Seres Therapeutics, Inc.

At this time, I would like to welcome everyone to the Ceres Therapeutics fourth quarter 2023 earnings conference call. Today's conference is being recorded and 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 that time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one a second time. Thank you. And I will now turn the conference over to Rob Windsor of Investor Relations. You may begin.

Thank you for the morning. Our press release for the company's fourth quarter 2023 financial results 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. I'd like to remind you that we'll be making forward-looking statements, including the availability of cash to fund operations and the potential sales for Vaust, including our ability to achieve sales targets and milestones, the timing and results of clinical studies and 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 have to 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 Schaff, Series Chief Executive Officer, Dr. Terry Young, Chief Commercial and Strategy Officer, Dr. Lisa Von Mulkey, Chief Medical Officer, and David Arkwitz, Chief Financial Officer. In addition, Dr. Matthew Henn, Chief Scientific Officer, and Dr. Dave Egge, Chief Technology Officer, will also be available to address questions. With that, I'll pass it over to Eric.

Thank you, Rob, and good morning, everyone. 2023 was an historic year for Ceres and an inflection point for our company and for patients. With the approval and launch of Voust, we brought to market our first-in-class oral microbiome therapeutic for patients with recurrent C. diff infection. We are proud of the impact Voust is having on patients, their families, and the entire recurrent C. diff community. As we enter 2024, our top priorities remain, first, delivering vows to patients, and second, advancing the potential of microbiome therapeutics more broadly, including with our SEER 155 Phase 1b readout in alloHSAT patients expected in Q3 of this year. Everything we do at CERES has been and always will be driven by a desire to support patients with significant unmet medical needs. It is the hope and resilience of each patient and their families that inspires us, and drives us to fulfill our mission. Voust is a perfect example of this. In Voust, we have developed an incredible and unique option for patients who battle recurrency disinfection, one with a strong efficacy and safety profile, as well as a convenient oral route of administration. In a particularly complex disease where historically innovation has been difficult, today Voust is changing lives. The U.S. launch of Vaust has exceeded our expectations. In partnership with Nestle Health Science, we are pleased with the broad patient access received thus far, with more patients gaining access to Vaust than expected. The hospital team continues its efforts to enhance hospital outflow, which we expect will continue to bear fruit into 2024. We are also seeing continued strong demand from a broad set of healthcare practitioners and across the recurrent C. diff patient pool including utilization in patients at their first recurrence. Terry will cover our commercial metrics in more detail shortly. I am extremely proud that we achieved over 2,000 VALS patient starts in 2023 following our launch in June. We continue to see substantial opportunity for growth given the broad label and the robust clinical profile of Vaust, which makes it an ideal choice for so many of the estimated 156,000 cases of recurrent CDI in the U.S. each year. I would like to thank the team at Ceres and Nestle for successfully executing our launch strategy together, collaborating with focus and urgency on behalf of our patients and their families. We look forward to seeing continued growth of Vaust utilization in 2024, and expect this positive trend to continue as patient outcomes on VAUST are more broadly recognized. We are excited by the potential of VAUST to become the standard of care for preventing further C. diff. occurrences. Building off our strong proof of concept with VAUST, we were excited to announce in December receipt of fast track designation for the 0155 program with a cohort two data readout anticipated in the third quarter of this year. We believe positive data from this readout would further validate the potential of our platform in infections, including in indications such as chronic liver disease, cancer neutropenia, solid organ transplant, and AMR infections more broadly in settings of high risk, such as intensive care units. Last year, we made the difficult decision to restructure the company and focus on Voust and CR155. This was an extremely difficult decision but a necessary one for positioning CERES optimally for the future. David will touch upon this later in the call, but financial discipline is at the forefront of CERES priorities in 2024 and beyond. We will continue to evaluate all options to strengthen our balance sheet. As we do so, we believe we will be well positioned to create value for our shareholders and deliver our mission for patients now and in the future. Recently, we announced the appointment of Morella Thorell as Executive Vice President and Chief Financial Officer of Ceres following David's retirement. We welcome Morella and look forward to benefiting from her extensive strategy, corporate finance, and operational experience. I would also like to thank David for his leadership and significant contributions over the past three years, and we wish him the very best in retirement. With the continued success of the VEST launch and the clinical readout from SIR 155 later this year, we look forward to 2024 as a year that will further validate SIR's platform and the promise in microbiome therapeutics. I would like to now pass the call over to Terri to cover the significant progress we've made bringing VEST to patients.

Thank you, Eric. I'm pleased to report that along with our collaborators at Nestle Health Science, We continued to make significant progress on our launch priorities in the fourth quarter, building upon earlier momentum observed with Devel's launch. As you'll recall, our four focus areas are scaling HCP education efforts, creating a positive customer experience, establishing payer coverage, and optimizing hospital outflow. I'll now provide an update on each of these. Our HCP education efforts emphasize the importance of microbiome restoration and recurrent CDI, and the unprecedented efficacy and safety profile of valves. We have made significant progress in this area, supported by the promotional efforts of the Nestle field teams. As a result, demand continued to grow in the fourth quarter, as reported to us by Nestle Health Science. In total, between our June launch and year end, we received 2,833 completed prescription enrollment forms for Vaust, including 1,322 in the fourth quarter alone. Of the total enrollments last year, 2015 culminated in new patient starts, including 1,082 in the fourth quarter alone. We received prescription enrollment forms from 1,330 unique prescribers between approval and year end, nearly doubling the number of prescribers versus what we saw at the end of Q3. Approximately 65% of these prescribers of VALS were from gastroenterology, with the remainder from other specialties. Of these 1,330 HCPs who prescribed VALS, 340 of them prescribed VALS to more than one patient. Although, as expected, the majority of 2023 utilization for VALS was in the multiply recurrent patient group, we continue to see use in patients with their first recurrence. We expect this to continue to grow over time as HCPs gain experience with an entirely new modality and develop an understanding of the foundational and distinct role that VALS plays in preventing recurrence. We recently completed a round of market research with HCPs who have used VALS. Findings from that research support that HCPs remain highly receptive to the profile of VALS, and users have had a positive experience obtaining patient access, supported by the Nestle Field Teams and the VALS Voyage Patient Hub. These encouraging results align with our view that VALS can become a foundational treatment for recurrent CDI and a highly significant commercial opportunity over time. Providing a positive experience for patients and providers is our second launch priority. Our VALS Voyage Hub continued to increase its successful conversion of enrollment to new patient starts in Q4. In terms of free drug utilization, approximately 46% of the 2015 new patient starts in 2023 were dispensed via our free drug program. In the fourth quarter specifically, That percentage was 44%, down from the 48% we reported for Q3. As a reminder, the use of free drug that we are seeing is mostly due to patient affordability challenges with copays or other cost-sharing requirements after the prescription was approved by their insurer. We believe these programs are an important investment to support future demand across the broad RCDI patient population, and the need for these programs is likely to decline as the Inflation Reduction Act provisions governing Medicare Part D benefit design and specifically patient cost sharing requirements come into effect over the next year. Our third focus area is engaging payers to insurer access and to date we have been pleased with the broad patient access we are seeing with the vast majority of patients able to gain access to VALS through their insurer. As of year end, we had received coverage for VALS across approximately 80% of commercial and 54% of Medicare Part D lives and estimate that the remaining plans will issue coverage policies in the coming quarters. Through year end, we saw 54% of our 2015 new patient starts reimbursed through the patient's drug benefit. Our gross to net rate remains modest with minimal discretionary rebates at this stage of the launch David will say more about our gross to net rates momentarily. In summary, the vast majority of patients who are prescribed VALS are able to obtain approval for the product either through the medical exception process prior to a policy being issued or via the prior authorization or appeals process. As first recurrent demand for VALS builds, we will continue to work with prominent payers to ensure that we preserve the broad patient access to VALS that we are currently observing. Finally, the hospital selling team continues its efforts to enhance hospital outflow, and we believe these efforts will accelerate demand in 2024. As a result of this team's efforts, we are starting to see valves added to discharge protocols at some of the large institutions, as well as added to inpatient formularies. Scaling these efforts are critical to ensuring structural modifications to how RCDI patients are discharged. Education of hospital-based HCPs, and development of protocols for RCDI that can include VALS will enable more consistent consideration of VALS as patients flow from the inpatient to the outpatient setting. These 2023 results since the launch of VALS in June show the strong start of a significant opportunity to change the treatment paradigm across the entire RCDI patient pool. In fact, our results exceeded our expectations across multiple dimensions. We, along with our collaborators at Nestle Health Science, will continue our focus on HCP education, customer experience, payer coverage, and hospital outflow, and expect to see continued acceleration of demand and progress on our key priorities as we move through 2024. As a result, we have confidence that we will ultimately achieve our goal of VALS becoming a foundational therapy for our CDI, potentially reaching or surpassing the highest sales-based milestone threshold in the 2021 Nestle co-commercialization agreement of $750 million. I would now like to pass the call over to Lisa to give more details about SEER 155 and our ongoing clinical trial.

