Seres Therapeutics, Inc.

My name is Kate and I will be your conference operator today. At this time, I would like to welcome everyone to the Q4 2024 series Therapeutics Incorporated Earnings Conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed with the number one on your telephone keypad. If you would like to withdraw your question, press star 1 again. Thank you. I would now like to turn the call over to Carlo Tanzi of Investor Relations. Please go ahead.

Thank you and good morning. Our press release with the company's fourth quarter and full year 2024 financial results and business updates became available at 7 a.m. Eastern Time this morning and can be found on the Investors & News section of the company's website. The company has also posted an updated corporate presentation to the website. I'd like to remind you that we'll be making forward-looking statements, including statements about the timing and results of our clinical studies and data readouts, future product candidates, clinical development plans and commercial opportunities, interactions with regulatory agencies, receipt of future payments related to the valve sale, operating plans and future cash runway, our ability to generate additional capital, our planned strategic focus, our efforts to secure partnerships, and anticipated timing of any of the foregoing and other statements which are not historical fact. 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, with prepared remarks, I'm joined by Eric Schaaf, Ceres President and CEO, Matthew Henn, CSO, Lisa Von Mulkey, CMO, Mirella Thorell, CFO, and Terry Young, Chief Commercial and Strategy Officer. And with that, I'll pass the call over to Eric.

Thank you, Carlo, and good morning, everyone. This has been a productive period for Ceres, highlighted by substantial progress advancing our lead program, CER 155, as a novel biotherapeutic to prevent life-threatening bloodstream infections, including those that can harbor antimicrobial resistance. We are developing ser155 initially for alloHSCT recipients who are at high risk of infection. Our excitement around ser155 is based on the highly encouraging clinical results we reported late last year from a placebo-controlled Phase 1b study in patients undergoing alloHSCT for the treatment of hematologic malignancies. This study showed a clinically meaningful 77% relative risk reduction in bloodstream infection rate for those patients administered 0155. DSIs represent a frequent and serious complication and a growing risk to immune compromised patients undergoing HSCT, which can result in adverse impacts on patient outcomes. I would like to highlight the progress we have made since obtaining these initial clinical data over the past several months. Earlier this year, we released exploratory translational biomarker results from the completed 0155 Phase 1B study. Matt will cover these data in more detail in a moment. But at a high level, the biomarker data reinforced the drug's mechanisms of action and are consistent with a significant BSI reduction and safety profile observed in the clinical study. The data indicate that BSI risk is reduced by promoting epithelial barrier integrity, which can decrease the likelihood of translocation of bacteria and the entry of pro-inflammatory molecules from the gastrointestinal tract into the bloodstream. Our data also suggests CR155 is positively impacting systemic immune and inflammatory responses, which support the opportunity for our biotherapeutics to provide benefit to patients living with serious gut-related inflammatory and immune diseases, such as inflammatory bowel disease, ulcerative colitis, and Crohn's disease. These remain large and underserved patient groups, and the therapeutic and commercial opportunities could be substantial. We have also made substantial progress in working with the FDA to advance CR-155. In December of last year, the FDA granted breakthrough therapy designation to 0155 for the reduction of bloodstream infections in adults undergoing allo-HSCT. In recent months, we have been engaged with the FDA regarding the further development of 0155 in allo-HSCT. The FDA has shared its preference for a 0155 Phase II study, as well as other parameters relating to the study design, including support for the proposed primary efficacy endpoint of reduction in bloodstream infections at day 30 post-HSCT for our next study. We also obtained confirmation of FDA's expectations on key elements of our biotherapeutic manufacturing processes, specifications, and release testing. Based on the guidance received, we are currently working to refine the clinical study protocol for our next study which Lisa will expand upon. We intend to seek additional guidance from the FDA regarding our clinical plans over the coming months consistent with prioritized engagement expected with a breakthrough therapy designation. While we plan further engagement with the FDA, we continue to move with urgency to operationally prepare for the 0155 next study. We are in the process of selecting a clinical research organization to lead study execution, and we are manufacturing drug supply. At this juncture, it would be premature to provide timing guidance regarding initiation of the next 0155 study. However, while we are still developing study protocol and plans, we can share initial projections of time to key study milestones after study initiation. Given the tractable standalone phase two anticipated study size and the experience we gained from the prior CR155 phase 1B, we believe we could expeditiously enroll patients and obtain clinical results. Based on the size of a potential phase two standalone study, our preliminary operational plans and anticipated enrollment rates We believe we could obtain interim results within 12 months after initiation of the study, informing next steps to support product approval and additional development opportunities. We also project obtaining full top line data approximately nine months thereafter. Additionally, we continue to consider various options to support the development of CR155 and our other promising biotherapeutics. We are advancing discussions, seeking a collaborator who shares our vision for the expansive 0155 opportunity and who would provide financial support and other capabilities to enable us to maximize the broad potential of 0155. We are also seeking the perspectives of potential partners regarding plans for further 0155 development, which will help inform our path forward. We look forward to providing updates as our work advances. I will now pass the call over to Lisa.

