Seres Therapeutics, Inc. (MCRB) Q1 2020 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Seres Therapeutics Q1 Earnings Conference Call. At this time all participants are in a listen mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions] I must advice you that this conference is being recorded today May 7, 2020. I would now like to hand the conference over to your speaker for today, Dr. Carlo Tanzi of Investor Relations. Carlo, please go ahead.

Thank you, and good morning. Our press release with the company's first quarter 2020 financial results and a business 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 will be making forward-looking statements relating to the timing, enrollment and results of our clinical studies, regulatory approval, the promise and potential impact of any of our microbiome therapeutics, the sufficiency of our cash and cash equivalents to fund operations, and the availability of additional cash resources. Additional resources 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 Eric Shaff, Seres' President and CEO; Lisa von Moltke, Chief Medical Officer; and Matt Henn, Chief Scientific Officer. With that, I'll pass the call to Eric.

Thanks, Carlo, and good morning, everyone. During the last several years, Seres has been working hard to advance a new treatment modality with our microbiome therapeutics platform. We are now entering a period where we expect to obtain important clinical study results. These results, including from our upcoming SER-109 Phase III study for C. diff infection, have the potential to provide definitive validation of the microbiome approach. We believe that positive clinical data will clearly demonstrate that the time for microbiome therapeutics has arrived and will help to highlight the potential for this new treatment modality across multiple serious diseases. COVID-19 continues to have an impact on Seres as it has on the rest of society. We are closely monitoring the impact to all aspects of our business, and we are making the necessary changes to our business to ensure that our operations continue, and that our employees and those involved in our clinical studies remain safe. Seres' administrative employees continue their work outside of our offices, and laboratory R&D and manufacturing activity remain ongoing, with modifications made that prioritize employee safety. As an example, Amidst COVID-19 protocols, we successfully completed a SER-301 fill run at our Cambridge facility last week. Overall, while how we work has changed, we have adapted and we are pleased to continue advancing our pipeline and moving the business forward despite the complexity associated with the pandemic. Seres' immediate focus and priority is on our SER-109 program. We have recently completed enrollment of our SER-109 Phase III ECOSPOR III study, and we are now eagerly looking forward to reporting top line results in the middle of this year. Later this month, on March 27 and ahead of the SER-109 data readout, Seres' management and an external subject matter expert will host SER-109 investor event. We plan to provide a deeper discussion of the burden of C. diff infection, and discuss the need for effective and safe new treatment approaches. We will also review the ongoing SER-109 Phase III study and the potential to fundamentally change the treatment of C. diff. We recently welcomed Dr. Lisa von Moltke as our Chief Medical Officer. Lisa joined the company after an extensive career leading clinical teams at prominent biopharma companies, including Alkermes, Sanofi Genzyme, Millennium and Takeda. We are very happy to have Lisa onboard. I'll now pass the call to her to review our clinical programs.

