Q4 2021 Seres Therapeutics Inc Earnings Call
Ladies and gentlemen, please remain on your lines the fourth quarter 2021 Therapeutics, Inc. Earnings Conference call will begin momentarily. Once again. Please remain on your lines. Your conference call will begin momentarily. Thank you.
[music].
Ladies and gentlemen, thank you for standing by and welcome to the fourth quarter 2021 series Therapeutics, Inc Earnings Conference call.
At this time all participants are in a listen only mode. After the speaker presentation, there will be a question and answer session.
I ask a question. During this session you will need to press star one on your telephone if you require any further assistance. Please press star zero. It is now my pleasure to introduce Dr. Carlo Tanzi head of Investor Relations.
Thank you and good morning, our press release with the company's fourth quarter 2021 financial results and a business update became available at seven am Eastern time. This morning, and can be found on the investors and use section of the company's website I'd like to remind you that we'll be making forward looking statements related to the timing enrollment and results of our.
Clinical studies.
Dissipated as safety profile of our products.
Timing potential regulatory approvals here one on the <unk>.
Success of our agreement with Nestle Health Science, the anticipated market for SER, one on on the promise and potential impact of any of our microbiome therapeutics 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.
Forward looking statements made on today's call purposes, 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 Shaff, President and Chief Executive Officer, Dr. Lisa Bell Mulkey, Chief Medical Officer, Dr. Matthew Kim Chief Scientific Officer, and Dr and David <unk>, Chief Financial Officer Jordan.
During the Q&A portion of the call. We will also be joined by Dr. Terry Young Chief commercial and strategy Officer, Dr. David Magee, Chief Technology Officer with that I'll pass the call to Eric.
Yeah.
Thank you Carlo and good morning, everyone.
2021 was a very productive year for series, where we have made meaningful advancements in our microbiome therapeutics pipeline.
The center of this progress was our lead tier one of nine program and our momentum towards an expected BLA filing in the middle of this year.
The significance of SER 109, and our successful pivotal clinical data in recurrent C. Difficile infection was recently highlighted by the publication of the Phase III study in the New England Journal of Medicine.
We believe that SER 109 has the potential to become the first ever FDA approved microbiome therapeutic a landmark for this emerging class of medicines pending.
Pending FDA approval.
<unk>, we believe we have the opportunity to transform the treatment of recurrent C diff infection.
To remind you of our SER 109 efficacy results are phase III data demonstrated a significant reduction in the proportion of our currency that's patients.
Experiencing a further recurrence demonstrating superiority versus antibiotics alone.
Furthermore, the phase III data surpass statistical thresholds that have been communicated to us by the FDA that could allow the single clinical study to fulfill efficacy requirements for a BLA.
The FDA had also communicated that our BLA. Finally shall include a safety database of at least 300 subjects, receiving the phase III dose and with a 24 week follow up.
Our SER one line open label study is fully enrolled and we continue to gather the required safety data.
Notably the SER 109 open label study also includes individuals', where the first recurrence of C diff infection and expansion compared to the phase III study population, which included only those with multiply recurrent CDI.
The combination of first recurrence in multiply recurrent patients across our studies represent a broad segment of patients living with recurrent CDI.
As we prepare for our SER 109, BLA filing we are also conducting a tier one of nine expanded access program.
This program is designed to enable adults with recurrent C diff infection, including those with the first recurrence to obtain access to tier one of nine ahead of a potential FDA product approval.
We've continued to make excellent progress towards our planned rolling submission of the BLA and we continue to plan to complete the full BLA submission, including the required 24 week safety dataset in mid 2022 .
Given that SER 109 has obtained breakthrough therapy designation with the FDA, we anticipate receiving priority review.
This would result in an expedited timeline, including the two months BLA acceptance period, followed by a six month review period.
The approval and launch of SER 109 would represent a landmark event for patients living with recurrent CDI and for series.
In collaboration with our partners at Nestle Health Science, we continue to prepare for a successful commercial launch.
There are approximately 170000 cases of recurrent CDI in the U S per year and CDI results in over 20000 deaths deaths per year.
Current celiac patients do not have attractive treatment choices today.
These patients are currently being provided regimens some procedures that are not FDA approved including fecal microbiota transplantation and extended courses of antibiotics.
Pending product approval, we believe that SER 109 could address this entire patient groups suffering from recurrent CDI.