Thank you, Teri. As a reminder, SEER 155 is a cultivated microbiome therapeutic candidate that is designed to prevent enteric infections, including those that may harbor antibiotic resistance, and to reduce the incidence of graft versus host disease in patients undergoing hematopoietic stem cell transplantation. The peer-reviewed literature supports a strong connection between a disrupted GI microbiome and pathogen domination in the GI tract with the endpoints of infection, graft versus host disease, and mortality in patients undergoing alloHSCT. Last year, we reported promising phase 1B cohort 1 clinical data, with SIR 155 being well-tolerated in highly immunocompromised HSCT patients. Our data indicated that only a single patient had enteric pathogen domination within 30 days following stem cell transplant, which was a markedly lower incidence than that observed in a large reference cohort of patients. Enrollment is ongoing in Cohort 2, which incorporates a randomized, double-blinded, placebo-controlled design to further evaluate safety and engraftment, as well as clinical outcomes. This portion of the study will enroll approximately 50 subjects administered either SIR 155 or placebo at a one-to-one ratio, and we anticipate obtaining Cohort 2 study data in Q3 of this year. In addition to continued evaluation of the safety profile and drug pharmacology, outcomes assessed will be the ability of CR155 to decrease rates of pathogen domination, grade 3 or 4 acute GVHD, and the incidence of GI and related bloodstream infections. We also will assess the ability of CR155 to decrease rates of fever during neutropenia and the initiation of attendant antibiotic therapy. We believe positive data from this readout would further validate the promise of this novel therapeutic modality in addressing serious infection in medically vulnerable populations, including patients with chronic liver disease, cancer neutropenia, and solid organ transplant. We also believe that this approach could impact the problem of antimicrobial resistance more broadly in settings of high risk, such as intensive care units. These additional opportunities have the potential to extend the utility of SEER 155 and our preclinical stage pipeline and to establish a new approach in protecting immunocompromised patients from life-threatening infections and related clinical events. With that, I'll turn the call over to David for an update on financials.

Thanks, Lisa, and good morning. I'd like to discuss our financial performance for the fourth quarter starting with Vaust. Let me first remind everyone that Ceres does not recognize Vaust Net Sales and its financial statements, but instead we share equally with Nestle the commercial profits and losses, and we record our share in collaboration profit and loss sharing related parties. Voust profits and losses are determined based on Voust net sales, cost of goods sold, and sales and marketing expenses. Consistent with our pre-release in January, net sales of Voust for the fourth quarter were 10.4 million and based on 673 units of Voust sold during the period to specialty pharmacies and distributors. The net sales reflect estimated gross net reductions of approximately 11%. We estimate that at the end of last year, there was approximately two weeks of vouched inventory in the channel at specialty pharmacies. Ceres supplies vouched inventory to Nestle, and we received payments from Nestle related to their vouched supply purchases to meet market demand. During the fourth quarter, Nestle purchased approximately 9 million of vouched supply from us, and we received approximately 17 million in payments from Nestle related to prior quarter purchases. The total VAWS loss in the fourth quarter was $20.5 million, and our share of that was $10.3 million. The fourth quarter VAWS collaboration expenses, meaning COGS and sales and marketing expenses for VAWS, increased from the prior quarter. This increase was due to higher COGS given the variability of manufacturing costs for VAWS produced prior to approval, as well as some prior period adjustments and higher sales and marketing expenses due to increased free goods and the initiation and ramp up of some key marketing activities. For the fourth quarter, we also recognized as collaboration profit or loss sharing related party approximately 14 million of profit on the transfer of BAUST inventory to Nestle. This profit represents the supply price to Nestle net of the cost of the inventory for the units sold and free goods distributed by Nestle during the quarter. Because the vast majority of this vouched inventory was manufactured prior to approval, its cost was largely previously expensed, and therefore the inventory value is very low, resulting in the profit on the transfer of the vouched inventory that is close to its supply price. Over time, as the vouched preapproval inventory is consumed, the magnitude of this profit component from the transfer of inventory will diminish. Research and development expenses for the fourth quarter of 2023 were $26.8 million, reduced from $46.2 million for the same period in 2022. The year-over-year decrease in R&D expenses is primarily driven by VAUSE commercial manufacturing costs no longer being recognized in the series T&L following the product approval in April 2023, but instead capitalized and recognized on our balance sheet. General and administrative expenses for the fourth quarter of 2023 were $17.2 million, reduced from $22.4 million from the same period in 2022. As you know, in November of last year, we announced a significant corporate restructuring, which is expected to achieve $75 million to $85 million in annual cash savings in 2024. The restructuring was substantially implemented around year end last year. As a result, R&D and G&A expenses for the fourth quarter were minimally impacted by the restructuring as the reduced spend related to the restructuring started in earnest at the beginning of this year. We ended 2023 with $128 million in cash, cash equivalents and investments. And additionally, we have received net proceeds of approximately $18.5 million from the sale of common stock under our at the market equity or ATM program thus far this year. We anticipate that our cash balance in conjunction with the anticipated savings from the restructuring and assuming continued quarter over quarter revenue growth of VAUST, the expected receipt of the 45 million tranche B under our existing term loan facility with Oak Tree will support our operations into the fourth quarter of 2024. Thank you and I now turn the call back to Eric.

Thank you, David, and thank you again for all your contributions to CERES. We wish you well in your retirement. Before opening the call up to Q&A, I would like to express how proud I am of the team at CERES and the team at Nestle for bringing a first-in-class oral therapy to the market. 2023 was truly a trailblazing year for CERES, as well as for microbiome therapeutics. As we look forward into 2024, I'm excited about the continued success of Voust, as well as the possibilities with 0155. With that, we will conclude our remarks and open the line up to questions.

Thank you. And at this time, I would like to remind everyone in order to ask a question, press star and then the number one on your telephone keypad. To withdraw your question from queue, press star one a second time. And we'll pause for just a moment to compile our Q&A roster. And we will take our first question from Jeff Jones with Oppenheimer. Your line is open.

Thank you. Can you hear me? Yes, we can, Jeff. Good morning.

Great. Thanks, Eric.

I guess, can you speak to the main drivers of what looks to be about a $170 million spend in 2024? I know we've spoken to your second manufacturing site in the past. And then any discussions you might be having with Nestle regarding the, you know, now about 10-month runway?

Yeah, maybe I can ask David to start on the parameters of investment, and then I can take the second question on our partners.

Yeah, I would just say, Jeff, at a high level, about half of that relates to R&D. and a big chunk of that R&D spend relates to really ramping up our upcoming manufacturing facility in Bactera. So we're talking about tech transfer and really driving towards approval of that facility. So that's driving a lot of the spend. Keep in mind that we are also operating, we will be operating Bactera and our existing CMO simultaneously in 2024. As we get into 2025, that will drop off. We will move to primarily one CMO, so you'll see some of that spend dissipate. And then, you know, we've got G&A expenditures to operate as a public company, as well as our share of the VAUSE collaboration profit and loss.

