Seres Therapeutics, Inc.
Q1 2017 Earnings Call Transcript

Published: 6 May 2017

[Operator:]

Good day, ladies and gentlemen, and welcome to the Q1 2017 Seres Therapeutics Earnings Conference Call. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. [Operator instructions] I would now like to turn the call over to Carlo Tanzi, Head of Investor Relations and Corporate Communications. Please go ahead.

[Carlo Tanzi:]

Thank you, and good morning. A press release with the company's first quarter 2017 financial results and a progress update became available at 7 a.m. Eastern time this morning and can be found on the Investors & Media section of the company's website. I'd like to remind you that we'll be making forward-looking statements about those future expectations, the timing, design and potential results of our clinical studies, including the ECOSPOR III study and its potential to qualify as a pivotal trial; the result of using cytotoxin assays in the ECOSPOR III study and dysbiosis as an underlying cause of disease. Actual results may differ materially. Additionally, these statements are subject to certain risks and uncertainties, which are discussed under the Risk Factors section of our recent SEC filings. Any forward-looking statements made on today's call represent our views as of today only. We may update these statements in the future but we disclaim any obligation to do so. On today's call, I'm joined by Dr. Roger Pomerantz, Seres' President, CEO and Chairman; and Eric Shaff, Chief Financial Officer. I'll now pass the call over to Roger.

[Roger Pomerantz:]

Thanks, Carlo, and thank you all for joining us. Seres continues to make strong progress as we work to develop an entirely new field of medicine using bacteria to treat disease. We are advancing our microbiome therapeutics platform to develop a novel class of biologically active drugs designed to treat serious human diseases by restoring the function of a dysbiotic microbiome where the natural state of bacterial diversity is imbalanced. Seres is specifically focused on serious human diseases where dysbiosis in the gastrointestinal tract is thought to play a key role. Seres is the pioneer and leader in this new microbiome field, and we have continued to advance our understanding of the underlying new science with the goal of developing innovative novel therapeutics. We believe that microbiome therapeutics have the potential to address multiple serious and -- diseases and our R&D efforts target three therapeutic areas

[Eric Shaff:]

Thank you, Roger, and good morning, everyone. Seres reported a net loss of $25.5 million for the first quarter of 2017 as compared to a net loss of $19.7 million for the same period in 2016. The increase in first quarter net loss was driven primarily by continued growth in clinical and development expenses as well as increased headcount and ongoing developments of the company's microbiome therapeutics platform. The first quarter net loss figure was inclusive of $3 million in revenue recognized associated with the company's collaboration with Nestlé Health Science. Research and development expenses for the first quarter were $20.1 million as compared to $15.4 million for the same period in 2016. The increase in R&D expense was primarily due to expenses related to our microbiome therapeutics platform, the clinical development of SER-109, SER-262 and SER-287 as well as the company's preclinical programs. General and administrative expenses for the first quarter were $8.8 million as compared to $7.2 million for the same period in the prior year. The increase in G&A expense was primarily due to increased headcount, an increase in professional fees and facility expansion to support overall growth. The decrease in cash balance during the quarter was $27.8 million. Seres ended the first quarter with approximately $202.2 million in cash, cash equivalents and investments. I'll now pass the call back over to Roger.

[Roger Pomerantz:]

This has been a highly productive period for Seres as we have advanced our pipeline with continued progress in preparing for the start of a new study for SER-109, our lead clinical program. We have also continued to execute on our two ongoing Phase Ib studies for SER-262 and SER-287. We will move our pipeline programs forward with determination and focus, and we are looking forward to an eventful year ahead. In the coming months, we expect to initiate a new potentially pivotal clinical study with SER-109. We also look forward to two data-rich clinical readouts from our SER-262 and SER-287 microbiome programs in the second half of the year. In addition, we continue to make progress in our other R&D efforts, including those in inflammatory diseases, metabolic diseases, liver diseases and immuno-oncology. We look forward to providing you with timely updates on these diverse but focused preclinical programs. Thank you for your continued interest in Seres, and we look forward to keeping you updated on our progress during the coming year.

[Carlo Tanzi:]

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

[Operator:]

Thank you. [Operator instructions] Our first question comes from Tazeen Ahmad with Bank of America.