Furthermore, we believe that SER 100 represents a substantial economic opportunity for series the cost of a patient with recurrent CDI has been estimated to result in approximately 34000 in annual direct healthcare expenses and this does not include the substantial indirect costs associated with this disease.
We believe that with a highly attractive SER 100 profile and the tremendous level of unmet need this could translate into significant value for patients payers and for the company.
Based on our discussions with health care practitioners, there is an eagerness for new safe effective and FDA approved treatment options. We believe here I'm wondering if you could provide a transformational new therapeutic option for recurrent C. D. I and we are working with urgency to bring our therapeutic forward to the market as quickly as possible.
During the fourth quarter, we announced the collaboration with Baxter era, a global leader in biopharmaceutical product manufacturing that increases our longer term SER one on product supply.
This collaboration adds to our existing manufacturing capabilities.
There is building a dedicated facility for commercial manufacturing and its new Microbiome Center of excellence, a manufacturing site dedicated to the production of live biotherapeutic products.
We look forward to working with Pax era to expand our current production capacity, which we expect to fully support the initial launch period.
With this agreement, we anticipate meeting demand growth beyond the initial phase of launch and under all anticipated commercial uptake scenarios.
Beyond the direct benefit that SER 109 demonstrated in recurrent CDI and our phase III study. We also believe that our data provide important proof of concept for the potential for microbiome therapeutics and infection protection more broadly.
In January we held an investor event that detailed the supporting data and our strategy to address this important opportunity.
We believe that an infection protection represents a tremendous strategic opportunity for series and we intend to advance additional therapeutic programs in 2022 and beyond.
I'd like to now pass the call over to Lisa to discuss our clinical initiatives in more detail.
Thanks, Eric.
Since obtaining the initial SER 109 topline results in July of 2020, we have presented various datasets at a number of prominent conferences attended by infectious disease physicians and Gastroenterologists.
More recently in January we were very pleased to publish the complete phase III study results in the New England Journal of Medicine.
The publication highlights study results that demonstrated SER 109 to be superior to placebo and reducing C. D. Iva current with 88% of SER 109 patients achieving a sustained clinical response.
Paired to 60% on placebo.
This was a highly statistically significant difference.
In this study SER 109 was also observed to be well tolerated with a side effect profile comparable to placebo and no serious drug related adverse events observed.
The New England Journal publication has had the benefit of increasing physician awareness and interest in SER 109.
As a result of the publication, we have seen a marked increase in the number of inbound inquiries. We've received about the program and we believe that there is a high level of physician interest in incorporating SER 109, pending FDA approval into their clinical practice.
In addition to demonstrating the opportunity for microbiome therapeutics to impact recurrent C. D. I, we believe that our SER 109 data have also provided clear clinical and mechanistic evidence supporting microbiome therapeutics potential impact on infection protection more broad.
Right.
The gastrointestinal tract is known to have an important role in preventing pathogen infection, including from life threatening pathogens that can harbor antibiotic resistance.
Increasing emergence of antibiotic resistance has become a significant public health threat and new non antibiotic treatment approaches are desperately needed.
Our SER 109 data demonstrate that microbiome therapeutics can result in significant restructuring of the gut microbiome and that these changes can lead to significant reductions in pathogenic bacteria.
Including those associated with antibiotic resistance.
We believe that there are numerous opportunities. In addition to C. Diff infection, where we can apply our microbiome therapeutic approach in infection protection.
More specifically, we plan to apply our technology toward multiple medically compromised patient groups, who are known to be at high risk of life threatening bacterial infections.
Beyond SER 109, our next most advanced program in infection protection is tier 155, which we are developing for individuals receiving allogeneic stem cell transplant.
These patients are at very high risk for serious infections as well as graft versus host disease, and we believe that SER 155 has the potential to address both issues.
We have an ongoing phase <unk> trial to assess the safety microbiome and graph, then and efficacy of SER 155, working with our partners at Memorial Sloan Kettering and the University of Chicago.
The subjects in this study will be undergoing treatment for hematologic malignancies, such as leukemia.
Based on historical data, we expect that over 50% of the subjects will experience infection or gvhd.
If tier 155 is able to reduce the incidence of these conditions. We believe we would meaningfully improve health outcomes for these patients.
