Seres Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by, and welcome to the Q4 2020 Series Therapeutics Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Dr. Carlo Tanzi of Investor Relations. Please go ahead.

Thank you and good morning. Our press release with the company's fourth quarter 2020 financial results and a business update became available at 7 a.m. Eastern time this morning and can be found on the investors and media section of the company's website. I would like to remind you that we'll be making forward-looking statements related to the timing, enrollment, and results of our clinical studies, potential regulatory approval, and the promise and potential of our microbiome therapeutics. Actual results may differ materially. Additionally, these statements are subject to certain risks and uncertainties, which are discussed in 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, with prepared remarks, I'm joined by President and Chief Executive Officer Eric Schaaf, Chief Medical Officer Dr. Lisa Von Mulkey, and Chief Scientific Officer, Dr. Matthew Henn. Dr. Terry Young, Chief Commercial and Strategy Officer, and Dr. David Ege, Chief Technology Officer, will also be available for the Q&A portion of the call. And with that, I'll turn the call over to Eric.

Thank you, Carlo, and good morning, everyone. 2020 was a pivotal year for CERES as we moved an important step closer to to realizing our goal of translating microbiome insights into an entirely new class of medicines. The year was highlighted by positive data from our Phase III CR109 ECOSPOR3 study in patients with recurrent C. diff infection, marking our transition towards becoming a fully integrated commercial organization. Since then, we have been taking actions necessary to file a CR109 BLA submission and preparing for a successful commercial launch following an FDA approval. As an organization, our top priority right now is to obtain the required SIR 109 safety database by completing our ongoing open-label study. We are also continuing supportive market assessment work, including primary research with physicians and payers, and pricing and reimbursement analyses. Furthermore, we have been scaling our market education efforts, including the hiring and training of an MSL team. We recognize that as we are working in an entirely new field of medicine, there is understandably a knowledge gap in the healthcare community regarding the broad and important role of the microbiome in health and disease. We are looking forward to continuing to engage with patient groups, physicians, and payers to educate the market about the substantial value of our microbiome therapeutic approach. We've also made strides to increase our drug supply capacity. Our SIR 109 process is already at commercial scale, and we have activities underway to expand our production capacity with a goal of ensuring that we are able to meet future commercial demand and assume rapid and broad uptake into the recurrent CDI population, as well as support our expanding clinical trial activity. In addition to SIR 109, we are advancing a pipeline of additional investigational microbiome therapeutics led by SEER 287, our Phase IIb candidate for ulcerative colitis. SEER 287 has the potential to transform the management of this disease intended to provide an effective alternative treatment approach that is well-tolerated and is not immunosuppressive. We are very pleased to report today that the SEER 287 Phase IIb study has achieved target enrollment of 201 subjects, and we look forward to reporting top-line data in mid-year. With that, I'll now turn the call over to Lisa.

