Seres Therapeutics, Inc.
Q4 2020 Earnings Call Transcript

Published: 2 Mar 2021

[Operator:]

Ladies and gentlemen, thank you for standing by, and welcome to the Q4 2020 Seres Therapeutics' 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. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dr. Carlo Tanzi, of Investor Relations. Please go ahead.

[Carlo Tanzi:]

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

[Eric Shaff:]

Thank you, Carlo, and good morning everyone. 2020 was a pivotal year for Seres as we moved an important step closer 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 3 SER-109 ECOSPOR III 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 SER-109 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 SER-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 the 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 have also made strides to increase our drug supply capacity.

[Lisa von Moltke:]

Thanks, Eric, and good morning everyone. I'll begin with a review of our SER-109 program. Last summer, efficacy endpoint in patients with recurrent C. difficile infection, showing a substantial absolute reduction of recurrent inflection compared to placebo, at eight weeks post treatment. We are - ECOSPOR III 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 un-blinding. 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 CDI of 27%, compared to placebo at eight weeks post treatment, which is a relative risk reduction of 69%. Study results show that SER-109 administration resulted in similar efficacy when examined by groups stratified by age or by the prior antibiotic therapy. Additionally, the data demonstrates that SER-109 efficacy is maintained over the duration of the 24-week study. From a tolerability perspective, we were also extremely pleased with the Phase 3 study data. We observed a highly favorable safety profile, with SER-109 the need for -- by the recent announcement from a major stool bank stating that it plans to halt operations. We believe our SER-109 Phase 3 data represents a substantial advancement over the standard of care, with the potential to transform how CDI is managed. Furthermore, we believe that SER-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 SER-109 Phase 3 study results College of Gastroenterology Annual Scientific Meeting. And we plan to present additional data at medical meetings later presenting mechanistic support for the efficacy observed in the Phase 3 study. And Matt will discuss those data in more detail.

[Matthew Henn:]

Thank you, Lisa, and good morning everyone. We are aware that we are having some sound issues and we are resolving that. So, I'll continue. Seres continues to invest significantly in our reverse translation discovery and development platform that can delineate at high resolution microbiome biomarkers from human clinical data and integrate these data with preclinical assessments using human cell based assays in 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 SER-109 Phase 3 pre-defined microbiome readouts earlier this year at the Keystone Microbiome Symposium that confirmed the drug candidate's mechanism of action. The Phase 3 study data demonstrated that SER-109 bacteria species rapidly engraft into the gastrointestinal tract. Engraftment was observed as early as one week post-treatment and found to be durable through 24 weeks.

[Eric Shaff:]

Thanks, Matt. And we are aware that we lost the piece of Lisa's section, and I think we lost her when she was talking about the facts from a tolerability perspective for SER-109. We were in our extremely pleased with the Phase 3 data, and that we observed a highly favorable safety profile with SER-109 adverse events being similar to placebo. And we'll ensure that the transcript from this call is available after the call. So let me transition to our financials are fourth quarter and full-year P&L are included in this morning's press release. So, I won't reiterate them here. Seres ended the year 2020 with approximately $303.4 million in cash, cash equivalents and short and long-term investments. We enter 2021 in a position of strength, poised for growth as we continue to advance our pipeline and transition to a fully integrated commercial organization. Seres is building upon our microbiome platform leadership position and driving forward a multiproduct clinical pipeline that is led by SER-109. We believe that our SER-109 ECOSPOR III results provide validation and support for the broader series pipeline and our capabilities in this new area of medicine. Seres 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 SER-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 SER-287. In addition, we intend to continue to invest in core microbiome drug discovery and CMC capabilities to ensure that Seres 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 SER-109 open-label study, and progress with pre-commercial, top line results from the SER-287 Phase 2b study, advancement of our multiple earlier-stage clinical programs, and further strengthening our microbiome platform capabilities, enabling us to bring the next way of therapeutic candidates into the clinic. Seres 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.

[Operator:]

Thank you. Our first question comes from Ted Tenthoff with Piper Sandler. You may proceed with your question.

[Ted Tenthoff:]

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 enrollments in the open-label extension study? And can you give us a sense for when that might be complete or you might report data on that. Thanks, Eric.

