Seres Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by and welcome to the CERES Therapeutics First Quarter 2021 Earnings Conference Call. After the speaker's presentation, there will be a question and answer session. Please be advised that this conference call is being recorded. I would now like to hand the conference over to your speaker 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 2021 financial results and a business update became available at 7 a.m. Eastern time this morning and can be found on the investors and media section of the company's website. I'd like to remind you that we will be making forward-looking statements relating to the timing, enrollment, and results of our clinical studies, the anticipated safety profile of our products, regulatory approval, and the promise and potential impact of any of our microbiome therapeutics. Additional 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, with prepared remarks, I'm joined by President and Chief Executive Officer Eric Schaaf, Chief Medical Officer, Dr. Lisa Valmolke, Chief Scientific Officer, Dr. Matthew Henn, and Chief Technology Officer, Dr. David Ege. Dr. Terry Young, Chief Commercial and Strategy Officer, will also be available for Q&A. And with that, I'll pass the call to Eric.

Thank you, Carla, and good morning, everyone. CERES entered 2021 building on strong momentum created in 2020 Catalyzed by the success of our CIRA 109 program, we have continued to make progress across multiple functions within the company, including clinical, regulatory, manufacturing, and commercial. Collectively, these efforts bring us closer to our goal of translating our scientific microbiome insights into an entirely new class of medicines to treat serious human diseases. Since reporting positive data from our Phase 3 SIR109 ECOSPOR3 study in patients with recurrent C. diff infection, our focus has centered around taking the necessary steps to enable a high-quality BLA submission and following potential FDA approval, preparing for a successful commercial launch. Our immediate priority has been to complete the required SIR109 safety database through our ongoing open-label study. We are very pleased with the pace of the study's enrollment, and we now expect to achieve the full 300 patient target during the third quarter of this year. Our organization is also preparing for a successful commercial launch. We believe that a substantial commercial opportunity exists for SEER-109. The recurrent C. diff population includes approximately 170,000 patients in the U.S. Our medical education and awareness efforts continue, and we have recently begun to deploy our medical science liaisons. We are encouraged by the positive reception we are receiving from the medical community, which speaks to the high level of unmet need in the category. The importance of medical education is critical, especially when introducing a new approach, and we feel we are already making important inroads. We are also continuing supportive market assessment work, including primary research with physicians and payers to support launch campaign development and pricing and reimbursement decisions. We look forward to continuing to engage with patient groups, physicians, and payers to educate the market about the substantial value of our microbiome therapeutic approach. In addition to SIR-109, we are advancing a pipeline of investigational microbiome therapeutics led by SIR-287, our Phase IIb candidate for ulcerative colitis. SIR 287 has the potential to transform the management of this disease intended to provide an effective treatment approach that is well-tolerated with what we expect will be a favorable safety profile. As we announced last quarter, the SIR 287 Phase 2b study has achieved target enrollment, and we look forward to reporting top-line clinical data mid-year with additional mechanistic results in the second half of the year. SEER 287 has the potential to provide UC patients with a meaningful new therapy, and we also believe that this investigational therapy could be a very meaningful value driver for the company. We are eagerly looking forward to the Phase 2b study results in mid-year. With that, I'll now turn the call over to Lisa for a more detailed overview of our clinical programs.