Thanks, Eric. As Eric shared, we have continued to receive constructive feedback from the FDA to clarify further development plans for SEER 155 as part of a Type B breakthrough therapy designation engagement. By pursuing a deliberate and thoughtful dialogue with the agency, we believe that we ensure that we are moving the program forward in a manner that is aligned with the FDA. The FDA recommended that further development include a Phase II study to facilitate and refine the design of a registrational trial and dataset. In a next study, the agency indicated support for a reduction in bloodstream infections at 30 days post-HSCT as the primary endpoint. Notably, in our prior Phase Ib study, this was the period in which all BSIs occurred. We are pleased with this outcome and expect to replicate many elements from our prior successful SEER 155 Phase 1B study in our next protocol. In addition, the FDA confirmed their ongoing expectations for chemistry, manufacturing, and control parameters. Based on the feedback obtained, our team continues to refine the design of the planned next study, which could be either a standalone Phase 2 study or a Phase II as part of a seamless Phase II-III. In either case, we anticipate the study will include an adaptive design with a meaningful interim analysis when approximately half of the enrolled patients have reached the primary endpoint, informing the study path forward and potential indication expansion. We plan to submit a draft study protocol to the FDA during the second quarter. with input expected from potential development partners, and to seek further clarity on our proposed study design from the agency. Now, before I pass the call to Matt to discuss our recent SEER 155 exploratory biomarker results, I'd like to remind you of the clinical results we shared a few months ago. In September, we announced encouraging top-line clinical data from Cohort 2 of our Phase 1B study of SEER-155 in alloHSCT. This segment of the study utilized a randomized, double-blinded, one-to-one placebo-controlled design to evaluate further safety, drug strain engraftment, and the incidence of bacterial bloodstream infections, as well as outcomes such as incidence of febrile neutropenia and cumulative antibiotic exposure. From an efficacy perspective, in the SEER-155 arm, two out of 20 patients experienced a BSI versus six out of 14 in the placebo arm, resulting in a highly meaningful relative risk reduction of approximately 77%. This is an important result, especially given that bloodstream infections are a leading cause of death in alloHSCT patients. During the 100-day observation period, febrile neutropenia occurred at a lower incidence in CR155-treated patients versus placebo patients, with 13 out of 20, or 65%, experiencing febrile neutropenia, compared to 11 of 14, or 78.6%, respectively. In clinical practice, HSCT patients who experience a BSI or febrile neutropenia are typically aggressively treated with broad-spectrum antibiotics. In our study, we observed a meaningfully lower mean cumulative exposure to systemic antibacterial and antimicotic therapies with SIR 155 treated patients being administered these drugs for a mean duration of 9.2 days versus 21.2 days for placebo patients. Additionally, SIR 155 was generally well tolerated. No serious adverse events were attributed to SIR 155 and no SIR 155 species were identified in any cultures from any subjects. The favorable safety profile of SIR 155 is especially important given the highly immunocompromised state of the target patient population. In summary, Our data show important potential clinical benefits associated with SEER 155 across multiple measures, along with a favorable safety profile, all of which we believe support the potential of this live biotherapeutic to fundamentally transform outcomes for many patient groups at risk for bloodstream infections. Finally, members of our team recently attended the Tandem meeting. which is sponsored by the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research. At this conference, one of the principal investigators in our Phase 1b study presented a summary of the study outcomes. The feedback we received from KOLs at the conference underscored the significant need to address BSIs as well as the meaningful outcomes observed in our Phase 1b study. With that, I'll turn the call over to Matt.

