Q4 2022 Seres Therapeutics Inc Earnings Call

Speaker 1: The.

Speaker 1: I.

Speaker 2: on mute to prevent any background noise. After the speaker's remarks there will be a question and answer session. If you'd like to ask a question during this time simply press star followed by the number one on your telephone keypad.

Speaker 2: If you'd like to withdraw your question, again, press star 1. Thank you. I will now turn the call over to Dr. Carlo Tanzi of Investor Relations. Dr. Carlo Tanzi, please go ahead.

Speaker 3: Thank you and good morning. Our press release for the company's fourth quarter 2022 financial results and a business update 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 potential approval and launch.

Speaker 3: of investigational microbiome therapeutics CIR-109 and its status as a first-in-class oral therapeutic, the anticipated indication for CIR-109, the availability of product supply, the potential for microbiome therapeutics to protect against infection, the use of cash to fund operations, and the use of CIR-109.

Speaker 3: 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.

Speaker 3: We may update these statements in the future, but we're disclaiming the obligation to do so. On today's call, with prepared remarks, I'm joined by Eric Schaff, SERS President and CEO , David Arkowitz, Chief Financial Officer, Dr. Lisa Von Mulkey, Chief Medical Officer, and Dr. Terry Young, Chief Commercial and Strategy Officer.

Speaker 3: During the Q&A section, Dr. Dave Eggie, Chief Technology Officer, and Dr. Matthew Henn, Scientific Officer.

Speaker 3: will also be available to answer questions. With that, I'll pass the call to Eric. Thank you, Carlo, and good morning, everyone.

Speaker 2: CERES continues to make excellent progress advancing our microbiome therapeutics pipeline. I'll begin with CERE 109.

Speaker 2: We are highly focused on securing FDA approval for CIR-109, our lead microbiome therapeutic candidate for recurrent C. difficile infection, and the FDA's PDUFA action date for this program is April 26.

Speaker 2: As we approach the FDA's expected decision, we are also continuing our work to execute a successful commercial launch pending approval.

Speaker 2: With CIR-109, we believe we may have an opportunity to transform the management of recurrent C. difficile infection and provide a meaningful new therapeutic option for patients.

Speaker 2: Our optimism is supported by compelling data from our phase three studies.

Speaker 2: This includes data showing high levels of durable efficacy and a well-tolerated safety profile.

Speaker 2: This clinical profile is accompanied by a patient-friendly oral root of administration.

Speaker 2: Furthermore, we believe that our proprietary pathogen inactivation process may provide C-109 with important safety advantages.

Speaker 2: In addition to the impact that CIR-109 may have for a current CDI, the approval of this investigational therapeutic would also be significant as this could be the first ever oral microbiome therapeutic approved by the FDA.

Speaker 2: Ser 109 could represent the beginning of a broader application of microbiome-based approaches across multiple medical conditions, and we believe that series is well positioned to continue to lead this pioneering effort.

Speaker 2: As we approach the FDA-Pedufe Decision date of April 26th, our interactions with the agency continue to be highly active and we believe constructive.

Speaker 2: We remain on track with a priority review process and we are optimistic about the pending approval decision.

Speaker 2: Our organization and our collaborator, Nestle Health Science, continue to make excellent progress preparing for the CIR-109 commercial launch pending a favorable approval decision.

Speaker 2: We expect to be prepared to commercially launch in the weeks following an approval.

Speaker 2: In a few minutes, Terry will provide more detail on commercial readiness activities.

Speaker 2: As we prepare for a potential CER 109 launch, we have also continued to build our CER 109 drug supply while enhancing future supply capacity.

Speaker 2: Our goal has been to create supply to meet zero one and one market demand in all anticipated uptake scenarios. And we believe we are on track to achieve this goal.

Speaker 2: In addition, we are focused on ensuring that we have sufficient supply in the year's post launch.

Speaker 2: In late 2021, we entered into a collaboration with Baxera designed to augment our drug supply capabilities as well as to provide another layer of redundancy.

Speaker 2: I'm pleased to report that our plan in working with BAC-CERA is proceeding well and on track.

Speaker 2: Our CMC teams are working together in an integrated manner and we anticipate that Baxero will be ready to begin to produce commercial drug product in 2024 for release in 2025 as the expected number of patients treated with CER-109 expands.

Speaker 2: I'll now pass the call over to Lisa.

Speaker 4: Thanks Eric.

Speaker 4: We are now within two months of CER 109's PDUFA date, and as you might expect, this is a busy period for the organization as we approach potential approval decision.

Speaker 4: During the last several months, we have also continued to publish SEER 109 clinical data, and alongside our collaborator, Nestle Health Science, we have continued to make excellent progress advancing appropriate educational efforts with physicians.

Speaker 4: I'd like to highlight several recent CIR 109 publications that we believe further illustrate the efficacy and safety profile observed in clinical trials.

Speaker 4: We believe that CIR 109 is differentiated not only by the magnitude of the efficacy observed but also by the duration of activity.

Speaker 4: In October , additional data from the Phase III EcoSpore III study were published in the Journal of the American Medical Association, and we presented these results at the ID Week at American College of Gastroenterology.

Speaker 4: 2022 annual meetings. These data showed that prevention of recurrent CDI was apparent as early as two weeks post-administration.

Speaker 4: and that CIR109 activity was durable, with recurrence rates continuing to be markedly different from placebo at 24 weeks.

Speaker 4: We believe that the efficacy results observed, including the durability data, are clearly differentiated compared to other reported study results and highlight the substantial clinical benefit that CIR-109 could provide if approved.

Speaker 4: Last month, we announced the publication of two noteworthy CIR 109 papers in JAMA Network Open.

Speaker 4: One summarized the results of the CIR109 Phase III ECOSPORE IV study.

Speaker 4: EcoSpore 4 was designed to provide additional safety information in adults with recurrent CDI who were treated with standard of care antibiotics and then CIR-109.

Speaker 4: This was a 24-week study that included 263 enrolled subjects with a history of reference EDI, including individuals that had experienced only a single recurrence of CDI. Overall, the safety profile through 24 weeks of follow-up indicated that CIR109 was well tolerated.

