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spk10: Hello, my name is Chris and I'll be your conference operator today. At this time, I'd like to welcome everyone to the Q1 2023 series therapeutics earnings conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question during this time, simply press star, then the number one on your telephone keypad. To withdraw your question, please press star 1 again. Thank you. Dr. Carlos Tanzi, Investor Relations. You may begin.
spk09: Thank you and good morning. Our press release for the company's first quarter 2023 financial results in the business update became available at 7 a.m. Eastern time this morning and can be found in the investors and news section of the company's website. We will also be reviewing new year 155 Phase 1B study results, and we have posted slides on our corporate website that will accompany our remarks. I'd like to remind you that we'll be making forward-looking statements, including the timing of commercial launch, the availability of VAUST, the commercial success of VAUST, the timing and results of clinical studies, the timing of additional clinical data, final study results, the ability for microbiome therapeutics to modulate for microbiome and treat or prevent infection, our ability to achieve certain sales targets and the receipt of future milestones and debt tranches, and other statements which are not historical fact. Actual results may differ materially. Additionally, these statements are subject to certain risks and uncertainties which are discussed under the risk factors section of our recent SEC filings. Any forward-looking statements made on today's call represent our views as of today only. We may update these statements in the future, but we disclaim any obligation to do so. On today's call, with prepared remarks, I'm joined by Eric Schaaf, series president and CEO, David Arkowitz, chief financial officer, Dr. Lisa Von Mulkey, chief medical officer, and Dr. Matthew Henn, chief scientific officer. Additionally, Dr. Terry Young, chief commercial officer, and Dr. Dave Agee, chief technology officer, will also be available to answer your questions.
spk04: And with that, I'll pass the call to Eric. Thank you, Carlo, and good morning, everyone.
spk03: On April 26th, we were delighted to announce that the Food and Drug Administration had approved VAUST, formerly known as SIR-109. VAUST is indicated for the prevention of recurrent C. difficile infections in adults following antibiotic treatment for recurrent CDI. We believe VAUST has the opportunity to transform the management of recurrent C. diff infections and provides a meaningful new therapeutic option for patients. We are very happy with the label we've received which includes all adult patients with a recurrent CDI, including those with a first recurrence. The approval of Voust represents an incredible moment for Ceres, and we think it is indicative of the therapeutic potential of this new medical modality. We believe that our microbiome approach could address a range of infectious diseases and other serious indications. This will be highlighted in today's call as we review our new, highly encouraging CR155 data. We believe that the progress we are making with CR155 is illustrative of the breadth of potential applications for our microbiome technology. With the approval of Voust, we are now working to commercialize Voust alongside our long-term collaborator, Nestle Health Science. We discussed the recurrent CDI commercial opportunity and the Vaust launch plans recently at our product launch approval call, so we won't reiterate all that information again here. However, I can share a few short real-time updates. The Nestle customer-facing teams have been trained on the final package insert and core materials to enable them to meet with customers starting last week. The reaction to the clinical profile of Vaust in the field has been extremely positive, and HCPs are eager for product availability, which we expect in June. Our patient services hub went live the day following approval with a first call received in the morning of April 27th. The medical and commercial teams across Ceres and Nestle are excited to be attending DDW in Chicago this week on the heels of Voust approval with a number of activities planned at that key conference, which Lisa will discuss further in a moment. Finally, our supply and distribution teams across the companies are well prepared for launch, and we remain on track to have product available in June. We are thrilled, along with our collaborators at Nestle, to offer Voust as a much-needed treatment option for all recurrent C. diff patients, including those with the first recurrence, and to start to hear those stories firsthand from HCPs and patients who have experience with the product. As we commercialize Voust, We also continue to build our drug supply in collaboration with our long-term contract partner, Resiform, while enhancing future supply capacity. We believe that we will be able to meet vast market demand in all anticipated uptake scenarios. In late 2021, we entered into a collaboration with Vaxera designed to further scale our drug supply capabilities. This collaboration is proceeding well, and our plans remain on track. Our CMC teams are working together in an integrated manner, and we anticipate that Baxero will be ready to begin to produce commercial drug products in 2024 for release in 2025 as the expected number of patients treated with Voust expands. I'd like to pass the call now over to Lisa.