Thank you, Lisa. Our lead program, SEER-155, is a live biotherapeutic product designed to decolonize specific GI pathogens, improve epithelial barrier integrity to prevent bacterial bloodstream infections, including those involving pathogens with antimicrobial resistance, or AMR, and to induce immune homeostasis in patients undergoing alloHSCT. Our mechanistic goals were to reduce the likelihood of harmful bacteria and pro-inflammatory products moving from the gut into the bloodstream, and also to reduce systemic inflammatory responses. The SEER-155 Phase 1B study was designed to be a translationally rich study and included the analysis of various exploratory biomarkers selected to enable a deeper understanding of the mechanisms of action of SEER-155, the drug's clinical pharmacology, and how we may apply our novel drug modality towards the treatment of additional diseases. We recently presented biomarker results in a poster presentation at the Tandem Conference. Notably, the SEER-155 Phase 1b Placebo-Controlled Study Exploratory Biomarker data in alloHSCT recipients reinforces the drug's mechanism of action and are consistent with clinical results showing a significant reduction in BSIs and the observed safety profile. Exploratory Translational Biomarker assessments included fecal albumin, an established biomarker of epithelial barrier integrity, as well as systemic inflammatory biomarkers measured in plasma that included interferon gamma, TNF alpha, IL-17, and IL-8. These assessments were evaluated during the HSCT peri-transplant period, which is the period from the end of the first treatment course of CR155 through to neutrophil engraftment. Following CR155 administration, And in the peritransplant period, CR155 was associated with lower levels of fecal albumin and lower concentrations of certain plasma biomarkers of systemic inflammation, specifically interferon gamma, TNF alpha, IL-17, and IL-8. More specifically, there was a statistically significant decrease in fecal albumin. The presence of fecal albumin in fecal matter, which is produced in the liver and normally circulates in the bloodstream, indicates a breakdown in the epithelial barrier and the gut, excuse me, bloodstream, and that translocation albumin from the blood to the intestinal tract has occurred. Fecal albumin concentrations in the SIR-155 arm following the first treatment course of treatment were lower than levels observed in the healthy subjects cohort, while placebo subjects were significantly higher than the SIR-155 in healthy subjects. This is consistent with barrier damage induced by HSCT conditioning in the placebo arm and not in the CR155 arm. Fecal albumin levels remain low in CR155 patients and are similar to healthy control subjects throughout the peritransplant window. Concentrations of IL-17 and IL-8 were significantly lower in CR155 treated subjects compared to placebo following the first treatment course. and concentrations remained generally lower in the CR155 arm compared to placebo through HSCT conditioning. Interferon gamma concentrations in the CR155 arm were significantly lower than placebo at the time point following neutrophil engraftment, and concentrations of both interferon gamma and TN-alpha in CR155 treated patients were lower than placebo patients following HSCT conditioning, but differences were not statistically significant. These exploratory translational biomarker data provide further mechanistic evidence of the potential of SIR-155 to reduce BSIs to the promotion of epithelial barrier integrity, thereby preventing translocation of bacteria and pro-inflammatory molecules from the GI tract into the bloodstream and to positively impact systemic inflammatory responses. Based on the totality of the clinical and biomarker results we have obtained, we believe that allo-HSCT represents only a portion of a substantial opportunity available with our biotherapeutic approach. Firstly, BSI's are a major challenge for many patient groups, and ser155 and ser155 and our other biotherapeutic candidates such as ser15147 could represent an important and novel approach that could transform how many groups of medically vulnerable patients, including immunocompromised cancer treatment and cirrhosis patients, are managed. Additionally, the mechanistic data we obtained from the exploratory biomarker results support the potential utility of our live biotherapeutics to address various gut-related inflammatory and immune diseases, such as IBD, which includes ulcerative colitis and Crohn's disease. In each disease, gut epithelial ovarian compromise has been identified as a core component of underlying pathology and the inflammatory host pathways denoted earlier are linked to disease. We are developing SEER-147 for compromised patients living with metabolic disease. SEER-147 is designed to prevent gut-seeded infections and associated downstream infections and spontaneous bacterial peritonitis and chronic liver disease. While our focus this year is primarily on SEER-155, we continue to advance IND-enabling work for 147 with modest resource investments. We also continue to explore research collaborations to help advance our early-stage pipeline programs. With that, I'll now pass the call to Teri.

