Seres Therapeutics Inc. Q1 2023 Earnings Call
[music].
Hello, My name is Christian 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 Speakers' 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 one again.
Thank you Dr. Carlo Tanzi Investor Relations you may begin.
Thank you and good morning, our press release for the company's first quarter 2023 financial results and a business update became available at seven a M. Eastern time. This morning, and can be found in investors and news section of the company's website. We will also be reviewing your tier 155.
Phase one B study results and we had close to two slides on our corporate website that will accompany our remarks I'd like to remind you they will be making forward looking statements, including the timing of commercial launch the availability of ballast the commercial success of Dallas.
Timing and results of clinical studies, the timing of additional clinical data.
Final study results.
The ability for microbiome therapeutics to modulate from 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.
Today's call with prepared remarks, and joined by Eric Shaff serious President and CEO , David Arc with Chief Financial Officer, Dr. Lisa von Mulkey, Chief Medical Officer, and Dr. Matthew <unk>, Chief Scientific Officer. Additionally, Dr. Terry Young Chief Commercial officer, and Dr de Bakey Chief Technology Officer.
We will also be available to answer your questions and with that I'll pass the call to Eric.
Thank you Carlo and good morning, everyone.
On April 26th we were delighted to announce that the food and drug administration had approved that was formerly known as SER 109.
<unk> is indicated for the prevention of recurrent C difficile infections and adult following antibiotic treatment for recurrent CDI.
We believe bausch 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 our label, we've received which includes all adult patients with recurrent CDI, including those with a first recurrence.
The approval of <unk> represents an incredible moment for series 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 SER 155 data.
We believe that the progress we are making with 0155 is illustrative of the breadth of potential applications for our microbiome technology.
With the approval of <unk>, we are now working to commercialize thousand alongside our long term collaborator Nestle Health science.
We discussed the recurrent CDI commercial opportunity.
And the vast launch plans recently at our product launch approval call.
So we won't reiterate all of 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.
Reaction to the clinical profile that's out in the field has been extremely positive and H C piece are eager for product availability, which we expect in June .
Our patient services hub went live the day following approval with first call received in the morning of April 27th.
The medical and commercial teams across series of Nestle are excited to be attending D. D. W. In Chicago. This week on the heels of vast 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 <unk> as a much needed treatment option for all recurrent C diff patients, including those with a first recurrence and to start to hear those stories firsthand from ACP is in patients who have experienced with the product.
As we commercialize vest. We also continue to build our drug supply in collaboration with our long term contract partner rest of foreign while enhancing future supply capacity.
We believe that we will be able to meet vast market demand and all anticipated uptake scenarios.
In late 2021, we entered into a collaboration with back Sara 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 back several will be ready to begin to produce commercial drug product in 'twenty 'twenty four for release in 2025 at the expected number of patients treated with <unk> thousand expanse.
I'd like to pass the call now over to Lisa.
Thanks, Eric.
I will begin with <unk>, our FDA approved oral therapy indicated for the prevention of recurrent C. Difficile infection in adult following antibiotic treatment for our CDI.
First as a consortium affirm acuity 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 infection.
Importantly, the indication received for the broad population of adult recurrent patients.
Those tests are straightforward oral dosing regimen of four capsule once a day for three days following antibiotic treatment and use of a laxative to remove residual antibiotic from the Gi tract.
That was just stored in the original packaging and has no refrigeration requirement.
The full label is available on <unk> website at <unk> Dot com.
The approval of <unk> is supported by two phase III studies.
Our placebo controlled eco spore three study demonstrated that approximately 88% of patients did not experience a recurrent at the primary eight week endpoint compared to 60% in the group with antibiotics alone.
We also evaluated vast efficacy over longer periods of time, and we observed durability of response out to 24 weeks.
<unk> 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 III clinical data supporting the last approval and I would point you to that event for additional information.
Now C difficile infections create a substantial health care 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 156000 recurrences in the United States per year, and at least 20000 deaths due to C diff infections.