The study is set up with two cohorts. The first cohort, including 10 subjects is designed to assess safety and in grassman. This tier 155.
The second cohort includes 60 patients in a randomized double blinded design to further evaluate safety and in craftsman as well as efficacy.
This will be measured by assessing the rates of bloodstream infections and acute gvhd.
Ideally, we would see significant a significantly reduced incidence of bloodstream infections and or acute gvhd associated with tier 155 administration.
The study will help guide future clinical effort, and which outcomes, we should target with future studies.
Furthermore, positive results and preventing gvhd would support not only pursuing this outcome in future trials, but exploring next steps forward in immune modulation.
I'll now pass the call to Matt to further discuss our broader plans and infection protection as well as our efforts in ulcerative colitis.
Yes.
Thank you Lisa.
As we highlighted in detail during our January 31st Investor event, we believe that both our clinical and preclinical data provides strong evidence supporting the potential for microbiome therapeutics in infection protection.
We see the potential to reduce the abundance of targeted pathogen decrease the potential for pathogen transmission.
Strengthened epithelium barriers to further reduce the frequency of bloodstream infections, and modulate immune responses to tackle medical complications such as graft versus host disease.
<unk> has developed an integrated platform that has enabled the discovery of novel therapeutic candidates designed to protect patients from infection.
We are building on the success of SER 109, with tier 155, and we've also initiated additional preclinical programs targeting infection protection.
These include evaluating opportunities in patients receiving autologous HSC team and designing consortia to deploying setting such as cancer neutropenia, and solid organ transplant as well as combining the slow pandemic of anti microbial resistant infection more broadly we are driving towards initiating an additional clinical development program in <unk>.
2023, and progressing additional programs into the clinic over the next few years now.
Now moving to our ulcerative colitis efforts.
You see as an area of strategic interest for series and we believe it is a disease that may be particularly well suited for microbiome intervention.
I'll begin with a recap of our efforts targeting you see in some prior datasets.
Last summer, we announced topline results from our phase two eco reset study evaluating SER 287, a donor derived investigational microbiome therapeutic candidate in patients with mild to moderate colstrip quiet well.
While both dosing regimens of SER 287 were generally well tolerated. The study did not meet its primary endpoint of improving clinical remission rates compared to placebo.
Late last year, we announced additional microbiome drug pharmacology data from the phase II study that indicated that the in Grafman of SER 287 back to where it was on average across patient statistically.
Significant compared to placebo.
However, we did not observe metabolomics changes that we had anticipated and that we believe are important for therapeutic impact.
In addition to Sears to 87, we also continue to evaluate data from our phase one B study for SER 301, a next generation rationally designed cultivated microbiome therapeutic candidate for the treatment of E C.
The phase one B study is designed to include approximately 65 patients distributed across two cohorts cohort.
Preliminary SER 301 data has been analyzed from the first cohort, which included 15 subjects evaluation of the first cohort data by an independent data safety monitoring board indicated that it would be safe to proceed the placebo control second coke.
While clinical efficacy was not a defined endpoint in the first cohort evaluation of outcome data indicated that no subjects achieved clinical remission using an F. D. A three component definitions definition, though there were improvements in one or more individual components of the disease score, including endoscopic stool frequency.
He and rectal bleeding sub scores.
Furthermore, serictery went bacteria, where absorption craft in subjects across the trial period, and notably we observed changes in the metabolic landscape in the gastrointestinal tract interestingly the degree of metabolic changes observed following SER 301 administration appeared to be dependent on the baseline metabolic profile of the.
Study subjects. This is an area of particular interest that we continue to explore.
You see is known to be a remarkably clinically and biologically heterogeneous disease and this is hindered the development of various drug efforts for decades.
Based on our available SER 301, NCR to 87 data, we believe that certain UC patients may be more receptive to microbiome therapeutics based on definable baseline characteristics or research in this area remains ongoing and we continue to conduct analyses to inform next steps for further development in <unk>.
Of colitis.
With that I'll now turn the call to David to provide an overview of our financials.
Thanks, Matt the details of our full year and quarterly financials were included in this morning's press release, so I won't reiterate all the figures here.
Series ended the fourth quarter of 2021 with approximately $291 million in cash cash equivalents in marketable securities.
We're pleased to announce today that we have amended our debt financing agreement with Hercules capital, providing the company with a debt facility of up to $100 million.