Thanks, Eric, and good morning, everyone. I'll begin with a review of our SEER 109 program. Last summer... ...efficacy endpoint in patients with recurrent C. difficile infection... showing a substantial absolute reduction of recurrent infection compared to placebo at eight weeks post-treatment. Ecosport 3D data through the final 24-week time point. These results reflect the final categorization of all subjects in the protocol specified intent to treat population following study completion and full unblinding. This completed analysis reflected minimal changes from the interim analysis and demonstrated a remarkable sustained clinical response rate of approximately 88% at eight weeks post-treatment. The primary endpoint showed an absolute reduction of recurrence of CVI of 27% compared to placebo at eight weeks post-treatment, which is a relative risk reduction of 69%. Study results show that CR109 administration resulted in similar efficacy when examined by groups stratified by age, or by the prior antibiotic therapy. Additionally, the data demonstrate that SEER-109 efficacy is maintained over the duration of the 24-week study. From a tolerability perspective, we were also extremely pleased with the Phase III study data. We observed a highly favorable safety profile with SEER-109. The need for by the recent announcement from a major stool bank stating that it plans to halt operations. We believe our SEER-109 Phase III data represent a substantial advancement over the standard of care with the potential to transform how CDI is managed. Furthermore, we believe that SEER-109 has the potential to improve treatment of CDI, a disease that results in the death of over 20,000 people in the U.S. each year. In October of last year, we presented our preliminary SEER-109 Phase III study results to the American College of Gastroenterology Annual Scientific Meeting, and we plan to present additional data at medical meetings later this year. In January, we presented to the American College of Gastroenterology and the American Museum, presenting mechanistic support for the efficacy observed in the Phase III study, and Matt will discuss those data in more detail. We look forward to submitting the remarkable SEER-109 Phase III results for this novel treatment modality to a leading journal for publication. Importantly, SEER-109 ECOSPOR-3 study results far exceeded the efficacy threshold communicated to us by the FDA, and we expect this single study to provide the efficacy basis for a SEER-109 BLA filing. The FDA position is that at least 300 patients will be required for a SEER-109 safety database to support the BLA. And we continue to enroll our ongoing SEER-109 open-label study in patients with recurrent CVI. We expect this study to fulfill the remainder of our required safety database. We continue all across the U.S. and Canada. Now let's turn to our ongoing SEER-287 Phase IIb study in patients with mild to moderate arthritis. SEER-287 is an orally administered drug candidate comprised of commensal bacterial spores isolated from the healthy human gastrointestinal tract. Our objective with SEER-287 is to develop a first-in-class microbiome therapeutic that modulates the microbiome and microbiome-associated metabolites to treat ulcerative colitis. We believe that CR287 may provide a much-needed non-amino suppressive treatment option for UC. CR287 is intended to reduce the impact of a disrupted microbiome as both a trigger and an amplifier of inflammation. We believe that CR287 has the potential to be used as both a monotherapy and potentially also in combination with other approved agents. Data from the Phase 1b study demonstrated that SIR287 administration was associated with high rates of clinical remission, endoscopic improvement, modulation of the gastrointestinal microbiome, and a favorable safety profile. These results and data supporting the underlying mechanisms of action were recently highlighted as the cover article in the January 2021 print edition of the peer-reviewed journal Gastroenterology. To remind you, the SEER-287 Phase 2B Eco-Reset Study is a randomized, placebo-controlled, three-arm induction for 201 patients with active, mild to moderate ulcerative colitis who have failed prior therapy. In Arm A, patients receive a short course of conditioning, followed by the 10 weeks of daily regimen that was used in the arm of the previous 1B study that showed the highest clinical remission rate. In arm B, patients received vancomycin preconditioning, followed by two weeks of the same SEER287 daily regimen used in arm A, followed by eight weeks of a lower dose. In arm C, patients received placebo. As Eric mentioned, we have achieved target enrollment with several patients remaining in the screening process. And in an acceleration of our previous expectations, We now expect top-line study results from Eco-Reset in mid-2021. Demonstrate that CR287 results in a significantly higher rate of patients achieving clinical remission than those administered placebo. We believe that the safety profile of our microbiome therapeutic approach based on commensal healthy bacteria, is a major advantage and anticipate that the safety profile of SEER-287 will be highly favorable, particularly as compared with the current standard of care, which can be immunosuppressive. We expect that if we are able to achieve this clinical profile and with an orally administered therapy, SEER-287 would represent a highly attractive new medicine SEER-287 has the potential to provide mild to moderate UC patients, representing a majority of all UC patients, with an effective treatment of immunosuppressive. The SEER-287 study will also be important to inform our broader multi-product and longer-term efforts to develop transformative new medicines for inflammatory bowel disease and, more broadly, modulating host immunity. the development of the microbiome therapeutic field remains in its adolescence. And as a learning, data-driven, science-based organization, we expect that CERES will gain important insights both from our pending Phase IIb clinical data and from mechanistic data coming later this year that could inform the further development of CER 287 as well as that of CER 301 and our future compositions designed to modulate host inflammation and immune pathway signaling. With that, I'll now turn the.