Approximately 50% of all patients with recurrent is have a CDI related hospital readmission.
Patients suffered 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 those 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 Eco score for our Phase III Open label single arm study, which found that nearly 95% of individuals' for free of CDI at eight weeks remained free of CDI through week 24.
This therapeutic benefit was observed regardless of the number of priors C difficile infections.
These results add to the previous positive data from the randomized placebo controlled eco spore three phase III study.
Our medical Affairs team continues to hear excitement from the clinical community as they await drug availability.
At the ongoing EDW meeting there is a broad awareness of the valor data published in the New England Journal and Jama and the strength of that data as well as a vocal sentiment that treatment of our CDI should now include consideration of microbiome restoration.
Okay.
Moving now to our new SER 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 Gvhd.
And mortality in patients undergoing allogeneic hematopoietic stem cell transplantation or allo HFC T.
SER 155 is an investigational oral cultivated microbiome therapeutic designed to prevent and characterized infections, and resulting bloodstream infections as well as to induce immune tolerance responses to reduce the incidence of gvhd, particularly.
Particularly severe acute gvhd in patients undergoing allo HFC T.
The development of SER 155 is supported by strong exploratory proof of concept data from the tier 109 Eco score three phase III study, which we have previously discussed and shows that SER 109 administration resulted in the D colonization of gut pathogens, including bacteria.
Carrying antibiotic resistance genes.
These data have been previously reported at various conferences as updated in the past.
Hello, HFC T 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 microbiome are highly disrupted from numerous factors, including antibiotic treatments and chemotherapy regimens.
And their immune systems are severely compromised.
As Matt will discussed.
Discuss published data in the literature has specifically linked the incidents of pathogen domination in the GI microbiome two the risk of both of these downstream outcome.
The SER 155 phase <unk> study is being run at a number of leading U S cancer centers and includes two cohort with cohort one designed to assess safety and drug pharmacology, including the grassman of drug bacteria in the Gi tract.
The data available today are based on results from cohort one patients through day 100 post HFC T.
Cohort one included 13 subjects, who receive SER 155, and 11 of those subjects subsequently received an allogeneic stem cell transplant.
And patients completed de 100 with one patient who was transplanted discontinuing the study prior to further SER 155 treatment due to complexities in their clinical course unrelated to study drug administration.
Nine subjects had a valuable 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, our Milo proliferative neoplasia as their primary disease.
And most received reduced intensity conditioning pre transplant.
Most subjects receive peripheral blood stem cells from a matched unrelated donor.
The majority received attacker alignments based regimen for Gvhd prophylaxis.
Stem cell and <unk> was observed in all subjects.
SER 155 was well tolerated in this population.
With no sae's attributed to study drug.
There were no deaths within the first 100 days post <unk>.
So cohort one is an open label cohort focused on determining if this immuno compromised group of vulnerable patients could safely be dosed during <unk> <unk>.
And on evaluating drug pharmacology.
Given the relatively small number of patients. It was not designed to assess clinical response endpoint and we look forward to learning more particularly around the incidents 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.
Thank you Lisa the gastrointestinal microbiome plays an important role in preventing pathogen infection, including that of pathogen second harbor antibiotic resistance or AMR.
The gastrointestinal microbiome has the potential to transform how we protect people from these microbial infections and address other these complications more broadly through various functional mechanisms.
In the context of Allo, HFC T antibiotics as well as other treatment insults can reduce beneficial microbes from downstream negative impacts that notably can include domination in the Gi bioterror pathogens.
Which frequently harbor antibiotic resistance.
Domination is a state in which a single type of bacteria is unusually abundant in the Gi at.
As shown in the tier one to $5 five phase <unk> de 100 slides released this morning on slide nine pellet at all in 2020 and research supported in part by series reported that gastrointestinal bacterial domination events are common across patients undergoing HSC T with events being observed in a majority of patients.