[Tazeen Ahmad:]

Hi. Good morning. Thanks for taking my questions. Maybe just a couple. About the new sites that you've picked for the next study, can you just remind us how many of these sites overlap with sites you might have used in the previous study? And can you also remind us what your previous analysis revealed about any discrepancies that might have existed in the procedures between the different sites? And then maybe for 287, can you talk to us about what you think the actual market opportunity is? Of the 700,000 UC patients in the U.S., how many of them are not getting to goal with their current therapies, whether it be related to efficacy or safety?

[Roger Pomerantz:]

Thanks, Tazeen, for two good questions. So operationally, when you look at the different sites for SER-109, I'll remind you that we're going to have over 100 in this new trial. We had approximately 27 in the previous trial and we're adding Canadian sites. We're -- without going into exact numbers, we do have many of the sites which will be used again, and they have investigators. One of the nice things about this is that we have these sort of up and running already. We have the IRBs who know us that agree with -- quickly with the trials. We have nurses and clinics that are used to taking these patients. So, as I said in my remarks, it should speed things up. We did not -- and this was part of our root-cause analysis, I think I had mentioned it on one call but I'll say it again, we did not see any differences in the sites based on performance or their ability to make diagnoses. We did look at that, as anyone would in a root-cause analysis for a Phase II drug, but we did not see that. What I will remind you is that, objectively, the most important thing that we had sorted out was using cytotoxin versus PCR. And we think that is going to, again, make C. diff objective again and make the different sites having little judgment. We're trying to make the calls on true recurrence based on this approach very tight. So, we're happy where we are, and we're glad we have many of the other sites that we've used in the prior Phase II now in the ECOSPOR III trial. To your second question on 287. So, ulcerative colitis has approximately, as I've said, 700,000 people in the U.S. About 200,000 are failing first-line therapy. If you think about what first-line therapy is, it is not a biologic, it's not immunosuppressive. It's 5-ASA plus/minus boluses of steroids. When you fail that, though, you go into immunosuppressant therapy, whether they're oral immunosuppressants like azathioprine or IV immunosuppressants like the monoclonal antibodies, the TNF and other targets. So, we think the opportunity here in this first trial is for these patients before they have to make a decision whether they go into immunosuppressants or not. And this is all their goal is, is to try to stay out of being immunosuppressed for obvious reasons, as I mentioned, with opportunistic infections and tumors associated with it. We feel that we expect SER-287 to be non-immunosuppressive; we don't see a reason for it to be. And if it is efficacious in this population of the patients who are failing first-line therapy, we think that we offer them just a great opportunity to have a drug to keep them out of immunosuppressant biologics such as monoclonals or drugs such as azathioprine. But the other point I'll mention to your question is this is not where we would stop. If we have a good Ib trial with 287 and we move forward, as we expect, to a Phase II trial, we will consider other lines of therapy in ulcerative colitis and, as I've said before, potentially even Crohn's. What we would say is that if you go in those other lines of therapy, it is somewhat longer treatment. And what I'm thinking about is maintenance therapy. This is an induction trial. We would consider maintenance after that. We would consider other areas of ulcerative colitis, maybe later, people who are failing monoclonal antibodies. But right now, we're looking forward to seeing this data.

[Tazeen Ahmad:]

Okay. Thanks, Roger, for that very good explanation. Maybe just a follow-up on that. You're trying to get 55 patients into the study. You've been enrolling for some time. Is the reason that it's taking a bit longer to enroll that you have a very specific profile of patients that you're trying to enroll? Or is it that there is some stickiness in current therapies and patients might be a little bit averse to trying something new?

[Roger Pomerantz:]

Yes, there are -- certainly, in some areas, there's stickiness in therapy. As a physician I know that and was probably guilty of it. But we have not seen that. We actually think this trial is moving quite well. The physicians have been incredibly open to using the microbiome drug. We've had no pushback. We have to make sure that we have the proper patients in the study. We're being as careful as possible. And remember, they're evaluated with a long evaluation, including endoscopy upfront. So, it has nothing to do with enrollment or doctor stickiness in this the case, but we are making sure that the patients are well evaluated before they come in. And we are close, as I've said, to completion.

[Tazeen Ahmad:]

Okay. And then a last question for me on the 109 study. Have you talked about what you want to power it for?