spk07: Thanks, Eric. I will begin with Voust, our FDA-approved oral therapy indicated for the prevention of recurrent C. difficile infection in adults. following antibiotic treatment for RCDI. Voust is a consortium of Firmicutes bacteria in their spore form. This therapy is thought to facilitate restoration of the gut microbiome and thereby reduce the risk of future recurrences of C. difficile infections. Importantly, the indication received is for the broad population of adult recurrent patients. Vaust has a straightforward oral dosing regimen of four capsules once a day for three days following antibiotic treatment and use of a laxative to remove residual antibiotic from the GI tract. Vaust is stored in the original packaging and has no refrigeration requirement. The full label is available on Vaust's website at vaust.com. The approval of Vaust is supported by two phase three studies. Our placebo-controlled ECOSPOR-3 study demonstrated that approximately 88% of patients did not experience a recurrence at the primary eight-week endpoint, compared to 60% in the group with antibiotics alone. We also evaluated Voust efficacy over longer periods of time, and we observed durability of response out to 24 weeks. Voust was well-tolerated and patients administered the drug had no serious treatment emergent events or deaths that were attributed to study drug. At the time of approval, we provided a more detailed review of the phase three clinical data supporting the vouched approval. And I would point you to that event for additional information. C. difficile infections create a substantial healthcare burden and have been characterized as an urgent health threat by the Centers for Disease Control and Prevention. Recurrent CDI is a serious disease that often results in hospitalization and can even lead to death. There are 156,000 recurrences in the United States per year and at least 20,000 deaths due to C. diff infections. Approximately 50% of all patients with recurrences have a CDI-related hospital readmission. patients suffer debilitating symptoms, such as frequent diarrhea, that prevent them from conducting their normal daily activities, and these symptoms significantly lower quality of life. We continue to present and publish VOUST results as we work to educate the medical community. At the Digestive Disease Week annual meeting currently being held in Chicago, we presented new data from ECOSPOR-4, our Phase III open-label, single-arm study, which found that nearly 95% of individuals who were free of CDI at 8 weeks remained free of CDI through week 24. This therapeutic benefit was observed regardless of the number of prior C. difficile infections. These results add to the previous positive data from the randomized placebo-controlled ECOSPOR3 phase 3 study. Our medical affairs team continues to hear excitement from the clinical community as they await drug availability. At the ongoing DDW meeting, there is a broad awareness of the VAWS data published in the New England Journal and JAMA and the strength of that data, as well as a vocal sentiment that treatment of RCDI should now include consideration of microbiome restoration. Moving now to our new SEER 155 results, which are included in the presentation posted earlier today. The medical literature supports a strong connection between pathogen domination and lack of diversity in the GI tract with the endpoints of infection, graft versus host disease, which is GVHD, and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation, or alloHSCT. SEER-155 is an investigational, oral, cultivated microbiome therapeutic designed to prevent enteric-derived infections and resulting bloodstream infections, as well as to induce immune tolerance responses to reduce the incidence of GVHD, particularly severe acute GVHD, in patients undergoing LOHSCT. The development of SEER-155 is supported by strong exploratory proof-of-concept data from the SEER-109 ECOSPOR-3 Phase III study, which we have previously discussed, and shows that SEER-109 administration resulted in the decolonization of gut pathogens, including bacteria carrying antibiotic-resistant genes. These data have been previously reported at various conferences as updated in the past. LOHSCT patients are at high risk of enteric-derived infections and acute GVHD. These adverse events are frequently seen in the first 100 days following the procedure. This is a period when the patient's microbiomes are highly disrupted from numerous factors, including antibiotic treatments and chemotherapy regimens, and their immune systems are severely compromised. As Matt will discuss, published data in the literature has specifically linked the incidence of pathogen domination in the GI microbiome to the risk of both of these downstream outcomes. The SEER-155 Phase 1B study is being run at a number of leading U.S. cancer centers and includes two cohorts, with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the GI tract. The data available today are based on results from cohort one patients through day 100 post-HSCT. Cohort one included 13 subjects