[Eric Shaff:]

Yes, 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 3, and then a number of patients that are enrolled into the open-label from the ECOSPOR III 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 continue to make progress enrolling patients, increasing the number of sites. I will say that we started a little bit more slowly that I would have liked, perhaps in part based on the pandemic. But we're really seen a lot of positive momentum and traction in the last period of time. So, we're very encouraged about getting this done. Just as a reminder, we know that we can execute on this, in part based on the fact that the FDA has allowed us to include the 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 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 and 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 in some point soon.

[Ted Tenthoff:]

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

[Eric Shaff:]

Sure, Ted. And maybe I'll ask Lisa to comment. Just to start, as a reminder, we do have a breakthrough therapy designation with SER-109, so 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.

[Lisa von Moltke:]

Yes, 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 patients 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.

[Ted Tenthoff:]

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

[Eric Shaff:]

Thanks for the question, Ted.

[Operator:]

Thank you. Our next question comes from Joseph Thome with Cowen & Company. You may proceed with your question.

[Joseph Thome:]

Hi there. Thank you for taking my questions. I know you detailed it a little bit for us, but if you could just give me a little bit more detail on sort of the initial physician response that you're seeing in terms of the data from SER-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 SER-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. What are the inputs that you're looking for there to make that decision? Thanks.

[Eric Shaff:]

Yes, Joe, good morning, and thanks for the questions. I'm going to ask Lisa to comment on the physician response. I mean I'll just start by saying, obviously, with recurrent C. diff this is a field that hasn't seen 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 how we're thinking about defining success.

[Lisa von Moltke:]

Yes, this has been a delta -- an efficacy result that the field has never seen for C. diff in terms of 88% of people after eight weeks continuing to be free of recurrence. And so, 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.

[Eric Shaff:]

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 still excited about the SER-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 from my perspective, as we continue 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. The 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-immunosuppressant approach for these patients. But maybe I can ask Lisa to comment more completely on 287.

[Lisa von Moltke:]

Yes. And there's a real gap, especially for the mild-to-moderate patients between , and then there's a gap, and you get into these big-gun immunomodulators, and 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-immuosuppressive agent, this is exactly what these patients are looking for. So, we're very excited to get the readout for 287.

[Joseph Thome:]

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

[Eric Shaff:]

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

[Operator:]

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

[Mark Breidenbach:]

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 enrolment and with the open biome quarantine shipping hold in place, can you give us a sense for what courses are still competing for enrolment when it comes to C. diff patients?

[Eric Shaff:]

Yes, 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 ECOSPOR III study. We've got a target of over 100, and we have been making steady significant progress. As I said before, we are doing this in the midst of the pandemic. And even though the pandemic is really trending in the right direction, particularly from the infectious disease side of things, we're competing for resources at clinical sites with some of the COVID clinical work, but what I can tell you that we're 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 the slope of the curve and be in a better position to provide definitive guidance. Lisa, anything else to add on that?

[Lisa von Moltke:]

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.

[Mark Breidenbach:]

Yes, Okay. That's, that's helpful. And with respect to ECO-RESET and SER-287, assuming ECO-RESET is successful, can you give us a sense for what a second pivotal trial and you see 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 ECO-RESET study?

[Eric Shaff:]

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

[Mark Breidenbach:]

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

[Eric Shaff:]

Thanks, Mark. Thanks for the question.

[Operator:]

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

[Terence Flynn:]

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 sales force build? And again, maybe where you stand with specifically I know the MSL teams at the leading edge of that, but just as 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.

[Eric Shaff:]

Yes, Terence, thanks for the question. Great question, we have not provided guidance on OpEx or burn. What I will say is that, we're continuing the efforts to move forward and preparing to commercialize the product. And maybe I can ask Terri 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. And since the top line result, the preliminary top line results in August. We're in the process of bringing MSLs, we're in the process of training them. But maybe I can ask Terri to comment on the last part of your question as it relates to the feedback from the payer universe. Do we have Terri?

[Terri Young:]

Sorry, I'm here. I'm muted. 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 today specifically indicate a willingness to pay for innovation in this category. And in fact, I would point you to Slide 13 in our current corporate slide deck filed today, which shows that payers have SER-109 a very high value rating, really in the same neighborhood as some life saving HCV medications. And finally, I would say with the ECOSPOR III 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 SER-109.

[Eric Shaff:]

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

[Operator:]

Thank you. Our next question comes from Chris Howerton with Jefferies. You may proceed with your question.