Thank you, Lisa, and good morning, everyone. We are aware that we're having some sound issues, and we are resolving that. So I'll continue. CERES continues to invest significantly in our reverse translational discovery and development platforms that can delineate at high resolution microbiome biomarkers from human clinical data and integrate these data with preclinical assessments using human cell-based assays and in vitro, ex vivo, and in vivo disease models to evaluate drug mechanism of action and to design consortia of bacteria with specific pharmacological properties. We reported results from SEER-109 Phase III predefined microbiome readouts earlier this year at the Keystone Microbiome Symposium that confirmed the drug candidate's mechanism of action. The Phase III study data demonstrated that SIR109 bacterial species rapidly engrafted into the gastrointestinal tract. Engraftment was observed as early as one week post-treatment and found to be durable through 24 weeks. The presence of SIR109 bacteria was significantly greater in subjects that received SIR109 versus placebo, and all differences were maintained in all subpopulation analyses. SIR109 administration also rapidly shifted the gastrointestinal metabolic landscape including a significant decrease in primary bile acids and an increase in secondary bile acids, providing a mechanistic basis for both the inhibition of C. difficile spore germination and vegetative growth. Notably, in early time point samples, C. difficile and other bacterial pathogens known to harbor antibiotic-resistant genes were significantly more prevalent in placebo-treated subjects. These data confirm observations from series prior trials that SIR-109 resulted in a reduction of other clinically relevant bacterial pathogens. The detailed mechanistic learnings we have obtained from SEER-109, combined with our ability to link these learnings to clinical outcomes and confirm observations in human subjects in a non-clinical setting to demonstrate causality, has proven immensely beneficial, and we are already applying this knowledge to the design and future planned microbiome therapeutic compositions. Moving now to our SEER-301 program. CR301 is a next-generation, orally dosed, rationally designed, cultivated microbiome therapeutic candidate for the treatment of ulcerative colitis. The consortia of bacteria in CR301 is designed to modify the microbiome and microbe-associated metabolites in the gastrointestinal tract to reduce the presence of pro-inflammatory bacteria and modulate pathways linked to gastrointestinal inflammation and epithelial barrier integrity in patients with ulcerative colitis. SEER 301 was designed using series reverse translational discovery and development platforms. The design incorporated learnings from the SEER 287 Phase 1B study related to the bacterial species and the microbiome functional signatures associated with clinical efficacy. Additionally, the design incorporated insights on the engraftment dynamics of different bacteria and also the association of specific bacteria with the modulation of inflammatory and immune pathways in human subjects that have been observed across our broader clinical portfolio and confirmed using our non-human cell-based assays and in vivo models. In November of 2020, we announced the dosing of our first patient in our CR301 Phase 1B study in adults with mild to moderate ulcerative colitis, and enrollment is ongoing. The study is being conducted in Australia and New Zealand, with a target enrollment of 65 patients in total. The objectives for the study are to evaluate drug safety and pharmacokinetics, and further to evaluate clinical remission and other measures of efficacy as secondary endpoints. The Data Safety Monitoring Board recently reviewed preliminary safety data from the first set of patients enrolled, and we encourage to see that the drug tolerability has been favorable. Turning to our Phase 1b study for SEER-401. SIR-401 is an orally administered microbiome therapeutic candidate comprised of bacteria associated with response to checkpoint inhibitor immunotherapy. Our objective with SIR-401 is to enhance the efficacy of approved immunotherapies by modulating the patient's immune response to these medicines. As we have previously discussed, that the SIR-401 study has been impacted by COVID-19, and enrollment has therefore been slower than anticipated. We are currently evaluating our SEER-401 development plan with our study collaborators at the Parker Institute of Cancer Immunotherapy and MD Anderson Cancer Center. Now moving to SEER-155. SEER-155 is an orally dosed, rationally designed, cultivated microbiome therapeutic candidate designed to prevent mortality due to gastrointestinal bacterial infections, bacteremia, and graft-versus-host disease in immunocompromised patients receiving allergenic hematic stem cell transplantation. SEER 155 builds on our expertise in both infectious disease and immunology and is designed to prevent bacterial infections, particularly those that harbor antibiotic-resistant genes, and the onset of graft-versus-host disease. The SEER 155 program is supported by CARB-X grant that provides financial and operational support. We are making continued progress advancing SEER 155 into the clinic in collaboration with our partners at Memorial Sloan Kettering Cancer Center, and we expect to submit an IND during the first half of this year. We continue to resource our microbiome pipeline in a number of indications beyond both SEER 155 and SEER 301, which over time will serve as a product engine for our growing commercial organization. our clinical programs and our reverse translational discovery platforms continue to provide meaningful insights and knowledge into the underlying mechanisms by which microbes in the GI tract engage with pathogenic bacteria and human cells and tissues to impact disease. Moreover, advances in series microbial cultivation and bioprocessing know-how and commercial-scale GMP capabilities continue to broaden access to the diversity of microbes in the human GI that can be harnessed in potential new product candidates and development programs. With that, I'll now turn the call back to Eric.