Thanks, Eric, and good morning, everyone. I'll begin with our SEER 109 program. SEER-109 is a first-in-class investigational microbiome therapeutic administered orally following antibiotics and designed to reduce recurrence of C. difficile infection. SEER-109 is comprised of purified firmicute bacterial spores. This class of bacteria was specifically selected based on the impact they have on the growth and survival of C. difficile and their broader functional importance in the microbiome of individuals without disease. Our previously reported ECOSPOR-3 Phase III study results demonstrated that SIR-109 met the study's primary efficacy endpoint in patients with recurrent C. difficile infection, showing a substantial absolute reduction in recurrent infection compared to placebo at eight weeks post-treatment, which was the study's primary endpoint. The results 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, and a relative risk reduction of 68%. Study results show that SIR-109 administration resulted in similar efficacy when examined by groups stratified by age or by the prior antibiotic therapy. Additionally, the Phase III data demonstrate that SIR-109 efficacy is maintained over the duration of the 24-week study. We are very pleased with our SIR-109 clinical data, and we believe that the clinical profile observed is highly differentiated from other therapeutics in development for recurrent CDI. In addition to the differentiated clinical profile, CIRES employs various manufacturing processes to support patient safety, including steps designed to inactivate and remove vegetative bacteria, parasites, and viruses. We believe these processes help to minimize risks for patients, even from emerging infectious diseases where diagnostic assays may not yet be available. We believe that our approach provides SEER-109 with distinct safety advantages compared to minimally processed investigational microbiome approaches. From a tolerability perspective, we observed a highly favorable safety profile, with SIR-109 adverse events being similar to placebo. We are working toward publishing the remarkable SIR-109 Phase III study results in a leading journal. Overall, we believe our SIR-109 Phase III data represent a substantial advancement over the standard of care, with the potential to fundamentally transform how CDI is managed. Furthermore, we believe that SEER-109 has the potential to meaningfully improve outcomes for patients with recurrent CVI, a disease that results in the death of over 20,000 people in the U.S. each year. From a regulatory perspective, the SEER-109 ECOSPOR-3 study results far exceeded the efficacy threshold communicated to us by the FDA for the study to serve as a single pivotal trial. As a result, We expect this single study to provide the efficacy basis for a SEER-109 BLA filing. The FDA has also communicated to us that at least 300 patients will be required for a SEER-109 safety database to support a BLA and product approval. To this end, we continue to enroll our SEER-109 open-label study in patients with recurrent CDI, and as Eric mentioned, we have made excellent recent progress with this study. We have added dozens of new clinical sites across the U.S. and Canada beyond those included in the Phase III, and we have seen substantial physician enthusiasm for SEER-109. We have also recently modified the open-label study protocol to enable flexibility in the testing methods used to diagnose patients entering into the study. We expect this change to facilitate patient participation in the study and access to SEER-109. I'm happy to report that SEER-109 open-label study is now over two-thirds enrolled, and based on recent trends, we expect to achieve target enrollment during the third quarter of this year. The FDA has requested that six months of safety follow-up be included in the safety database. Completion of the safety database will support a BLA filing and potentially enable SEER-109 to become the first-ever FDA-approved microbiome therapeutic. Now, while the specifics of any potential product label would, of course, depend on discussions with the FDA during BLA review, our expectation is that SIR-109 could be indicated for the broad recurrent CDI patient population, a group estimated to include approximately 170,000 individuals in the U.S. Also, we would not expect specific labeling requirements regarding diagnostic approach. as this is typically left to the discretion of the treating physician and reflects local practice factors. Consistent with these expectations, the SEER-109 open-label study includes enrollment of the broad recurrent CDI patient population. Next, let's turn to our ongoing SEER-287 Phase IIb study in patients with mild to moderate ulcerative colitis. SEER-287 is an orally administered drug candidate comprised of commensal bacterial spores isolated from the healthy human gastrointestinal tract. Our objective with SEER-287 is to develop a first-in-class microbiome therapeutic that modulates the microbiome and microbiome-associated metabolites to treat ulcerative colitis. Several lines of evidence suggest that the gastrointestinal microbiome may act as an important underlying cause of inflammation in patients with ulcerative colitis. CR287 is designed to modulate the microbiome in these patients and potentially provide a much-needed non-immunosuppressive treatment option for UC. Furthermore, because of the safety profile that we expect from our approach, we believe that SIR-287 has the potential to also be used in combination with other approved agents. Data from our completed Phase 1b study demonstrated that SIR-287 administration was associated with a favorable safety profile as well as high rates of clinical remission, endoscopic improvement, and modulation of the gastrointestinal microbiome. These results and data supporting the underlying mechanisms of action were highlighted as the cover article in the January 2021 print edition of the peer-reviewed journal Gastroenterology. We are currently running a CR287 Phase IIb study termed EcoReset. This is a randomized placebo-controlled three-arm induction trial. This study is fully enrolled with 203 patients with active mild to moderate ulcerative colitis who have had an inadequate response to 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 previous 1B study that showed the highest clinical remission rate. In arm B, Patients receive vancomycin preconditioning, followed by two weeks of the same CR287 daily regimen used in RM-A, followed by eight weeks of a lower dose. In RM-C, patients receive placebo. We expect top-line clinical results from EcoReset in mid-2021. As a well-designed and meaningfully sized Phase IIb study, We expect this to be a data-rich study readout that will enable us to make well-informed decisions regarding further development. In addition, we expect to obtain a great deal of information about the mechanism of our microbiome drugs in UC patients that will continue to inform our UC franchise and microbiome targets in other indications. Clinically, our primary objective in the Phase 2b study is to demonstrate that SEER287 results in a significantly higher proportion of patients achieving clinical remission than those administered placebo. In evaluating our upcoming data, we plan to carefully examine the overall rates of remission across the study cohorts, and we will also examine the impact of SEER287 on important secondary measures, such as endoscopic improvement. We believe that the safety of our microbiome therapeutic approach, based on commensal healthy bacteria, is a major advantage and anticipate that the safety profile of SEER287 will be highly favorable, especially as compared with current treatments, which are often immunosuppressive and expose patients to significant risks. We expect that if we are able to achieve our target clinical profile, showing clear efficacy and favorable safety, And with an orally administered therapy, SEER-287 could represent a highly attractive new medicine with the potential to transform the management of UC. SEER-287 could have the potential to provide mild to moderate UC patients, representing the majority of all UC patients, with a novel and effective treatment option that is not immunosuppressive. The SEER-287 study will also be important to inform our broader, multi-product, and longer-term efforts to develop transformative new medicines for inflammatory bowel disease and, more broadly, for modulating host immunity. We expect to gain important insights from our pending Phase IIb clinical data and from microbiome biomarker data coming later this year. Both will inform the further development of SEER-287. as well as that of SEER 301, and other future compositions designed to modulate host inflammation and immune pathway signaling. With that, I'll now turn the call over to Matt.