This debt financing as a term loan, which we drew down 50 million upon closing last week.
This amendment replaces our prior $50 million debt facility with Hercules and approximately $22 million of the proceeds we received last week under the amended agreement will pay off the remaining amount owed.
With respect to our operating expenses and efforts over the near term we continue to be focused on a number of critical SER 109 related activities, which include.
Preparing and filing the BLA submission.
Continuing to ramp up manufacturing operations for commercial supply, including increasing longer terms here, one or nine product suppliers, who are back there a collaboration.
And in conjunction with Nestle, continuing and accelerating launch readiness activities.
In addition, we continue to invest to advance and expand our pipeline with a focus on infection protection opportunities and further build upon and enhance our platforms and capabilities.
As a result of these high priority and value generating activities, we expect our expenses to increase in the coming quarters.
At a moderating rate of growth as we have already expanded our capabilities across much of the organization.
In summary, we believe the company is well resource to prepare for SER 109, commercialization drive our ongoing development and preclinical programs. While also deploying resources to continue to advance our research platforms, where we believe we have differentiated proprietary and sustainable advantages.
I'll now pass the call back to Eric.
Thanks, David.
I will conclude our remarks by recapping key 2021 progress milestones as well as upcoming anticipated value drivers for the year ahead.
These include.
<unk> target enrollment in our SER 109 open label study and our preparations for a BLA filing in the middle of 2022.
Continued progress executing on SER 109, pre commercial readiness working closely with Nestle health science immune including expanded market education efforts.
The initiation and ongoing execution of our SER 109 expanded access program.
The expansion of our longer term commercial supply capabilities, including our collaboration with Baxter era.
Continued data analysis to inform future development and ulcerative colitis.
SER 155 study initiation and ongoing execution.
And expansion of our efforts targeting the infection protection an area of incredible opportunity to serve patients which directly builds upon the success of SER 109.
We also continue to strengthen our microbiome research platform and preclinical efforts in.
In 2022, we expect to advance new microbiome therapeutic candidates towards clinical development, particularly and infection protection, where we believe we have clear clinical and mechanistic data supporting our approach.
Sirius is well positioned to lead the microbiome therapeutic field and we intend to continue to execute on our mission working hard to improve the lives of patients with that now operator, we'll open the call up to questions.
Certainly as a reminder to ask a question you will need to press star one on your telephone.
If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.
Our first question comes from the line of Mark Breidenbach with Oppenheimer.
Hi, Good morning, this is jacqueline from Martin.
A question.
My first question.
Baseline metabolic profile.
In one.
In one study.
Many individual about Microsoft.
Thanks, Sean.
Thank you.
Good morning, and thanks for the question, Matt do you want to do want to take that one.
Sure we've been looking at a whole suite of disease relevant metabolic biomarkers in our UC patients that he had predefined to be important.
And in addition to that we have been looking at and discovering novel Biomarkers.
That we believe are important and relevant for disease based on the data sets that we've generated.
We haven't spoken disclosed yet the specifics of the number of Biomarkers, but what I can tell you is that we have identified a few biomarkers that are consistent.
And that we believe could be used potentially for patients stratification indoor selections.
Okay. That's good to know.
And also do you plan to monetize that compensation necessary kill one based on the observation.
Right.
Yeah. So all of our data today are so.
Port that the pharmacological properties of SER 301.
Our consistent with their design and that the drug is exhibiting pharmacological properties as it was designed to do so at this time, we do not anticipate any changes to the consortium.
Okay.
Next question is from Garden.
287.
Based on the biomarker profiling what fraction.
Moderate patients can you think could be good.
It is for us.
Oh, Gee 87 anchor at Hawaii, and also is there any difference in the ballpark well defined population you're considering for continued development of both molecules.
Matt do you want to start with that one and I'll offer some comments on top.
Sure Yeah. So.
We do think that the patient subpopulation that we've identified still represent a significant portion of patients with with ulcerative colitis.
So those that we have identified to be most receptive or somewhere on the order of about 30% to 40% of the patients in the population.
We havent provided any details further than that at this time.
Yeah, I might just add as a larger comment.
We are.
Learning Iterating.
And I think it's worth noting that we have a significant amount of data here with the 287 study results both clinical and microbiome now the first 15 subjects of the 301 study we will continue to learn and adjust from the study results and we'll follow the data and I think it's.