who received SIR-155, and 11 of those subjects subsequently received an allogeneic stem cell transplant. Ten patients completed day 100, with one patient who was transplanted discontinuing the study prior to further SIR-155 treatment due to complexities in their clinical course unrelated to study drug administration. Nine subjects had evaluable samples for microbiome data analysis. The average age for subjects in cohort one was 60 years old, and most subjects had acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasia as their primary disease. and most received reduced intensity conditioning pre-transplant. Most subjects received peripheral blood stem cells from a matched unrelated donor. The majority received a tacrolimus based regimen for GVHD prophylaxis. Stem cell engraftment was observed in all subjects. 0155 was well tolerated in this population with no SAEs attributed to study drug. There were no deaths within the first 100 days post-HSCT. So cohort one is an open-label cohort focused on determining if this immunocompromised group of vulnerable patients could safely be dosed during HSCT and on evaluating drug pharmacology. Given the relatively small number of patients, it was not designed to assess clinical response endpoints, and we look forward to learning more particularly around the incidence of enteric-derived infections and severe acute GVHD, in the ongoing placebo-controlled cohort two portion of the study. I will now pass the call to Matt to discuss the pharmacology results.
spk14: Thank you, Lisa. The gastrointestinal microbiome plays an important role in preventing pathogen infection, including that of pathogens that can harbor antibiotic resistance, or AMR. Gastrointestinal microbiome has the potential to transform how we protect people from these microbial infections and address other disease complications more broadly through various functional mechanisms. In the context of alloHSCT, antibiotics, as well as other treatment insults, can reduce beneficial microbes from downstream negative impacts that notably can include domination in the GI by enteric pathogens, which frequently harbor antibiotic resistance. Domination is a state in which a single type of bacteria is unusually abundant in the GI. As shown in the SEER-155 Phase 1B Day 100 slides released this morning on slide 9, Pellett et al. in 2020, in research supported in part by CERES, reported that gastrointestinal bacterial domination events are common across patients undergoing HSCT, with events being observed in a majority of patients across four large transplant centers. This study and additional published research from MSK that are noted on slide 10 have shown that the GI domination by pathogens can be statistically significantly linked to reduced overall survival post-transplant and are significantly associated with increases in life-threatening bloodstream infections and risk for acute graft-versus-host disease. SIR-155 was designed to target the problem of bacterial pathogen domination in the GI of HSCT patients by preventing colonization and reducing the abundance in the GI of escaped pathogens of clinical concern. Specifically, Enterobacteraceae that may have carbapenem resistance, also known as CRE, and Enterococaceae that often have vancomycin resistance, commonly known as VRE. and further to reduce the potential downstream consequences of overgrowth by these and other potentially harmful bacteria. The 16 strains in SEER-155 were selected using CERI's MBTX platform that can elucidate disease-associated biomarkers and targets and drug mechanisms of action, PK and PD, at high resolution. The design of SEER-155 incorporated insights from observational data from our partners at MSK, and also from the University of Cologne to identify both bacterial taxa and functional signatures that were depleted post-transplant and associated with reduced risk of bloodstream infections and GVHD. We also incorporated clinical data from trials CERES has conducted to date to understand which species have a high probability to engraft in the GI tract broadly across patients. and that have strong associations with modulation of various disease-relevant pathways. Lastly, leveraging our extensive strain library, we screened consortia that were combinations of over 140 strains of bacteria that represented nearly 100 different bacterial species. This included species not previously described in the literature, and screening multiple strains for many species to select strains that optimally exhibited functional properties that prevent the growth of VRE and CRE, promote epithelial barrier integrity, and modulate immune pathways relevant to graft-versus-host disease in vivo. In the patients evaluated in cohort one, SEER-155 showed pharmacological activity consistent with its design. bacteria in the SIR155 consortia engrafted into the GI microbiome with the magnitude and kinetics consistent with expectations from prior clinical results from other series microbiome therapeutics, indicating the well-tolerated safety profile observed in these highly immunocompromised