Thanks, Eric. I'll start with an update of SER-109, and this is definitely an exciting time for me to be joining the company. As Eric mentioned, the study has completed enrollment, and our clinical team is working hard to prepare for the pending readout. Our SER-109 program aims to meaningfully improve the treatment options available for recurrent C. difficile infection. Today's treatments for this debilitating disease have important limitations: Antibiotics, while effective in treating an acute C. difficile infection, ultimately leave patients at risk of future recurrences, because they do not address the damage done to the microbiome. Unapproved fecal microbiota transplant, known as FMT, is also widely used for recurrent C. difficile infection under an FDA enforcement discretion policy. We've closely studied all available clinical evidence supporting FMT, and we, along with leading experts in the field, recently published a peer-reviewed paper on this topic in the journal Open Forum Infectious Diseases. In summary, the degree of clinical efficacy of FMT and the safety of FMT have not been well established. The clinical data supporting FMT have been limited by the small size, open-label trial designs and inconsistent methods and amounts of product administered. As a result, we simply don't have an adequate understanding of the degree of efficacy of FMT. Furthermore, we are there are serious questions about the risk of transmission of infectious disease through this approach. We believe that rigorously conducted clinical studies, such as our ongoing SER-109 Phase III trial, will provide definitive clinical evidence and potentially enable the availability of new, well-characterized and FDA-approved treatments for this serious disease. SER-109 is an orally administered drug candidate designed to restructure the microbiome and prevent recurrent C. difficile infection. SER-109 was designed based on our understanding of the disruptions to the microbiome observed in individuals that are at risk received a C. difficile recurrence. SER-109 has been designed specifically to address these deficiencies. Now our SER-109 manufacturing process fractionates and purifies bacterial spores, and inactivates vegetative bacteria and many potential pathogens. This includes pathogens that have been linked to FMT-associated disease transmission, such as drug-resistant E. Coli, and viruses like SARS-CoV-2. We believe that our unique SER-109 manufacturing process provides a critically important safety advantage to our products. Based on SER-109 clinical and microbiome data, we have obtained both breakthrough therapy and orphan drug designations from the FDA. SER-109 is now being evaluated in a randomized placebo-controlled Phase III study in patients with recurrent C. diff infection. All ECOSPOR III study subjects are treated with standard of care antibiotics to address the qualifying C. diff infection, and subjects are then randomized one-to-one to receive either SER-109 or placebo. We completed enrollment with 182 subjects. All patients enrolled in ECOSPOR III are required to test positive for C. diff cytotoxin. We have taken this rigorous step to ensure that we have enrolled only patients with an active C. diff infection, and not those who are simply carriers of the C. difficile bacterium. The cytotoxin assay will also be used to confirm on-study recurrences. The ECOSPOR III primary endpoint compares the C. diff recurrence rate in patients who received SER-109 versus placebo at up to eight weeks after dosing. We aim to obtain clinically compelling results, showing that patients who receive SER-109 have a meaningfully lower rate of recurrence compared to those on placebo. In addition, we hope to observe a favorable safety profile as we've seen with all Seres' microbiomes clinical data thus far. Based on FDA discussions to date, we believe that if we obtain compelling results, the ECOSPOR III study may support SER-109 product registration. However, this would depend on the strength of the data and additional safety data may be required. Our clinical team is working to prepare for database lock and analysis of the study results this summer. Operational progress has been steady, and only three patients still need to achieve the eight week end point. We have been conducting quality control and study data on an ongoing basis, and we are well prepared for data lock and analysis of the study results. Now on a personal note, it is exciting to be awaiting data pertaining to the treatment of such an intractable disease, and with an approach that holds so much potential promise for patients with this as well as other serious conditions. Now, let me turn to our SER-287 program, which is an ongoing Phase IIb study in patients with mild to moderate, clinically active ulcerative colitis. SER-287 is an orally-administered biologically derived drug candidate, comprised of commensal bacterial spores derived from the healthy human gastrointestinal tract. Our objective with SER-287 is to develop a first-in-class microbiome therapeutic that modulates the microbiome and microbiome associated metabolites in UC patients. SER-287 is intended to reduce the impact of a dysfunctional microbiome as a trigger and amplifier of inflammation. Moreover, we believe that SER-287 may provide a much needed non-immunosuppressive treatment option for this serious disease. To remind you, the 287 Phase IIb ECO-RESET study is a randomized placebo-controlled 3-arm induction trial that was designed to enroll 201 patients with active, mild to moderate ulcerative colitis, who have failed prior therapy. In Arm A, patients receive a short course of vancomycin preconditioning, followed by 10 weeks of the same daily regimen that was used in the arm of the Phase Ib trial that showed the highest clinical remission rate. In Arm B, patients receive vancomycin preconditioning followed by two weeks of the same SER-287 daily regimen used in Arm A, followed by 8 weeks of a lower dose. In Arm C, patients received placebo. As we previously reported, the COVID-19 pandemic has had an impact on our currently enrolling clinical studies, including the SER-287 Phase IIb trial. The SER-287 Phase IIb study is approximately 60% enrolled based on the original 201 patient target. Enrollment continues to be adversely impacted by the COVID-19 pandemic, and multiple clinical sites have halted endoscopies and other nonessential medical procedures. We continue to evaluate various options for study execution in light of the situation. Our overall goal is to obtain a high-quality, clinically meaningful data set that provides a clear assessment of the drug's clinical profile, and allows us to make a data-driven decision on further development. ECO-RESET remains open, and we continue working to enroll patients. Our clinical team has implemented a number of mitigation strategies aimed at maintaining forward progress, including providing increased clinical support to clinical sites, and additional flexibility regarding data capture. We also continue to evaluate various options, including potential trials design modifications, consistent with our overarching goals of obtaining a high-quality, clinically meaningful data set expeditiously. Now moving to SER-401 in our oncology portfolio. SER-401 is an orally administered biologically derived microbiome therapeutic candidate, comprising bacteria reflective of the microbiome signature associated with response to checkpoint inhibitor immunotherapy. With SER-401, we are targeting an increase in efficacy of checkpoint inhibitor immunotherapy and improvement in patient outcomes. In collaboration with The Parker Institute for Cancer Immunotherapy and MD Anderson Cancer Center we continue to enroll a randomized, placebo-controlled Phase Ib study of SER-401. The study was designed to enroll 30 patients with metastatic melanoma. All patients received nivolumab, an FDA-approved anti-PD-1 therapy, and are randomized at a 2:1 ratio to either SER-401 or placebo. The study will evaluate safety, clinical response and various potential biomarkers of response, including microbiome signatures of response. We plan to examine tumor biopsies to evaluate immunologic activity and other potential pharmacodynamic biomarkers. The SER-401 study remains open, but COVID-19 has slowed enrollment. And we, along with our collaborators, are assessing potential changes to the study plan. Now, I will hand the call over to Matt.

