Seres Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by. My name is Desiree and I will be your conference operator today. At this time, I would like to welcome everyone to the Series Therapeutics First Quarter 2025 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 by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. I would now like to turn the conference over to Dr. Carlo Tanvi of Investor Relations. You may begin.

Thank you and good morning. Our press release with the company's first quarter 2025 financial results and business updates became available at 7 a.m. Eastern time this morning and can be found on the investors and 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, communications with, feedback from, or submissions to the FDA, upcoming presentations, future payments related to the valve sale, operating plans and our future cash runway, our ability to secure partnerships and or generate or obtain additional capital or financing, are planned strategic focus, anticipated timing of any of the foregoing or other statements which are not historical facts. 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, Series President and CEO, and Mirella Thorell, Chief Financial Officer. Additional members of the management team, including Dr. Matthew Henn, Chief Scientific Officer, Dr. Terry Young, Chief Commercial and Strategy Officer, and Dr. Dennis Walling, Senior Vice President of Clinical Development, will be available during the Q&A portion of the call. And with that, I'll pass the call to Eric.

Thank you, Carlo, and good morning, everyone. Today, I'll share business highlights from the first quarter and provide an update on our progress advancing 0155. During our recent full-year 2024 results call, we provided an in-depth review of our programs and recent data, and therefore, we will keep our remarks more abbreviated today and focus on progress updates. Advancing 0155 into the next stage of development in alloHSCT remains our top corporate priority, and we are making significant progress towards initiating the next clinical study. As a reminder, our Phase 1b study showed that 0155 administration resulted in a 77% relative risk reduction in bloodstream infections compared to placebo. This represents a highly meaningful outcome in this high-risk alloHSCT patient population. We also observed a favorable safety profile in this study, consistent with the favorable safety profile we've seen historically across our live biotherapeutic product platform. The clinical results generated to date underscore the potential of 0155 to redefine the standard of care for alloHSCT recipients, and the many other vulnerable patient groups at risk of bloodstream infections. We believe that developing 0155 and other live biotherapeutics to prevent infections in alloHSCT and other adjacent patient groups, including autologous HSCT patients, cancer patients with neutropenia, CAR-T recipients, individuals with chronic liver disease, and solid organ transplant recipients, could represent significant improvement for patients and multiple substantial commercial opportunities for CERES. Last month, members of our team attended the recent European Society for Blood and Marrow Transplantation Conference, and we obtained encouraging commentary from the transplant community that provides support for our mission and echoes what we've heard from U.S.-based physicians. Healthcare providers emphasized that preventing bloodstream infections remains a major clinical challenge and new approaches are desperately needed. Many physicians also expressed enthusiasm for both the safety and efficacy results observed in our SEER 155 Phase 1B study. Importantly, many also communicated their interest in participating in further SEER 155 development efforts. Our planned phase two study is expected to include multiple sites in Europe, so it is certainly encouraging to hear the support from European physicians. Additionally, our poster received the best clinical poster award from the EBMT Scientific Organizing Committee, providing external validation of both the patient need for CR155 and the rigor of our science. We also reported compelling exploratory translational biomarker data that reinforced the intended mechanisms of action of 0155. The data support that 0155 strengthens gut epithelial barrier integrity and induces immune homeostasis, findings that align with the observed clinical efficacy. These results further demonstrate the broader potential for live biotherapeutics to address inflammatory and immune diseases. Guided by constructive FDA feedback, including recently received, wherein the FDA recommended that we conduct a standalone phase two study as our next step, we plan to submit a 0155 phase two study protocol to FDA in the coming weeks. Our aim is to achieve a time and capital efficient path to clinical data. We are pleased with the productive interactions we've had with the FDA, which have been facilitated by CR155 having breakthrough therapy designation. And we are incorporating FDA's feedback into the design of the Phase II study protocol. As a result of our interactions with the FDA, we believe that we have the information needed for a rigorous Phase II protocol design. The study is expected to be well-powered, placebo-controlled, and target enrollment of 248 participants undergoing alloHSCT with a primary endpoint of preventing of bloodstream infections. We anticipate incorporating an adaptive design and an interim data analysis when approximately half of the enrolled participants have reached the primary endpoint. Based on our preliminary operational plans and anticipated enrollment rates, we believe we could obtain interim results within 12 months of study initiation thereby rapidly informing next steps in allo-HSCT development in pursuit of additional clinical development opportunities targeting adjacent patient populations such as auto-HSCT. If successful, we think the efficacy and safety parameters of the Phase II study could be used to support the design of what we anticipate being a single registrational study for approval of SIR 155 in allo-HSCT. As we prepare for the phase two study, we are moving forward with operational activities to support study initiation and execution, including having selected a CRO, commencement of study startup activities, and manufacturing clinical trial material. In parallel with these internal efforts, we are actively engaging in partnership discussions. As previously discussed, we would seek to collaborate with an entity that can provide financial support and that would help CERES realize the full clinical and commercial value of CR155. As you know, the biotech financing environment remains challenging, and we believe that obtaining the support of an external party who can provide financial and other resources is our best option to move CR155 forward and achieve the next clinical data milestones. Regarding our broader strategic goals, we believe 0155 and other live biotherapeutics have significant potential not only in the HSCT patient population, but also in additional patient groups at risk of bloodstream infections, including other blood cancer patients, CAR-T recipients, solid organ transplant recipients, individuals with chronic liver disease, and individuals in the ICU and long-term care facilities. I also want to highlight the potential that we see for live biotherapeutics to address various gut-related inflammatory and immune diseases, such as IBD, including ulcerative colitis and Crohn's disease. In each of these diseases, the gut epithelial barrier is known to be compromised, and this has been identified as a core component of underlying pathology. During the first quarter, we presented exploratory biomarker data from our Phase I study showing that SIR-155 was associated with improved epithelial barrier integrity and lower concentrations of various plasma biomarkers associated with systemic inflammation, such as interferon gamma, TNF-alpha, IL-17, and IL-8 in the HSCT peritransplant period, which is the period from the end of the first SIR-155 treatment course through to neutrophil engraftment. Additionally, at the recent Digestive Disease Week Conference, we presented data that could help identify and stratify patient subgroups most appropriate for a live biotherapeutic intervention and that could facilitate clinical development efforts in IBD and other immune-related diseases. We were very pleased to have received a Poster of Distinction Award in the Microbiome and Microbial Therapies subgroup at DDW. We continue to assess options, including through potential partnerships, to further evaluate these exciting I&I opportunities. With that, I'll now turn the call over to Mirela to review the financial results.