Speaker 4: This was consistent with the safety profile observed in the placebo-controlled ECOSPOR3 study.

Speaker 4: We also evaluated CDI recurrence rates in EcoSpore4.

Speaker 4: At the eight-week endpoint, 91.3% of patients remained free of recurrence.

Speaker 4: Supporting positive data from the CER109 placebo controlled EcoSport 3 study.

Speaker 4: Our data also showed that the response was durable out to the final 24-week endpoint.

Speaker 4: Importantly, similar results were observed in all subgroups, including those with a single recurrence of CDI.

Speaker 4: We believe the ECOSP4 data provide additional evidence indicating that CIR109 may provide clinical benefit to a broad population of recurrent CDI patients.

Speaker 4: Earlier this year, we also published another notable manuscript and German network open based on secondary data from the Ecospore 3 Phase 3 study, which showed that SEAR 109 Administration was associated with a rapid and steady improvement.

Speaker 4: in health-related quality of life, an important patient-reported outcome as compared to placebo.

Speaker 4: Now moving to CIR 155, which is being developed to reduce the risk of infection, including antimicrobial resistant infections and graft versus host disease in individuals receiving allogeneic stem cell transplant.

Speaker 4: Protecting vulnerable individuals from infection is an area of particular interest to CERES.

Speaker 4: And we believe that microbiome therapeutics may provide a novel approach to addressing infection with potential widespread clinical utility in medically compromised populations. The ongoing CIR 155 Phase 1B study is being conducted in individual...

Speaker 4: undergoing treatment for hematologic malignancies, such as leukemia. The study is designed to evaluate safety and drug pharmacology, including the engraftment of CIR-155 in patients' gastrointestinal tracts.

Speaker 4: In addition, data are being collected on the reduction in abundance of bacterial pathogens in the GI tract, and to evaluate clinical outcomes including rates of bloodstream infections and acute GVHD.

Speaker 4: The SIR155 Phase 1B study includes two cohorts.

Speaker 4: Cohort 1 included 13 subjects that received CIR 155 and was designed to assess safety and drug pharmacology, including assessing engraftment of drug bacteria in the GI tract.

Speaker 4: Earlier this year, we reported that the study's Data and Safety Monitoring Board had reviewed available Cohort 1 clinical data in a pre-planned analysis and had cleared advancement to the second study cohort. We are now enrolling subjects in Cohort 2.

Speaker 4: In parallel, we continue to analyze the pharmacology data from Cohort 1.

Speaker 4: and we expect to report preliminary safety and pharmacology data in May 2023.

Speaker 4: With these pending data, we hope to observe clear evidence that 0155 bacteria have successfully engrafted.

Speaker 4: and that these bacteria are resulting in the intended pharmacological effects.

Speaker 4: We look forward to continuing to provide updates as we execute this important study.

Speaker 4: And with that, I will now pass the call to Terri.

Speaker 5: Thanks Lisa. The commercial organization is energized and excited about the upcoming potential approval of CIR-109. We have been working closely with our collaborators at Nestle Health Science as an integrated team and are now nearing full launch readiness.

Speaker 5: We believe the C109 market opportunity is substantial. In fact, we estimate that there will be approximately 156,000 cases of recurrent CDI in the U.S. this year alone.

Speaker 5: This disease is significantly debilitating and isolating for patients, with mortality rates estimated at over 20,000 deaths per year.

Speaker 5: Current treatment options are suboptimal and healthcare practitioners and patients are eager for better solution that can provide high levels of efficacy in a well-tolerated oral formulation.

Speaker 5: Cere1-9 represents a product profile that uniquely meets patient and prescriber needs for prevention of recurrent CDI. If approved, we believe that Cere1-9 has the potential to transform how recurrent CDI is managed, resulting in far better patient outcomes, as well as greatly reducing the burden that this disease is placing on our health care.

Speaker 5: current CDI.

Speaker 5: The series of Nestle teams have been executing on a number of pre-commercialization activities, including the market education that Lisa discussed, continued engagement with payers, and expansion of Nestle's existing field sales infrastructure.

Speaker 5: Specifically, Nestle recently hired a hospital selling team of 20 to profile the top-volume hospitals across the country during the remainder of our prelaunch phase. Post approval, this team will also cover the infectious disease specialty and we will deploy the existing 150 person gastroenterology sales force at Nestle.

Speaker 5: Finally, the Nestle Payer Field Team continues their pre-approval information exchange efforts with payers and have already engaged with payers covering more than 150 million lives.

Speaker 5: The feedback we have received so far is encouraging.

Speaker 5: Overall, I am pleased with the status of both companies' launch preparations and we stand ready to execute immediately if we receive a favorable FDA decision.

Speaker 2: With that, I'll now turn the call to David to provide an overview of our financials. Thanks, Terry. The details of our fourth quarter and four-year financials are included in the press release issue this morning, so I won't reiterate all the figures here. Here is ended the fourth quarter of 2022 with approximately 181 million in cash, cash equivalents, and marketable securities. Regarding our efforts and resources over the near term.

Speaker 2: continue to be focused on a number of critical SIR109 related activities, which include continuing to ramp up manufacturing operations for commercial supply internally and with our partner Resafarm, including building up SIR109 commercial inventory,

Speaker 2: as well as expanding longer-term SEAR 109 product supply capacity to our back-there collaboration. And in conjunction with Nestle, continuing and accelerating launch readiness activities. We also continue to invest to advance and expand our pipeline for the focus on infection protection opportunities.

Speaker 2: and further build upon and enhance our platforms and capabilities.

Speaker 2: As we have already expanded our capabilities across much of our organization, we expect our expenses leading up to the CIR 109 approval and launch to grow modestly.

Speaker 2: In summary, the company continues to be well-resourced to execute effective CIR-109 commercialization activities pending FDA approval and to drive our ongoing development and preclinical programs. We will also continue to efficiently deploy resources to advance our research platforms. I'll now turn the call back to Eric.

Speaker 2: Thank you, David. This is an exciting period for CERES as we near the potential approval of CERA 109, which would be a tremendous milestone for the company and for the entire field.