Thank you, Lisa, and good morning, everyone. SEER continues to invest and focus on our reverse translational discovery and development platforms that can delineate at high resolution microbiome biomarkers from human clinical data and integrate these data with preclinical assessments using human cell-based assays and in vitro, ex vivo, and in vivo disease models to evaluate drug mechanisms of action and to design consortia of bacteria with specific pharmacological properties. Our drugs are designed to target multiple disease-relevant pathways. We reported earlier this year at the Keystone Microbiome Symposium on SEER-109 Phase III Predefined Microbiome Readouts that confirmed the drug candidates' mechanisms of action. The SEER-109 Phase III study data demonstrated that the bacterial species in the drug rapidly engrafted into the gastrointestinal tract. Engraftment was observed as early as one week post-treatment and found to be durable through 24 weeks. The presence of SEER-109 bacteria was significantly greater in subjects that received SEER-109 versus placebo, and all differences were maintained in all subpopulation analyses. SEER-109 administration also rapidly shifted the gastrointestinal metabolic landscape. As an example, there was a significant decrease in primary bile acids and an increase in secondary bile acids, providing a mechanistic basis for both the inhibition of C. difficile spore germination and vegetative growth. Notably, in early time point samples, C. difficile and other bacterial pathogens known to harbor antibiotic-resistant genes were significantly more prevalent in placebo-treated subjects. These data confirm observations from series prior trials that 0109 resulted in a reduction of other clinically relevant bacterial pathogens. The detailed mechanistic learnings we have obtained from 0109, combined with our ability to link these learnings to clinical outcomes and confirm observation in human subjects in the non-clinical setting to demonstrate causality, have proven immensely beneficial, and we continue to apply this knowledge to the design of future planned microbiome therapeutic compositions. Moving now to our SEER301 program. SEER301 is a next-generation, orally dosed, rationally designed, cultivated microbiome therapeutic candidate for the treatment of ulcerative colitis. The consortium of bacteria in SEER301 is designed to modify the microbiome and microbe-associated metabolites in the gastrointestinal tract to reduce the presence of pro-inflammatory bacteria and modulate pathways linked to gastrointestinal inflammation and epithelial barrier integrity in patients with ulcerative colitis. SEER 301 was designed using SEER's reverse translation discovery and development platforms. The design incorporated learnings from our SEER 287 Phase 1b study related to the bacterial species and the microbiome functional signatures associated with clinical efficacy. Additionally, the design took insights related to the engraftment dynamics of different bacteria and also the association of specific bacteria with the modulation of inflammatory and immune pathways in human subjects that have been observed across our broader clinical portfolio and confirmed using our non-clinical human cell-based assays and in vivo models. As a result, the unique composition of CR301 was designed to optimize drug species engraftment and the pharmacological properties that our clinical and preclinical research have identified as potentially important microbiome drivers of a treatment effect. We expect that we will continue to learn more about the activity of our microbiome therapeutic approach in ulcerative colitis from the CR287 Phase II results, and that these translational learnings will continue to inform our future development efforts in this indication and in biologically adjacent disease indications. We are currently enrolling a FEAR-301 Phase 1b study in adults with mild to moderate ulcerative colitis. This study is being conducted in Australia and New Zealand with a target enrollment of 65 patients in total. The objectives for this study are to evaluate drug safety and pharmacokinetics, and to evaluate clinical remission and other measures of efficacy as secondary endpoints. Moving now to SEER-155. SEER-155 is an orally dosed, rationally designed, cultivated microbiome therapeutic candidate designed to decrease the incidence of gastrointestinal bacterial infection, bacteremia, and graft-versus-host disease in immunocompromised patients receiving allergenic hematopoietic stem cell transplantation. SEER 155 builds on our expertise in both infectious disease and immunology and is designed to both prevent bacterial infections, particularly those that harbor antibiotic-resistant genes, bacteremia, and the onset of graft-versus-host disease. The SEER 155 program is supported by a CARB-X grant that provides financial and operational support. We've made excellent recent progress towards advancing SEER 155 into the clinic in collaboration with our partners, at Memorial Sloan Kettering Cancer Center. We expect to initiate clinical development later this quarter. Turning now to our earlier stage pipeline, we are evaluating a number of potential new indications for our microbiome therapeutics. Our clinical programs and our reverse translation discovery platforms continue to provide meaningful insights and knowledge into the underlying mechanisms by which microbes in the GI tract engage pathogenic bacteria and human cells and tissues to impact disease. Moreover, advances in series microbial cultivation and bioprocessing know-how and commercial scale GMP capabilities continue to advance and broaden access to the diversity of microbes in the human GI that can be harnessed in potential new product candidates and development programs. I'll now turn the call over to Dr. Dave Ege, our Chief Technology Officer provide more color on Ceres' differentiated manufacturing capabilities.