HSCT patients was in the context of drug bacteria present in the patient's GI. As reported on slide 11, strikingly, The cumulative incidence of domination by escape pathogens in the GI in the bacterial families enterococaceae, enterobacteraceae, streptococaceae, and staphylococaceae were rare, with only a single domination event occurring in a single patient's GI through days 30 post-hematic stem cell transplantation. These results are in sharp contrast to the cumulative incidence observed in the reference HSCT population cohort at MSK, where the cumulative incidence of these same escape pathogens was 64% compared to the 11% observed in SEER155 cohort 1. It is notable that we observed only one additional subject with domination events across the cohort 1 patient through day 100 post-HSCT. And all domination events were transient, which was not the case in previously published results. These initial results from Cohort 1 confirm that SIR-155 was well tolerated and pharmacologically active in Cohort 1 patients, and we look forward to obtaining additional biomarker measures of microbiome and host immune response later this year from these patients. We believe that the favorable GI domination data we have observed to date from Cohort 1 provides a clear mechanistic support for SIR-155. These early results are highly encouraging and increase our confidence in achieving meaningful clinical responses. As reported earlier this year, the Safety Data Monitoring Board approved the advancement of cohort two as no predefined stopping rules were met and cohort two is actively enrolling. Cohort two targets 60 patients and enables the evaluation of safety and drug pharmacology in the context of a randomized double-blind placebo comparator arm. Data from Cohort 2 will further extend data from a broad set of translational biomarkers to further elucidate the mechanisms of action of CR155 from biomarkers of clinical and mechanistic activity, and to obtain important insights such as the impact of CR155 on the incidence of GI infections, resulting bloodstream infections, graft-versus-host disease, and other clinical outcomes. These data will inform both the CER15 program specifically and additional opportunities infection and immunomodulation more broadly. CER155 has the potential to address significant unmet needs in patients undergoing stem cell transplant. Ceres believes that the medical benefit and commercial potential for CER155 may be substantial. As noted on slide 14, approximately 9,000 individuals per year receive alloHSCT in the U.S., with nearly 30,000 in the U.S. and EU combined. Infections and graft-versus-host disease are estimated to result in nearly half of all mortality associated with alloHSCT, according to the Center for International Blood and Marrow Transplant Research database. Complications are frequent and costly, with substantial additional costs associated with complications due to infections and graft-versus-host disease. With that, I'll now turn the call to David to provide an overview of our financials.
spk13: Thanks, Matt. The details of our first quarter financials are included in the press release issued this morning, so I won't reiterate all the figures here. Ceres ended the first quarter of 2023 with approximately $107 million in cash, cash equivalents, and marketable securities. With the FDA approval of Vaust in April, we are due to receive a $125 million milestone payment from Nestle. In addition, as we previously announced in late April, we entered into a $250 million secured debt facility with Oaktree. We received $110 million in funding at closing, with three additional tranches available in the future, including $90 million in two tranches of $45 million, each available upon the achievement of certain Vaust sales targets and an additional $50 million will be available at Oak Tree's discretion to facilitate potential future business development activities. Of the $110 million received at closing, approximately $53 million retired outstanding debt, and after deducting fees and expenses, the net proceeds to us were approximately $50 million. As a result, our pro forma cash balance at the end of the first quarter was approximately $282 million, which includes the vouched approval milestone, and net proceeds from our debt financing with Oak Tree. Once Vaust is launched, we will be sharing equally with Nestle in the commercial profits and losses. In addition, per the co-commercialization agreement with Nestle, we have the opportunity to earn sales target milestones totaling up to $225 million. We are responsible for supplying Vaust inventory to Nestle, and we have been building commercial supply in anticipation of launch. In the near term, we expect to receive payments from Nestle related to their purchase of the inventory that we have already produced, and in the future, we expect a steady pattern of inventory purchases by Nestle to meet market demand. From an accounting perspective, we expect that our 50 percent share of VAUST operating income or loss will be recognized in our P&L in the operating expense