Maybe I can just add Jeff, to the second part of the question. In general, we are highly focused on cash, on runway, on investments, and ways in which we can continue to support the company. And certainly you saw at the end of last year action from us with the restructuring, you know, 41% reduction in headcount. We estimate between 75, 85 million reduction in 2024 spend. So our three priorities for this year are, one, supporting the launch of Vaust, two, driving towards a 155 readout, and three, supporting the company both through augmenting the balance sheet, reducing spend, and looking actively at ways in which we can continue to support our operations. I would say from our partners' perspective, I think we both are pleased with the launch to date. We know that Vaust is important to Nestle. We know that There's real synergy between Zempep and Voust, and I won't go further than that. But, you know, obviously we care deeply about supporting the company, and we're actively working to try to put ourselves in the best position to serve patients in the long term.

Just one quick follow-up on that and the work at Bacteria, which involves manufacturing batches. Any chance that some of those batches can be used commercially and so that spend there actually goes to, you know, saleable product?

Yeah, I can comment on that there, but maybe we've got Dave here who can comment on the specific question around the batches.

Hi, good morning. Yes, the simple answer is that is correct. Like, it's anticipated that the PPQ batches for validation will be saleable and ultimately would go into commercial supply.

And I would just add, you know, we continue to make progress with Baxera in supporting continued augmentation of our capacity. And, you know, we're working with them as well to think about ways in which we can continue to support both companies and our relationship move forward.

I appreciate it. I'll jump back into the queue, guys. Thanks, Jeff.

And we will take our next question from John Newman with Canaccord. Your line is open.

Hi, guys. Good morning. Great progress. Lots of hard work on the VAUST launch. Very good. You know, obviously appreciating that you are currently very focused on commercialization of VAUST, as well as the current STEER 155 Phase 1B study, I'm just curious, Where do you see future opportunities for the drug technology itself?

Yeah, John, good morning, and thank you for the question. Maybe I can start, and I'll invite Matt, who's here to provide some commentary as well. But I think I'll start where your question led off, which is we are focused. Our priorities for 2024 are VAWS launch, 155, and supporting the financial condition of the company. we are deeply committed to the strict allocation of capital along those key priorities. And focus, I think, is the name of the game for us in the short term. That said, that doesn't mean that we can't be excited about what could potentially be opened up with a positive readout in the 155 study. So we are particularly excited about that. Maybe I can invite Matt to comment further.

Yeah, John, I mean, thinking about that kind of potential, as Eric said, that could be opened up. Really, when you think about the past decade, there's really just been an incredible explosion in the research that's defined a really substantial role for the microbiome in both states of disease, states of health. And importantly, we've learned a tremendous amount mechanistically about how that happens. And this is best understood in the context of the gastrointestinal tract, which is where CERES is focused, our research to date and our programs to date. And there's a role to be played around infections, as we've talked about, priming both the adaptive and the immune systems, general metabolism and And quite frankly, data supporting gut-brain access, et cetera. But, you know, as I think about the development of microbiome therapeutics and the various strategies that we can pursue here, I think of it similar to gene therapy. It's early. There's really sound science. There's really a lot of potential. But translation takes some time. And to succeed here, People need to build platforms that can really kind of get at the heart of scientifically and mechanistically what's happening and as well strategically broaden our pipeline. And in short, CIRES has built such a platform and we're pursuing such a pipeline strategy. We have the ability to go from early stage discovery all the way through to manufacturing of these therapeutics. we can interrogate a very, very high resolution microbe-microbe, microbe-host interactions that allows us to really get at specific pathways, specific targets that we can that we can target. And then our portfolio strategy has been building incrementally. So, VALS provides us very strong proof of concept around the concept to be able to address infections in the gut. And our CER155 program is building on that knowledge to go after a broader set of pathogens, as well as leverage critical insights we have from a preclinical and clinical standpoint on how we can have an impact on preventing infections and colonization of various pathogens. how we can actually induce immune tolerance in the gastrointestinal tract, as well as actually look at the epithelial barrier and have impacts there. So this is all built into this 155 program. And as you heard on the call today, we see that really just as the initial point for that expansion, where we can move into additional medically compromised patients where we see disrupted microbiome, people at risk for these same kinds of factors that include cancer, neutropenia, solid organ transplant, chronic liver disease, and really that problem of AMR more broadly in the ICU. So we see really broad potential, and we're excited to get to the next points to sort of enable us to be able to pursue that. But right now, we're focused on FALSE and our 155 program.

Okay, great. Thank you. Thanks for the question, John.

And we will take our next question from Tess Romero with JP Morgan. Your line is open.

Hello. Good morning, guys. Thanks so much for taking our question.

So how should we think about the sales trajectory in 2024 for Voused? And specifically, what is the right way to forecast percent of free drugs over the course of 2024 given the the patient affordability challenges you cited. And then the second question is, can you clarify what you mean by the strengthened promotional campaigns and expanded reach of digital promotion by Nestle and what this means with respect to expected pull through to the launch? Thanks.

Yeah, Tess, thanks for the questions and good morning. Let me invite Terry to comment on both questions. I would just start by saying Terry spent most of last week with the Nestle commercial group and leadership. So I think it's a good time to ask that question and provide some visibility as to how we look at 2024 and the trends that are important.

Yeah, so in 2024, we're obviously, as with any launch, looking for continued growth, breadth and depth of prescribing specifically, right? We're seeing good access. We seek to preserve that. So it's really about HCP trial and adoption in 2024. And I'll touch on pre-drug last test. Digital promotion is actually a key tactic that it's important for a brand to leverage after you've educated your top prescribers and KOLs. So we've spent with Nestle the first months after the launch making sure that we had deep conversations, deep education efforts with the top prescribers, activating the high volume prescribers. And from there, we're really seeking to enhance breadth of trial. And so you can do that leveraging the Salesforce that we have, but we really aim to go broader than that. And that's the role of digital promotion. So you tend to scale that anywhere from four to six months after approval and launch. And so that's what we've done. So we had a new campaign that launched and was rolled out to the representatives in October of last year, right around ID week. And that campaign was significantly scaled digitally to HCPs. We also scaled patient promotion. You typically do that six months after a launch because you don't want to send activated patients into a physician and have the patient be the first source of awareness about a new product. So we want to make sure that physicians are aware of the new product before we turn patients on and send them in. So all of that is in the rearview mirror now, and it's about those campaigns delivering the additional breadth of prescribing and subsequent depth that we would expect, because we know once physicians try VALS, they're having a good experience, and they're willing to try it on additional patients in their practice, and we're seeing that in the results. So we're very happy about, you know, scaling that promotion and look forward to the additional growth that we'll get this year as a result of it. Switching to free drug, I mentioned that we saw the rate come down in Q4 from Q3, right? But we've got three quarters now in sort of the mid 40s. So, you know, in terms of forecasting, those are the data points that we have. I think we've got 46, 48, and 44 in the three different quarters in 2023. We have said and I have said that we expect the utilization of these programs to go down. The voucher program will go down as we get policies on board. So you could imagine we might see some declines this year as payer policies are issued for the majority of the population. But specifically in 2025, with the IRA provisions going into effect, the patient assistance program, the more traditional PAP that we have that's income qualified in Medicare Part D patients, that's where we're seeing the majority of the utilization, that should really decline in 2025. So that's sort of the data points that we have and the knowledge that we have around patient assistance.

Thanks for the question.

Thank you. And we will take our next question from Peyton Bonsack with TD Cowan. Your line is open.

Hey, good morning, guys, and thanks for taking our questions. I guess to kind of build up on the previous question talking about launch trajectory, I was wondering if you could give us a little more detail about the potential penetration in the first RCBI population, and are there any specific strategies that you guys can do to kind of build further into that population, or is it just mostly a position education effort? And then I have a call up.

Sure. Peyton, why don't I give the first one to Terry?