Thank you, Matt, and good morning, everyone. We believe that Ceres' GMP manufacturing and quality control platforms are important core capabilities that provide our company with meaningful competitive advantage. First and foremost is our differentiated product safety profiles. Pathogen inactivation and clearance steps are incorporated into the manufacturing process and validated, coupled with rigorous GMP product testing using proprietary assays. These measures are designed to maximize patient safety, including against emerging pathogens such as SARS-CoV-2. Second, CERES has developed considerable proprietary expertise and know-how regarding how to efficiently produce and test anaerobic bacterial strains in both vegetative and spore formulations. Our differentiated strategies to pursue both donor-derived and cultivated rationally designed complex consortia has been highly synergistic and gives us a substantial technical advantage in how we advance our pipeline. We believe these investments in manufacturing and quality control over many years now puts Ceres in a strong position to reliably support late-stage development of our pipeline and commercial supply, as well as our early-stage programs. And with that, I'll now turn it back to Eric.

Thanks, Dave. The details of our quarterly financials are included in this morning's press release, so I won't reiterate them here. Ceres ended the first quarter of 2021 with approximately $272.5 million in cash, cash equivalents, and short and long-term investments. As we conclude our remarks, I'd like to recap several of the important milestones that we're looking forward to during the remainder of this year. These include, first, achieving full enrollment in our CR109 open-label study during the third quarter of this year, continued progress executing on CR109 pre-commercial readiness, including our market education efforts, top-line clinical results from the CR287 Phase IIb study mid-year, and continued enrollment of our SEER 301 study and the advancement of our SEER 155 study into clinical development. Our organization also continues to work to extend our microbiome therapeutic leadership position. With SEER 109, we expect to pave the way towards achieving the first ever approved microbiome therapy. Along with what we believe to be SEER 109's best in class clinical profile, we expect to have a substantial first mover advantage that will support successful commercialization. We are also continuing to make progress advancing our pipeline, and we expect that in the coming years we will be bringing additional new microbiome therapeutics into late-stage development, and hopefully to patients seeking new treatment options. Finally, we are devoting meaningful resources to strengthen our already field-leading core capabilities, including those focused on microbiome drug discovery, as well as with our advanced microbiome manufacturing capabilities. Supported by the Solid Foundation, we believe that CERES is well-positioned to continue to drive the microbiome therapeutic field forward. Before I conclude, I'd like to mention that, as announced in our press release this morning, we will be holding a virtual investor event on June 21st focused on ulcerative colitis, including a detailed review of our CERES-287 and CERES-301 programs. This should be a very interesting program that will include one of the leading academic experts working in the area, and we hope that you'll be joining us.

With that operator, we'll turn the call over now to questions. Thank you. As a reminder, to ask a question, please press star, then the number one on your telephone keypad. Again, that's star one to ask a question. Please stand by while we compile the Q&A roster. Your first question comes from Mark Wadenbeck from Oppenheimer.

Hey, good morning, guys, and congrats on the progress this quarter. I was wondering if you could first give us a little bit more color on the modification to the testing methodology that's being used to qualify patients for enrollment into the open-label study of SARA-109.

Sure, Mark. Good morning, and maybe I'll ask Lisa to comment on the effort.