Across four large transplant centers.
This study and additional published research from SK that are noted on slide 10 have shown that the Gi domination by packages can be statistically significantly linked to reduced overall survival post transplant and are significantly associated with increases in life threatening bloodstream.
Actions and risk for acute graft versus host disease.
SER 155 was designed to target the problem of bacterial pathogen domination in the Gi of HFC T patients by preventing colonization and reduced the abundance in the Gi of escape pathogens of clinical concern.
Specifically enterobacter AC that may have carbo Pan am resistance also known as CRE.
And enter Okaka 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 16th strains and steer 155 were selected using series <unk> platform that can elucidate disease associated biomarkers and targets and drug mechanisms of action PK and PD at high resolution.
The design of SER 155 incorporate insights from observational data from our partners at MSA and also from the University of Cologne to identify both bacterial taxa and functional signatures that were depleted post transplant and associate it with reduced risk of bloodstream infections and gvhd.
We also incorporate a clinical data from trials series 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 where 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.
<unk> optimally exhibited functional properties that prevent the growth of vre and CRE promote epithelia barrier integrity, and modulate immune pathways relevant to graft versus host disease in vivo.
In the patients evaluated in cohort one SER 155 showed pharmacological activity consistent with its design.
Bacteria in the SER 109, five consortia engrafted into the Gi microbiome with the magnitude and kinetics consistent with expectations from prior clinical results from other series of microbiome therapeutics, indicating the well tolerated safety profile observed in these highly immunocompromised HFC T patients within the <unk>.
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 and the bacterial families enter okaka Enterobacter, ACI, Streptococcus ICA and Staphylococcus assay, where rare with only a single domination event occurring in a single payer.
<unk> Gi through day, 30 post hematic stem cell transplantation.
These results are in sharp contrast to the cumulative incidence observed in the referenced HFC T population cohort of MSA with a cumulative incidence of these same escape pathogens was 64% compared to the 11% observed in SER 155 cohort.
It is notable that we observed only one additional subject with domination events across the cohort one patients through day 100 posts HFC and all domination events were transient which was not the case in previously published results.
These initial results from cohort one confirm that tier one <unk> was well tolerated and pharmacologically active in cohort one 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 one provides a clear mechanistic support for SER 155. These early results are highly encouraging and increase our confidence in achieving meaningful clinical responses.
Cohort two targets of 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 two will further extend data from a broad set of translational biomarkers to further elucidate the mechanism of action of SER 155 from Biomarkers of clinical and mechanistic activity and to obtain important insights such as the impact of SER 155 on the incidence of Gi infections, resulting bloodstream.
Infections graft versus host disease and other clinical outcomes. These.
These data will inform both the SER, one five programs, specifically and additional opportunities infection and immuno modulation more broadly.
SER 155 has the potential to address significant unmet needs in patients undergoing stem cell transplant.
Series believes that the medical benefit and commercial potential for SER 155 may be substantial.
As noted on slide 14, approximately 9000 individuals per year receive allo HFC tea in the U S with nearly 30000 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 allo HFC T. According to the center for international.
<unk> 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.
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 series ended the first quarter of 2023 with approximately $107 million in cash cash equivalents and marketable securities.
With the FDA approval of <unk> 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 trough.
<unk> available in the future, including $90 million in two tranches of $45 million each available upon the achievement of certain <unk> sales targets and an additional $50 million will be available at <unk> 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 vast approval milestone and net proceeds from our debt financing with oaktree.
Once <unk> 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 <unk> inventory to nestle and we have been.
Building commercial supply in anticipation of launch.
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% share of <unk> operating income or loss will be recognized in our P&L in the operating expense section as collaboration profit or loss sharing related party.
<unk> operating income or loss will be determined based on <unk> net sales cost of goods sold and sales and marketing expenses. In addition, with the approval of <unk> 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 vast commercial manufacturing costs.