Speaker 6: we approach the PDUFA date confident in the data provided to the FDA and well prepared to effectively execute a product launch pending approval.

Speaker 6: In addition to CER109, CER10155, we are also advancing additional promising earlier stage microbiome therapeutic candidates.

Speaker 6: With these programs, we believe that there are significant opportunities to help additional, multiple, medically compromised patient groups such as those with cancer-neutrachemia, cirrhosis, and solid organ transplant patients.

Speaker 6: Over the course of the year, we look forward to providing you with progress updates on CIR-109, CIR-155, as well as our additional microbiome therapeutic programs.

Speaker 6: With that, I will conclude our prepared remarks and open the call up to questions.

Speaker 2: Certainly. At this time, if you'd like to ask a question, please press star 1 on your telephone keypad.

Speaker 6: Mark Breitenbach with Oppenheimer, your line is open. Hey, good morning, guys. Thanks for taking the questions and congrats on recent progress. Just a couple quick ones from me. First of all, can you comment on the current stockpile of SIR-109 you have available immediately?

Speaker 6: question is really just maybe aimed at David that I'm wondering in addition to the $125 million milestone that would come with potential approval in April . If you're expecting any additional development or commercial milestones.

Speaker 6: from Nestle in 2023 that we should be keeping our eyes out for. Thanks for taking the questions.

Speaker 2: Yeah, Mark, good morning and thank you for the questions. Let me start with the first one and we've got Dave Eggie on the line. I'll ask him to provide his perspective too. So in terms of stockpiling of inventory or maybe preparing for launch, what we have said is that we've been working on this process for some time. We're pleased to be taking our Phase III process to launch.

Speaker 2: and we have been preparing for a number of different launch scenarios. So, we're really pleased with where we are, and we expect to be well prepared for the approval and then for launch thereafter. In terms of the divide of in-house versus what we do with CDMO, maybe I can ask Dave to comment further on that.

Speaker 2: Thank you, Eric and Mark. Thanks for the question. As it relates to the in-house and the bacteria, it has been our strategy for quite some time that as Eric mentioned a moment ago, we are bringing our phase 3 process forward to launch. It is adequate in scale and volume to meet the near-term.

Speaker 2: forecast that we have together with Nestle and by design back there as was mentioned earlier in the call we'll start producing material ahead of the facility approval in 2024 and we anticipate an approval of for that material to reach the market in 2025. So that's augmenting capacity as a market grows as well as providing redundancy with what we have internally and

Speaker 2: upon CER 109 approval. The other cash flow that we expect relates to CER 109 commercial supply that we have been producing leading up to approval and thereafter, and we have been doing that at our cost. We will sell that inventory to Nestle.

Speaker 2: add or around approval and then thereafter they'll be kind of think about it as a steady cadence of purchases by Nestle from a supply standpoint. So that will provide an initial bolus of cash coming in and then a steady supply thereafter.

Speaker 6: All right, that's helpful. Thanks for taking the questions and congrats again.

Speaker 6: All right, that's helpful. Thanks for taking the questions in and congrats again. Thanks again, Mark.

Speaker 6: John Newman with Canaccord, your line is open. Thanks for taking my question. I just wondered if you could talk to us a little bit more about the initial launch targeting for CIR 109. I know that you've got a really interesting focus on the outpatient setting. I'm just curious if you could talk just a little bit more about the initial launch targeting for CIR 109.

Speaker 6: the types of physicians that you'll be targeting initially. Thanks. Yeah, John , let me start and then I'll ask Terry to comment. But I would say that for some time we've been doing quite a bit of research and interaction with healthcare providers. Terry and I, with our partners at Nestle, have spent quite a bit of time recently with a number of different folks.

Speaker 6: I can tell you there's a lot of excitement around the potential of SIR109. I think the idea of having a new tool to help patients in this space when it's been so long without something that is effective, that is something that has a favorable safety profile, something that is in particular oral and scalable.

Speaker 6: we can kind of hear the hunger in the voices of those treating physicians for something new. But maybe, Terry, you can comment further on that.

Speaker 5: Sure. Good morning, John . With the gastroenterology sales force that Nestle is currently deploying with one of their in-line products, we'll be leveraging that sales team to reach their existing gastroenterology targets where they already have deep, long-standing relationships.

Speaker 5: at launch will deploying that sales team. And will also be via that sales force reaching a small number of other physician extenders in those offices, NPs and PAs, for example, and other high volume physicians.

Speaker 5: So that's the gastroenterology outpatient sales force. I also mentioned that we recently stood up a hospital selling team that will be profiling in it ultimately selling to the largest institutions across the country that see the highest patient volume of recurrent CDI patients.

Speaker 5: That team will, in addition, call on infectious disease physicians because, as we know, most of those ID physicians spend the vast majority of their time within the walls of the hospital. Now, as a reminder, we're targeting the hospital not to target the inpatient business, but, as you said, rightly pointed out.

Speaker 5: rather be what I call the hospital to home segment. Patients who may begin antibiotic therapy in the hospital, who are then discharged to complete their antibiotic regimen, and then would also take CER109 on the back of the completion of that regimen, therefore in the outpatient setting. So that gives you a flavor of the type of physician.

Speaker 5: that we'll be calling on post approval. And we are finalizing our call plans currently as we approach the PDUFA date with our colleagues at Nestle Health Science. I hope that helps. Thanks, John .

Speaker 5: post approval and we are finalizing our call plans currently as we approach the PDUFA date with our colleagues at Nestle Health Science. I hope that helps. Thanks, John . Yes, thank you.

Speaker 7: Thanks for the question, John .

Speaker 6: Ted Tentoff with Piper Sandler, your line is open. Great, thanks very much. Senator, for the producer data as well. I guess my question is without an outcome.

Speaker 6: and I'm not sure that you're at this point yet, but when it comes to label discussions, how do the conversation go around first or second returns?

Speaker 6: How important do you ultimately think that's going to be to the launch and the initial success of one or none?

