produce short-chain fatty acids, which are the signaling molecules to increase the T reg tone, T regulatory cell tone. So we believe that is how this drug works in animals and how fecal transplants may work in some of the human studies by reintroducing a normal microbiome, reintroducing the signaling molecules, that increase T reg tone, which dampens down the ulcerative colitis inflammation.

Our next question comes from the line of John Newman of Canaccord.

I just had a question on the -- this Phase III SER-109 study. I think you mentioned that the primary endpoint in terms of recurrence will be measured up to 8 weeks. I'm just wondering if there will be other time points besides 8 weeks when you will be looking at recurrence?

So thanks for that question. The primary efficacy endpoint agreed on with the FDA is 8 weeks. But like we've done in all our trials, we will follow these patients for both safety as well as efficacy at 12 and 24 weeks. What I would remind you is, one of the problems when you take these complex patients out over time is many of them need antibiotics for other reasons. Sick, older people left with multiple medical problems. So we had to both in thinking in our Ib trial and II, and I expect III. As you get farther out, some of this data will be corrupted by the need for broad-spectrum antibiotics again. But we will have that data. What's important to remember is as we think about commercializing this drug, of course, based on hopeful persuasive data in Phase III, is that that's what makes this such an interesting drug. There is no resistance to this drug. So that as people get 109 and are cured of their recurrent C. diff and then need broad-spectrum antibiotics, which a lot of them will in the real world, as they get sick from other causes and they take antibiotics. If they get C. diff, they can still just take 109 again. So retreatment should not have -- there is no resistance as you would see with the standard use of an antibiotics. So we're interested in that. And we think we'll get data on that in Phase III and certainly in post-marketing, assuming we can commercialize the drug.

And in the Phase III Study for 109, will you be allowed to retreat patients after the initial dose?

Remember, we are having both an open-label extension and expanded access after recruitment. So we think, especially with the open-label extension, everyone will be offered an active drug. It's the most important thing in building a safety database that is necessary for approval and it also is the ethical thing to do in this disease. No one wants to join a trial where they can't get the active agent. So there will be some retreatment in patients that have gotten 109, failed in the trial and then are retreated in an open-label extension, if they chose to join.

Our next question comes from the line of Carol Werther of H.C. Wainwright.

So with 109, what is the power of the trial? And what difference are we looking for?

Yes, so we haven't described that exactly. I can tell you that it is highly powered and it's for superiority of SER-109 and placebo. With 320 patients, the power is -- even though we haven't given the exact number, is extremely high and not a worry.

Okay. And then with the higher dose, are you concerned at all that you might get more diarrhea?

So it's an interesting question. There have been studies with fecal transplants that have shown that early on after the transplant, some patients get a little bit of an upset stomach and a little bit of diarrheic syndrome for a day or 2. We might have seen some of that in Phase II. It was hard to tell because of small numbers. I would remind you that we're not seeing it. We haven't had patients drop out for any reason in 287, which as I said, have gotten up to 50x the dose. So I'm not sure that's a huge worry, but we'll monitor for it. And again, it wasn't seen in the Phase Ib trial, which is important because in the first cohort there were patients who got the same dose that were giving in the Phase III. So.

Okay. That's helpful. And then you said that there was just another article saying that there's higher incidence of recurrent C. diff. Do you have any idea about whether or not the FMTs are on the rise, the use of FMT?

So I -- we don't follow the use of it. We know that it's being used. I -- when I was practicing in the '90s, we even used it. I would say sitting in front -- I have this article in front of me by Ma et al in the Annals. I didn't mention, but the difference in increase over the decade that was studied here in recurrent C. diff, this is not primary, is almost 200%. This is not a small increase. Significantly higher than primary C. diff. So again, as I've said before on these calls, the -- most of the suffering in patients, most of the cost and a significant amount of the deaths are actually in the recurrent population. If you break the back of recurrence and we don't think the FMTs can do that. We think you need an oral, safe, a reproducible easy-to-take true drug. But that's going to be -- that's going to be the important part of breaking the back of the epidemic, both financially for the health system and, of course, for the patients suffering with it. It's by the numbers and the quality of the problem is highest in recurrence.

And then my last question is on 287. Do you imagine that when, I'm assuming positive results, when you go forward, would you need to compare it to second line drugs like the anti-TNFs and other immunosuppressive drugs, if that's where you're positioning it?

Yes, I mean, it's a good question. Let us see the data, let us see how robust it is then we'll know whether we go after -- what the next trial design looks like, whether it's superiority, whether it's compared or where we go. But certainly in the future, as I alluded to in the talk, one of the things that's important is there is another inflammatory bowel disease out there, it's called Crohn's, and that would be the other decision based on the data we see in the Phase Ib trial.

And at this time, I'm showing no further questions. I'd like to turn the call back over to the company for any closing remarks.

Thanks. This is Roger. I would like to thank everyone on the call for their thoughtful questions. We had a very productive quarter. We advanced our pipeline, transitioning Seres into a late-stage biopharmaceutical company, and we've extended our position as the leader in the microbiome therapeutic development field. Looking ahead, we are entering an exciting second half of the year with the pending SER-287 study results on ulcerative colitis and continued advancement of our early-stage microbiome programs. I want to thank all the listeners for your continued interest in Seres and please reach out to us with any additional questions. We will be participating in 2 upcoming investor conferences, including Canaccord, next Wednesday and the Baird Conference in September. And with that, we will conclude today's call. Thank you very much.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everybody have a great day.