Thanks, Matt. And we are aware that we lost a piece of Lisa's section, and I think we lost her when she was talking about the fact from a tolerability perspective for 0109, we were and are extremely pleased with the Phase III data and that we observed a highly favorable safety profile with 0109 adverse events being similar to placebo and And we'll ensure that the transcript from this call is available after the call. So let me transition to our financials. Our fourth quarter and full year P&L are included in this morning's press release, so I won't read it right from here. Series ended the year 2020 with approximately $303.4 million in cash, cash equivalents, and short and long-term investments. We entered 2021 in a position of strength. poised for growth as we continue to advance our pipeline and transition to a fully integrated commercial organization. CIRES is building upon our microbiome platform leadership position and driving forward a multi-product clinical pipeline that is led by CIR-109. We believe that our CIR-109 ECOSPOR-3 results provide validation and support for the broader CIRES pipeline and our capabilities in this new area of medicine. Sirius has advanced non-commoditized unique platforms that are being deployed for the development of microbiome therapeutics. These technologies and our proprietary scientific insights have already generated a pipeline of promising microbiome therapeutic candidates, each targeting a serious medical condition and each providing the potential to fundamentally transform how diseases are treated. Our top priority is preparing for a high-quality BLA submission for SEER 109, as well as readying the company for a successful commercial launch for what we expect will be the first FDA-approved microbiome products. We are continuing to advance what we believe to be a highly promising pipeline led by SEER 287. In addition, we intend to continue to invest in core microbiome drug discovery and CMC capabilities to ensure that CERES is well positioned to continue to lead the microbiome therapeutics field in these important areas. We expect 2021 to be an eventful year for the company. We are looking forward to continued enrollment in our CERES-109 open label study and progress with pre-commercial activities. Top line results from the CERES-287 Phase IIb study advancement of our multiple earlier stage clinical programs, and further strengthening our microbiome platform capabilities, enabling us to bring the next wave of therapeutic candidates into the clinic. Sirius has a strong and experienced team in place, and we are working with urgency to achieve our goals and fulfill our mission of transforming the lives of patients worldwide with revolutionary microbiome therapeutics. We look forward to keeping you informed on our progress. With that, operator, we'll open up the call now to questions.

Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Ted Tentoff with Piper Sandler. You may proceed with your questions.

Great. Thank you very much. Congrats on all the update and looking forward to the ulcerative colitis data. I think that's going to be an interesting indication to expand the applicability of the technology. Quick question. I'm not sure if I missed it because of the line breaking up a little bit, but what is the latest with respect to 109 enrollment in the open label extension study? And can you give us a sense for when that might be complete or you may report data on that. Thanks, Eric.

Yeah, Ted, good morning, and thanks for the question. So maybe just as a reminder, when we announced preliminary top-line data in August, we had said that we had 105 subjects on the dose that was, of course, successful in the Phase III and then the number of patients that had rolled into the open label from the ECOSPOR3 study. So what we said was that the FDA had asked us to have at least 300 subjects on therapy. So we were moving forward with the open label study in order to fulfill that request. And we've continued to make progress enrolling patients, increasing the number of sites. I will say that we started a little bit more slowly than I would have liked, perhaps in part based on the pandemic. But we've really seen a lot of positive momentum and traction in the last period of time. So we're very encouraged about getting this done. You know, just as a reminder, We know that we can execute on this, you know, in part based on the fact that the FDA has allowed us to include first recurrent subjects into the study, which, of course, increases the number of available subjects. As we mentioned, and I think this might have gotten lost in Lisa's comments, but, you know, one of the largest stool bank providers has been shut, actually has announced that they're winding down. But really more than anything, Ted, it's the profile itself. It's the safety, the efficacy, and we are continuing to add sites. So we're getting closer to the point where we've got a sense of the slope of the curve. I will say it's improving significantly, and I think we'll be in a position to provide more specific guidance at some point soon.