Furthermore, during future quarterly financial updates, we plan to provide key launch metrics to enable a better understanding of <unk> commercialization progress.
Regarding our efforts and resources over the remainder of 2023, we are prioritizing the valves commercial launch and the continued production of commercial supply. In addition, we continue to expand our longer term valves product supply capacity through our Baxter collaboration and in parallel we are appropriately resourcing the expansion of our pipeline with a focus.
On an infection protection opportunities.
As we've expanded our capabilities across much of our organization in support of vast 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 <unk> with our partner Nestle and to drive our ongoing development and preclinical programs.
Now I'll turn the call back to Eric.
Thank you David.
This is an exciting period for series as we have received approval for <unk>. The first ever orally administered microbiome therapeutics and we will soon begin to commercialize. This product. We are also very excited about the progress we are making with SER 155, with the new data we have shared today.
We are hopeful that the mechanistic data that we have seen in cohort one will translate into meaningful clinical results and we are looking forward to cohort two data next year.
We also look forward to providing additional information about the progress we are making the advanced and 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 <unk> 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 up to questions.
Thank you as a reminder, if you would like to ask a question. Please press Star then one on your telephone keypad.
First question is from Mark Breidenbach with Oppenheimer. Your line is open.
Hey, good morning, guys. Thanks for taking our questions and congrats on the quarter.
First one for me just kind of on the cohort two that youre enrolling for SER 105.
So im wondering if youre, taking any steps to standardize.
Gvhd prophylaxis okay.
Grass.
<unk> pipe and conditioning regimen across the different clinical sites that are involved in the trial, obviously those things can have.
Actual impact on things like incidence of Gvhd in infection rate.
And secondly, I'm curious if you can comment on the three deaths that occurred after a day 100, what were the causes of those deaths.
Viral infections or underlying malignancy.
Any information you can provide there.
Would be really helpful.
Last question for me is just on on on <unk>.
Sure.
Now that you have the FDA approval in hand can you comment on any new plans for approaching European regulators following FDA approval.
Thanks for taking my questions.
Mark Thanks, very much good morning, let me ask Lisa to comment on your first two questions, which is the <unk>.
Standardization of variability.
<unk> desk, and then ill talk about Europe .
Yes, 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 result 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.
The kinds of graph the kind of.
Prophylaxis Theyre getting both in terms of gvhd and even anti Infectives. So we feel pretty good about the fact that we'll be able with particularly with the 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 sorry.
Yes.
And then the other question was on the on the deaths correct. Yes. So these these patients had things related to their disease progression and.
In one case it was at hospice care for just and stayed in another case it was disease relapse within an infection resolved and then.
Third case, it was actually an aspiration pneumonia in the setting of disease progression.
And then Mark let me take the last one which is just on the European plans for <unk> and I would say.
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 .
We had mentioned before him that are our base case was that we expected to run another study.
And we will be in conversations with nestle as to as to the timing and approach to that.
Okay. Thanks, so much and congrats again.
Thanks.
The next question is from Joseph <unk> with Cowen Your line is open.
Hi, there good morning, Congrats on the data update and thank you for taking our questions maybe.
Maybe the first one.
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.
Did have zero contact treatment.
The capacity the nomination was was transient.
Yes.
Just kind of any additional color on that and in terms of risk that these two patients have any predisposing factors that put us.
The other patient response, either thanks.
Joe Good morning, and thanks for the question, let me ask Matt to start and maybe at least the comment afterwards, yes, Joe good morning, So with respect to the escape pathogen domination being transient versus long term and potential additional risks there are certainly advantages in this patient population.
What have durable pathogen domination keep in mind. These are highly immuno compromised patients, particularly post to HFC tea, while they have neutropenia. They are at high risk of infection and so the more domination of events that you have.
And the longer they are the greater the risk of those bacteria crossing the barrier and becoming a bloodstream bloodstream infection.
And a further downstream complication so.
Yes, and then with regard to the clinical course.