Speaker 6: Yeah, Ted, thanks for the question and good morning. I might ask both Terry and Lisa at the comment. I will always preface our comments with, you know, we don't speak for the EPA and nor do we just speak to the label discussion. We have said continue to believe that the right approach here is a...

Speaker 6: David can at least sit on the regulatory side, or the label side, comment on importance, and then Terry can speak from the commercial side too.

Speaker 4: No, so as Eric said, we have based our desire to have the broad label on the fact that clinicians see this as a homogeneous disease once you get into the recurrent population. But it's also based on the FDA's own guidance. If you look at the FDA's labeling guidance...

Speaker 4: They go into quite a bit of extensive detail on situations where pathophysiology is the same and risk benefit can be also then assumed to be the same as a reason for why they would deviate, if you will, from the exact details of how something was run in a trial.

Speaker 4: There was also a jamma paper.

Speaker 4: last spring actually reviewing the number of times that FDA does do that. And it is very, it's fairly common. So we feel very confident given the fact that the community, the medical community already views this as a similar situation, whether you're in first or current, second recurrence, whatever.

Speaker 4: We know that's what the pathophysiology is, and the agency has a history of looking at things with that lens. So I'll turn it to you. Yeah, let's get back to your question, which is, do we think it'll be important? And maybe Terry can comment on that.

Speaker 4: We know that's what the pathophysiology is, and the agency has a history of looking at things with that lens. So I'll turn it to you. Yeah, so let's get back to your question, which is, do we think it'll be important? And maybe Terry can comment on that. Absolutely. Wait wait wait wait.

Speaker 5: I mean, sure, the recurrent population, as Lisa said, is seen as a fairly homogeneous population. And I think the person who summarized that best with Dr. Karl Crawford in the investor event that I referenced in my prepared remarks back in December where he described this fork in the road.

Speaker 5: So, you know, it's clearly also important, you know, having the broad label and being able to serve a broad population because as you look at the epidemiology of the disease, quite a few of our patients are considered in that first recurrent pool, right? So, we're very eager to finalize our label with the FDA and...

Speaker 3: This is Stephen on for Chris. I was wondering if you could comment on what key launch metrics that you and ESSA plan to share during the early launch so that we and investors can track the launch. And also related to that, will prescription trend data be available through services like IKIVIA? Thank you. CSUS FOR Emes Analytics Intelligence

Speaker 6: Yeah, thanks for the question. I'll start, maybe Terry can add some color. We have not gotten to the point where we've disclosed what the volant metrics will be. We are in the process of working through that with our partners that Nestle. We have said, and we can reiterate that there are 156,000 cases of...

Speaker 6: with a set of parameters that we expect to provide.

Speaker 5: Yes, I think the only thing I can say to build on that is maybe to tackle your second question, which is around the availability of prescription data. We're not anticipating that that would be broadly available because we are, as I mentioned previously, going to be very careful and deliberate with our distribution partner selection. We are working with a small number.

Speaker 5: a very experienced specialty pharmacies in order to provide the best in-class patient experience when physicians and patients need to use their 109. So we really want to control that experience. And so one way to do that is by being very selected with distribution partners.

Speaker 7: Thank you very much.

Speaker 7: Thank you very much. Thank you very much. Thanks for the question.

Speaker 8: Peyton Vontak with TD Cowen, your line is open. This is Peyton, I'm for Joe. Congrats on the very productive last year and thanks for taking our questions. I was guessing just maybe the first one, how are you thinking about pricing, especially given that Ruby IOD is now available? Are you evaluating something that's comparable per course? Yeah, Peyton, good morning and thanks for the question. I'm for Joe.

Speaker 6: of root of administration. And in the recurrent seedest space, there just hasn't been the type of profile that we have with Sir 109. And as Terry and I have interacted with HCPs, I think that that resonates with us. That this is different, right? And the type of value and the type of innovation that we're delivering is not comparable to and right. And maybe Phsyll, it means that we can only contribute, pass gas between our economic return to our politicians and our political divorce karma. And thank you and if you can see that you're not an equal right that they expect is not zero, not zero, but no equal right? If you need a part day to get help, we can give a personal floor to do.

Speaker 6: standardized FMT, not antibodies, not the other types of antibiotics. It's just a different. So we are in the process of working with our partners that Nestle to...

Speaker 6: to finalize a price that is reflective of the value that we can provide, but also represents the opportunity to deliver value to the system. It patients recur. They're more likely to recur again. And if you think about the cumulative costs of recurrence upon recurrence.

Speaker 6: Now, these can be really sick patients and they can have comorbidities. So if you can stop that cycle of recurrence, you can create value for the patient, you can create value for the system. We think we can create value for shareholders. That's a win-win. So that's how we're thinking about it.

Speaker 8: Great. That's really helpful. I mean, I guess now moving on to the SARE 155 program, and we're looking forward to the data update in May. Could you maybe comment about the level of excitement and feedback for the therapy you've seen at the initial sites and in cohort one, and maybe give a range about how quickly just thinking cohort two can be enrolled based off that feedback and what you're thinking about in terms of the data.

Speaker 7: Task Four co-hosts you.

Speaker 6: Yeah, maybe I'll ask Lisa to comment on both, Peyton. I mean, we have a lot of excitement, I'll tell you. You know, there's a disproportionate amount of our time, energy, and I think yours and others focus on 109, but we think that 109 is really just the beginning of the story as it relates to the microbiome and our ability to help patients.

Speaker 6: 155 is up next. We were really pleased to clear the pre-planned DSMB at the end of the year and go to cohort 2. We were really careful and deliberate with the first cohort, knowing that this is a fundamentally more complex patient population than what we've done within the past. But we have increased the number of sites into the second cohort and we do expect to move more quickly.

Maybe you leave some comment more on the excitement within our partners on the HCP side as released to 155. Yeah. Psytment really has been very sustained. I mean, this is a big problem. Both infections and GVHD are big problems in this population. And there are no...

great options. And I think we're doing this trial on the backdrop of a time when antimicrobial resistance is also really coming to the fore as an issue for patients who need a lot of antibiotics. And that's certainly this population.