Thank you, Eric, and good morning, everyone. I'll start by noting that we have classified all historical operating results for the Vaust business within discontinued operations in the Consolidated Statement of Operations for the comparative period presented being the three months ended March 31st, 2024. There is no ongoing activity in the current period related to disc ops. Ceres reported net income from continuing operations of $32.7 million in Q1 2025 as compared to a net loss from continuing operations of $32.9 million in the first quarter of 2024. The net income in 2025 is primarily driven by the previously announced $50 million installment payment received from Nestle in January of this year, consistent with the company fulfilling its transition obligations. Research and development expenses for the quarter were $11.8 million compared to $19.5 million in the first quarter of 2024, reflecting lower personnel expenses, a decrease in platform investments, and lower costs related to the CR155 Phase 1B study. General and administrative expenses were $11.9 million in the first quarter, a decrease from $14.9 million in Q1 2024, driven primarily by lower personnel and contractor expenses. As of March 31st, 2025, we had cash and cash equivalents of $58.8 million. We are due a second installment payment of approximately $23.5 million net after deduction for employment related obligations from Nestle in July of this year. We remain in compliance with the transition service agreement terms. and therefore anticipate receipt of this payment as expected. Based on our current cash balance, the expected installment payment from Nestle in July, and our current operating plans, we expect to fund operations into the first quarter of 2026. On April 21st of this year, we effected a 1 for 20 reverse stock split of our common stock. Trading of our common stock on the NASDAQ Global Select Market commenced on a split adjusted basis on April 22, 2025. Yesterday, we were notified by the NASDAQ listing qualification staff that we have now regained compliance with the bid price requirement. We remain highly disciplined in our financial management, ensuring that we are prioritizing activities that advance our clinical and strategic goals and looking for means to preserve cash without compromising the achievement of these goals. As is prudent in today's challenging financing climate, we continue to explore sources of capital in addition to partnerships to provide potential optionality for financing our phase two study. I'll now pass the call back to Eric.