[Chris Howerton:]

Great, thanks so much for taking my questions, and congratulations across the board, lots of progress. So, I guess for me, I have most of my questions on all sort of colliders. 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, 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'd 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 Mark's question around what the go-forward strategy would be is that, 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.

[Eric Shaff:]

Yes, Chris. Good morning, and thanks for the questions. Maybe I can let me ask, 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?

[Lisa von Moltke:]

Sure, to your point, we do not expect a placebo response rate of 0, I think we've worked with some KOLs to try to get a sense of what could be expected, 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 where a portion of the patients is going to mean that they're not in this group necessarily that it 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.

[Eric Shaff:]

Yes, so Chris, let's do second question related to the strategy induction versus maintenance. I think it's worth just reminding folks that the Phase 2 is designed to inform both induction and maintenance, and we have, I think the travel and former 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. I will say we're looking first for induction. But by no means does that preclude other approaches and including maintenance, 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 efficacy side of things. I think, Chris the last question related to manufacturing. And what I'll say is that, we feel very good about where we're. Of course, with the Phase 3 results, we expect to launch product, right? So we are building the capacity to be able to support that responsibility to the 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 products, not only in the commercial side of things, but also in what is a growing pipeline, both on the biological side of the house as well as the synthetic side of the house. And there is -- we think unique capabilities in both sides of that.

[Chris Howerton:]

Okay, very good. Yes, Thanks, Eric. Maybe if you -- 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?

[Eric Shaff:]

Lisa, do you want to provide thoughts on that?

[Lisa von Moltke:]

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

[Chris Howerton:]

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

[Eric Shaff:]

Thanks for the questions.

[Operator:]

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

[John Newman:]

Hi, guys. Thanks for taking my questions, and congrats on the progress, especially with 287 enrollment. Some great news. I had two questions, the first one is, back when we were awaiting for the initial, SER-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 having an effect on recurrent 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 SER-287 study really would have any effect just on its own action, and also if the agency has commented at all there? 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 and enrollment is due to the greater availability of endoscopy as COVID-19 starts to wane. Thank you.

[Eric Shaff:]

Yes, John, thanks for the question. And let me answer the second one, and then I'm going to ask Matt to maybe comment on vancomycin piece, but so the reasons for - I think Lisa can help me with this one as well, but we were incredibly pleased to be at a point of hitting target enrollment today. You might remember, I think many others might remember that when the pandemic first hit and in the spring in March and April, there was kind of a seasoning of clinical activity and it wasn't clear at that point with an initial shock, whether we would be able to enroll this study. And I am incredibly pleased that we're at a point now with -- of reaching target enrollment. We think that there is a number of factors that contributed John. One is of course, as you mentioned, the rebound or maybe improvement in the availability of endoscopies, we require endoscopies as part of our clinical protocol. And that was really shut down in April and May that 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 to the validation of the platform we think was really helpful. Third is certainly the need in the space, just as Lisa mentioned beforehand, that the fact that 287 is intended to serve a patient population, 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, a group of folks that are incredibly dedicated to seeing our programs through and 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.

[Lisa von Moltke:]

Sure. No, go ahead.

[Matthew Henn:]

Yes. Hi, John. Good morning. Yes, so it's a great question about the vancomycin preconditioning treatment and 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 are treating to allow the engraftment of the bacteria and our drug are Gram-positive bacteria, and vancomycin is particularly active against Gram-positive that we know that will concede with the bacteria and our drug safety. That's basis of that therapeutic treatment on the front that vancomycin preconditioning prior to the therapeutic treatment with SER-287. We use oral vancomycin because it's non-absorbed antibiotic with a very strong safety profile that's quite well understood. And then, in terms of its potential impact on the responses data, there has 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 that they have not been well supported. And in fact, there has been recent publication several in 2018 where there was an actual evidence that vancomycin as a standalone against 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, because they can be susceptible to C. diff and other pathogen. So, it's really combining that preconditioning, opening 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.

[John Newman:]

Okay, great. Thank you very much.

[Eric Shaff:]

Thanks for the question, John.

[Operator:]

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

[Eric Shaff:]

So, thank you, Operator. And, thanks everyone for your time. As I mentioned beforehand, recognizing that we had a little bit of a technical disruption, we will 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.

[Operator:]

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