[Roger Pomerantz:]

Yes. So, we've said before that we're looking -- we have it overpowered. We were allowed by the FDA to do that, which is a great thing. And we have a -- over -- a 95% or a little overpower in this study. Remember, 320, we want excellent statistics. We want to excellent powering. We're -- we've made this trial so that if the data is persuasive, there will be the parameters for the FDA to consider it a pivotal trial. Statistics is just one part of that.

[Tazeen Ahmad:]

Okay. Thanks Roger.

[Roger Pomerantz:]

Thank you, Tazeen. Good questions.

[Operator:]

Our next question is from Joseph Schwartz with Leerink Partners. Your line is now open.

[Dae Gon Ha:]

Hi guys. Thanks for taking the question. This is actually Dae Gon dialing in for Joe. Two quick ones for me. With regards to the entry criteria for the Phase III ECOSPOR III trial, can you maybe go into a little more detail about the market opportunity there using the stringent diagnostic protocol? And sort of following up on that, not to get into the weeds here or anything, but just wanted to see if you will be providing a single cytotoxin assay to all the clinical trial sites to minimize any kind of variability between the commercial vendors. And also, how many replicas will each site be conducting to make sure they're not seeing any false positives or negatives?

[Roger Pomerantz:]

Yes. So sorry, you might have missed this. I said in the remarks, we're going to use a central site, so -- for accuracy and consistency just, to your point. So, there will be several replicates, just as done in any of these diagnostics, and it will be done in a central site. And we're -- we've shown that we're able to do it quickly so that it does not hurt diagnosis and treatment. So that's how we're going to deal with it. I can tell you that FDA-approved cytotoxin assays are available everywhere, and they were used everywhere for decades. It's just that PCR, for reasons that have more to do with primary C. diff and epidemiology, took over the standard of care as first-line diagnostics in many centers. We believe that, that will not be a problem, obviously, in the trial, as we do a central site, nor when we expect to market the drug as this is available throughout the country. I -- your other question, I think you had one more that I missed. What was the other one, Dae Gon?

[Dae Gon Ha:]

Yes. So, using the entry criteria for the Phase III, what do you think is the market opportunity?

[Roger Pomerantz:]

Oh, yes. Yes. No, that's another great question. So again, we believe this is not a stringent test. This is the test that was used all the time. When I trained, we only used cytotoxin assays. So, we don't expect this to be a stringent test. What we do expect it to be is truly find patients that are -- that have failed antibiotic therapy and have recurred. We don't think this is going to have a meaningful decrease in what we think is a robust, albeit orphan market. Because we also have an epidemic that's growing at north -- a CAGR of north than 3%. And if we find the right patients with the increasing epidemic, we think we can make a meaningful impact to both the patients and to the epidemic as it spreads by stopping these recurrences. I hope that helps.

[Dae Gon Ha:]

Great. Sorry. One more quick follow-up, if I may. So, given the root-cause analysis and the comprehensive nature of it, I wanted to see if you had any clues to how the phages and the dynamic between bacteria and phage may have created any problems at all?

[Roger Pomerantz:]

That's a great question. You should come work for us. We are very interested in the virome of -- as it's called, of the intestine. As you pointed out, it's not just stages. There are other viruses that are endogenous to our microbiome, and we are very interested in that and have some research going on. Right now, I don't have anything to say about it, but it does show the complexity of the microbiome. I would point out to you that there are no viruses or phages in our drug because they are depleted by -- when we isolate the spores to near purity. So, it would only be the interactions that happen in the host. We have no data for that having an effect in this drug. But it's an interesting question.

[Dae Gon Ha:]

Great. Well, thank you very much for taking our questions.

[Roger Pomerantz:]

Thanks for the good questions.

[Operator:]

Our next question is from Bill Tanner with Cantor Fitzgerald. Your line is now open.

[Bill Tanner:]

Thanks for taking the questions. Roger, I had a couple for you on 109. And I don't know if you want to speak in any detail or even generally on your SAP for the planned pivotal, but I was just wondering if there's an opportunity that the data might be looked at from a responder analysis. And I guess, responder speaking more to engraftment, or if you're confident -- I mean, I would presume that you're confident that the changes to the dosing, the amount and the number of doses, would lead to higher engraftment. And then the second question on that would be you mentioned that the patients enrolled would have experienced 3 or more C. diff episodes. Wondering if you could speak to what that might -- what the result might be there as you look at labeling, and then the recommendations.