That's really helpful, Eric. I appreciate that color. And then maybe you could add, by just sort of explaining kind of what the process would be with respect to open label extension data and BLA filing, you know, would it basically, you know, you unblind the data, report the data, and file, or will you be reporting that data? Just maybe a little bit more color and sort of the mechanics behind transitioning to the BLA filing. Thanks a ton.

Sure, Ted, and maybe I'll ask Lisa to comment. Just to start as a reminder, we do have a breakthrough therapy designation with 0109. So, you know, we are in dialogue with the FDA around the path forward. But maybe I can ask Lisa to comment about the mechanics of the open label and folding that into the BLA process.

Yeah, sure. We have been cleaning data and preparing the BLA shells and everything as we've been going along so that we anticipate when we get our last patient out of that open label, we'll be able to immediately execute on the final analysis and drop that into the BLA. So we're setting it up to seamlessly be able to roll into the BLA as fast as humanly possible in terms of calculating and getting things in.

Sounds good. Thanks so much for the update, everybody.

Thanks for the question, Ted. Thank you. Our next question comes from Joseph Dome with Town & Company. We have received your question.

Hi there. Thank you for taking my questions. I know you detailed it a little bit for us, but if you could just give a little bit more detail on sort of the initial physician response that you're seeing in terms of the data from CR-109. Is there a specific portion of the data package that physicians are finding compelling, or how long do they want to see this response last? And then on SEER 287, how should we be thinking about a go-forward decision here? Is there a specific clinical response rate that you're looking for? I think it was mentioned additional mechanistic data are expected potentially later this year. Sort of what are the inputs that you're looking for there to make that decision? Thanks.

Yeah, Joe, good morning, and thanks for the questions. I'm going to ask Lisa to comment on the physician response. I'll just start by saying, you know, obviously with recurrency, this is a field that hasn't seen, you know, meaningful innovation in quite some time. And the feedback that we've gotten from our KOLs and from our PIs has been incredible. But let me ask Lisa to comment further on that, and then we can comment on 287 and, you know, how we're thinking about defining success.

Yeah, this has been a delta, an efficacy result that the field has never seen for C. diff in terms of, you know, 88% of people after eight weeks continuing to be free of recurrence. And so that right away is important. We know that when recurrences happen, they tend to happen very quickly. But in addition, our data is showing that not only are we good at eight weeks, 12 weeks, we now can see that that durability of response goes out to 24 weeks, and we're looking forward to getting that data out there. So that plus the safety profile has really been a complete package, and it's not an understatement to say that people are seeing this as a paradigm shifter.

And then, Joe, I think your second question related to 287, and for us, and again, I'll ask Lisa to comment more completely, but There's obviously the clinical data. There's the microbiome analysis that, as part of our approach, we think really go hand in hand. And it's one of the reasons that we're so excited about the Sphere 109 result was not only do we have the 109 clinical data, the safety profile, but as Matt talked about, we've got the microbiome analysis that really corroborates the clinical result. But, you know, from my perspective, as we've continued to work in this field, it just is so clear that there is an opportunity to help patients, particularly in the mild to moderate segment, with an approach which is safe, which is effective, and which is oral. A number of agents that are on the market or are in development can carry with them significant side effects, including immunosuppression. And what we have heard is that there really is an opportunity for a non-immunosuppressive approach for these patients. But maybe I can ask Lisa to comment more completely on 287.