Thanks, Matt, and good morning, everyone. As we've discussed, bacterial bloodstream infections are a medically significant and life-threatening complication experienced by multiple patient groups, including allergenic and autologous stem cell transplant recipients, CAR-T recipients, other cancer patients with neutropenia, individuals with chronic liver disease, solid organ transplant recipients, as well as patients in the intensive care unit and long-term acute care facilities. Our analysis indicates that the commercial opportunity in alloHSCT alone could be sizable and that there's considerable ability to extend this opportunity via indication expansion to some of these adjacent patient populations. To better characterize the opportunity in alloHSCT, We recently completed multiple rounds of market research with U.S. healthcare professionals, or HCPs, and payers. The results confirmed a high unmet need to prevent BSIs and a desire for better prophylactic options. The results were supportive of a strong value proposition and a robust commercial opportunity for SEER 155. Both HCPs and payers indicated an awareness of the high clinical burden of BSIs driven by the frequency of occurrences and poor associated outcomes. Both groups cited a lack of efficacious prophylactic therapies and expressed significant ongoing concerns around the risk of BSIs, febrile neutropenia, sepsis, and antibiotic-resistant infections in this already vulnerable patient population. Specific to SEER 155, the proposed risk reductions of BSIs and related endpoints were seen as clinically meaningful and incited enthusiasm amongst respondents. U.S. payers also shared their expectation that CER155 would primarily be reimbursed via the outpatient pharmacy benefit, given the timing and route of administration, which allows for dosing outside of the inpatient hospital setting. Notably, in our Phase 1b study, 100% of patients received their first dose of CER155 outside of the hospital setting. The reimbursement pathway for SIR-155, along with the very high incremental cost for patients who do experience BSI's post-transplant, are indicators of strong pricing potential in the category. There are an estimated 9,300 alloHSCP procedures conducted annually in the U.S. The European Society for Bone Marrow Transplant recently updated their incidence estimates for Europe, reporting approximately 20,000 procedures in 2023. With a higher number of reported procedures than the U.S., and the presence of shared market dynamics with the U.S., such as unmet need and a high cost of care for these patients, we also see a robust opportunity for CR155 in Europe. To summarize, we are excited about the initial CR155 opportunity to prevent infections in alloHSCT patients. Beyond this anchor population, we have the opportunity to extend to medically relevant adjacencies across hematologic malignancies, as well as to other areas outside of oncology. We believe that with this strategy, SEER 155 and our additional biotherapeutics could deliver multiple highly significant blockbuster opportunities. With that, I'll now pass the call to Mirela.