Again, we are small numbers, but it is interesting that that these two folks had.
Complexities in their in their clinical course that could be related I think we'll know way more when we get bigger numbers.
Perfect. That's helpful. And then maybe one on <unk> I guess going forward when you start having product availability and sales.
How granular do you expect youre going to be in terms of <unk> sales, here's how much nestle return beyond those efforts and here's our profit or is it going to be more here's a profit or loss from.
From the quarter.
I guess, how much how much can you share on that on that point going forward.
Yes, 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.
<unk> is more around the financials.
Yeah. Thanks, Thanks, Joe Yeah, we're looking forward to providing some combination of of operational and financial metrics that will help.
Investors and analysts just better understand our progress as it relates to move outs commercialization, we'll share that was at the <unk>.
At the next earnings call.
Okay perfect. Thank you very much.
Thanks for the question Jeff.
The next question is from Tessa Romero with Jpmorgan. Your line is open.
Hi, Good morning, guys. Thank you so much for taking my question.
One for Mike on <unk>.
While we're coming off of the approval not very long ago, what have been the early feedback you've heard from the marketplace around the price of the product.
And then second part of my question.
If I could just follow up with the second part.
If you can help us understand a little bit better how youre thinking about it.
Accessing the product.
<unk> process.
<unk>.
Thanks, so much.
Thanks, Thanks for the questions I'm going to invite Terry to comment I'll just preempt.
To answer a little bit to say that.
Whereas we had.
It's the price the morning after approval, we certainly had been doing a great deal of work.
Fire to that announcement and really <unk>.
<unk> and establishing the price.
For us combines the key metrics of value and innovation and access, but maybe I can ask Terry to comment further on on the first and second questions.
Yeah.
Sure. Thanks for the question.
Really the reactions have been very much like reactions. We've received the launch although from an EQT standpoint on a much larger scale because we were quite fortunate to have the Didi <unk> Congress in Chicago right on the heels of our Shrieval. So we've had quite a high number.
Of Kols and HCP interactions and I'll tell you there is high interest and excitement regarding the availability of <unk> 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 you evaluate the many consideration factoring into that very important decision for patient and shareholder was spot on.
From payers, it's very early days of course.
Yes. It is.
Again of the extensive work that we did pre launch on the heels of the receipt of the eco score three 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.
We'll be very much in line with the feedback we've received prelaunch and pre approval.
Regarding the medical exception process, what I can tell you is that this is not unique to valves. So that's very important to understand all products. Upon approval are subject to new to market blocks across.
Different health plans and Pbms until the product can be evaluated and a coverage decision can be made so during that period of time, a physician has to go through a process that's not too dissimilar from the prior authorization process and Thats. The very reason that we establish such a robust hub cake.
Ability in our valves 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 our priority coverage decisions being made.
Does that help.
Very helpful.
Can you give us a little bit any sense of if you think.
The medical exception process will be.
More commonplace.
<unk>.
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 that will be there.
Absolutely will that process remains in place until the coverage decision is made.
Field team as I've mentioned before we deploy them over a year ago.
Preapproval interactions with payers as they are 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 can be ready to go in and get in the queue immediately post approval. So that we can.
Could get those coverage decisions.
Or rather than later, but until those coverage decisions or need the medical exception process remained please.
Okay. Thanks, so much for taking our question.
Youre welcome Pat Thanks for the question.
The next question is from John Newman with Canaccord Genuity. Your line is open.
Hi.
Good morning, and thanks for taking my question. So just a question on.
Tier 155, really really interesting program here, just curious if kind of longer term when we're thinking about.
The key outcomes potential endpoints.
The 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.
We are and how <unk> can have the greatest benefit for transplant patients. Thanks.
So John Thanks for the question and good morning.
I'll have the quick answer which is yes, but I'll ask Lisa to expand a little bit more yeah, I mean, I think both.