Sure. So as you recall, this is an open-label study with no placebo arm, and as such, we wanted to facilitate as much access as we could for this population in this clinical trial. So physicians are now going to be able to use their local testing for study entry. A toxin-based testing approach will still be used to evaluate any potential recurrence while on study. But to enter the study, they can use whatever methodology is used at their institution or in their area.

Okay, got it. Also wondering if you can offer any guidance on the timing of data from the SARA 301 Phase 1B, and if you see any possibility of needing to modify SARA 301's composition based on the insights you get from the microbiome biomarker data of EcoReset.

Yeah, Mark, let me – maybe I'll answer the first part of the question, and I'll answer Matt's comments on the second. We haven't provided guidance except to say that, you know, we're making great progress on 301, and we're thrilled to have what we think is a franchise within the UC and the IBD space, right? We've got 287. We've got 301. They're different shots on goal, different opportunities. 301 is being studied in a 1B study in Australia and New Zealand. We've made great progress. I think it's a technological achievement that we've been able to construct this this cultivated or synthetic approach based on the learnings from the 1B study from SIR 287. But at the same time, you know, we're incredibly excited about the signal we saw in the 1B study from 287, and we're thrilled about the opportunity to see these 287, 2B study results in mid-year. Maybe I can ask Matt just to comment on the learnings from one to the other and how we think about that in general going forward.

Sure. Good morning, Mark. So as a reminder, SIR-301 is a consortium of bacteria that was designed to reduce induction of pro-inflammatory activity, improve epithelial barrier integrity and TNF-alpha-driven inflammation in epithelial cells, then also to modulate various different UC-relevant anti-inflammatory innate and adaptive immune pathways. And as we talked about previously, the results from the 287 Phase 1B were certainly part of the design and use there, for example, understanding which specific bacteria are associated with clinical remission, which bacteria engrafted in different patient populations. But importantly, the design of SEER-301 also includes that type of knowledge from across our clinical portfolio and our broad preclinical research. work where we've been working to identify specific bacteria that modulate various different innate and adaptive immune pathways. And so the way I like to think about 301 is that it was designed to optimize the drug species engraftment and the pharmacological properties that our clinical and preclinical research have identified as potentially important microbiome drivers of a treatment effect. And so while there are similarities between the drugs, there are also differences in terms of the targets that are optimized. We will, of course, continue to learn from our portfolio. I think this is one of the values and differentiators for CIRES is that we have both biologically sourced, more complex consortia, as well as these defined consortia, both of which are in the clinic. And we can continue to improve our insights around which parts of the microbiome are most important and continue to design those into our drugs. But we have a high degree of confidence in both the 287 and 301 assets. Got it. And one final one from me.

I'm just wondering if we can expect any clarity on European regulatory requirements for SIR 109 later this year, if that's something we might get some news flow on in 2021.

Yeah, Mark, we're continuing to work with our partners at Nestle. Obviously, they were thrilled with the Phase 3 study results. And, you know, we're engaging with Nestle, who owns ex-North American rights, to SIR 109, and we continue to engage with non-FDA regulators, and those discussions continue.

Okay. Thanks for taking the questions, and congrats again. Thanks, Mark.

Your next question comes from Joe Thum from Cohen and Company. Your line is open.

Hi there, and thank you for taking my questions. First one, on the Open Label SEER-109 study, is there any way to estimate maybe how, what proportion of patients would have only one recurrence in this study? And do you think the proportion of patients that do have one recurrence in any of the FDA's labeling discussions And then maybe one on SEER 287. Just when we're thinking about remission rates here, is there a level that you are shooting for? And the enrollment patient population is a little bit different than the Phase 1B. So how should we be thinking about kind of the data in the context of what we've already seen from the program? Thanks.

Yeah, Joe, thanks for the questions. And I think I'm going to ask Lisa to comment on both of these. The first was just As a reminder, in the open label study, we had asked the FDA to allow us to include first recurrent subjects, to which they agreed. And we were pleased with that response. Of course, it opens up the pool of patients available to us, you know, in terms of enrollment for the open label study. But we also think, and Lisa made the comment in her prepared remarks, that, of course, the label will be determined as part of a negotiation with the FDA. As part of the BLA process, it's an encouraging data point as we think about, you know, the field and how they may be looking at this. Lisa, do you want to comment on Joe's question regarding the proportion of first recurrence versus multiple recurrence in the open label study and how we think about the label? And then maybe I'll ask Lisa to comment further on expectations around 287 with our midyear readout.