Sure, so absolutely. The strategy that we're taking is to definitely accelerate utilization into the earlier lines of therapy within our CVI. So there are a number of ways to do that. One is achieving breadth, and I went into some depth about the breadth there with Tessa a minute ago. But digital promotion is really a way that you can reach deeper into the prescriber base, even into primary care where a lot, not a lot, but many of the first recurrent patients are treated. So the breadth of prescribing, the breadth of promotion, the breadth of awareness, is really important to achieve, and that should go a long way toward unlocking additional use in that population. But we do see that our core set of prescribers actually see and are choosing VALST for these patients. And as they see VALST work, they see that it's easy to use, they will broaden their use. They told us that they would do that before launch. We're already seeing that with the depth and the repeat prescribing that we're observing and observed in 2023. So it's continuing to have the sales representatives on the Nestle side encourage their physicians to move the product earlier based on the amazing results that they're seeing in the patients that they initially chose. So it's a mixed bag of tactics, but we're very focused there with Nestle this year.

Positive experience can have a cascading effect.

Absolutely. Big accelerator.

Great. I guess you kind of actually touched on my second question, which was, you know, are you really seeing a lot of these first-order CDI patients that you have been seeing treated? Are these largely coming from GIs or your, like, targeted group of high prescribers? Are these from, like, people that are maybe not as high prescribing or principal care providers or infectious disease docs? And any additional details you can get on that would be much appreciated.

Yeah, it's

It's actually been one of the most interesting aspects of the launch and one way that the launch has exceeded our expectations is the breadth of use that we're seeing across physicians, across physicians the field's representatives are calling on, also physicians that they're not. And we're seeing within the physician user pool a large variety of where physicians are choosing to use it first. So we're not really seeing a pattern, interestingly, which I think is highly encouraging for the launch. Every physician is basically choosing the patient that they think is at risk based on the patient that happens to be in front of them in their office at the moment. And, you know, we are seeing the utilization in first recurrence as well as in multiple recurrence. So we feel good about the patterns that we are seeing and that there is not a pattern other than the doctors choosing a high-risk patient, irrespective of number of recurrences.

Great. Thanks for the additional color. Yeah, thank you for the additional color and for letting me ask the follow-up.

Thanks, Peyton. Thanks for the question.

And we will take our next question from Chris Shiwatani with Goldman Sachs. Your line is open.

Great. Good morning. I wanted to ask about SEER 155 and how we should be thinking about the decision tree that you'll have when the data is reported in the third quarter. In particular, when you think about the kind of scale and the budget that would be required to further advance in the event of positive data. How are you thinking about your capacity to fund this? Is this something where you're currently contemplating potential partnerships? And then secondly, I think you have access to a trosh of a loan from Oak Tree. Can you help us understand any of the mechanics that would be involved so that we can understand how that might be a lever to also help support financing of continued success with CR155 if positive data comes in the third quarter? Thank you.

Chris, good morning, and thanks for the two questions. What I'd like to do is maybe invite Lisa to comment a little bit on what we are expecting in the 155 readout or what we hope for. I will say, as it relates to resourcing, Chris, we said at the time of the restriction last year was that we would pursue 155 to the clinical readout with both the clinical and microbiome analysis that comes with it. but that we were gaining investment beyond that to the readout itself. So our expectation is that 155 will basically stand on its own. If it's successful, we think there are multiple ways in which we can support it, and it could bring additional resources into the company. But if it's not, then we're not going to pursue it without being able to fund it, obviously. So maybe I can ask Lisa to comment on that, and then David and I can take the question on O3.

Yeah, just a reminder that this study offers us the possibility to go in a number of different directions depending on the results. We could have a play in acute GVHD as well as on the infection side where we think there are a number of different endpoints that could show us a way forward and so we'd be looking to most likely choose a particular route, either the infection side or the acute GVHD side, and then hopefully do a very focused and accelerated path forward. With the kind of results that we would be hoping to see, we would not expect that this would be a large, long trial that we'd have to resource.

Yep. So we will follow the data. And the resourcing piece we hit, I would just also mention as a reminder that we did receive fast track designation. So we think that how we interact with the agency and thinking about the next study that Lisa mentioned I think should be augmented as well. Maybe I can ask David to comment on the Oak Tree question. I might add a couple comments on top.

Thanks, Eric. So when we established the debt facility with Oak Tree now almost a year ago, We set it up in a way that it would provide access to capital for us, not just initially, but also as the company grew and as the company evolved. There's actually two $45 million tranches that are available to us. Tranche B, which is based on six-month trailing VAU sales of at least $35 million. And then tranche C, which is based on 12-month trailing sales of at least $120 million.

And I would just reiterate again, Chris, that as we think about those potential sources of capital, I kind of think about that exclusive of 155. I think that 155 will stand on its own with positive results. But we think about the oak tree somewhat differently.

Great. And if I could just ask a follow-up on 155 amongst the different paths. Is there one that scientifically you think you have the highest probability of success, or at least you have a hypothesis that would be the case? And then is there one that maybe from a regulatory progress standpoint might be a shorter duration, more sort of focused, concise, efficient from a cost standpoint path? I ask those two questions in that way because hopefully they're related, but may not be the same. And again, looking for your perspective.

No, it's a great – thanks for the question. Maybe I'll ask Matt to start, and I might suggest that we start with the first cohort data that we saw, which is really encouraging to us, and then maybe Lisa can comment on her perspective as well as the regulatory landscape.

All right. So, Chris, as a reminder, SEER-155 is really designed to target two specific areas. One is the domination of pathogens and the incidence of that in the gastrointestinal tract, particularly of enterococcus and a couple enterobacteraceae species that are particularly problematic in this patient population. And the second is to improve immune tolerance in the gastrointestinal tract to have an impact on graft versus host disease, particularly in the GI where it's most prominent in these particular patients. There is a strong literature and a deep literature that connects in particular this disruption of the microbiome and that increased incidence in pathogen domination to these various downstream clinical sequelae that we're looking at that Lisa talked about earlier, enteric infections, associated bloodstream infections, and in particularly more severe forms of graft-versus-host disease. So we believe actually both endpoints in terms of thinking about infections and the various ways we're looking at that as well as graft-versus-host disease are very well founded and we have substantial preclinical and clinical data that support our drugs can have an impact there. And I think most significantly is the cohort one data that we released last year where we saw a substantial reduction in that incidence of pathogen domination in the gastrointestinal tract relative to control core. Remember, we saw a single patient having one of these pathogen overgrowth events, where we would have expected that to be substantially higher, on the order of about 60-plus percent of patients having such. So with that, I'll turn it over to Lisa.

Sure. So I would just say that both areas, the GVHD as well as the infection protection area, huge interest to both the medical community and the regulators. GVHD, we now have a guidance from the regulatory folks at FDA, so we know what they would want there. I think the infection protection side has numerous programs coming out of the agency to encourage development work there. It obviously is adjacent to the C. diff area in terms of our results and our ability to show results there. And we could imagine a number of endpoints lining up from very high frequency events such as neutropenia and fever and all the way down to the incidence of particular infections such as the GI tract. All of those lining up would make a very powerful story. And the agency has talked about that before with regard to primary and secondary endpoints lining up and the strength that that gives an approach.

Great. I appreciate the additional thoughts.

See, I have a little bit of a preference.

Yeah, no, that comes through. Thank you so much.

Thanks for the question, Chris.

And we will take our final question from Kay Nakai with Chardon. Your line is open.

Yes, thank you. So having implemented the headcount reduction late last year, to what extent, and again, I know you're very focused on the launch of VOWS, but to what extent, if any, at this point, do you feel like the current headcount and operating plan is in any way constraining what you'd like to do on the marketing side for VOWS? Thanks.

Yeah, good morning, and thanks for the question. I would say that our headcount reductions constrain a number of things, in particular on the R&D side of our portfolio. But from a marketing investment, we work with Nestle. We have contractual parameters by which the budget is set and executed against. So we don't believe... the headcount reduction has an impact on the investment to support the VAS launch.

Okay. Thanks. Sure.

And, ladies and gentlemen, there are no further questions at this time, so I will now turn the call back to Mr. Eric Schaaf for closing remarks.

Thank you, and thanks to everyone for joining us this morning. We look forward to keeping you updated on our progress. Hope you have a great morning, great day, and a great week. We'll talk soon. Thank you.