Thanks, Marilla. To summarize, we are making significant progress advancing 0155, bolstered by encouraging clinical and mechanistic data, constructive regulatory feedback, and the clear unmet medical need identified by key opinion leaders and clinical experts. We are moving with speed and focus to submit our Phase II protocol to the FDA in the coming weeks, and to prepare for the next clinical study. We are also making progress in our efforts to secure a partnership to capture the potential substantial therapeutic and commercial opportunities. I look forward to sharing additional updates as we advance our objectives in the months ahead and continue to attend medical and scientific conferences to increase awareness of and enthusiasm for 0155. Operator, you can now open the call up for questions.

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. If you are called upon to ask your question and are listening via speakerphone on your device, please pick up your handset to ensure that your phone is not on mute when asking your question.

Again, press star 1 to join the queue. And our first question comes from the line of Tessa Romero with JP Morgan.

Your line is open.

Good morning, team. This is Caroline Potron for Tessa Romero. Thanks for taking our questions. Just two from us. First, are the partnership discussions being gated by progress around the next steps for SEER 155? In other words, are prospective partners looking for the protocol to be submitted or the trial itself to be initiated before finalizing a deal? And then I have a follow-up.

Yeah, Carolina, thanks for the question and good morning. Without getting too deep into the play-by-play of our partnership discussions, let me offer a couple things. One is we're making progress, we're advancing those discussions. I will say that our interactions with the FDA have been constructive and let's call it regular. We have been in contact with FDA including as recently as last week, right, so whereas The news reports are sometimes, I don't know, dire as it relates to what's happening in FDA. I can tell you that we're getting feedback on our design of the next study. We're incorporating that feedback, and we think we have a path. So as it relates to our discussion with partners, we think that's a significant positive. In terms of gating items to start the study, We have said before, and I'll reiterate today, that the securing of a partnership for us is the key long lead time item for moving forward with this study. We're moving forward with all the key items that we have to do in terms of securing a CRO and manufacturing clinical material for the next study and thinking about site activation. So we're doing the things that we need to do to be in a position to move. but the partnership itself for us will be a gating item for initiating the study itself.

Okay, great. And then can you outline your proposed powering assumptions for the Phase II study of SCR 155 and provide a little more clarity as to what you mean by an adaptive design in the context of the Phase II study?

Thanks. Sure. So let me start, and maybe I'll kick it over to Dennis to comment. I think we're not in a position to share the stats themselves. It is a standalone phase two study, but we do think that the powering included in our design will allow us to use data from this study for both the efficacy and safety components of an overall package for submission to the FDA if we're successful. As it relates to the design of an interim look, let me offer a couple comments. One is that As we said in our prepared remarks, the timeline to get that read we think is approximately 12 months. And that should give us a pretty good sense of where we're pointing in terms of efficacy. So we're excited about that. But maybe I can ask Dennis to comment further on that question.

Yes, thank you. So we think that the adaptive design with the interim analysis is an opportunity to get an early look at our efficacy and safety data in a way that we can begin to engage with the FDA earlier with discussions around what a potential pivotal phase three program might look like. So the plan would still require that we have that end of phase two meeting conversations, but the interim analysis allows us a big head start to get to those conversations with the FDA early.

Great, thank you so much. Thanks for the question, Caroline. Our next question comes from the line of Joseph

Tom with TD College. Your line is open.

Hi there. Good morning. Thank you for taking my questions. Kind of similar, but obviously there have been a lot of FDA changes since you received your initial advice. And so is the department that you're working with, were there any large staffing changes there? And if anything, it almost seems like the new administration would be more supportive of microbiome therapeutics. So just kind of curious if you have had any sort of changes in dialogue, either positive or seems like not negative. And then is there any additional information that you can share regarding partnership discussions that give you confidence that you'll be able to get this done kind of by the end of the year and your current cash runway guidance? And do you think the partner would want input on the Phase 2 protocol at all? Thank you.

Yeah, Joe, thanks for the questions. On the first one, maybe I answered part of it in my last comments, but You know, it's hard for us to speak about FDA in general or the environment in general. What we can talk about is our own interactions, and our own interactions have been highly constructive and regular, and certainly we were concerned about it. We continue to monitor it, but we've been in regular contact with FDA, and we've gotten robust, specific feedback from them, which has been useful in us determining how we think about moving forward. Now, remember, we have breakthrough designation, so we think that, you know, and this is just my speculation, I think that's probably helpful. I mean, the FDA, on the heels of our Phase 1b results, determined that based on the unmet need and the early clinical signals, that SIR 155 was worthy of that designation. And so perhaps that is helpful in thinking about prioritization of work, but again, we don't speak for the FDA. All I can say is that we've been pleased with the interactions that we've had to date, and it allows us to move forward the way that we had hoped that we would. On the partnership dynamics and maybe timing, you know, look, it's hard to predict, you know, I would say based on our experience, there's not always a linear line between starting a process and ending a process, so it's a little bit difficult for me or challenging for me to opine, Joe. All I can tell you is that we are making progress. We are having discussions in terms of our design and our feedback from FDA with our partners or potential partners. And we're also mindful of, you know, our catch resources and time. And so, you know, we are moving forward with absolute urgency, and you can expect us to continue to do that.