Sure. Well, we can't really estimate right now. I mean, the trial is ongoing, and, I mean, we're really enrolling at a pretty good clip. So, I mean, you know, the profile could change at any particular moment. I would say that medically, we view the first recurrence, as do our KLLs, the first recurrence, second recurrence, all have the same pathophysiology based in the fact that they've had an initial bout of C. diff They've shown that their microbiome is not resilient enough to keep C. diff under control, and they start in on this recurrence cycle. So how many first recurrence versus others is going to be subject to a lot of factors, and I really couldn't give you a specific number. Did you want me to take the next question as well? Sure.

Why don't you comment on 287 as we think about expectations?

Yeah. So recall that we're in mild to moderate ulcerative colitis, and this is the biggest group of patients out there in the UC space. Right now, they can be on 5-ASA, which is where many of them are, and there's a big toxicity gap, if you will, in terms of having to jump up into a much more a significant set of toxicities for the next therapeutic steps. So there's a lot of white space between 5-ASA and the next thing. So we're looking to have a therapy that provides a meaningful benefit, a clear safety profile, and is oral. And with that, I think these patients who are smoldering along on their 5-ASA and unable or unwilling to move to the next step, we'll have another option.

Okay, thank you very much. Thanks for the question, Joe.

Your next question comes from Ted Stenthoff from Piper Center. Your line is open.

Hey, good morning, everyone, and thank you so much for the update. Exciting progress. My questions kind of have to do with sort of some of the commentary you were making on the manufacturing side. So with respect to the clinical supply for 109, 287, and then also 301 with the fermentation, is all of that currently done in-house or is it outsourced? And if outsourced, when will it be brought in? Thank you.

Yeah, Ted, thanks for that question. Maybe it's worth a little bit of perspective or background, and then I'll ask Dave to comment since he's with us this morning. And I think Dave is illustrative of some of the pivot that we're making as a company from clinical to commercial. But, you know, when the company was founded, there was, I think, an appreciation that in order to really control your destiny in a new modality that manufacturing is and owning key aspects of manufacturing would be critical. I think there's, in general, an underappreciation of the importance of what we do from a CMC perspective and a quality perspective, and the fact that those capabilities, both on the biologically sourced side of the house as well as the synthetic or the cultivated side of the house, they're just simply not commoditized, right? So there's There's key steps in both sides of the house that we control, that we own, that we think are, again, not commoditized. We do work with outside parties for certain aspects of the supply chain and the manufacturing process, but certainly we think that there's key capabilities that we've built up over the last decade that position us to move forward in both sides of our platform. with quality and with speed. And maybe I can ask Dave just to comment a little bit further on that.

Sure, Eric. Thanks, and nice to be with you. Nice to meet you, Ted. So, indeed, I've been with Ceres a little more than six months now. I've been really impressed with the work that they have done to invest in, you know, in both sides of the technology that we're talking about here, both those donor-derived programs as well as the cultivated, fermented programs. And so we do have the capability to support the pipeline of clinical supply for both sides of that house. And I think it's also really important to emphasize that CIRES has capabilities in anaerobic bacteria, both with spore and non-spore forming formulations. And so we really see that differentiating us in terms of our internal capabilities and with strategic partners that we do have to ensure that we're successful.

That's really helpful and I appreciate the approach. Thank you very much. Thanks for the question, Ted.

Your next question comes from Chris Houghton from Jefferies. Your line is open.

Thanks so much for taking the questions and obviously very exciting times for the company. All right, so maybe for me just a couple of kind of reminder housekeeping questions might be most helpful. First, with respect to the BLA submission for SEER 109, you know, once kind of the open label safety database is completed, can you kind of just walk us through what the expected next steps and timeline might be for that program? Yeah, go ahead, Eric, sorry.

Yeah, yeah, sorry, Chris. So we're continuing to do the work across functional areas to support the VLA. I think we've said before, and I'll reiterate this morning, the open label we feel is really the key critical path item in terms of moving forward. So as we said this morning, we're very pleased with the progress. We're over two-thirds enrolled. Obviously, we've got the follow-up, as Lisa mentioned, following the full enrollment that we expect in the third quarter. But we're continuing with the work around other aspects of the BLA, and we expect to be in a good position following this open-label completion.

Got it. Okay. Very good. And then maybe just a couple other ones, if I may. Okay. The, you know, I can't remember if we've discussed in the past just maybe are you expecting to have an advisory committee for this program would be another kind of just general housekeeping question. And then the second maybe category could be, you know, as we're kind of approaching commercialization as well as some very meaningful readouts, certainly for 287, Can you remind us of what, you know, any milestones might be achieved from your relationship with Nestle and any other, if you want to remind us kind of what the commercial relationship is there for 109.2? And then the third question, I guess, maybe is for Matt, which is, you know, I think it's interesting that we'll get the top line remission type data for 287 initially and then the biomarker data later. So just would love to hear your perspective on what that additional information would add to the story at that time. Thanks.