We have a lot of interest and we expect that interest to continue to fuel enrollment in cohort two. And you asked about the kinds of things we're looking for. I think some of the same things we'll be looking for in cohort one, including...

the ingrassment and function of the bacteria, pathogen reduction in the GI tract, as well as clinical sequelae, such as reduction in neutropenian fever, potential reduction in infection, and reduction in bloodstream infections in particular.

And maybe we can ask Matt just to comment. As usual, Peyton, our microbiome analyses and our clinical studies we think are incredibly important data sets. And maybe Matt can comment on how we think about the one that's coming up with 155 in the first cohort. Sure. I think Lisa hit on the key points. Sure.

From a pharmacological data perspective, we really are focused on some of the key mechanisms of action of the drug. So of course, engraphment is going to help inform our dosing strategies in this particular population. As Eric and Lisa pointed out earlier, we had a favorable report from the Data Safety Monitoring Committee with respect to cohort 1. So of course, observing drug on board and having that favorable safety.

profile will be something we'll be looking for. And then in terms of actually trying to understand the drug's pharmacology with respect to infection, we'll be looking at the reduction in bacterial pathogen. And of course that had significant meanings on a couple different fronts. One, as we reduce that abundance.

We would anticipate decreasing the likelihood of translocation events, so the bacteria moving from the gastrointestinal tract into the bloodstream to lead to bloodstream infections, as well as...

as well as the potential reduced patient-to-patient transmission. So we'll be looking at those types of factors. And of course, C-155 is a designed consortia that was optimized for a certain set of pharmacological properties that include this passage in abundance, but as well as protecting and repairing the epithelial barrier.

And so we'll be looking for those types of signatures in the data as well. Great. Thank you so much. It's super helpful and thanks for taking our questions. Thanks for the questions, please.

There are no further questions at this time, and it is now my pleasure to turn it back over to management for final remarks.

So thank you operator and thank you all for joining us this morning. We look forward to keeping you updated on our progress. Thanks again and have a great week.

This concludes today's call. We thank you for your participation. You may now disconnect.

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Thank you for holding and welcome everyone to the Series Therapeutics 4th quarter 2022 conference call. All lines have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question and answer session. Thank you for your time.

If you'd like to ask a question during this time simply press star followed by the number one on your telephone keypad. If you'd like to withdraw your question again press star one.

Thank you. I will now turn the call over to Dr. Carlos, Carlo Tanzi of Investor Relations. Dr. Carlo Tanzi, please go ahead.

Thank you and good morning. Our press release for the company's fourth quarter, 2022 financial results and a business update became available at 7 a.m. Eastern time this morning. It 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 potential approval and launch of an investigational microbiome therapeutic Tier 109 and its status as a first-in-class oral therapeutic.

The anticipated indication for C-109, the availability of products apply, the potential for microbiome therapeutics to protect against infection, the use of cash to fund operations, and other statements which are not historical facts. Actual results meet different materially. Additionally, these statements are subject to certain risks and uncertainties which are discussed under the risk factors.

David Arquitz, Chief Financial Officer, Dr. Leasevon Moky, Chief Medical Officer, and Dr. Terry Young, Chief Commercial and Strategy Officer. During the Q&A section, Dr. Dave Eggy, Chief Technology Officer, and Dr. Matthew Penn, Chief Scientific Officer.

We'll also be available to answer questions. With that, I'll have to call it to Eric. Thank you, Carlo, and good morning, everyone. Syriots continues to make excellent progress advancing our microbiome therapeutics pipeline. I'll begin with CER109. We are highly focused on securing FDA approval for CER109.

our lead microbiome therapeutic candidate for recurrent C. difficile infection, and the FDA's PDUFA action date for this program is April 26th. As we approach the FDA's expected decision, we are also continuing our work to execute a successful commercial launch pending approval.

With Sir 1-9, we believe we may have an opportunity to transform the management of recurrent C-Deficule Infection and provide a meaningful new therapeutic option for patients.

Our optimism is supported by compelling data from our Phase III studies.

This includes data showing high levels of durable efficacy in a well-tolerated safety profile. This clinical profile is accompanied by a patient-friendly oral root of administration. Furthermore, we believe that our proprietary pathogen and activation process may provide zero-109 with important safety advantages.

In addition to the impact that CIR-109 may have for a current CDI, the approval of this investigational therapeutic would also be significant as this could be the first ever oral microbiome therapeutic approved by the FDA.

CIR-109 could represent the beginning of a broader application of microbiome-based approaches across multiple medical conditions and we believe that CIRES is well positioned to continue to lead this pioneering effort.

As we approach the FDA PDUFA decision date of April 26, our interactions with the agency continue to be highly active and we believe constructive.

We remain on track with a priority review process and we are optimistic about the pending approval decision. Our organization and our collaborator, Nestle Health Science, continue to make excellent progress preparing for the Ciro-109 commercial launch pending a favorable approval decision.

We expect to be prepared to commercially launch in the weeks following an approval. In a few minutes, Terry will provide more detail on commercial readiness activities.

As we prepare for a potential CIR109 launch, we have also continued to build our CIR109 drug supply while enhancing future supply capacity. Our goal has been to create supply to meet CIR109 market demand in all anticipated uptake scenarios, and we believe we are on track to achieve this goal.

In addition, we are focused on ensuring that we have sufficient supply in the year's post launch. In late 2021, we entered into a collaboration with Baxera, designed to augment our drug supply capabilities, as well as to provide another layer of redundancy.

I'm pleased to report that our plan in working with Baxera is proceeding well and on track. Our CMC teams are working together in an integrated manner and we anticipate that Baxera will be ready to begin to produce commercial drug product in 2024 for release in 2025.

as the expected number of patients treated with CIR-109 expands. I'll now pass the call over to Lisa.

number of patients treated with ser109-X-Spans. I'll now pass the call over to Lisa. Thanks, Eric.

We are now within two months of CIR-109's PDUFA date. And as you might expect, this is a busy period for the organization as we approach potential approval decision. During the last several months, we have also continued to publish CIR-109 clinical data. And alongside our collaborator, Nestle Health Science, we have continued to make excellent progress advancing appropriate educational efforts with physicians.