Great. Thank you. And then maybe just on the phase two itself, just so I understand the interim analysis, I guess. When that occurs, do you have the optionality to increase the size of the study if you want more information? And obviously, given that you do have the breakthrough therapy designation, do you think there's a path where the FDA could say, let's just expand this phase two and make the phase three confirmatory? Or do we kind of know that a phase three would need to be the base case here? Thank you.

Yeah, Joe, thanks for the question. And maybe I'll start and I'll invite... Dennis to comment too. You know, it's a little tricky. We're careful not to speak for the FDA. There will be optionality as it relates to information that we could learn from the interim and how we might use it. either for 155 or, as we've said beforehand, thinking about adjacencies from allo into, say, auto. So we're incredibly excited about the design of this interim look. We think it'll give directionally a sense of where we're pointing. It'll give us information. It'll give FDA information. Our expectation is that the data that we get from this Phase 2 study will help inform a phase three study or a pivotal study. And that overall package will be used for licensure. But we don't speak for the FDA. We are very careful not to get ahead of them. And so, you know, as usual, we'll follow the data in consultation with them as we have in the past and will in the future. But Dennis, any other comments on that one?

Yeah, I think it's important to understand that this phase two study design is appropriately powered for a very robust and large data set that we will be able to analyze. And so the optionality at the interim is important to understand is that we do have the opportunity to make decisions if necessary at that time point. But the other important thing to understand is that we expect that this data from the phase two will be supportive of the total package that, you know, the FDA would evaluate for a potential approval. And, you know, as Eric said, it's premature to speak for the FDA as what they might want to do or not, but we are expecting to have robust engagement and conversations with them at the interim level and at the end of the phase two to complete a pivotal phase three design that would get us to an approval.

Excellent. Thank you so much. Thanks for the questions, Joe.

And our last question comes from the line of John Newman with Canaccord. Your line is open.

Hi, guys. Good morning. Thank you for taking my question. I just had two, actually. In terms of the phase two study and the primary endpoint, could you talk about how much follow-up the FDA might be looking for? And just curious if this particular study would be designed for you to be able to follow up for overall survival, or if that would be something that you would maybe add as a secondary endpoint in the phase three, or simply follow up as observation, thanks.

Yeah, thanks for the question. Maybe I'll start and then Dennis can kick in. So just at the high level, as we said before, we have engaged with the FDA. They provided feedback to us that we have incorporated into our design. We think that we have what we need to move forward. We're submitting the protocol, as we said, in the next couple of weeks. If there are questions or proposed adjustments, we expect to hear back. But, again, the partnership for us really is the gating item in moving forward. But maybe Dennis can comment specifically on the follow-up question.

So, I mean, as we've said before, the FDA has given us breakthrough therapy designation on the endpoint of bloodstream infection reductions, and that is our intended primary endpoint in this Phase II study. Protocol is still being finalized. Obviously we are going to be looking at a number of different things that could be potential efficacy signals and as well as safety. So at this point in time, we'll have to see what the data show at the phase two and then have those discussions with the FDA about what are the appropriate types of efficacy measures we would evaluate Phase three.

Great, thank you. This is Matt here as well. I give you one other piece of information regarding that. I mean, as you know, we always design rigorous studies that are data rich. And there are large cohort studies that have shown associations of the gastrointestinal microbiome with survivability in this patient population. And so we'll obviously be collecting that kind of data to look for signals there, but as Dennis said, the protocol is still in development with respect to those types of endpoints.

Okay, great. Thank you very much. Thanks for the question.

That concludes the question and answer session. I would like to turn the call back over to the management for closing remarks.

So thank you, operator, for your help this morning, and thanks to everyone for joining today's call, and we look forward to our continued engagement. Thanks. Have a great morning. Have a great rest of the week.

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