Sure. So I might lose the next three questions, but I think we started with the question around advisory committee. Maybe Lisa can comment. I think our expectation is that it's certainly possible that we would have an advisory committee. Maybe Lisa, if you want to comment, then I can take it back with you. with a milestone question?

I think just as you said, Eric said, it's a new modality, totally new modality, so our expectation would be yes.

We have not guided future milestones with Nestle, Chris, except just to remind folks that they've been a terrific partner for us. It was a great deal with them in 2016. Their support has been critical for the company in the last couple of years, but we have not guided as to what future milestones would be from them for clinical or commercial progress. I will remind you that Nestle owns ex-North American rights to SIR 109 commercial, right? So certainly as we have kind of driven the bus from a, from a clinical or regulatory perspective in the U.S., then those responsibilities and ownership lies with them, ex-North America. And then the last question around 287 I think is a great one, and maybe I'll ask Matt to take that one, just in terms of what we're expecting from a, or what we may learn from the microbiome analysis from 287. I think Matt might have commented on this a little bit earlier, but Matt, why don't you take that one?

Sure, thanks. Good morning, Chris. So yeah, so thanks for the question. Look, as Lisa said earlier, I think first and foremost, we've got to remember this mild to moderate patient population is a major unmet need where there's a real gap and also one of the least studied populations in UC. So the SEER 287 trial, Phase II trial, was designed, as all our trials are, to be translationally rich and including a fair number of time points, both in induction and maintenance, where we can evaluate the types of things we typically evaluate. Which are the bacterial species that are engrafting? How is that driving broader changes and restructuring of the microbiome in terms of other bacteria that may either be pro-inflammatory or other bacteria we know play important roles in host immunology? And then importantly, digging into both the functional changes that happen as a result of those changes in the microbiome, and then also how changes in gene expression in the colon and epithelial barrier change in response to those changes. And I think where we are as a company, as you know, we've been investing heavily into our research engine at the company for 10 plus years now where we have a broad strain library of bacteria that are functionally characterized, that are genetically characterized, various different proprietary data sets where we can generate high-resolution data information on species and even strains of species, all of which allow us to really dig into the key underlying mechanisms of the drug and identify which bacteria are specifically associated with clinical remission. or endoscopic improvement, and as well as what metabolites matter. And then I think the real power of our platform is we've invested just as significantly in all the various preclinical assays and customized human cell-based assays for doing microbiome studies and in vivo models where we can take our learnings about those bacterial signatures and biomarkers in the clinic and actually test causality in a laboratory setting. And it's the basis of that kind of work that has been at the heart of all of our rationally designed consortia as well.

Well, I certainly do appreciate that, Matt. And I think, you know, the great work that you've done to kind of develop all this in the field is certainly appreciated by me. So thanks for answering the questions as well.

Thanks, Chris. Thanks for the question, Chris.

Your next question comes from Terrence Flynn from Goldman Sachs. Your line is open.

Great. Thanks for taking the questions. I was just wondering if you could give us an update on where you stand with 109 commercial prep and any latest perspective from payer conversations you might have had lately. Thank you so much.

Yeah, Terrence, thanks for the question. We continue to do work as we outlined in the prepared comments, but maybe I can ask Terry to comment a little bit more specifically on your question.

Sure. Thank you, Terrence and Eric. Really, we've been quite busy, even since our last earnings call, getting ready for commercialization. And so I think Eric has mentioned some of this in his preface remarks, but in particular, scaling our market education efforts, right? We have an enormous effort around medical communications planning, which is included of late deploying an MSL force into the field. We're also obviously doing an enormous amount of publication planning, as well as Congress involvement and abstract presentations at upcoming Congresses. So, you know, more and more of the data from the very successful ECOSPOR3 trial we'll be reporting out, led by Lisa Von Mulkey's team in medical affairs. We're also developing, moving kind of to the payer. I'll kind of dip in and out, and then I'll go deeper into that at the end of my remarks. We're developing and deploying a robust payer value proposition, obviously, with the help of those very important customers. We have a lot to talk about with SEER 109, and so really narrowing the focus to what is most important to that very important customer audience is really the work that we're doing. We have a great story to tell. The feedback has been very positive. We're also continuing to enhance our understanding of the commercial opportunity segmenting physicians. We have work underway to do that and really prioritize the physician audience in terms of who we're going to reach when as we prepare for launch. We continue to do pricing and reimbursement analysis sort of in parallel with that value proposition work. And we're building infrastructure. I mentioned the deployment of the MSL team. We're also hiring. I've hired a couple of commercial leadership roles of late, and we're beginning to build out the team. So double-clicking on the payer a little bit, I think you may have noticed in our slide deck on our website, we have a slide that kind of summarizes the feedback that we're getting from payers and physicians. But what I would say is that the payer reception has been quite positive. They recognize the value that SEER-109 is bringing. And they actually, if you look at the value rating they give, it's very similar to the the not so recently launched life-saving HCV medications like Sovaldi and Harvoni. So we're quite pleased with the response to the profile. And our task now is to, as we move forward to launch, we have time to do this, but determine the right pricing corridor working with these external customers. And I'll turn it back to the next question.