And ladies and gentlemen, this concludes today's call and we thank you for your participation. You may now disconnect. Thank you. Thank you. Thank you. Thank you. Thank you. Ladies and gentlemen, good morning. My name is Abby and I will be your conference operator today. At this time, I would like to welcome everyone to the Ceres Therapeutics fourth quarter 2023 earnings conference call. Today's conference is being recorded and 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 that time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one a second time. Thank you. And I will now turn the conference over to Rob Windsor of Investor Relations. You may begin.

Thank you for the morning. Our press release for the company's fourth quarter 2023 financial results 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. I'd like to remind you that we'll be making forward-looking statements including the availability of cash to fund operations, the potential sales for Vaust including our ability to achieve sales targets and milestones, the timing and results of clinical studies 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 have to 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 Chief Executive Officer, Dr. Terry Young, Chief Commercial and Strategy Officer, Dr. Lisa Von Mulkey, Chief Medical Officer, and David Arkwitz, Chief Financial Officer. In addition, Dr. Matthew Henn, Chief Scientific Officer, and Dr. Dave Egge, Chief Technology Officer, will also be available to address questions. With that, I'll pass it over to Eric.

Thank you, Rob, and good morning, everyone. 2023 was an historic year for Ceres and an inflection point for our company and for patients. With the approval and launch of Voust, we brought to market our first-in-class oral microbiome therapeutic for patients with recurrent C. diff infection. We are proud of the impact Voust is having on patients, their families, and the entire recurrent C. diff community. As we enter 2024, our top priorities remain, first, delivering vows to patients, and second, advancing the potential of microbiome therapeutics more broadly, including with our SEER 155 Phase 1B readout in alloHSAT patients expected in Q3 of this year. Everything we do at CERES has been and always will be driven by a desire to support patients with significant unmet medical needs. It is the hope and resilience of each patient and their families that inspires us, and drives us to fulfill our mission. Voust is a perfect example of this. In Voust, we have developed an incredible and unique option for patients who battle recurrency disinfection, one with a strong efficacy and safety profile, as well as a convenient oral route of administration. In a particularly complex disease where historically innovation has been difficult, today Voust is changing lives. The US launch of Vaust has exceeded our expectations. In partnership with Nestle Health Science, we are pleased with the broad patient access received thus far, with more patients gaining access to Vaust than expected. The hospital team continues its efforts to enhance hospital outflow, which we expect will continue to bear fruit into 2024. We are also seeing continued strong demand from a broad set of healthcare practitioners and across the recurrent C. diff patient pool, including utilization in patients at their first recurrence. Terry will cover our commercial metrics in more detail shortly. I am extremely proud that we achieved over 2,000 VOWS patient starts in 2023 following our launch in June. We continue to see substantial opportunity for growth given the broad label and the robust clinical profile of Voust, which makes it an ideal choice for so many of the estimated 156,000 cases of recurrent CDI in the U.S. each year. I would like to thank the team at Ceres and Nestle for successfully executing our launch strategy together, collaborating with focus and urgency on behalf of our patients and their families. We look forward to seeing continued growth of Voust utilization in 2024, and expect this positive trend to continue as patient outcomes on VAUST are more broadly recognized. We are excited by the potential of VAUST to become the standard of care for preventing further C. diff. recurrences. Building off our strong proof of concept with VAUST, we were excited to announce in December receipt of fast-track designation for the 0155 program with a cohort two data readout anticipated in the third quarter of this year. We believe positive data from this readout would further validate the potential of our platform in infections, including in indications such as chronic liver disease, cancer neutropenia, solid organ transplant, and AMR infections more broadly in settings of high risk, such as intensive care units. Last year, we made the difficult decision to restructure the company and focus on Voust and Serum 155. This was an extremely difficult decision but a necessary one for positioning Ceres optimally for the future. David will touch upon this later in the call, but financial discipline is at the forefront of Ceres' priorities in 2024 and beyond. We will continue to evaluate all options to strengthen our balance sheet. As we do so, we believe we will be well positioned to create value for our shareholders and deliver our mission for patients now and in the future. Recently, we announced the appointment of Morella Thorell as Executive Vice President and Chief Financial Officer of Ceres following David's retirement. We welcome Morella and look forward to benefiting from her extensive strategy, corporate finance, and operational experience. I would also like to thank David for his leadership and significant contributions over the past three years, and we wish him the very best in retirement. With the continued success of the VEST launch and the clinical readout from CSER 155 later this year, we look forward to 2024 as a year that will further validate CSER's platform and the promise in microbiome therapeutics. I would like to now pass the call over to Teri to cover the significant progress we've made bringing VEST to patients.

Thank you, Eric. I'm pleased to report that along with our collaborators at Nestle Health Science, We continued to make significant progress on our launch priorities in the fourth quarter, building upon earlier momentum observed with the VALS launch. As you'll recall, our four focus areas are scaling HCP education efforts, creating a positive customer experience, establishing payer coverage, and optimizing hospital outflow. I'll now provide an update on each of these. Our HCP education efforts emphasize the importance of microbiome restoration and recurrent CDI and the unprecedented efficacy and safety profile of valves. We have made significant progress in this area supported by the promotional efforts of the Nestle field teams. As a result, demand continued to grow in the fourth quarter as reported to us by Nestle Health Science. In total, between our June launch and year end, we received 2,833 completed prescription enrollment forms for Vaust, including 1,322 in the fourth quarter alone. Of the total enrollments last year, 2015 culminated in new patient starts, including 1,082 in the fourth quarter alone. We received prescription enrollment forms from 1,330 unique prescribers between approval and year end, nearly doubling the number of prescribers versus what we saw at the end of Q3. Approximately 65% of these prescribers of VALS were from gastroenterology, with the remainder from other specialties. Of these 1,330 HCPs who prescribed VALS, 340 of them prescribed VALS to more than one patient. Although, as expected, the majority of 2023 utilization for VALS was in the multiply recurrent patient group, we continue to see use in patients with their first recurrence. We expect this to continue to grow over time as HCPs gain experience with an entirely new modality and develop an understanding of the foundational and distinct role that VALS plays in preventing recurrence. We recently completed a round of market research with HCPs who have used VALS. Findings from that research support that HCPs remain highly receptive to the profile of VALS and users have had a positive experience obtaining patient access supported by the Nestle Field Teams and the VALS Voyage Patient Hub. These encouraging results align with our view that VALS can become a foundational treatment for recurrent CDI and a highly significant commercial opportunity over time. Providing a positive experience for patients and providers is our second launch priority. Our VALS Voyage Hub continued to increase its successful conversion of enrollment to new patient starts in Q4. In terms of free drug utilization, approximately 46% of the 2015 new patient starts in 2023 were dispensed via our free drug program. In the fourth quarter specifically, That percentage was 44%, down from the 48% we reported for Q3. As a reminder, the use of free drug that we are seeing is mostly due to patient affordability challenges with co-pays or other cost sharing requirements after the prescription was approved by their insurer. We believe these programs are an important investment to support future demand across the broad RCDI patient population and the need for these programs is likely to decline as the Inflation Reduction Act provisions governing Medicare Part D benefit design and specifically patient cost sharing requirements come into effect over the next year. Our third focus area is engaging payers to insurer access and to date we have been pleased with the broad patient access we are seeing with the vast majority of patients able to gain access to VALS through their insurer. As of year end, we had received coverage for VALS across approximately 80% of commercial and 54% of Medicare Part D lives and estimate that the remaining plans will issue coverage policies in the coming quarters. Through year end, we saw 54% of our 2015 new patient starts reimbursed through the patient's drug benefit. Our gross to net rate remains modest with minimal discretionary rebates at the stage of the launch David will say more about our gross to net rates momentarily. In summary, the vast majority of patients who are prescribed VALS are able to obtain approval for the product either through the medical exception process prior to a policy being issued or via the prior authorization or appeals process. As first recurrent demand for VALS builds, we will continue to work with prominent payers to ensure that we preserve the broad patient access to VALS that we are currently observing. Finally, the hospital selling team continues its efforts to enhance hospital outflow, and we believe these efforts will accelerate demand in 2024. As a result of this team's efforts, we are starting to see valves added to discharge protocols at some of the large institutions, as well as added to inpatient formularies. Scaling these efforts are critical to ensuring structural modifications to how RCDI patients are discharged. Education of hospital-based HCPs, and development of protocols for RCDI that can include VALS will enable more consistent consideration of VALS as patients flow from the inpatient to the outpatient setting. These 2023 results since the launch of VALS in June show the strong start of a significant opportunity to change the treatment paradigm across the entire RCDI patient pool. In fact, our results exceeded our expectations across multiple dimensions. We, along with our collaborators at Nestle Health Science, will continue our focus on HCP education, customer experience, payer coverage, and hospital outflow, and expect to see continued acceleration of demand and progress on our key priorities as we move through 2024. As a result, we have confidence that we will ultimately achieve our goal of VALS becoming a foundational therapy for our CDI, potentially reaching or surpassing the highest sales-based milestone threshold in the 2021 Nestle co-commercialization agreement of $750 million. I would now like to pass the call over to Lisa to give more details about SEER 155 and our ongoing clinical trial.