Thanks, Terry, and good morning, everyone. First, I will briefly recap the terms of the vouched sale transaction which closed in September, and then share our quarterly and full-year financial results. With the Vaust transaction, Ceres received a payment of $155 million at closing, which represented consideration of $175 million, less approximately $20 million, related to the settlement of net payables to Nestle from Ceres. Included in the upfront consideration was a $60 million prepaid milestone and $15 million related to an equity investment in Ceres common stock by Nestle. A portion of these proceeds were used to retire our debt with Oak Tree, and we are now debt-free. Ceres received the first installment payment of $50 million in January of 2025, and we are due to receive an additional $25 million, less approximately $1.5 million in employment-related payments, in July of this year, provided we remain in material compliance with the terms of the transition services agreement, which we expect to do. Additionally, our operations are simpler, and our cash burn is lower following the transaction. The company's headcount is approximately 100 team members, and we have fewer facilities having transferred certain leases to Nestle. Turning to the results, Ceres reported a net loss from continuing operations of $15.7 million for the fourth quarter of 2024 as compared to a net loss from continuing operations of $34.7 million for the same period in 2023. We reported a net loss from continuing operations of $125.8 million for the full year 2024 as compared to a net loss from continuing operations of 190.1 million for 2023. The year-to-year reduction in net loss was due primarily to lower operating expenses of approximately $74 million and a $5.7 million gain on sale recognized in the fourth quarter of 2024 related to a lower than estimated VAUST collaboration loss in the quarter, partially offset by approximately $14 million of net other expenses representing a $23.4 million loss on debt retirement partially offset by $6.3 million of income from Nestle in the fourth quarter related to TSA services. Research and development or R&D expenses for the fourth quarter of 2024 were $12.8 million compared with $23 million for the fourth quarter of 2023. For the full year 2024, R&D expenses were $64.6 million compared with $117.6 million in 2023. The year-to-year decrease in R&D expenses was primarily driven by lower personnel expenses and a decrease in platform investments as the company focuses on its lead program, SEER 155. General and administrative or G&A expenses for the fourth quarter of 2024 were $12.5 million compared with $14 million for the fourth quarter of 2023. For the full year 2024, G&A expenses were $53.2 million compared with $77.5 million in 2023. The year-to-year decrease in G&A expenses was primarily a result of reduced personnel and contractor expenses and other cost management activities. Manufacturing services expenses, a new category in 2024, were $3.5 million for the fourth quarter and year-ended December 31, 2024. These costs relate to the provision of manufacturing services under the Transition Services Agreement with Nestle. The associated reimbursement received from NSLI related to these expenses is recognized in other expense and income net as mentioned earlier. Notably, many of the transition service activities will be fully complete as of the end of March. Certain activities such as IT transition have been extended through May. And consistent with the original transition plan, manufacturing support is provided through the end of this year. Moving now to our cash position, as of December 31st, 2024, we had $30.8 million in cash and cash equivalents. This does not include the previously mentioned $50 million installment payment that we received from Nestle in January of this year as part of the VAUST transaction. Based on existing cash and anticipated second installment payment to be received in July of this year, ongoing transaction related obligations and current operating plans, we expect to fund operations into the first quarter of 2026. We continue to evaluate opportunities to maximize value creation and as we seek to develop our live biotherapeutic programs in various patient groups. a partnership could deliver both financial and other capabilities and accommodate sharing of development costs while enabling us to potentially realize the commercial value of our products across multiple patient populations. We continue to advance these discussions. With that, I'll pass the call back to Eric.

Thanks, Marilla. We are excited about the progress we have made, especially in our efforts to further the development of SIRS-155. We have obtained confirmatory biomarker data that extend our understanding of this live biotherapeutic, supporting the intended mechanisms of action in the clinical setting. The regulatory progress we have made is also notable. We are very pleased to have obtained breakthrough therapy designation as well as the constructive guidance obtained from FDA related to continued development. Our team looks forward to continued dialogue with the agency as we seek the most efficient and expeditious approach to advancing 0155 forward. Before I close, I'd like to extend our appreciation to Lisa, who will be transitioning from CERES to another professional opportunity. Lisa has made significant contributions to CERES, including leading the clinical development and approval of VAUST, overseeing 0155 in the Allo HSAT Phase 1B study and our planned next steps for the 0155 program. Lisa has also built a strong clinical and regulatory team, and the company is well positioned for ongoing interactions with FDA and preparation for the next 0155 study activities. Moving forward, Kelly Brady, SVP Clinical Development, and Dr. Dennis Walling, SVP Clinical Development, and Ann Kurowski, SVP of Regulatory Affairs, will lead the advancement of our CR155 clinical plans and FDA interactions. Each of these individuals have decades of industry experience and key roles successfully developing FDA-approved medicines. I look forward to working closely with Kelly, Dennis, and Ann as we further the development of CR155 and our additional biotherapeutic programs. While our immediate focus is on SIR 155 and AlloHSCT, in the longer term, we believe that there are opportunities to broaden the target patient populations for this therapy into other medically vulnerable groups. We continue to engage in discussions with prospective partners and believe both SIR 155 and our broader portfolio represent attractive collaboration opportunities. We look forward to updating you as we advance our priorities across SIR 155 and AlloHSCT and the strategic goals we've outlined this morning. With that, we'll close our remarks. Operator, please open the call up for questions.

At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Joseph Tom with TD Cohen. Please go ahead.