Yes, there's a real gap, especially for the mild to moderate patients, between 5-ASA and then there's a gap and you get into these big gun immunomodulators in terms of the biologics, the JAKs, and there's a lot of patients who really are not fully controlled or well controlled on 5-ASA. And we've heard that if we could have an orally administered, non-immunosuppressive agent, this is exactly what these patients are looking for. So we're very excited to get the readout for 287.

Excellent. Thank you, and congrats again on the progress.

Thanks for the question, and we look forward to participating in the conference later today.

Thank you. Our next question comes from Mark with Oppenheimer. You may proceed with your question.

Hey, good morning, guys, and thanks for taking the question. Not to harp too much on the open label trial, but I was wondering if you could give us an update on how many trial sites are now open for enrollment. And with the open biome quarantine shipping hold in place, can you give us a sense for what forces are still competing for enrollment when it comes to C. diff patients?

Yeah, Mark, we've got about 70 sites that are up, which is, of course, significantly higher than what we had in the Phase 3 study, the ECOSPOR3 study. We've got a target of over 100, and we have been making steady, significant progress. You know, as I said before, You know, we are doing this in the midst of the pandemic, and even though the pandemic is really turning in the right direction, particularly from the infectious disease side of things, we are competing for resources at clinical sites with some of the COVID clinical work. But, you know, what I can tell you is that we are highly, highly encouraged with our momentum and the slope of the curve. As we continue to get closer to our target, again, north of 100, I think we'll have a better sense of, you know, the slope of the curve and be in a better position to provide definitive guidance. Lisa, anything else to add on that?

Nope. I agree completely. Once we get to sort of a steady state, we'll be able to model out more exactly when we think that the trial will finish.

Yeah. Okay. That's helpful. And with respect to EcoReset and SAR 287, assuming EcoReset is successful, Can you give us a sense for what a second pivotal trial in UC could potentially look like, at least in terms of size and scale and endpoints, and whether or not it would look very different from the current EcoReset study?

Yeah, Mark, you know, we haven't guided as to the next study. What I will say is that You know, we think there's an incredible opportunity with our approach, not only in 287, but 301. And that's what's so interesting to us is that there's a first-in-class, best-in-class approach where we've got, you know, two significant shots on goal. And, you know, each of them are unique and are significant opportunities in their own right. So, you know, whereas we haven't guided on the next step on 287 yet, You know, we think that it's important to recognize that we've got both 287 and 301, which are moving forward, and, you know, we'll see what the data says, and we'll see what it shows. But, you know, obviously, as we think about the paradigm moving forward, we're preparing for success in both.

Okay, fair enough. Thanks for taking the questions, and congrats on the progress.

Thanks, Mark. Thanks for the questions.

Thank you. Our next question comes from Terrence Flynn with Goldman Sachs. You may proceed with your question.

Great. Thanks for taking the questions. I was just wondering, Eric, if you can give us any sense of what's embedded in your OPEX guidance for timing of your Salesforce build, and again, maybe where you stand with specifically, I know the MSL team's at the leading edge of that, but just is that fully hired yet at this point, or is there still more to do? And then any early feedback you guys can share from payers. It sounds like you're starting to have some of those conversations, but would just be curious, any insights you can provide there. Thank you.

Yeah, Terrence, thanks for the question. It's a great question. We have not provided guidance on OpEx or Burn. What I will say is that, you know, we're continuing the efforts to move forward in preparing to commercialize the product. And maybe I can ask Terry to comment on some of the feedback that we're hearing from the payer universe. But Let me kind of tick off your question. So from an MSL perspective, we have started. I wouldn't say that it's complete, but we've made a lot of progress since the top-line result, the preliminary top-line result in August. We're in the process of bringing in MSLs. We're in the process of training them. But maybe I can ask Terry to comment on the last part of your question as it relates to the feedback from the peer universities.

Do we have Terry?