Thank you, Teri. As a reminder, SEER 155 is a cultivated microbiome therapeutic candidate that is designed to prevent enteric infections, including those that may harbor antibiotic resistance, and to reduce the incidence of graft versus host disease in patients undergoing hematopoietic stem cell transplantation. The peer-reviewed literature supports a strong connection between a disrupted GI microbiome and pathogen domination in the GI tract with the endpoints of infection, graft versus host disease, and mortality in patients undergoing alloHSCT. Last year, we reported promising phase 1B cohort 1 clinical data, with SIR 155 being well tolerated in highly immunocompromised HSCT patients. Our data indicated that only a single patient had enteric pathogen domination within 30 days following stem cell transplant, which was a markedly lower incidence than that observed in a large reference cohort of patients. Enrollment is ongoing in Cohort 2, which incorporates a randomized, double-blinded, placebo-controlled design to further evaluate safety and engraftment, as well as clinical outcomes. This portion of the study will enroll approximately 50 subjects administered either SIR 155 or placebo at a one-to-one ratio, and we anticipate obtaining Cohort 2 study data in Q3 of this year. In addition to continued evaluation of the safety profile and drug pharmacology, outcomes assessed will be the ability of SEER 155 to decrease rates of pathogen domination, grade 3 or 4 acute GVHD, and the incidence of GI and related bloodstream infections. We also will assess the ability of SEER 155 to decrease rates of fever during neutropenia and the initiation of attendant antibiotic therapy. We believe positive data from this readout would further validate the promise of this novel therapeutic modality in addressing serious infections in medically vulnerable populations, including patients with chronic liver disease, cancer neutropenia, and solid organ transplant. We also believe that this approach could impact the problem of antimicrobial resistance more broadly in settings of high risk, such as intensive care units. These additional opportunities have the potential to extend the utility of SEER 155 and our preclinical stage pipeline, and to establish a new approach in protecting immunocompromised patients from life-threatening infections and related clinical events. With that, I'll turn the call over to David for an update on financials.

Thanks, Lisa, and good morning. I'd like to discuss our financial performance for the fourth quarter, starting with Vaust. Let me first remind everyone that Ceres does not recognize Vaust Net Sales and its financial statements, but instead we share equally with Nestle the commercial profits and losses, and we record our share in collaboration profit and loss sharing related parties. Voust profits and losses are determined based on Voust net sales, cost of goods sold, and sales and marketing expenses. Consistent with our pre-release in January, net sales of Voust for the fourth quarter were 10.4 million and based on 673 units of Voust sold during the period to specialty pharmacies and distributors. The net sales reflect estimated gross net reductions of approximately 11%. We estimate that at the end of last year, there was approximately two weeks of vouched inventory in the channel at specialty pharmacies. Ceres supplies vouched inventory to Nestle, and we received payments from Nestle related to their vouched supply purchases to meet market demand. During the fourth quarter, Nestle purchased approximately 9 million of vouched supply from us, and we received approximately 17 million in payments from Nestle related to prior quarter purchases. The total VAUS loss in the fourth quarter was 20.5 million. Our share of that was 10.3 million. The fourth quarter VAUS collaboration expenses, meaning COGS and sales and marketing expenses for VAUS, increased from the prior quarter. This increase was due to higher COGS given the variability of manufacturing costs for VAUS produced prior to approval as well as some prior period adjustments and higher sales and marketing expenses due to increased free goods and the initiation and ramp up of some key marketing activities. For the fourth quarter, we also recognized as collaboration profit or loss sharing related party approximately 14 million of profit on the transfer of BAUST inventory to Nestle. This profit represents the supply price to Nestle net of the cost of the inventory for the units sold and free goods distributed by Nestle during the quarter. Because the vast majority of this vouched inventory was manufactured prior to approval, its cost was largely previously expensed, and therefore the inventory value is very low, resulting in the profit on the transfer of the vouched inventory that is close to its supply price. Over time, as the vouched preapproval inventory is consumed, the magnitude of this profit component from the transfer of inventory will diminish. Research and development expenses for the fourth quarter of 2023 were $26.8 million, reduced from $46.2 million for the same period in 2022. The year-over-year decrease in R&D expenses is primarily driven by BAUS commercial manufacturing costs no longer being recognized in the series T&L following the product approval in April 2023, but instead capitalized and recognized on our balance sheet. General and administrative expenses for the fourth quarter of 2023 were $17.2 million, reduced from $22.4 million from the same period in 2022. As you know, in November of last year, we announced a significant corporate restructuring, which is expected to achieve $75 million to $85 million in annual cash savings in 2024. The restructuring was substantially implemented around year end last year. As a result, R&D and G&A expenses for the fourth quarter were minimally impacted by the restructuring as the reduced spend related to the restructuring started in earnest at the beginning of this year. We ended 2023 with $128 million in cash, cash equivalents and investments. And additionally, we have received net proceeds of approximately $18.5 million from the sale of common stock, under our at the market equity or ATM program thus far this year. We anticipate that our cash balance in conjunction with the anticipated savings from the restructuring and assuming continued quarter over quarter revenue growth of VAUS, the expected receipt of the 45 million tranche B under our existing term loan facility with Oak Tree will support our operations into the fourth quarter of 2024. Thank you and I now turn the call back to Eric.

Thank you, David, and thank you again for all your contributions to CERES.

We wish you well in your retirement. Before opening the call up to Q&A, I would like to express how proud I am of the team at CERES and the team at Nestle for bringing a first-in-class oral therapy to the market. 2023 was truly a trailblazing year for CERES, as well as for microbiome therapeutics. As we look forward into 2024, I'm excited about the continued success of Voust as well as the possibilities with 0155. With that, we will conclude our remarks and open the line up to questions.

Thank you. And at this time, I would like to remind everyone in order to ask a question, press star and then the number one on your telephone keypad. To withdraw your question from queue, press star one a second time. And we'll pause for just a moment to compile our Q&A rosters. And we will take our first question from Jeff Jones with Oppenheimer. Your line is open.

Thank you. Can you hear me? Yes, we can, Jeff. Good morning.

Great. Thanks, Eric. I guess, can you speak to the main drivers of what looks to be about a $170 million spend in 2024? I know we've spoken to your second manufacturing site in the past. And then any discussions you might be having with Nestle regarding the, you know, now about 10-month runway?

Yeah, maybe I can ask David to start on the parameters of investment, and then I can take the second question on our partners.

Yeah, I would just say, Jeff, at a high level, about half of that relates to R&D. and a big chunk of that R&D spend relates to really ramping up our upcoming manufacturing facility in Bactera. So we're talking about tech transfer and really driving towards approval of that facility. So that's driving a lot of the spend. Keep in mind that we are also operating, we will be operating Bactera and our existing CMO simultaneously in 2024. As we get into 2025, that will drop off. We will move to primarily one CMO, so you'll see some of that spend dissipate. And then, you know, we've got G&A expenditures to operate as a public company, as well as our share of the VAUS collaboration profit and loss.