Hi there, good morning. Thank you for taking my question and best wishes to Lisa on her next step. Maybe just in terms of the feedback that you received from the FDA, it sounds like you got some feedback related to manufacturing and controls. I guess, is there anything that you'll need to implicate or do in terms of changing manufacturing between the Phase 1 and the potential Phase 2, Phase 2-3 And then second, when you think about the types of patients that would be enrolled in the next study, would you consider making any changes versus what you saw in the phase one? It sounds like your event rate kind of coincided with that 30-day post-HSCT. So it might be the right population, but are you anticipating making any changes? Thank you.

Hey, Joe. Good morning, and thanks for the question. So let me start I might ask Lisa to comment on your second question and Chris to weigh in on the CMC side. But let's step back for a second. We don't get into the kind of play-by-play with the FDA, but let me offer a couple of thoughts in general. We had received comprehensive feedback from the FDA, including their suggestion that we consider the next study for 155 to be a phase two, right? And subsequently from that, we had asked a set of clarifying questions. We have not heard answers to those questions yet, but let me be clear that our expectation then as now is that the next step for us is to submit the clinical protocol, right? And that will be the major next step in unlocking the next step in terms of clinical progress. Now, we talked about both a standalone Phase II and an adaptive 2.3. If the next study is a standalone phase two, our assessment is that we know what we need to do in order to move forward with that. And if it is an adaptive 2.3, then by definition, there will be more work to do and more alignment with FDA that will be required, both on the clinical side as well as, to your question, the CMC side. So we're in the process now of thinking about those relative trade-offs. and considering those. But maybe let me make one more comment before I pass it off. One is that we're moving. We're not waiting. We're doing those key critical path items to enable us to move forward in the next study, whether it's a standalone phase two or a seamless two-three. And the last thing I would just say is that because we're in a partnership process, our expectation is that a partner will want to have a point of view on some of these questions. So that's what we think about. Lisa, answer your second part, and then Chris, if I missed something on the first part.

Yeah, so with regard to the population, we think we have the right population. It's a broad population. In a bigger study, what you could see is us taking steps to make sure we can handle whatever variability, and there are multiple ways you can do that, either upfront or through stratifying or through planned analyses. But we think we have the population.

Chris, any other comments on the first part?

Thanks, Eric. This is Chris McAllagher, head of manufacturing and quality. You know, to your questions about manufacturing, you know, essentially the feedback from the FDA was confirmatory that our plans moving forward allow us to start manufacturing today. We're already in our manufacturing campaign. and have full confidence that we'll be able to supply the drug for either of the clinical options. Perfect. Thank you very much. Thanks for the question, Jeff.

Your next question comes from the line of Tessa Romero with J.P. Morgan. Please go ahead.

Good morning, team. This is Caroline Poacher on for Tessa Romero with J.P. Morgan. Thanks for taking our questions and also from us, best wishes to Lisa. So in terms of questions, how has the recent FDA feedback and insight you have received thus far fallen relative to your expectations going into these interactions? And how would a Phase 2-3 differ from just a Phase 2 study? And why do you think that the FDA recommended the next study be a Phase 2?

Yeah, Caroline, let me start first. And maybe I'll ask Lisa to comment further. I'd start with just a reminder that we received breakthrough therapy designation at the end of last year. We were really pleased with that. To us, that suggests a couple of things. One is that the FDA recognizes that this is an area of unmet need and that the evidence that was provided or the initial data that was provided in the Phase 1b was interesting to them. And they see this as an interesting path forward. In terms of how the FDA guidance or the feedback fell relative to our expectations, we thought it was a constructive and robust and comprehensive set of comments for us. And we think that there's a great deal that we can learn from it and that we will take forward. In terms of 2.3, I kind of outlined some of those pieces in the answer to the last question. I might ask Lisa to comment further, but there's a tradeoff in some sense of having certain items locked as part of a 2.3 seamless design and perhaps on the other side of that. the benefit of, we would hope, speed and reduced cost from not having a pause between a two and a three. But maybe Lisa can comment further.

Yeah, no, as Eric said, the main difference with a phase two, three seamless is that the requirement to pre-specify and lock things in up front. And that obviously can take more time and discussion with the agency to get that all settled. I think in any case what the agency was asking for is more data, and I think the existing data set, which was impressive enough to get us breakthrough designation, is still relatively small, and I think more data is something that would be helpful for us in designing the next study as well.