[Roger Pomerantz:]

Those again, several very good questions. If you look -- I wouldn't go through what we've discussed with the -- about the SAP with the FDA, but I would say that, again, we are looking for both an effect on the microbiome as well as a clinical response. We're not going to -- I don't like putting words in the FDA's mouth, but we doubt this will be a biomarker for it but -- at this point, but we certainly think this is the mechanism of action. I would just correct one thing you said. It's not just engraftment and the amount of engraftment of 109 species. It's the speed, it's the kinetics of engraftment. What we've shown as -- is that the die is cast early in this disease. It's really -- as we've said, it's a race to repair, from our 2 trials that we've learned. So, it's not just that we need more robust engraftment in everyone; we need it to happen rapidly before C. diff starts over. That's the race between C. diff and the reconstitution and repair of the microbiome. So, we think, as we've shown in our root cause analysis, the effects are not only in quantity of engraftment but speed of engraftment. And I hope that answers that question. What was your second one again?

[Bill Tanner:]

It was -- the subjects that are being enrolled have had 3 or more C. diff episodes, and I'm wondering...

[Roger Pomerantz:]

Yes, let me talk about that. As you know, the definition by both IDSA as well as the FDA of what is multiply recurrent means one occurrence and at least 2 recurrences, so 3 episodes of C. diff. That's the definition. That's how you got defined as multiply recurrent. Before that, no. So that would be what we would look for in a label of this drug to treat this orphan condition. What's important is that the number of recurrences that -- or the percentage of recurrence that happen after each recurrence increases in a stepwise fashion, from 25% to 40s or -- then to 60s then to 80s to 100%. And so, it is important that you have to have this definition of multiply recurrent, but you can have patients quite far into this recurrent cycle. I can tell you that both in our Ib and our II trials, the average is -- was around 4. But that's an important point. We believe that, that will be important in the label and there will be a definition of what multiply recurrent is. That does not mean that the drug will not be studied in the future, once marketed, in other indications in C. diff.

[Bill Tanner:]

Okay. That's helpful. And I'm glad you mentioned the word kinetics because that was part of the question I had on 287. Just wondering -- and you mentioned that the repetitive FMT has been shown to be somewhat effective for UC. So, I'm curious how much of it really is the kinetics important as you're thinking about with 287. And modeling, it would -- I mean, are you modeling it after what you might see with repetitive FMT? And I guess, this isn't necessarily germane to 286, because your prior remarks would make it sounds like it's germane also to 109 in C. diff.

[Roger Pomerantz:]

Oh, it's -- we know it's related to C. diff and the race to repair. The question is how is important kinetics in ulcerative colitis. I don't know that. I will empirically think that it is less than in the race with an infectious agent. This is a chronic inflammatory disease. Remember what the colon looks like in these two diseases. After they're treated with antibiotics, the colon is not greatly actively inflamed. It's the recurrence that is -- you're worried about. In ulcerative colitis, these are failing patients. They have inflammatory colons. And now you're trying to engraft a microbiome drug repetitively but engraft in an inflamed colon. That's why we did a few things. Again, looking at what we've seen in animal studies but also in the FMT literature, we gave the drug repetitively once a week for 8 weeks and once a day for 8 weeks in one arm, which is about fiftyfold of what we gave in a 109 trial of a biologically sourced spore-based product. So, we're taking this into account because of the inflammatory nature of what we are working with in ulcerative colitis. Why are we adding an antibiotic, vancomycin? Again, there is some human data, there is some animal data in our hands and in others that there may be better engraftment in this inflammatory -- ongoing inflammatory colon if you pretreat with an antibiotic that makes space in the dysbiotic microbiome of the UC patients. That's why we have four arms.

[Bill Tanner:]

And so, this then, in UC, may be more about keystone species than about kinetics?

[Roger Pomerantz:]

It may be. That's my hypothesis just based on empiric understanding of each of the disease states. Let's see what we find out.

[Bill Tanner:]

Okay. Thanks very much.

[Operator:]

Our next question is from John Newman with Canaccord.

[Roger Pomerantz:]

John, you there?

[Operator:]

And I'm showing no further questions. Ladies and gentlemen, thank you for participating in today's conference. You may all disconnect. Everyone, have a great day.