Thanks, Lisa. I'll begin with our inflammatory disease programs. SER-301 is our next-generation rationally designed fermented microbiome therapeutic candidate for the treatment of ulcerative colitis. Next-generation drugs like SER-301 may provide important benefits, including optimized pharmacological properties and streamlined manufacturing. SER-301 was designed using Seres' powerful in-human reverse translation, drug discovery and development platform. We have developed deep expertise regarding computational analysis, culturing, functional screening and manufacturing. Our approach integrates data from emerging microbiome research and insights from our own in-human clinical trial data. These combined insights have driven the identification and development of disease targets druggable by our technology and the design of our therapeutic candidates. The consortium of bacteria in SER-301 is designed to modify the microbiome and microbe associated metabolites in the gastrointestinal track in order to modulate anti-inflammatory immune pathways and improve epithelial barrier integrity in patients with ulcerative colitis. SER-301 is produced using our advanced fermentation, formulation and delivery platform. It includes strain-delivered in spore form as well as strains fermented in non-spore form or vegetative. And is delivered using enterically coded technology designed to release in the colon. Notably, this first ever product candidate to be comprised of both spore and non-spore bacteria is an important technological achievement. This formulation requires several manufacturing innovations, and we are pleased that we have been able to move this novel product candidate forward. We continue to make progress working to initiate a SER-301 Phase Ib clinical study in patients with ulcerative colitis. The study will be run in Australia and New Zealand, and pending regulatory approvals, we expect to start patients later this year. Moving now to SER-155. SER-155, an orally delivered, rationally designed fermented microbiome therapeutic candidate that we have decided to move forward toward clinical development. SER-155 builds on our expertise in infectious disease and immunology. It is designed to prevent mortality due to gastrointestinal infections, bacteremia, and graft-versus-host disease in immuno-compromised patients, including patients receiving allogenic hematopoietic stem cell transplantation. Since the SER-155 program's inception increasingly compelling data based on human cell-based assays, in vivo disease models and clinical data support advancing the product candidate forward. Somatic stem cell transplant patient data from our collaborators at Memorial Sloan Kettering Cancer Center, demonstrates a clear relationship between the gastrointestinal microbiome and clinical outcomes. We expect that the SER-155 clinical program will provide insight into the potential for microbiome therapeutics to improve outcomes in stem cell transplant patients. And also further our understanding of the potential for our technology to treat bloodstream infections more broadly in immuno-compromised patients, including in individuals infected with multidrug-resistant bacteria, such as Vancomycin-resistant enterococci, and carbapenem-resistant enterobacteriaceae. The SER-155 program is supported by a CARB-X grant that provides meaningful financial and operational support through Phase Ib clinical development. We plan to advance the program into a Phase Ib study later this year in collaboration with Memorial Sloan Kettering. I'll now pass the call back to Eric.

Thanks, Matt. Turning now to an overview of our recent financials. Seres reported a net loss of $19.9 million for the first quarter of 2020, as compared to a net loss of $24.3 million for the same period in 2019. The first quarter net loss was driven primarily by clinical and development expenses, personnel expenses and ongoing development of the company's microbiome therapeutics platform. The first quarter net loss was inclusive of $8.2 million in recognized revenue associated primarily with the company's collaboration with Nestlé Health Science and AstraZeneca. Additional financial information regarding the quarter can be found in our press release that we put out this morning as well as our 10-Q that we intend to file later today. Seres ended the quarter with approximately $75.1 million in cash and cash equivalents. The company's cash resources are expected to fund operating expenses and capital expenditure requirements excluding net cash flows from future business development activities or potential incoming milestone payments into the second quarter of 2021. This cash runway does not include a $10 million SER-301 Phase I-associated milestone payment that Seres would be entitled to as part of our Nestlé Health Science collaboration. We are all very excited about the period ahead. Positive late-stage clinical results could fundamentally transform Seres as well as the microbiome therapeutics field. We look forward to taking your questions. Operator, please let's now open up the line.

[Operator Instructions] Your first question comes from the line of Chris Shibutani with Cowen.

Can you talk about whether 109 would be considered suitable for product registration and included mention of the potential for additional safety data may be required, particularly in the context of COVID-19 and this morning's release shared some additional reminders of FDA's attentiveness to concerns around FMT. Can you share with us a little bit more about what kind of potential safety data may be required? Are you able to anticipate any of this? And in particular, as it regards maybe demonstrating proof of the inactivation of COVID-19, just broadly speaking, is that something that it would be reasonable to contemplate? And is that anything that you can already be doing? In other words, the safety, additional information add to your time lines? Or are you kind of already anticipating some of that work?