Okay, great. Thank you so much. Thanks for the question, Caroline.

Your next question comes from the line of Ted Tenthoff with Piper Sandler. Please go ahead.

Great. Thank you very much and congrats on the continued progress. My question really has to do with safety database. I know that that was part of the consideration with VALST approval and I was wondering whether you guys have started to discuss the size of the potential safety database, you know, based on the prior experience with VALS, does that at all increase the agency's comfort with microbiome therapeutics, or are they really looking at this as one-off? And obviously, there's differences in population and just size of population, but curious what the conversations have been around the safety database. Thanks.

Yeah, Ted, good morning, and thanks for the question. So I'm going to start in... I might start with a little bit of a caution that... You know, we're very careful not to speak for the FDA. We can offer our thoughts as to what we think they're thinking, but it's really just our perspective. Obviously, you mentioned Vaust as a precedent, and it's an important one. And in our experience with Vaust, it was clear that the FDA was looking for at least 300 patients in terms of exposure. How relevant that is or how much incremental comfort they've had on the modality, Let me ask Lisa for her opinion, but ultimately I think it's the FDA that's going to speak most importantly.

Yeah, generally the discussion on the safety database evolves as the safety profile evolves. And I think we know by guidance in our past life with Vaust that they have a sort of minimum threshold of 300. That's a nice number for them. But it really varies too with the population. It's not just the therapy, it's the population. We ourselves have been really careful and cautious with this population. We're very pleased with what we've seen so far, and we expect it to continue. But I think we'll have these conversations with the agency as we generate more data.

Makes a lot of sense. Thanks. And Lisa, wishing you all the very best. It's been an absolute pleasure working with you.

Thank you.

Thanks for the questions, Ted.

Your next question comes from the line of John Newman with CannaCard Genuity. Please go ahead.

Hi, guys. Thanks for taking my question. Lisa, it's been a pleasure to work with you as well. A lot of great accomplishments at CERES and best of luck going forward. My question is I'm wondering if you could give us any sense on the potential size of the next study for 155. Let's just assume at this point maybe you run a Phase II And also, in addition to the 30-day bloodstream infection endpoint, what might be some of the other potential efficacy endpoints that you could look at? I'm curious if you might look at things like acute GVHD, maybe with a little bit longer follow-up, et cetera. Thanks.

Yeah, John, maybe I'll start, and then I'll ask Lisa to comment. If, in fact, we're looking at a standalone phase two, I think one of the real advantages of that is that we think that there's an opportunity to get real data back reasonably quickly. And that's one of the reasons that we've designed an interim look that we think could provide meaningful data on both efficacy, safety, and help inform how we move forward to a pivotal study. So whereas we haven't guided on numbers, we did say in our prepared remarks that we think we could potentially hit an interim read within 12 months of starting a study, which is pretty tangible. But in terms of other endpoints that will be of interest, maybe Lisa can comment.

Sure. So in addition to the BSI's, we'll be looking at fever during neutropenia, antibiotic use, hospitalization, ICU utilization. We will absolutely follow GVHD rates just as part of our safety assessment. What we know from the field is that the rates are dropping pretty seriously, and we saw single-digit, low single-digit rates in our Phase 1 study. So probably these kinds of rates are not going to be something where we're going to be able to tease out any kind of efficacy benefit, but we will be able to chart that for safety.

And then, John, I might just add, you know, additional comments around GVHD and the impact of PTCI. You know, we also have potentially the opportunity to leverage an interim result to think about adjacencies from AlloHSCT. So, we've talked in the past about other areas that we think 155 could potentially be helpful and where we think the mechanism could be effective. So, there's a lot that we could have in a relatively short amount of time based on our clinical experience in the first study as well as our expectations on enrollment rates in the next study. Okay, thank you. Thanks for the question.

I will now turn the call back to management for closing remarks.

So thank you, operator, and thanks to all of you for joining us this morning. We appreciate the opportunity to update you on our progress. We hope that everyone has a great week, and we will speak again soon. Thanks very much, and have a good morning.

Ladies and gentlemen, that concludes today's call. Thank you, and have a great day.