I'd like to highlight several recent CR109 publications that we believe further illustrate the efficacy and safety profile observed in clinical trials.

We believe that CIR109 is differentiated not only by the magnitude of the efficacy observed, but also by the duration of activity. In October , additional data from the Phase III Ecospore III study were published in the Journal of the American Medical Association.

And we presented these results at the ID Week and American College of Gaster Entireology 2022 Annual Meetings.

These data showed that prevention of recurrent CDI was apparent as early as two weeks post-administration.

and that CER-109 activity was durable, with recurrence rates continuing to be markedly different from placebo at 24 weeks. We believe that the advocacy results observed, including the durability data, are clearly differentiated compared to other reported study results.

and highlight the substantial clinical benefit that CER109 could provide if approved. Last month, we announced the publication of two noteworthy CER109 papers in JAMA Network open.

One summarized the results of the CIR109 Phase III Ecospoir IV study. Ecospoir IV was designed to provide additional safety information in adults with recurrent CDI, who were treated with standard of care antibiotics and then CIR109.

This was a 24-week study that included 263 enrolled subjects with a history of referent EDI, including individuals that had experienced only a single recurrence of CDI. Overall, the safety profile through 24 weeks of follow-up indicated that CIR109 was well tolerated.

This was consistent with the safety profile observed in the placebo-controlled EcoSpore3 study. We also evaluated CDI recurrence rates in EcoSpore4.

At the 8-week end point, 91.3% of patients remained free of recurrence.

supporting positive data from the CIR109 placebo-controlled EcoSpore 3 study. Our data also showed that the response was durable out to the final 24-week endpoint. Importantly, similar results were observed in all subgroups.

including those with a single recurrence of CDI.

We believe the Ecospoor 4 data provide additional evidence indicating that SEAR 109 may provide clinical benefit to a broad population of recurrent CDI patients. Earlier this year we also published another notable manuscript in JAMA Network Open based on secondary data from the Ecospoor 3 Phase 3 study.

which showed that CIR109 administration was associated with a rapid and steady improvement in health-related quality of life, an important patient reported outcome as compared to placebo. Now moving to CIR155, which is being developed to reduce the risk of infection, including anti-multi-

may provide a novel approach to addressing infection with potential widespread clinical utility in medically compromised populations.

The ongoing CIR 155 Phase 1B study is being conducted in individuals undergoing treatment for hematologic malignancies, such as leukemia.

The study is designed to evaluate safety and drug pharmacology, including the engraftment of CIR-155 in patients' gastrointestinal tracts. In addition, data are being collected on the reduction in abundance of bacterial pathogens in the GI tract.

and to evaluate clinical outcomes, including rates of bloodstream infections, and acute GVHD. The CIR155 Phase 1B study includes two cohorts. Cohort 1 included 13 subjects that received CIR155 and was designed to assess safety and drug pharmacology, including assessing engraffment of drug bacteria in the GI tract.

Earlier this year, we reported that the study's data and safety monitoring board had reviewed available cohort 1 clinical data in a pre-planned analysis and had cleared advancement to the second study cohort. We are now enrolling subjects in cohort 2. We are now enrolling subjects in a pre-planned analysis and had cleared advancement to the second study cohort.

In parallel, we continue to analyze the pharmacology data from cohort 1, and we expect to report preliminary safety and pharmacology data in May 2023. With these pending data, we hope to observe clear evidence that 0155 bacteria have successfully ingrafted.

and that these bacteria are resulting in the intended pharmacological effects. We look forward to continuing to provide updates as we execute this important study. And with that, I will now pass the call to Terry.

Thanks Lisa. The commercial organization is energized and excited about the upcoming potential approval of C-109. We have been working closely with our collaborators at Nestle Health Science as an integrated team and are now nearing full launch readiness.

We believe the 0109 market opportunity is substantial. In fact, we estimate that there will be approximately 156,000 cases of recurrent CDI in the US this year alone. This disease is significantly debilitating and isolating for patients with mortality rates estimated at over 20,000 deaths per year.

Current treatment options are suboptimal and healthcare practitioners and patients are eager for better solution that can provide high level de-vefficacy in a well-tolerated oral formulation.

C-109 represents a product profile that uniquely meets patient and prescriber needs for prevention of recurrent CDI. If approved, we believe that C-109 has the potential to transform how recurrent CDI is managed, resulting in far better patient outcomes.

as well as greatly reducing the burden that this disease is placing on our healthcare system. Our preparations for the potential C-109 commercial launch are proceeding according to plan. I'll also remind you that last December , we held a webcast investor event where we discussed our launch plans in some detail and the substantial commercial opportunity in recurrent CDI.

The series of Nestle teams have been executing on a number of pre-commercialization activities, including the market education that Lisa discussed, continued engagement with payers, and expansion of Nestle's existing field sales infrastructure. Specifically, Nestle recently hired a hospital selling team of 20.

to profile the top volume hospitals across the country during the remainder of our pre-launch phase. Post-approval, this team will also cover the infectious disease specialty and we will deploy the existing 150-person gastroenterology sales force at Nestle.

Finally, the Nestle Payer Field Team continues their pre-approval information exchange efforts with payers and have already engaged with payers covering more than 150 million lives.

The feedback we have received so far is encouraging. Overall, I am pleased with the status of both companies' launch preparations, and we stand ready to execute immediately if we receive a favorable FDA decision. With that, I'll now turn the call to David to provide an overview of our financials. Thanks, Terri. The details of our fourth quarter and four-year financials.

are included in the press release issued this morning, so I won't reiterate all the figures here. CIRI's ended the fourth quarter of 2022 with approximately $181 million in cash, cash equivalents, and marketable securities. Regarding our efforts and resources over the near term, we continue to be focused on a number of critical CIR 109-related activities, which include continuing to ramp up manufacturing operations for commercial-

to advance and expand our pipeline for the focus on infection protection opportunities and further build upon and enhance our platforms and capabilities.