Yes, Chris. I missed the first part of your question. I don't know if that was just my line or yours. But I think I've got the gist of it. So, let me start it. I'm going to ask Matt to comment. And if we don't answer it completely, we can come back to it. So, in terms of where we end up with top line results in the middle of this year, you may remember that when we redesigned the study, we noted and have continued to note that the FDA in discussions provided the benchmarks for statistically what would provide a single pivotal study. And that we would engage in discussions with them around the next steps in terms of safety, right. And I would say that in the time that's passed, in my mind, the playing field has changed in some sense as it relates to safety. First, because of the patient deaths that happened over the summer from FMT. The FDA meeting that was held in November as a consequence of that death. And then we've seen additional safety issues earlier in March, and most recently, as I think you noted, Chris, the FDA noted a warning about the potential transmission of COVID through stool, right. We believe that our approach is differentiated because of our CMC process and the inactivation steps that we've taken that we've always taken. We've talked about safety for some time. I think it's unfortunate that these safety events and the general environment of the sensitivity of the safety around COVID, I think, is now perhaps putting us to the tipping point where those safety, and inactivation steps and that differentiation is maybe becoming more clear. But we do think that our approach is most consistent, most aligned with patient safety, because we think that the donor screening is necessary but insufficient, right? It's inherently reactive and COVID is a great example of that. We have been in discussions with the FDA around our approach. We noted in our press release that we put out on March 30th, that we have been in discussions with the FDA. Our view is that the FDA considers us different from FMT. And how this all plays out, we'll see. Obviously, we're focused on achieving the right top line results and then engaging with the FDA thereafter. Maybe I can ask Matt to comment, and Chris, I know I missed the first part of your question, so we can come back if we miss something.

Chris. Yes, I mean, I think Eric hit on all the key points. I will emphasize the point that our view is that donor screening alone is insufficient, in that SER-109 is fundamentally different from FMT. And this results from 2 factors, one factor being that the manufacturing process fractionates the spores-forming bacteria, which we believe to be the active component, and that has the benefit of isolating those spores and removing vegetative bacteria that can lead to infections, such as those reported in the various FDA reports as well as importantly, the ability to knock back various viruses and other potential agents of unknown origin at a given time. So that ethanol process is very selective for the spores, and purifies our product to remove those safety threats.

Great. No, that's helpful. And then if I can just follow-up quickly on 287, can you just remind us where you are in terms of stage of that trial? It sounds as if unsurprisingly, COVID-19 have had some headwinds relative to conducting that at the original pace you hoped to. Is the 3-Arm study that you've been doing where you're aiming for 201 patients, are you thinking that you would continue to keep the protocol with that many patients and just potentially have the readout of the top line results delayed? Or is there some leeway within that study designed to keep things on track and modify the protocol with perhaps smaller patient numbers? Talk to us how you're prioritizing adjusting in this context that we're in currently?

Yes. Chris, thanks for the question. Let me start, and then I'm going to ask Lisa to chime in and provide her commentary. As we said, we certainly have been impacted by the pandemic as it relates to SER-287, and specifically the availability of endoscopies, right. And our trial sites, a number of our trial sites have shut down as it relates to offering endoscopies that's deemed nonessential procedures, more typically, the large academic centers. We do have smaller GI-focused practices that continue to be open. So we continue to screen and we continue to enroll, but certainly not at the same rate where we were earlier in the year. So, Chris, where we are now is evaluating, and there's a number of different dimensions at play. As you remember, the IIb, we were told by the FDA, it could be 1 of 2 pivotal studies, of course, that's important. But we're also thinking about the availability of data, time and all of that is coming together into a number of different scenario analyses that are currently underway. And that analysis continues. Obviously, some of it depends on how quickly the world gets back to not necessarily the state that it was, but in a state where endoscopies are more freely available. And we're starting to see a little bit of daylight as it relates to that. So, the analysis continues. I will say that where we are today is 5% enrolled with a 3-arm study as compared to the Ib study, where we had 4 arms, we already have significantly more subjects in than we had in the Ib. We care about quality, data sets, both clinical and microbiome, and we're confident that we will get quality data from this no matter what the choice ends up being. But that's how we're thinking about it. Lisa, can you add anything that I may have missed?

Yes. No. I mean, I think, as you noted, we're doing a lot of things in parallel, and lots of work with the sites to support their activities and help them find new ways to complete their activities. We are looking absolutely at potential trial designs and what those would look like, again, with the goal that we need to have a data set that gives us a clear indication of what kind of drug we've got in a timely fashion. And as Eric said, we're also -- this is a dynamic landscape. And we've seen even this week that Florida, for example, is starting to open up some of its medical sites. And so we really are going to be doing a lot of this in parallel and assessing in real time.

Great. Thanks. We look forward to the May 27 event to help everyone get on the same page to understand those top line results midyear.