section as collaboration profit or loss sharing related party. Voust operating income or loss will be determined based on Voust net sales, cost of goods sold, and sales and marketing expenses. In addition, with the approval of Voust, going forward the commercial manufacturing costs will no longer be recognized as R&D expenses in our P&L, but instead will be capitalized and recognized on our balance sheet as inventory. Because the commercial manufacturing costs will now be capitalized, we expect that our total R&D expenses will decline going forward. For additional context, our first quarter 2023 financial results reflected $44 million of total R&D expenses, of which approximately $16 million, or 36%, was vouched commercial manufacturing costs. Furthermore, during future quarterly financial updates, We plan to provide key launch metrics to enable a better understanding of VAWS commercialization progress. Regarding our efforts and resources over the remainder of 2023, we are prioritizing the VAWS commercial launch and the continued production of commercial supply. In addition, we continue to expand our longer-term VAWS product supply capacity through our BACTERA collaboration. And in parallel, we are appropriately resourcing the expansion of our pipeline with a focus on infection protection opportunities. As we've expanded our capabilities across much of our organization in support of Vaust approval and launch, we are very much focused on driving operational efficiencies, and we are continuing to pursue opportunities to optimize our cost structure. In summary, the company continues to be well-positioned to effectively commercialize Vaust with our partner, Nestle, and to drive our ongoing development and preclinical programs. I'll now turn the call back to Eric.
spk03: Thank you, David. This is an exciting period for Ceres as we have received approval for Voust, the first ever orally administered microbiome therapeutic, and we will soon begin to commercialize this product. We are also very excited about the progress we are making with 0155 with the new data we have shared today. We are hopeful that the mechanistic data that we have seen in Cohort 1 will translate into meaningful clinical results, and we are looking forward to Cohort 2 data next year. We also look forward to providing additional information about the progress we are making, advancing other development candidates over the course of this year. I'd like to close by thanking the talented and dedicated series team for their hard work. It is this team that is responsible for the approval of VAUST and for the progress that we have made advancing new therapeutic candidates to patients in need. With that, we will conclude our remarks and open the call to questions.
spk10: Thank you. As a reminder, if you would like to ask a question, please press star then one on your telephone keypad. Our first question is from Mark Breidenbach with Oppenheimer. Your line is open.
spk06: Hey, good morning, guys. Thanks for taking our question and congrats on the quarter. First one for me is kind of on the cohort two that you're enrolling for SARA 155. I guess I'm wondering if you're taking any steps to standardize GVHD prophylaxis and graft source type and conditioning regimen across the different clinical sites that are involved in the trial. Obviously, those things can have a substantial impact on things like incidence of GVHD and infection rate. And second, I'm curious if you can comment on the three deaths that occurred after day 100, what were the causes of those deaths? Was it like viral infections or underlying malignancy? Any information you can provide there would be really helpful. And the last question for me is just on ballast and, you know, now that you have the FDA approval in hand, can you comment on any new plans for approaching European regulators following the FDA approval? Thanks for taking our questions.
spk03: Mark, thanks very much. Good morning. Let me ask Lisa the comment on your first two questions, which is the standardization, the variability, the patient deaths, and then I'll talk about yours.
spk07: Yeah, so we're not actively specifying what people need to have to be able to come into the trial, but as you could see from just our results, that we are, in terms of enrolling, we are getting what is a pretty typical population, and we are seeing consistency in most of the patients in terms of the kinds of grafts, the kinds of prophylaxis they're getting, both in terms of GVHD and even anti-infectives. So we feel pretty good about the fact that we'll be able, particularly with a placebo arm, to be able to pick out signals in spite of the fact that these patients do have complicated regimens, no question. And then the other question was on the deaths, correct? Yeah. So these patients had things related to their disease progression. In one case, it was hospice care for just end stage. Another case, it was disease relapse within an infection result. And then in a third case, it was actually an aspiration pneumonia in the setting of a of disease progression.