As we have already expanded our capabilities across much of our organization, we expect our expenses leading up to the SEAR 109 approval and launch to grow modestly. In summary, the company continues to be well-resourced to execute effective SEAR 109 commercialization activities pending FDA approval and to thrive our ongoing development and pre-clinical programs.

We will also continue to efficiently deploy resources to advance our research platforms. I will now turn the call back to Eric. Thank you, David. This is an exciting period for series as we near the potential approval of CERA 109, which would be a tremendous milestone for the company and for the entire field.

We approach the PDUFA date confident in the data provided to the FDA and well prepared to effectively execute a product launch pending approval. In addition to SIR109 and SIR155, we are also advancing additional promising earlier stage microbiome therapeutic candidates.

With these programs, we believe that there are significant opportunities to help additional, multiple medically compromised patient groups such as those with cancer neutropenia, cirrhosis, and solid organ transplant patients.

Over the course of the year, we look forward to providing you with progress updates on CER109, CER155, as well as our additional microbiome therapeutic programs.

With that, I will conclude our prepared remarks and open the call-up to questions. Certainly. At this time, if you'd like to ask a question, please press star one on your telephone keypad. Mark Brangbach with Oppenheimer. Your line is open. Hey, good morning guys. Thanks for taking the questions and anything that's on progress. Let's talk all together.

Just a couple of quick ones for me. First of all, can you comment on the current stockpile of CER-109 you have available immediately upon potential launch, approval and launch? And maybe just also comment on the current stockpile of CER-109 you have available immediately upon potential launch?

the in-house manufacturing capacity versus what additional capacity back Sarah could could add on top of what you guys can already make.

And then the second question is really just maybe aimed at David. I'm wondering, in addition to the $125 million milestone that would come with potential approval in April , if you're expecting any additional development or commercial milestones, I'd be happy to ask you an area like Digital and look for projects and opportunities to complement

from Nestle in 2023 that we should keep your eyes on for. Thanks for taking the questions. Mark, good morning and thank you for the questions. Let me start with the first one and we've got Dave Ege and Align. I'll ask him to provide his perspective too. So in terms of stockpiling of inventory or maybe preparing for launch, what we have said is that

We've been working on this process for some time. We're pleased to be taking our phase three process to launch. And we have been preparing for a number of different launch scenarios. So, we're really pleased with where we are. And we expect to be well prepared for the approval and then for...

to the in-house and the back there. So it's been our strategy for quite some time. As Eric mentioned just a moment ago, we're bringing our phase three process forward to launch. It's adequate and scale and volume to meet the near-term forecast that we have together with Nestle.

And by design back there, as was mentioned earlier in the call, we'll start producing material ahead of the facility approval in 2024. And we anticipate an approval for that material to reach the market in 2025. So that's augmenting capacity.

as a market growth, as well as providing redundancy with what we had internally and with the rest of the form currently. We're really pleased with where we are with the rest of the farm and our relationship and the work that we've done with them. Mark, maybe on your second question I can ask David to comment.

Yeah, thanks. Thanks Mark. So as you indicated, as we have talked about, we are eligible for $125 million milestone from Nestle upon CIR-109 approval. The other cash flow that we expect relates to CIR-109 commercial supply that we have been producing leading up to approval and thereafter, and we have been doing that at our cost.

we will sell that inventory to Nestle at or around approval, and then thereafter there'll be kind of a, think about it as a steady cadence of purchases by Nestle from a supply standpoint. So that will provide an initial bolus of cash coming in, and then a steady supply thereafter. All right, that's helpful. Thanks for taking the questions, and congrats again.

Thanks again, Mark. John Newman with Canaccord, your line is open. Thanks for taking my question. I just wondered if you could talk to us a little bit more about the initial launch targeting for CIR 109. I know that you've got a really interesting focus on the outpatient setting. I'm just curious if you could talk about that.

I can tell you there's a lot of excitement around the potential of CIR109. I think the idea of having a new tool to help patients in the space when it's been so long without something that is effective, that is something that is as a favorable safety profile, something that is...

in particular oral and scalable. We can kind of hear the hunger in the voices of those treating physicians for something new. But maybe Tyra, you can comment for the run then. Sure, good morning, John . With the gastroenterology sales force, that Nestle is currently deploying with one of their inline products, we'll be leveraging that sales team.

to reach their existing gastroenterology targets where they already have deep, long-standing relationships at launch while deploying that sales team. And we'll also be via that sales force reaching a small number of other physician extenders in those offices, MPs and PAs, for example, and other high-volume physicians. So that's the gastroenterology outpatient sales force.

I also mentioned that we recently stood up a hospital selling team that will be profiling in an ultimately selling to the largest institutions across the country that see the highest patient volume of recurrent CDI patients. That team will, in addition, call on infectious disease physicians because, as we know, most of those ID physicians spend the vast majority of their time within the walls of the hospital.

on the back of the completion of that regimen, therefore in the outpatient setting. So that gives you a flavor of the type of physicians that will be calling on post-approval. And we are finalizing our call plans currently as we approach the fidupe date with our colleagues that have not yet been necessarily helped sign it. I hope that helps. Thanks, Sean.

Yes, thank you. Thanks for the question, John . Ted Tentoff with Piper Sandler, your line is open. Great, thanks very much. That's an exciting set of further producer data as well. I guess my question is without an outcome.

And I'm not sure that you're at this point yet, but when it comes to label discussions, how can the conversation go around first or second returns?

How important do you ultimately think that's going to be to the launch and the initial success of one or more? Thanks. Thanks for the question and good morning. I might ask both Terry and Lisa at the comment. I will always preface our comments with you know we don't speak for the FDA and and

and the second is recurrence. And when someone has recurrence, their microbiome has been injured to the point where if there's susceptible to future recurrences. But maybe I'm going to ask.

If you can at least sit on the regulatory side or the label side, comment on importance and then Terry can speak to the commercial side too.