And your next question comes from Terence Flynn with Goldman Sachs.

Hi. Thanks for taking the question. This is Missy on for Terence. With respect to the midyear 109 data, can you be any more specific about the timing? Is it reasonable to expect that in early June? And at that point, will you be in a position to disclose if do you think the data will support approval or if it will require any additional conversations with the FDA?

We are guiding to midyear. We have guided and we will continue to guide the midyear. I think that we're in an incredibly privileged position as a company, given this unprecedented pandemic to be able to deliver this critically important top line result on time and on plan. We're grateful for that. That doesn't mean that there's not a considerable amount of work that needs to be done and has been done to put us in this position. And we've -- our clinical group has been very hard at work finalizing enrollment, cleaning the data, accessing data, liaison with sites with PIs and KOLs. So, there's a lot to do between now and then. But we will continue to guide to midyear. As it relates to next steps, I think we have historically said, and I'll reiterate today, we're focused on seeing this top line results and then engaging with the FDA afterwards. And remember that this is a breakthrough orphan-designated program, so we really look forward to that engagement and the next steps, giving this time to hopefully to patients as quickly as possible.

Your next question comes from Mark Breidenbach with Oppenheimer.

This is Matt on for Mark. Eric, I'm just wondering if you've noticed any headways from COVID in sourcing donor material or the donor-derived products at least? And has there been any changes or amendments to the manufacturing protocol since the outbreak? And then, I guess, how confident are you if there were changes that those changes won't, in any way, affect potential BLA filing for SER-109?

I think it's an important one. There's probably a couple of different dimensions that -- to your question. The first is how are we as it relates to clinical supplies? And I can tell you that we're in a very good spot in terms of our clinical supplies. And as we've noted, we continue to move forward with our operations, both not only on the R&D side, but also on the CMC side. And the fact that we were able to do this drug fill last week in Cambridge amidst the COVID-19 protocols, I think it's just a great accomplishment by the team and is indicative of how we're moving forward amidst a lot of adversity, right. As it relates to sourcing of biological material, again, we feel good about where we are as it relates to the studies and our availability of supplies. We have been in discussions with the FDA. We are instituting the right adjustments to make sure that we're being as field-leading in our donor screening protocols as we need to be. But I think it just gets back to the point, and maybe I can have Matt to comment on this as well, that as it relates to SER-109, as it relates to FMT, as it relates to approaches in the recurrent CDI space, donor screening is necessary but insufficient, right? It is inherently backward-looking, and as we think about, not only COVID-19, but the next virus that comes along, we know that we are differentiated. Our process is unique, and we believe most consistent with patient safety because we have the inactivation steps in our process. Matt, do you want to comment further?

Yes. Matt, as Eric noted, we have not had any product impacts owing to the COVID pandemic. We have always precluded the donor screening side of things. We have always precluded travel to countries and regions where diarrheal diseases are endemic, which included countries such as China. We've always had a rigorous screening protocol for individuals who might fall ill, and ensuring that they're not included in the collection process. So we've been very proactive on the donor screening side of things. But again, importantly, it's really our manufacturing process, and the purification of fractionation process of spores that really allows us to isolate what we believe to be the key active component for treating this disease, from acute spore-forming bacteria, and exclude vegetated bacteria that are potentially a problem and can lead to infections as well as viruses. And I as well will point folks to -- we did recently publish some data on the previous SER-109 trial, where we released the various inactivation data from our manufacturing process, which shows we removed that bacteria such as coronaviruses.

Okay. That's helpful. And then maybe just tagging along with one of the prior questions on ECO-RESET, you did mention potentially amending the trials' protocol, is touching the primary endpoint to get rid of endoscopy, something that you're considering? And then I guess it is, how much do you think that would affect the quality of the data?

Yes. Matt, it's hard for us to comment in a lot of detail on that. Obviously, endoscopies were part of our clinical protocol. We do think that they are an important objective measure. The FDA has provided guidance, as which indicates that they intend to be flexible amidst the pandemic. On the other hand, it was somewhat light in terms of specifics. So, we are considering all alternatives and options, including, by the way, forging forward, but -- as the study was originally planned. But those are the types of considerations that we're thinking about right now.

Your next question comes from Gbola Amusa with Chardan.

On SER-109, can you comment a little bit on the benefits of a breakthrough therapy designation during a COVID-19 pandemic? Whether the benefits are now? Or maybe you expect any benefits in the year or 2 ahead? Because I think one company in another state mentioned that, that enabled them to keep their facilities open, for example. And then secondly, I may have missed it because I missed part of the call, but could you talk about how you think about powering your studies for 287 or 401? If you do have to do modifications, how much impression do you actually have to maintain clinically interpretable study results?