Maybe I can just add Jeff, to the second part of the question. In general, we are highly focused on cash, on runway, on investments, and ways in which we can continue to support the company. And certainly, you saw at the end of last year action from us with the restructuring, 41% reduction in headcount. We estimate between 75, 85 million reduction in 2024 spend. So our three priorities for this year are, one, supporting the launch of Vaust, two, driving towards a 155 readout, and three, supporting the company both through augmenting the balance sheet, reducing spend, and looking actively at ways in which we can continue to support our operations. I would say from our partners' perspective, I think we both are pleased with the launch to date. We know that Vaust is important to Nestle. We know that There's real synergy between Zempep and Voust, and I won't go further than that. But, you know, obviously we care deeply about supporting the company, and we're actively working to try to put ourselves in the best position to serve patients in the long term.

Just one quick follow-up on that and the work at Baxera, which involves manufacturing batches. any chance that some of those batches can be used commercially and so that spend there actually goes to saleable product?

Yeah, I can comment on that there, but maybe we've got Dave here who can comment on the specific question around the batches.

Hi, good morning. Yes, the simple answer is that that is correct. It's anticipated that the PPQ batches for validation will be saleable and ultimately would go into commercial supply.

And I would just add, you know, we continue to make progress with Baxera in supporting continued augmentation of our capacity. And, you know, we're working with them as well to think about ways in which we can continue to support both companies and our relationship move forward.

I appreciate it. I'll jump back into the queue, guys. Thanks, Jeff.

And we will take our next question from John Newman with Canaccord. Your line is open.

Hi, guys. Good morning. Great progress. Lots of hard work on the VAUST launch. Very good. You know, obviously appreciating that you are currently very focused on commercialization of VAUST, as well as the current STEER 155 Phase 1B study, I'm just curious, Where do you see future opportunities for the drug technology itself?

Yeah, John, good morning, and thank you for the question. Maybe I can start, and I'll invite Matt, who's here to provide some commentary as well. But I think I'll start where your question led off, which is we are focused. Our priorities for 2024 are VAUST launch, 155, and supporting the financial condition of the company. We are deeply committed to the strict allocation of capital along those key priorities, and focus, I think, is the name of the game for us in the short term. That said, that doesn't mean that we also can't be excited about what could potentially be opened up with a positive readout in the 155 study, so we are particularly excited about that. Maybe I can invite Matt to comment further.

Yeah, John, I mean, thinking about that kind of potential, as Eric said, that could be opened up. Really, when you think about the past decade, there's really just been an incredible explosion in the research that's defined a really substantial role for the microbiome in both states of disease, states of health. And importantly, we've learned a tremendous amount mechanistically about how that happens. So, and this is best understood in the context of the gastrointestinal tract, which is where Ceres is focused. our research to date and our programs to date, and there's a role to be played around infections, as we've talked about, priming both the adaptive and the immune systems, general metabolism, and quite frankly, data supporting gut-brain access, et cetera. But as I think about the development of microbiome therapeutics and the various strategies that we can pursue here, I think of it similar to Gene therapy, it's early. There's really sound science. There's really a lot of potential, but translation takes some time and to succeed here, people need to build platforms that can really kind of get at the heart of scientifically and mechanistically what's happening and as well, strategically broaden our pipeline. And in short, CERES has built such a platform and we're pursuing such a pipeline strategy, right? We have the ability to go from early stage discovery all the way through to manufacturing of these therapeutics. We can interrogate at very, very high resolution microbe-microbe, microbe-host interactions that allows us to really get at specific pathways, specific targets that we can that we can target. And then our portfolio strategy has been building incrementally. So, VALS provides us very strong proof of concept around the concept to be able to address infections in the gut, and our SEER 155 program is building on that knowledge to go after a broader set of pathogens, as well as leverage critical insights we have from a preclinical and clinical standpoint on how we can have an impact on preventing infections and colonization of various pathogens. how we can actually induce immune tolerance in the gastrointestinal tract, as well as actually look at the epithelial barrier and have impacts there. So this is all built into this 155 program. And as you heard on the call today, we see that really just as the initial point for that expansion, where we can move into additional medically compromised patients where we see disrupted microbiome, people at risk for these same kinds of factors that include cancer, neutropenia, solid organ transplant, chronic liver disease, and really that problem of AMR more broadly in the ICU. So we see really broad potential, and we're excited to get to the next point to sort of enable us to be able to pursue that. But right now, we're focused on Foust and our 155 program.

Okay, great. Thank you. Thanks for the question, John.

And we will take our next question from Tess Romero with J.P. Morgan. Your line is open.

Hello, good morning, guys. Thanks so much for taking our question.

So how should we think about the sales trajectory in 2024 for Voused? And specifically, what is the right way to forecast percent of free drugs over the course of 2024, given the patient affordability challenges you cited? And then the second question is, can you clarify what you mean by the strengthened promotional campaigns and expanded reach of digital promotion by Nestle and what this means with respect to expected pull through to the launch? Thanks.

Yeah, Tess, thanks for the questions and good morning. Let me invite Terry to comment on both questions. I would just start by saying Terry spent most of last week with the Nestle commercial group and leadership. So I think it's a good time to ask that question and and provide some visibility as to how we look at 2024 and the trends that are important.

Yeah, so in 2024, we're obviously, as with any launch, looking for continued growth, breadth and depth of prescribing specifically, right? We're seeing good access. We seek to preserve that. So it's really about HCP trial and adoption in 2024. And I'll touch on pre-drug last test. Digital promotion is actually a key tactic that it's important for a brand to leverage after you've educated your top prescribers and KOLs. So we've spent with Nestle the first months after the launch making sure that we had deep conversations, deep education efforts with the top prescribers, activating the high volume prescribers. And from there, we're really seeking to enhance breadth of trial. And so you can do that leveraging the Salesforce that we have, but we really aim to go broader than that. And that's the role of digital promotion. So you tend to scale that anywhere from four to six months after approval and launch. And so that's what we've done. So we had a new campaign that launched and was rolled out to the representatives in October of last year, right around ID week. And that campaign was significantly scaled digitally to HCPs. We also scaled patient promotion. You typically do that six months after a launch because you don't want to send activated patients into a physician and have the patient be the first source of awareness about a new product. So we want to make sure that physicians are aware of the new product before we turn patients on and send them in. So all of that is in the rearview mirror now, and it's about those campaigns delivering the additional breadth of prescribing and subsequent depth that we would expect because we know once physicians try VALST, they're having a good experience, and they're willing to try it on additional patients in their practice, and we're seeing that in the results. So we're very happy about, you know, scaling that promotion and look forward to the additional growth that we'll get this year as a result of it. Switching to free drug, I mentioned that we saw the rate come down in Q4 from Q3, right? But we've got three-quarters now in sort of the mid-40s. So, you know, in terms of forecasting, those are the data points that we have. I think we've got 46, 48, and 44 in the three different quarters in 2023. We have said and I have said that we expect the utilization of these programs to go down. The voucher program will go down as we get policies on board. So you could imagine we might see some declines this year as payer policies are issued for the majority of the population. But specifically in 2025, with the IRA provisions going into effect, the patient assistance program, the more traditional PAP that we have that's income qualified in Medicare Part D patients, that's where we're seeing the majority of the utilization, that should really decline in 2025. So that's sort of the data points that we have and the knowledge that we have around patient assistance.

Thanks for the question.

Thank you. And we will take our next question from Peyton Bonsack with TD Cowan. Your line is open.

Hey, good morning, guys, and thanks for taking our questions. I guess to kind of build up on the previous question talking about launch trajectory, I was wondering if you could give us a little more detail about the potential penetration in the first RCBI population, and are there any specific strategies that you guys can do to kind of build further into that population, or is it just mostly a position education effort? And then I have a call up.

Sure. Peyton, why don't I give the first one to Terry?