No, so as Eric said, you know, we have faced our desire to have the broad label on the fact that clinicians see this as a homogeneous disease once you get into the recurrent population. But it's also based on the FDA's own guidance. If you look at the FDA's labeling guidance,

They go into quite a bit of extensive detail on situations where pathophysiology is the same and risk benefit can be also then assumed to be the same as a reason for why they would deviate, if you will, from the exact details of how something was run in a trial. There was also a JAMA paper last spring actually reviewing the number of times that FDA does do that and it is very common.

I can come up with that. Absolutely. I mean, sure, the recurrent population, as Lisa said, is seen as a fairly homogeneous population. And I think the person who summarized that best with Dr. Karl Crawford in the investor event that I referenced in my prepared remarks back in December where he described this fork in the road.

So, you know, it's clearly also important, you know, having the broad label and being able to serve a broad population because as you look at the epidemiology of the disease, quite a few of our patients are considered in that first recurrent pool, right? So we're very eager to finalize our label with the FDA and determine our path forward from there. So, we're very eager to finalize our label with the FDA and determine our path forward from there.

Great, that's super helpful and good luck with everything. I know you guys want to put a lot of work. Get ready. Thank you, Ted. Chris Chubutani with Goldman Sachs. Your line is open.

Thank you for taking the question. This is Steven on for Chris. I was wondering if you could comment on what key launch metrics that you and ESSA plan to share during the early launch so that we and investors can track the launch. And also related to that, will prescription trend data be available through services like Broadcast?

Yeah, thanks for the question. I'll start and maybe Terry can add some color. We have not gotten to the point where we've disclosed what the launch metrics will be. We are in the process of working through that with our partners at Nestle. We have said, and we can reiterate, that there are 156,000 cases of recurrent C. diff in the U.S. and I think our enthusiasm has only grown based on our recent interactions with HCPs. So, Terry, you can comment further on how we think about metrics and then…

We will be coming to the street in the relative short term with a set of parameters that we expect to provide. Yes, I think the only thing I can say to build on that is maybe to tackle your second question, which is around the availability of prescription data. We're not anticipating that that would be broadly available because we are, as I mentioned previously, going to be very careful and deliberate with our distribution partner selection. We are working with a small number of very experienced specialty pharmacies in order to provide the best.

in class patient experience when physicians and patients deemed to use Tier 109. So we really want to control that experience. And so one way to do that is by being very selected with distribution partners. Ouff a

Thank you very much. Thanks for your question. Peyton Zonfack with TD Cowan. Your line is open.

This is Peyton for JioKundrecht. I'm very productive last year and thanks for taking our questions. I was guessing just maybe the first one, how are you thinking about pricing, especially given that Ruby Iota is now available? Are you evaluating something that's comparable per course?

Yeah, Peyton, good morning and thanks for the question. So I think that the way we would say this, we don't think that there are great comps in the space for 109. And as we talked about actually at the Calvin conference yesterday, you know, really what we think about when it comes to prices is value. What kind of value are we delivering to the patient?

that that resonates with us that this is different, right? And the type of value and the type of innovation that we're delivering is not comparable to standardized FMTs, not to antibodies, not to other types of antibiotics. It's just as different. So, we are in the process of working with our partners at Nestle to...

to finalize a price that is reflective of the value that we can provide, but also represents the opportunity to deliver value to the system. If patients recur, they're more likely to recur again. If you think about the cumulative costs of recurrence upon recurrence, these can be really sick patients and they can have comorbidities. So if you can stop that cycle of recurrence, you can create value for the patient, you can create value for the system.

we think we can create value for shareholders, that's a win-win. So that's how we're thinking about it. Great. That's really helpful. I guess now moving on to the SARE 155 program, and we're looking forward to the data update in May. Could you maybe comment about the level of excitement and feedback for the therapy you've seen at the initial sites and in cohort one, and maybe give a range about how quickly just in cohort two can be enrolled based off that feedback that you've seen?

in our ability to help patients. So 155 is up next. We were really pleased to clear the pre-planned DSMB at the end of the year and go into cohort two. We were really careful and deliberate with the first cohort knowing that this is a fundamentally more complex patient population than what we've dealt with in the past.

but we have increased the number of sites into the second cohort and we do expect to move more quickly. But maybe you leave the comment more on the excitement within our partners on the HCP side as well as the ones I thought. Yeah. Sightment really has been very sustained. I mean, this is a big problem in both infections and GVHD, our big problems in this population. And there are no great options. And I think we're doing this.

trial on the backdrop of a time when antimicrobial resistance is also really coming to the fore as an issue for patients who need a lot of antibiotics and that's certainly this population. So we have a lot of interest and we expect that interest to continue to fuel enrollment in cohort 2.

And you asked about the kinds of things we're looking for. I think there'll be some of the same things we'll be looking for in cohort one, including the ingrassment and function of the bacteria, pathogen reduction in the GI tract, as well as clinical sequelae, such as reduction in neutropenian fever, potential reduction in infection, and reduction in...

bloodstream infections in particular. And maybe we can ask Matt just to comment. You know, as usual, Peyton, our microbiome analyses in our clinical studies we think are incredibly important data sets and maybe Matt can comment on how we think about the one that's coming up with 1-5-5 in the first cohort.

Sure. I think Lisa hit on the key, excuse me, the key points, but from a pharmacological data perspective, we really are focused on some of the key mechanisms of action of the drug. So of course, engraphment is going to help inform our dosing strategies in this particular population. As Eric and Lisa pointed out earlier, we had a favorable... ...but...

report from the Data Safety Monitoring Committee with respect to cohort 1. So, of course, observing drug on board and having that favorable safety profile will be something we'll be looking for. And then in terms of actually trying to understand the drug's pharmacology with respect to infection, we will be looking at the reduction in bacterial pathogen. And of course, that had significant meanings on a couple different fronts. One, as we reduced that abundance, we would anticipate decreasing the likelihood of translocation events. So, the bacteria moving from the gastrointestinal track into the bloodstream to lead the bloodstream infections.

Thanks for the questions, Payne.

There are no further questions at this time. It is now my pleasure to turn it back over to management for final remarks. Thank you, operator, and thank you all for joining us this morning. We look forward to keeping you updated on our progress. Thanks again and have a great week. This concludes today's call. We thank you for your participation. You may now disconnect.