Yes. Gbola, thanks for the questions. On the first, I think it's probably both, and some of that is kind of on the come. So, it's hard to speak in detail. I would say that maybe beyond just breakthrough, we think that there is significant need for a drug in the space, right. We think that the FDA's action to put together the meeting in November as a result of the patient death, we think is indicative of -- never mind the subsequent safety issues and the warning related to FMT, it's related to COVID or the potential transmission of COVID through FMT, we think that it's suggestive of the fact that the FDA is really looking for a new solution here. We obviously, we don't speak for the FDA, but we think that, that is maybe as significant as the breakthrough designation. We're always engaged proactively with the agency. We have a strong working relationship. And I think enforcement discretion is a choice that has come under a lot of scrutiny, and we'll continue to do so, particularly with positive data from a clinical study like ours. On the 401 and the 287 side, Gbola, I'd say that we continue to evaluate. And certainly, the powering of the studies it's something that we're keenly focused on. I think the 287 and 401 are somewhat different, in the sense that 401 is a Ib study, 287 is a IIb study, somewhat different goals and objectives. But certainly, that's one of the key dimensions that we consider as we think about alternatives, if in fact, there is an alternative beyond the status quo.

Our next question comes from John Newman with Canaccord.

I apologize if this question has already been asked, but just curious to what type of a benefit you believe you would need to show in order for the SER-109 recurrent C. diff study to be a pivotal study with FDA? Second question I have is a little bit more philosophical one. So, I think you have very appropriately included a positive C. diff toxin test that is required for enrollment into your study, which I think will significantly increase the robustness of the results. The question I have is, given that some doctors in the hospital setting may still utilize a PCR-based test do you believe that if physicians see that your drug is beneficial for those with the positive C. diff toxin test, that they will also feel comfortable using it for those where they have a positive PCR test?

Yes, John, what do we need for success for 109? In our minds, it's a couple of things. One is it's a result that is statistically significant and clinically meaningful, right. And we're looking for -- we're expecting a safe drug and I think that both are areas of significant unmet medical need in this space. On the efficacy side, as you noted, remember that we're acquiring toxin, which we think will give us the clearest, most interpretable, most reliable data set. And we've seen evidence that this is a space, a disease where there is significant unmet medical need. From a safety perspective, as we've said before, we intend to read out the top line results. We'll engage with the FDA in an end-of-Phase-III study, and then we'll determine what the right next step is. And as I mentioned beforehand, I think that the landscape has shifted in terms of the appreciation of safety as a key dimension in this disease in FMT as a in our view in a suboptimal treatment option. On the second question, John, again, toxin, we think, is critically important. We think it should provide, as I said before, the most clear and most interpretable data set, the most reliable data set. Whether doctors continue to use PCR in their clinical practice, I think to be determined, our expectation is that our label is not likely to be restricted to toxin. And that it's not likely to be an impediment to clinical utilization.

Our next question comes from Vernon Bernardino with H.C. Wainwright.

Just wondered if you could remind us, when was the last 109 patient enrolled? And regarding the effects of COVID-19 on the microbiome, what have you seen as far as patients with recurrent C. diff that the presence of a coronavirus in the microbiome? And its progression during the patient's own independent reconstitution of their microbiome? And what changes have you seen as far as the microbiome during 8 weeks of infection of coronavirus, if you could? If there's any data out there?

On the patient numbers, so we announced that we were closing the study at the end of March with 171 subjects. We actually randomized 172nd subject subsequent to that announcement. And then on your questions as it relates to COVID, maybe I'll ask Matt to comment. But of course, this is blinded data. So I'm not sure what -- maybe I missed the entirety of the question. But maybe, Matt, you can comment on what we know?

Yes. So, two things. First, just we completed enrollment with 182 subjects in the existing trial --

Sorry, 182.

Sorry, could you please repeat your question on COVID? I apologize, but you were kind of -- it's hard to hear the question?

Sure. It's not specific to the trial itself, but I'm curious, and one reason why I asked about the last patient, because it's still rather unknown, let's say, how COVID affects -- the extent COVID-19 affects a microbiome. So, I'm curious about the reconstitution of the microbiome in patients just in general, who've experienced COVID-19? And what have you seen as far as changes during the microbiome during an 8-week period, from the beginning of their diagnosis. I'm trying to ask to see if this perhaps has had an effect on what kind of results you might see in those last patients considering that perhaps the virus has appeared even as early as December, but let's definitely say January, February on the clinical trial results for 109?

Sure. Okay. Sure. Thanks for repeating the question. I think it's really too early to speak definitively about the impacts of the COVID virus on the modification to the microbiome. There has been very minimal information published to date around this. And so I think there's really limited information, and anything we were to say would be speculation at this point. What I can say is based on the data that I have seen published to date, which is a single study, that I would not anticipate COVID-19 having a big impact on the bacteria that we are looking to repopulate in the guts.