Your next question comes from from JMP. Your line is open.

Hi, congratulations on the progress with and thanks for taking our question. I guess for me, just curious, in a coronavirus world where we're seeing, for example, lower rates of flu and probably increases in other diseases, are you guys seeing any differences in terms of CDI in populations and compared to what it was before and would be curious if you can share any comments about how patients are doing on efficacy-wise with first-time CDI versus what was studied in the open label. Or if not, maybe you'd be willing to help us how we should be thinking about that. And then related to the prior program that you guys had in development, I believe this was – one or 262 maybe for primary CDI. If, you know, assuming there's a label that allows you broad applicability, how should we be thinking about 262 coming forward if at all then? Thanks.

Yeah, there's a few questions there. Maybe I'll try to hit them. In terms of coronavirus, it's a good question in terms of are we seeing fewer cases. All I can tell you is that, you know, There's only so many data points that we have. One of the data points is just the enrollment in the open label study, right? And from that perspective, I think we feel strongly that particularly with, you know, the profile that is available with 0109, we have a lot of confidence this continues to be a major issue. And sometimes when you have the type of profile or step function advancement in the potential of helping patients that we're showing with 109, the opportunity becomes even more acute. So in terms of those data points, I think we certainly continue to be comfortable and confident that there's a major unmet medical need that we can help. In terms of efficacy and the open label, you know, we don't have that. We certainly have not commented on that data. On 262, let me just comment that I think that there's a major franchise here that we're thinking about. Obviously, with the data on 109, we're thinking about how we can help patients across certainly not just infectious disease or C. diff, but certainly our opportunities have other indications more broadly. But within 109, within the recurrent C. diff population, within the C. diff population, we are thinking about other ways in which we can help patients, and we're actively involved in discussions on that. I will say our efforts have been really titrated and focused on getting 109 to patients first, but certainly we're thinking about other opportunities to help patients within that franchise.

Thank you.

Thanks for the question.

Your next question comes from Vernon Bernardino from H.C. Wainwright. Your line is open.

Hi, everyone, and congrats on continued progress with all the clinical programs. Definitely looking forward to the total 109 reveal and approval. The only question I had left was, could you remind us what Nestle's role is in 109 commercialization, what they currently are doing to prepare for the launch, and will you provide any details on the results of your market research? Terry provided some details, I think. or things that you might talk about, but just wondering what kind of details you reveal from your market research. Thanks.

Yeah, Vernon, just to remind you and the group, Nestle has ex-North American commercial rights to CR109, so Ceres owns U.S. rights, actually North American rights to CR109 commercials. So that's the structure of that relationship. I do think we put out a fair amount of detail, including in our corporate deck, related to some of the findings from Terry's work. And Terry, I think, has provided some additional color and comments around that. And I think it's likely that we'll continue to do that as we move forward. But, you know, bottom line is that the reception that we're getting from the field is has been, continues to be very positive and gives us a lot of confidence in the commercial opportunity in this agent going forward. Not easy to find comps, not easy to find analogs, simply just because there really hasn't been the combination of efficacy and safety that we saw in the Equus 4 KC results. So we do think that CR-19 is going to stand by its own, and we're thrilled with the opportunity to help patients with it.

Okay, and can you comment on what NSLI is doing ex-North America?

Well, as I mentioned before, you know, we're processing the phase three results. We're in discussions with them around next steps, and we continue to be in discussions with ex-North American regulating bodies as well in terms of how we move forward with 109.

Okay, thank you. We'll be staying tuned. Thanks. Great. Thanks, Vernon.

There is no further question this time. You may continue.

So thanks to everyone. We appreciate your time this morning. We look forward to continue to update you on our progress, including at our UC investor event on June 21st. Be healthy and well and have a great week. We look forward to speaking with you soon. Thanks very much.

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