spk03: And then, Mark, let me take the last one, which is just on the European plans for Vaust. And I would say we feel we are as adept as anyone of walking and chewing gum at the same time. On the other hand, with Nestle, our focus really has been on getting to the finish line with the FDA with the approval of Vaust. and our resources and energy have been devoted towards that alongside this first cohort of 155. We're obviously incredibly encouraged by both of those meaningful events for the company, but we will consider next steps with Nestle as we think about the opportunity in Europe. I think we had mentioned beforehand that our base case was that we expected to run another study, and we will be in conversations with Nestle as to the timing and approach of that.
spk06: Okay, thanks so much, and congrats again. Thanks.
spk10: The next question is from Joseph Tomei with Cowan. Your line is open.
spk11: Hi there. Good morning. Congrats on the data update, and thank you for taking our questions. Maybe the first one, you know, just in terms of this escape pathogen domination, when you think about potential events after this, how important are transient cases versus kind of long-term consistent escape pathogen domination. I know you mentioned the patients that did have 0155 treatment, you know, the pathogen domination was transient. Just kind of any additional color on that. And in terms of risk, did these two patients have any predisposing factors that would have led to this transient pathogen domination versus the other patients that did not see this? Thanks.
spk03: Joe, good morning. Thanks for the question. Let me ask Matt to start and maybe Lisa to comment afterwards.
spk14: Yeah, Joe, good morning. So with respect to the escape pathogen domination being transient versus long-term and potential additional risk, there are certainly advantages in this patient population to not have durable pathogen domination. Keep in mind, these are highly immunocompromised patients. particularly post HSCT while they have neutropenia, they are at high risk of infection. So the more domination events that you have and the longer they are, the greater the risk of those bacteria crossing the barrier and becoming a bloodstream infection and a further downstream complication. So the transient is meaningful.
spk07: Yeah, and then with regard to the clinical course, Again, we have small numbers, but it is interesting that these two folks had complexities in their clinical course that could be related. I think we'll know way more when we get bigger numbers.
spk11: Perfect. That's helpful. And then maybe one on VAUST. I guess going forward when you start having product availability and sales, how granular do you expect you're going to be in terms of you know, here's our sales, here's how much we would spend on those efforts, and here's our profit, or is it going to be more here's our profit or loss from the quarter? I guess how much can you share on that point going forward?
spk03: Yeah, Joe, I think Terry has talked in the past about the types of questions that we'll be thinking about from a metrics perspective. Maybe I can ask David to comment on maybe your questions more around the financials.
spk13: Yeah, thanks, Joe. Yeah, we're looking forward to providing some combination of operational and financial metrics that will help investors and analysts just better understand our progress as it relates to VAUSE commercialization. We'll share those at the next earnings call.
spk11: Okay, perfect.
spk10: Thank you very much. Thanks for the questions, Jeff. The next question is from Tessa Romero with J.P. Morgan. Your line is open.
spk00: Hi, good morning, guys. Thanks so much for taking our question. One from us on Baust. While we're coming off of the approval not very long ago, what has been the early feedback you've heard from the marketplace around the price of the product? And then second part of my question. Oh, if I could just follow up with a second part. If you can help us understand a little bit better how you're thinking about physicians accessing the product via a medical exception process before a payer review finishes? Thanks so much.
spk03: Thanks for the questions. I'm going to invite Terry to comment. I'll just preempt the answer a little bit to say that whereas we had announced the price the morning after approval, we certainly had been doing a great deal of work prior to that announcement and really considering and establishing the price that for us, combines the key metrics of value and innovation and access. But maybe I can ask Terry to comment further on the first and second question.