Sure, so absolutely. The strategy that we're taking is to definitely accelerate utilization into the earlier lines of therapy within our CVI. So there are a number of ways to do that. One is achieving breadth, and I went into some depth about the breadth there with Tessa a minute ago. But digital promotion is really a way that you can reach deeper into the prescriber base, even into primary care where a lot, not a lot, but many of the first recurrent patients are treated. So the breadth of prescribing, the breadth of promotion, the breadth of awareness, is really important to achieve and that should go a long way toward unlocking additional use in that population. But we do see that our core set of prescribers actually see and are choosing VALST for these patients. And as they see VALST work, they see that it's easy to use, they will broaden their use. They told us that they would do that before launch. We're already seeing that with the depth and the repeat prescribing that we're observing and observed in 2023. So it's continuing to have the sales representatives on the Nestle side encourage their physicians to move the product earlier based on the amazing results that they're seeing in the patients that they initially chose. So it's a mixed bag of tactics, but we're very focused there with Nestle this year.

Positive experience can have a cascading effect.

Absolutely. Big accelerator.

Great. I guess you kind of actually touched on my second question, which was, you know, are you really seeing a lot of these first-order CDI patients that you have been seeing treated? Are these largely coming from GIs or your, like, targeted group of high prescribers? Are these from, like, people that are maybe not as high prescribing or principal care providers or infectious disease docs? And any additional details you can get on that would be much appreciated.

Yeah, it's

It's actually been one of the most interesting aspects of the launch and one way that the launch has exceeded our expectations is the breadth of use that we're seeing across physicians, across physicians the field's representatives are calling on, also physicians that they're not. And we're seeing within the physician user pool a large variety of where physicians are choosing to use it first. So we're not really seeing a pattern, interestingly, which I think is highly encouraging for the launch. Every physician is basically choosing the patient that they think is at risk based on the patient that happens to be in front of them in their office at the moment. And, you know, we are seeing the utilization in first recurrence as well as in multiple recurrence. So we feel good about the patterns that we are seeing and that there is not a pattern other than the doctors choosing a high-risk patient, irrespective of number of recurrences.

Great. Thanks for the additional color. Yeah, thank you for the additional color and for letting me ask the follow-up.

Thanks, Peyton. Thanks for the question.

And we will take our next question from Chris Shiwatani with Goldman Sachs. Your line is open.

Great. Good morning. I wanted to ask about SEER 155 and how we should be thinking about the decision tree that you'll have when the data is reported in the third quarter. In particular, when you think about the kind of scale and the budget that would be required to further advance in the event of positive data. How are you thinking about your capacity to fund this? Is this something where you're currently contemplating potential partnerships? And then secondly, I think you have access to a trosh of a loan from Oak Tree. Can you help us understand any of the mechanics that would be involved so that we can understand how that might be a lever to also help support financing of continued success with SEER 155 if positive data comes in the third quarter? Thank you.

Chris, good morning, and thanks for the two questions. What I'd like to do is maybe invite Lisa to comment a little bit on what we are expecting in the 155 readout or what we hope for. I will say, as it relates to resourcing, Chris, we said at the time of the restriction last year was that we would pursue 155 to the clinical readout with both the clinical and microbiome analysis that comes with it. but that we were gaining investment beyond that to the readout itself. So our expectation is that 155 will basically stand on its own. If it's successful, we think there are multiple ways in which we can support it, and it could bring additional resources into the company. But if it's not, then we're not going to pursue it without being able to fund it, obviously. So maybe I can ask Lisa to comment on that, and then David and I can take a question on O3.

Yeah, just a reminder that this study offers us the possibility to go in a number of different directions depending on the results. We could have a play in acute GVHD as well as on the infection side where we think there are a number of different endpoints that could show us a way forward. And so we'd be looking to most likely choose a particular route, either the infection side or the acute GVHD side, and then hopefully do a very focused and accelerated path forward. With the kind of results that we would be hoping to see, we would not expect that this would be a large, long trial that we'd have to resource.

Yep. So we will follow the data. And the resourcing piece we hit, I would just also mention as a reminder that we did receive fast track designation. So we think that how we interact with the agency and thinking about the next study that Lisa mentioned, I think should be augmented as well. Maybe I can ask David to comment on the Oak Tree question. I might add a couple comments on top.

Thanks, Eric. So when we established the debt facility with Oak Tree, now almost a year ago, We set it up in a way that it would provide access to capital for us, not just initially, but also as the company grew and as the company evolved. There's actually two $45 million tranches that are available to us. Tranche B, which is based on six-month trailing VAU sales of at least $35 million. And then tranche C, which is based on 12-month trailing sales of at least $120 million.

And I would just reiterate again, Chris, that as we think about those potential sources of capital, I kind of think about that exclusive of 155. I think that 155 will stand on its own with positive results. But we think about the O-Tree somewhat differently.

Great. And if I could just ask a follow-up on 155 amongst the different paths. Is there one that scientifically you think you have the highest probability of success, or at least you have a hypothesis that would be the case? And then is there one that maybe from a regulatory progress standpoint might be a shorter duration, more sort of focused, concise, efficient from a cost standpoint path? I ask those two questions in that way because hopefully they're related, but may not be the same. And again, looking for your perspective.

No, it's a great, thanks for the question. Maybe I'll ask Matt to start, and I might suggest that we start with the first cohort data that we saw, which is really encouraging to us, and then maybe Lisa can comment on her perspective as well as the regulatory landscape.

All right. So, Chris, as a reminder, SEER-155 is really designed to target two specific areas. One is the domination of pathogens and the incidence of that in the gastrointestinal tract, particularly of enterococcus and a couple enterobacteraceae species that are particularly problematic in this patient population. And the second is to improve immune tolerance in the gastrointestinal tract to have an impact on graft versus host disease, particularly in the GI where it's most prominent in these particular patients. There is a strong literature and a deep literature that connects in particular this disruption of the microbiome and that increased incidence in pathogen domination to these various downstream clinical sequelae that we're looking at that Lisa talked about earlier, enteric infections, associated bloodstream infections, and in particularly more severe forms of graft-versus-host disease. So we believe actually both endpoints in terms of thinking about infections and the various ways we're looking at that as well as graft-versus-host disease are very well founded and we have substantial preclinical and clinical data that support our drugs can have an impact there. And I think most significantly is the cohort one data that we released last year where we saw a substantial reduction in that incidence of pathogen domination in the gastrointestinal tract relative to control core. Remember, we saw a single patient having one of these pathogen overgrowth events. where we would have expected that to be substantially higher, on the order of about 60-plus percent of patients having such. So with that, I'll turn it over to Lisa.

Sure. So I would just say that both areas, the GVHD as well as the infection protection area, huge interest to both the medical community and the regulators. GVHD, we now have a guidance from the regulatory folks at FDA. we know what they would want there. I think the infection protection side has numerous programs coming out of the agency to encourage development work there. It obviously is adjacent to the C. diff area in terms of our results and our ability to show results there. And we could imagine a number of endpoints lining up from very high frequency events such as neutropenia and fever and all the way down to the incidence of particular infections such as the GI tract. All of those lining up would make a very powerful story and the agency has talked about that before with regard to primary and secondary endpoints lining up and the strength that that gives an approach.

Great, appreciate the additional thoughts.

See, I have a little bit of a preference.

Yeah, no, that comes through. Thank you so much.

Thanks for the question.

And we will take our final question from Kay Nakai with Chardon. Your line is open.

Yes, thank you. So having implemented the headcount reduction late last year, To what extent, and again, I know you're very focused on the launch of VOWS, but to what extent, if any, at this point, do you feel like the current headcount and operating plan is in any way constraining what you'd like to do on the marketing side for VOWS? Thanks.

Yeah, good morning, and thanks for the question. I would say that our headcount reductions constrain a number of things, in particular on the R&D side of our portfolio. But from a marketing investment, we work with Nestle. We have contractual parameters by which the budget is set and executed against. So we don't believe the headcount reduction has an impact on the investment to support the VAS launch.

Okay. Thanks.

And ladies and gentlemen, there are no further questions at this time, so I will now turn the call back to Mr. Eric Schaaf for closing remarks.

Thank you, and thanks to everyone for joining us this morning. We look forward to keeping you updated on our progress. Hope you have a great morning, great day, and a great week. We'll talk soon. Thank you.

And ladies and gentlemen, this concludes today's call, and we thank you for your participation. You may now disconnect.