Is she on mute? Sorry. I'm here, unmuted. So payer feedback to date really indicates that they realize this is a defined population relative to other areas that they actively manage, so they're really not actively managing it today. They definitely see the unmet need in this disease state, and they're very receptive to a product that can more effectively treat these difficult-to-manage patients. and prevent the recurrences that involve additional hospitalizations and antibiotic use. So those whom we've engaged to date specifically indicate a willingness to pay for innovation in this category. In fact, I would point you to slide 13 in our current corporate slide deck filed today, which shows that payers have given CR-109 a very high value rating, really in the same neighborhood as some life-saving HCV medications. And finally, I would say with the ecosystem, or three data, we have a very strong clinical value story to share, and I look forward to engaging this important customer set with the actual profile of 0109.

Thanks for the question, Terrence. Why don't we take the next one?

Thank you. Our next question comes from Chris Harden with Jeff Rees, and we proceed with your question.

Great. Thanks so much for taking the questions and congratulations across the board. Lots of progress. So I guess for me, I have most of my questions on ulcerative colitis. So with respect to the 287 readout here, I think one of the things that's puzzling to me and just trying to figure out translation moving forward is what kind of the expected performance might be on the placebo arm. You know, obviously had 0% clinical remission in your previous study, and some more recent results have demonstrated a little bit higher of a placebo response in this mild to moderate patient population. So it would be helpful to get your thoughts on what the expected performance might be there. The second question that I would have is just kind of thinking a little bit closer to the you know, Mark's question around what the go-forward strategy would be is that, you know, what is the company's view of induction versus maintenance of remission, and if there would be an opportunity as a maintenance therapy if the induction results were not what you would have hoped or expected for. And then the third question that I have is with respect to manufacturing. I think the comments you made, Eric, were around the idea that your process is at the scale that you would like it to be, but the capacity is not where you would like it to be with respect to commercial scale. So what is the process like to get to the scale that you would like? And I think in particular I'm interested in knowing if there's anything associated with tech transfers, opening up new sites, or things of that nature. Thank you.

Yeah, Chris, good morning, and thanks for the questions. Let's go through these, and let me ask Lisa to comment on her thoughts related to the placebo arm in this patient population for 287.

Sure. To your point, we do not expect a placebo response rate of zero. I think we've worked with some KOLs to try to get a sense of what could be expected in We're using central reads in terms of endoscopy at baseline, so that certainly helps ensure disease to start with. We also are allowing patients in this study who failed biologics. So obviously that, for a portion of the patients, is going to mean that they're not in this group necessarily that has a higher rate of spontaneously improving. So we do know that it will be likely higher, potentially higher than you might see in moderate to severe, but I think we'll be watching closely to see if it looks like what's been seen in a little lower given the factors that I mentioned.

Yeah. So, Chris, let me, let's, your second question related to the strategy induction versus maintenance, I think it's worth just reminding folks that the Phase II is designed to inform both induction and maintenance. And we have, you know, I think the trial will inform our opportunity in maintenance, right? Based on the drug mechanism of action, we believe that there's a potential to have an impact on both induction and maintenance. You know, I will say we're looking first for induction, but by no means does that preclude you know, other approaches including maintenance, you know, potentially including combination therapy. I think that the safety dimension of our approach or what we expect will be the safety dimension of our approach really brings up some really interesting options for these patients that obviously have needs on both the safety and the efficacy side of things. I think, Chris, the last question related to manufacturing and, you know, what I'll say is that we feel very good about where we are Of course, with the Phase 3 results, we expect a launch product, right? So we are building the capacity to be able to support that responsibility to patients, and it's something that we take very seriously. So obviously, even though we are at commercial scale, we will be looking to continue to augment our capacity, ensure that we can reliably supply patients products not only in the commercial side of things, but also in what is a growing pipeline, both on the biologically side of the house as well as the synthetic side of the house. And there's, we think, unique capabilities on both sides of that.

Okay, very, very good. Yeah, thanks, Eric. Maybe if I, I don't know if you'll answer it, but a quick question with respect to the 287. Could you give us some color in terms of how many patients you might expect would have seen prior biologics?

Lisa, do you want to provide thoughts on that?

Yeah, we certainly will provide that kind of information when we read out, but we're really not ready to discuss that or have actually an accurate information probably outside the immediate office.

Okay. All right. Well, like I said, I really appreciate taking the questions, and congratulations. Thank you. Thanks for the questions.