spk01: Sure. Thanks for the question, Tessa. You know, really the reactions have been very much like reactions we received pre-launch, although from an HCP standpoint on a much larger scale because we were quite fortunate to have the DDW Congress in Chicago right on the heels of our approval. So we've had quite a high number of KOL and HCP interactions, and I'll tell you there's high interest and excitement regarding the availability of VALS. The feedback specifically on the price from our KOLs has been that it's in the range of what was expected, which tells you again that all the work and all the diligence that we did to evaluate the many considerations factoring into that very important decision for patients and shareholders was spot on. From payers, it's very early days, of course, and yet it isn't because, again, of the extensive work that we did prelaunch on the heels of the receipt of the ECOSPOR3 data back in the summer of 2020, we began our work to set the price, working with our collaborators at Nestle, so very, very early days, but my expectation is the feedback will be very much in line with the feedback we received pre-launch and pre-approval. Regarding the medical exception process, what I can tell you is that this is not unique to valve, so that's very important to understand. All products upon approval are subject to new to market blocks across the different health plans and PBMs until the product can be evaluated and a coverage decision can be made. So during that period of time, physicians have to go through a process that's not too dissimilar from a prior authorization process, and that's the very reason that we established such a robust hub capability in our VALST Voyage patient support services. So we're very confident that we'll be able to support patients and physicians as they go through this process prior to coverage decisions being made. Does that help?
spk00: very helpful and you know can you give us a little bit of a sense of if you think the medical exception process will be more commonplace um you know in the in the first six to 12 months here or just kind of trying to get a sense of kind of how much scope you think there will be there absolutely well that process remains in place until the coverage decision is made so field team as i've mentioned before we deployed them over a year ago
spk01: for pre-approval interactions with payers as they're permitted to do. And part of the goal of that deployment was to determine exactly what the payer coverage process is and what the timing is so that that team could be ready to go in and get in the queue immediately post-approval so that we could get those coverage decisions sooner rather than later. But until those coverage decisions are made, the medical exception process remains in place.
spk00: Okay, thanks so much for taking our questions.
spk01: You're welcome, Tessa. Thanks for the question.
spk10: The next question is from John Newman with Canaccord Genuity. Your line is open.
spk05: Hi, team. Good morning, and thanks for taking my question. So I have a question on GEAR 155, really, really interesting program here. Just curious if kind of longer term when we're thinking about the key outcomes, potential endpoints for a study later on. Should we be thinking more about reduction in serious infections, or should we be thinking more about the reduction of GVHD, or maybe both of those things? Just kind of curious as to how you think about where and how the 5-5 can have the greatest benefit for transplant patients. Thanks.
spk03: So, John, thanks for the question, and good morning. And I'll have the quick answer, which is yes. But I'll ask Lisa to expand a little bit more.
spk07: Yeah. I mean, I think both acute GVHD and enteric-derived infections are going to be where we're going to be focusing. And, you know, as you heard us talk today about the first 100 days, and we could probably even narrow that in a little closer in to the actual HSCT procedure window. I mean, that's the time period where patients' microbiomes have been really assaulted by not only anti-infectives, but certainly their chemotherapeutic regimens as well. And so we're really going to be looking there for infections that occur in the GI tract, and particularly those that then launch bloodstream infections from the intestine. And then with regard to the GVHD, the acute GVHD at that time, we'll be looking to see if we actually see a reduction in severe cases and the number of cases that are steroid refractory. And just recall that the infection and GVHD are important causes of death within the entire transplant journey. I think it's important to emphasize that we're not going to be casting such a wide net in terms of endpoints that we, you know, it's going to be too diffuse to understand. Of course, for safety, we will register things, but with regard to mechanism, it's enteric-derived bacteria infections, particularly those caused by organisms that Matt talked about, and reduction in the severity of acute GVHD.
spk04: Great, thank you.
spk07: Yeah.
spk10: Thanks for the question, John. The next question is from Chris Shibutani with Goldman Sachs. Your line is open.