Okay. And then one last question, if I may. Any ideas about something like SER-155 and its potential in something like acute respiratory distress syndrome?

Matt, you want to take that?

Yes, sure. So, SER-155 is a fermented rationally designed microbiome therapeutic, which is targeted for Allo-HSCT patients receiving stem cell transplant. We've developed this drug to decolonize key pathogens in the GI tract that lead to bacteremias, improve epithelial barrier integrity to reduce translocations as well as modulate host immune responses to reduce graft-versus-host disease. We do know that the modulation of microbiome in the gastrointestinal track can have systemic effects from an immune perspective. Again, I'd come back to, I think if there's an interesting potential opportunity to think about microbiome therapeutics, and how they may impact COVID infection and immunological cascades in the lung. But that's an active area of work.

Yes. And Matt, thanks for the clarification on my first answer. The enrollment is 182. And Vernon, thanks for the questions.

Your next question comes from Roger Song with Jefferies.

So, I have three questions here. So, the first one, is you may all are aware -- it's Rebiotix, they reported kind of top line positive CDS data recently. I'm just curious how you think this data will change the regulatory pathway for 109? And the potential competitive landscape in CDS?

Yes, Roger, thanks for that question. Look, in general, I'd say that positive data is a good thing. It's a good thing for patients, it's good for the sector. It's -- overall, it's a good thing. There wasn't much in terms of specifics to react to, so it's hard for me to comment in substance. I will say that, far more than anyone else's data, we are most excited to release our data in the middle of the year. And we are a scientifically rigorous company. So, we think that this field needs rigorous data and we're committed to providing clear data. There really is a significant need in the recurrency of this space, which is why I think you're seeing a number of different companies working to provide new approaches. And we think that we have a differentiated approach, both in terms of our utilization of the spore fraction, in terms of the rigor of our study and requirement cytotoxin, which we think will lead to the most interpretable, most reliable data set. And certainly, as you think about the considerations of safety, which is on everyone's mind today, our CMC process, we think, is most consistent with patient safety. So we think it's going to be an important year in the microbiome space, but we're really focused on our data release to drive that.

Yes, that makes sense. We all kind of look forward to some positive news for the entire kind of microbiome space. And the second question is really very interesting. For SER-301, I think the first time you disclosed the consortium will include the non-spore form bacteria. Just curious, so what do you think -- how significant potentially in the clinical readout do you expect to see for SER-301 versus 287 biological resources, mostly kind of spore-form bacteria?

Yes. Let me -- first just say, I think it's a significant technological achievement by our team, both Matt's team in R&D as well as our CMC group in getting to this point. But maybe I can ask Matt to comment further on that question.

Sure. So, SER-301 was designed based on critical preclinical insights based on human cell-based assay screen as well as disease model data sets. And then importantly, we leveraged our key critical learnings from our SER-287 trial and the identification of various different bacterial species that we saw responsible for generating key microbiome mutated metabolites that had an impact on disease outcomes. So we integrated those information into the design of the drug as well as importantly, information about the engraftment dynamics, meaning the population of bacteria in the gut post-treatment with a microbiome therapeutic into the design. And that required us to include strains in the composition that were both good at forming spores and strains that were not so good at forming spores. And so we advanced our manufacturing capabilities for manufacturing these particular strains to be able to get to the titers needed for dosing for both based on spore formulations and non-spore formulations. And as Eric said, I think we're pretty excited about those advances, both for SER-301, but also, I think that gives us an incredible amount of flexibility as a company moving forward in terms of future products and kind of the bacteria that can be included in those compositions.

Got it. Okay. Great. So, just helpful for the engraftment dynamic and etcetera. Okay, great. And then last question from me, Matt, is -- so it's good to see you have additional kind of pipeline candidates, 155. So, just curious, what is your kind of strategic plan to move from this candidate beyond Phase Ib if data is supportive. Just -- it's okay if you say it's a little bit too early, but just curious your thoughts current thoughts?

Yes. It's early, but let me make a comment on then -- since Matt is really leading this program, I'll ask him to comment as well. I would say this, Roger. This is an important year for the company, and we've been very careful in how we allocate capital in this last period. And we try to be as efficient as possible. And I would say that we've been able to do quite a bit based on the support of some really outstanding partners, whether that's our support from Nestlé in general, but also specifically with SER-301. Our work with AZ and I/O, but also our work with CARB-X and MSK on 155. So it allows us to really deploy our resources to 109 and 287 and to plan for success in those 2 late-stage programs. But we're really pleased to be able to move forward with these really important significant shots on goal in the microbiome in different disease areas, where we hope and think we can help patients. And maybe I can ask Matt to comment on that further.