Thank you. Our next question comes from John Newman with Canaccord. You may proceed with your question.

Hi, guys. Thanks for taking my questions, and congrats on the progress, especially with 287 enrollment. It's great news. I had two questions. The first one is, you know, back when we were waiting for the initial SEER 109 readout last summer, there was a lot of discussion among investors about, the role of vancomycin and whether that would actually, in and of itself, have an effect on the current C. difficile. Of course, the study turned out to be wildly successful. Just curious if you can comment on whether the vancomycin preconditioning that you're using for the SEER 287 study really would have any effect based just on its own action. And also, if the agency has commented at all, And then the second question I have is if you could just confirm that part of the reason that the study has been able to sort of pick up an enrollment is due to the greater availability of endoscopy as COVID-19 starts to wane. Thank you.

Yeah, John, thanks for the question. And let me answer the second one, and then I'm going to ask, I'm going to ask Matt to maybe comment on, on the vancomycin piece, but so, so the reasons for, and Lisa can help me with this one as well, but look, we were incredibly pleased. We are incredibly pleased to be at a point of, of hitting target enrollment today. Uh, you might remember, I think many others might remember that when the pandemic first hit in the spring and in March and April, um, there was kind of a seizing of, of clinical activity and, and, uh, It wasn't clear at that point with that initial shock, you know, whether we would be able to enroll the study, and I am incredibly pleased that we're at a point now of reaching target enrollment. We think that there's a number of factors that contributed, John. One is, of course, as you mentioned, the rebound or maybe the improvement in the availability of endoscopies. We require endoscopies as part of our clinical protocol, and and that was really shut down in April and May. That has improved, continues to improve. That's first. The second is we really do think that there was a benefit from the 109 study, even though it's a different patient population, just the validation of the platform we think was really helpful. Third is certainly the need in the space, just as Lisa mentioned beforehand, the fact that we're The 287 is intended to serve a patient population, you know, before the biologics, and there really is a significant need there. The last comment I would just make is I think the reason that we're here is that we just had an exceptional effort and performance from our team. I think that we've got a group of folks that are incredibly dedicated to seeing our programs through, and, you know, they faced adversity that a lot of folks haven't faced beforehand in the clinical paradigm, and they deserve a ton of credit for that. Lisa, unless you've got something else to add, maybe I can ask Matt to comment on the vancomycin question.

Sure. No, go ahead.

Hey, John, good morning. Yeah, so it's a great question about the vancomycin preconditioning treatment and its potential impact on the outcome. Of course, we use that preconditioning as a means to open an ecological niche in the microbiome of patients that we're treating to allow the engraftment of the bacteria in our drug to bacteria in our drug are gram-positive bacteria, and vancomycin is particularly active against gram-positives that we know will compete with the bacteria in our drug. So that's the basis of that therapeutic treatment on the front, the vancomycin preconditioning prior to the therapeutic treatment with SIR287. We use oral vancomycin because it's a non-absorbed antibiotic with a very strong safety profile. That's quite well understood. And then In terms of its potential impact on the response we've seen, there's been a handful of publications over the years looking at the potential use of antibiotics as a treatment paradigm for ulcerative colitis, and the results are not encouraging. They have not been well supported. And in fact, there's been recent publications, several in 2018, where there was actual evidence that vancomycin as a standalone agent for ulcerative colitis could actually lead to detrimental impacts. Keep in mind that a microbiome that is undergoing antibiotic treatment, just like in C. diff, can be susceptible to C. diff and other pathogens. So it's really combining that preconditioning to open that niche, but then following that with our therapeutic treatment, which then restructures the microbiome to get the impacts that we want that we believe is driving that therapeutic response.

Okay, great. Thank you very much. Thanks for the question, John.

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back over to the company for any further remarks.

So thank you, operator, and thanks, everyone, for your time. As I mentioned beforehand, recognizing that we had a little bit of technical disruption, we'll make sure that the transcript is available, and we look forward to connecting with each of you soon. Thanks. Be well, be safe, and have a great week.

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.