spk08: Hi, this is Steven on for Chris. Thanks for taking our questions. I had a question on CR155. I believe it was stated that one of the three patients that died had an infection. I was wondering if you could speak to the other patients that received a transplant, if any of those had infections or graft-versus-host disease. and kind of what you would expect over that valuable course in terms of what percent would be anticipated to have any of those events. And I believe there's a comment during David's section in the prepared remarks about a focus on driving operational efficiencies and optimizing cost structure. Just curious about if you could elaborate there in terms of what steps you're planning on taking. Thank you.
spk03: Yes, Steven, good morning. Maybe I can ask Lisa to comment on the first, and then I'll take the second with David and Dave.
spk07: Yeah. So as we started in the prepared remarks, this is a really small number for trying to tease out clinical events. We, of course, have some internal benchmarking numbers, but it's really going to be critical to have a placebo-controlled arm, which we anticipate will be very reflective of the arm that's getting treatment, right? Because as somebody else has already mentioned there are these other variables and we expect that they will be evenly distributed across both arms and so we'll be able to get a much better sense of what we're seeing once we have that data set all put together. I think that's, you know, and again we've been looking at our data with the KOLs in this area and we remain amazingly excited about the fact that we're seeing this lack of domination, given the fact that the adjacency between domination and clinical sequelae is pretty well established. There's a very deep literature. But each time we review the data, we are always reminded, with such small numbers, it's really perilous to start looking at clinical events. And so we're heeding that advice and we're sticking with our top line messaging. I'll also add that we also want to preserve our ability to be able to present and publish this information when we are able to put it as a cohesive data set with cohort two.
spk03: Steven, maybe I can start the second question, which is just on the efficiency side. David in his prepared remarks talked about some of the structural changes post-approval, including what had been the build of inventory which flowed through the R&D line, which will not going forward. But I would just say that we have scaled up and put the pieces in place to support VAUST. There are aspects of where we are where we think that there are efficiencies that we can drive. And one of them, as one example, is the shelf life based on the stability of the product that maybe I'll ask Dave to comment on. And then David can follow with any other comments.
spk12: Yeah, sure. So we were really pleased that the FDA gave us good shelf life, multi-year shelf life for our drug intermediates, as well as three-year shelf life for the final product. So this gives us a lot of flexibility about where we can build and maintain inventory along our supply chain and better manage our production in that way.
spk13: And I would just add to that, Stephen, we're looking at a variety of opportunities. Just for example, we outsource certain donor medical testing. Those are activities that we're looking to bring in-house that will generate some meaningful savings. We're also taking a close look at our office facilities and looking to rationalize that. So those are just a couple examples, but we are very much focused on this.
spk08: Okay. Thank you all for the color. That's very helpful.
spk10: Thanks for the questions. Again, that's star one. If you'd like to ask a question, the next question is from Kay Nake with Chardon. Your line is open.
spk02: Yes. A couple of questions about 155 in the graph that you observed. First question, is the degree of engraftment consistent across the different component species included in the product? And then in the case where you did have domination, is the amount of engraftment lower than in the other patients? I guess what I'm trying to understand is there's some threshold of engraftment that needs to be achieved in order to provide protection. Thanks.
spk03: Yeah, thanks for the question. Let me ask Matt to comment.
spk14: Sure. Thanks, Kay, for those questions. So the engraftment results, a couple important points around that. So one, they confirmed our drug formulation and were as expected. So I think that that's a very important observation. We saw the majority of strains engraft across the various different patients. And so that was an important observation as well. and that was consistent. Those engraftment patterns were absolutely consistent with what we would have expected based on our prior trial results. You asked a question, and let me just say we're consistent with our dosing strategy as well. You asked the question about whether in the case where we saw domination events, whether engraftment was less. Great question, and actually part of what gives us confidence in the pharmacological activity of this drug is that where we saw the domination event was a patient where we saw the weakest engraftment signature.
spk04: Okay, great.
spk10: Thanks for the question, Kev. We have no further questions at this time. We'll turn it back over to management for any closing remarks.
spk03: So thanks to everyone for joining us this morning. We look forward to updating you on our progress. Hope that you have a great day and a great week. We'll talk soon. Thanks very much.
spk10: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
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