Yes. I mean, to Eric's point, with 155, this has been a close collaboration with our partners at Memorial Sloan Kettering, who have really led the field in terms of understanding how the microbiome can have an impact on clinical outcomes in hematic stem cell transplant patients, as well as our partners at CARB-X, who are -- have been highly supportive of this program, and as I said earlier, are supporting it through Phase Ib. SER-155 is a very interesting program for many reasons: One, it's allowed us to really build off of our scientific expertise and knowledge of the microbiome. And as we thought about our future pipeline, we are looking to really leverage key critical insights that we have learned from our clinical trials as well as other human data sets that have been published, in terms of one of the key microbiome biomarkers and diseases that can be targeted. And in the case of 155, we've put together a composition that we think can have a very meaningful impact on mortality in these immuno-compromised patients as well as graft-versus-host disease. I think the opportunity for 155, when you think about the issue of bacteremia, the problems with antibiotic resistance emerging, you have a real opportunity to be thinking about how we advance microbiome therapeutics in immuno-compromised patients more broadly and as a means to combat antibiotic resistance bacteria.

And your next question comes from Justin Zelin with Canaccord.

Most of my questions have been actually been asked and answered. But just curious if you can just briefly touch on how your platform is differentiated versus some other competitive programs in the space?

Yes, Justin, it's somewhat of a general question. Look, I would say the following. I think that this is going to be an incredibly important year for the microbiome. And we get the question quite a bit, what is it that really moves the needle in this space? What moves hearts and minds? And in our mind and in our view, what really is likely to move the needle is late-stage data. It's line of sight to a BLA, and visibility that the microbiome is here to help patients today. Not 10 years from now, not sometime in the future, but today. And in that respect, we are believers that, if this space is as big as we think it will be, there's opportunities for multiple approaches to help patients. And that's really why we're here. What I will say is that we've been at this for some time. It's a new field. We've learned quite a bit. And we feel strongly that we have key capabilities, which we've invested in over a significant period of time, which put us in the best position to be successful, not only to achieve clinical data, but following clinical data, right? And in particular, I would point to our microbiome sciences group under Matt, as well as our CMC capabilities, which I think are probably an underappreciated aspect of this space. CMC is not a commodity. There's aspects of growing the drugs beyond just our approach on biologically sourced side of the house. As I said before, the technological achievement associated with 301 and 155, I think, are considerable. So, I think that we've got the tools in place to put us in the position to leverage positive results, and then take the company forward and increase our probability of success as we think about areas within ID, areas within IBD, areas within IO, and there's a lot of opportunity there. There's a lot of unmet medical need to help patients, and we feel strongly that we'll be in a very good position to apply these capabilities forward. Maybe I can ask Matt to talk about our reverse translational capabilities based on human data sets, which, again, I think is a key point. There's only so much you can learn from an animal. The best way to test a human microbiome is in the human microbiome. And we're humble in this new space as we move forward, but we also know that we have clinical data sets from human experiments, which put us in the position to learn and move forward. Matt, do you want to comment?

Yes. I mean, Eric hit on a lot of key points, and I'll emphasize, we launched the company back in 2011. And since then, from inception, the company was focused on building a reverse translational platform, which would enable us to leverage human data sets and key clinical insights to identify drug targets for this novel modality, and then design drugs that can target those and evaluate them. And I think some key differentiators for the company, one, we've been, for a long time, investing heavily in the generation of a strain library, which is a -- we have now a very large collection of strains of bacteria. They've been isolated from both healthy and diseased individuals. These strains have been rigorously characterized using various different functional based assays to define their characteristics. We've -- with our strain library as well as key critical insights from our human studies have been able to refine our reference databases that we use to detect a bacteria in human subjects, and that's really important because it increases both the specificity and the sensitivity of our analyses and our ability to detect changes in the microbiome in terms of which bacteria and functionally, which metabolites and other functional signatures are changing. And we've really gone from the beginning, putting in place an end-to-end capability from target ID, which starts with these clinical human data sets, building a biorepository of samples through key strategic collaborations, the ability to understand the various different bacteria, grow them, culture them, study them in unique ways, such as using human cell-based assays. We've developed a whole host of different assays that we use as well as then improving the animal models that we use to then confirm that we're actually targeting various different disease pathways. Each of these pieces intersect and come together, I think, to provide unique capabilities as a company. And then that is only carried forward to our manufacturing, as Eric said. We have active area of research and development in our manufacturing capabilities, and the ability to bring -- actually design fermented strains forward with the key characteristics.

And we have no further questions at this time. I'll turn it back over to the presenters for any closing remarks. Presenters please proceed with your closing remarks.

All right. Thank you, operator. Sorry, I was on mute. Thank you, operator. Thanks for your continued interest in Seres. We hope you are able to join our SER-109 investor event on May 27. Be safe. Be well. Have a great day. We'll talk soon. Thanks very much.

Ladies and gentlemen, that does conclude today's conference. We thank you for your participation and ask that you please disconnect at this time.