Acute gvhd and and characterized infections are going to be where we're going to be focusing and as you heard us talk today about the first 100 days in it we can probably have a narrow that a little closer in to the actual HFC procedure window I mean, that's the time period, where.
<unk> microbiome have been really assaulted by not only anti infectives, but certainly there chemotherapeutic regimens as well.
And so we were really going to be looking there for infections that occur in the Gi tract and particularly those that then launch bloodstream infections from the 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 number of cases that are steroid refractory.
And just recall that the.
Infection and Gvhd are important causes of death within the.
The entire transplant journey.
So we won't be I think it's important to emphasize that we're not going to be casting such a wide net in terms of endpoints.
That.
It's going to be too diffused to understand.
Of course by for safety, We will register things, but with regard to mechanism. It's enteric derived bacterial infections, particularly those caused by organisms that Matt talked about and reduction in the severity of acute gvhd.
Okay, great. Thank you.
Yes.
Thanks for the question John .
The next question is from Chris <unk> with Goldman Sachs. Your line is open.
Hi, This is Steven on for Chris Thanks for taking our questions I had a question on SER 109 five.
I believe I 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 views and kind of what you would expect over the Evaluable Evaluable course in terms of what percent would be.
Anticipated to have any of those events and I believe there was a comment during David touched on the prepared remarks about.
Our focus on driving operational efficiencies and optimizing cost structure. Just curious about if you could elaborate there in terms of what steps you are planning on taking thank you.
Yes, Stephen Good morning, maybe I can ask Lisa to comment on the first and then I'll take the second with the David and Dave Yeah. So as we started.
In our 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 thats 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 of what we're seeing.
Once we have that dataset all put together.
I think that's and again, we've been looking at our data with.
Excited about the fact that we're seeing this lack of domination given the fact that the adjacency between domination and clinical supply is pretty well established as a very deep literature, but each time, we review the data.
We are always reminded with such small numbers.
Parallel to start looking at clinical events.
So we're we're heating that.
Advice, and we're sticking with our top line messaging.
I'll also add that we.
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 dataset with cohort two.
And then Stephen maybe I can take the start the second question, which is on the efficiency side.
David in his prepared remarks talked about some of the structural changes post approval, including.
Then maybe I'll ask Dave to comment on and then David can follow with any other comments, yes sure. So we were really pleased that the FDA gave us.
Good shelf life multiyear 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 and better manage our our production.
In that way.
And I would just just to add to that Steve we're looking at a variety of opportunities.
<unk> for example.
We outsource certain donor medical testing those are activities that were that were looking to bring in house that will generate some meaningful savings. We're also taking a close look at our at our office facilities and looking to rationalize that so those are just a couple of examples but we are we are very much focused on this.
Okay. Thank you all for the color Thats very helpful.
Thanks for the questions.
Again, Thats star one if you'd like to ask a question. The next question is from Jay <unk> with Chardan. Your line is open.
Yes couple of questions about $1 five in the graph that you observed.
First question is the degree of the graph.
Consistent.
Across the different <unk>.
<unk> species included in the product.
Case, where you did have domination.
Is the amount of in graph.
Lower than in.
In the other patients I guess, what I'm trying to understand is there some threshold open graph that needs to be achieved in order to provide protection.
Yes. Thanks for the question, let me ask Matt to comment sure. Thanks Kaye for the for those questions.
So the and graduate results a couple of important points around that one they confirmed our drug formulation and were as expected.
So I think that's a very important observation.
We saw the majority of strange strains in graft across the various different patients.
And so that was an important observation as well.
And that was consistent as in graphic patents were absolutely consistent with what we would've expected based on our prior.
Trial results you asked a question and let me just say were consistent with our dosing strategy as well.
You asked the question about whether in the case, where we saw domination events, whether <unk> was less great.
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 and grasp and signature.
Okay great.
Thanks for the question.
We have no further questions at this time I will turn it back over to management for any closing remarks.
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.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
[music].
Sure.