Worth, noting if you'll think back maybe to the the one O nine experience after the phase II study result.
We had a lot of confidence in the underlying thesis in a lot of data to support it but we didn't just say look let's let's run the stuff, let's run another study and hope that it kind of ends up clinically, where we kind of where we'd like it to.
So we made a number of adjustments based on data turns out that those adjustments you know, let us to a very pretty positive spot and that certainly is a process that we have intended to take with with our efforts in IBD and you see and that's what we're doing now.
Great. Thanks.
That's it for me thanks.
Thanks again for taking our question.
Thanks for the questions.
Thank you and.
And our next question comes from the line of Ted 10 Dolls with Piper Sandler.
Great. Thank you guys are really selling point for the company.
I'm, just trying to get a better sense as to prep for the BLA, obviously very strong data set here and will.
Will you be.
We're presenting the safety data or will that be something that simply goes into the BLA and then also if I may with respect to the relationship with Nestle. How are you guys working to kind of prep for lunch together. Thanks, so much.
Yeah, Ted good morning, and thanks for the questions maybe.
I'll ask Lisa to start with the second and I'll ask Terry just to hit the sorry.
Alright.
The first wanted to start with the second one on the first maybe I'll just.
Start by commenting that we are still in the process of following these patients out but maybe at least if you can comment further on on the on the open label study and how well we'll track it yet so we haven't said yet Oh, how we'll we'll make those data are public and how to communicate but I will say that we are eyeing.
Our possibilities in terms of conferences and other ways to disclose as soon as we have that dataset finalized.
And then Terry can you just comment on our work with the with Nestle Health Science and some of the.
Pre commercial work that we have conducted together.
Sure thing well I guess I'd start by highlighting that we ramped these efforts on upon receipt of the data right in the phase III data the remarkable data that we had and then yet again with Nestle after signing the co commercialization agreement last year. So we've now integrated the team at Nestle and traffic and we've worked together at our scale.
Both our market education, but also our data dissemination effort and these are primarily being led in the medical affairs to amicus team and I'll ask her to come I'll hand, it back here in a minute to comment on that but also in our market access team for example, we're developing a robust.
Pay your value proposition.
That is supported by the really strong category, leading profile of tier one of nine but also the high cost of treating recurrent Eric highlighted in his time in his remarks today.
And you know this is treating recurrent after recurrence in these patients and they look at the options today are quite limited and Nestle has an existing payer field team to engage this important audience and we'll be doing that prelaunch in accordance with existing FDA guidance on preapproval information exchange.
So that that's a pretty big book of work on the payer front in diet proposition front. We also continue to work with them to deepen our understanding of the market opportunity and we're progressing items like brand positioning efforts H C P payer and patient segmentation and branded campaign development.
And finally last year, we launched a broad disease education campaign at I D. We can multi amplifying that campaign as we move throughout 2022.
Finally, we're continuing to hire an.
Industry, leading commercial talent into both of our organizations now I'd like to ask Felicia specifically to comment on the medical affairs activities in France, particularly in light of the recent publication of the pivotal data in New England Journal of Medicine.
Yes, Thanks Terry.
Yeah. So the the Med affairs efforts really are spanning a number of areas that you would expect including publications on the New England Journal was incredibly impactful with regard to the reception in the in the physician community and we've already heard of infectious disease.
<unk>, bringing this up on rounds in in in their discussions with their colleagues.
The the Nestle group is is an alien group are fully integrated as we move through our planning further publications mobilizing the M. S cells, they're out there on the ground talking to physicians.
There are lots of education activities that are going to be culminating in CME programs and we're also working with the patient advocacy groups and we're.
We're very pleased with how the the Nestle amine team is.
Blending in and being part of that effort.
Very very helpful very thorough answer I appreciate it everybody.
Thanks for the question Ted.
Thank you and.
And our next question comes from the line of patent von <unk> with Cowen.
Hey, good morning, guys and thanks for taking our questions I'm on for Joe.
So just a real quick question about the expanded access program in the U S. I was wondering how many patients have been treated through the <unk> program. How the demand has been and whether you can share any details about whether this has been mostly first recurrence of multiple recurrent patient. Thank you.
Yeah, Peyton I would say, we're you know we're just getting started with the with the.
Expanded access just having no idea.
At the end of the year concluded the open label.
300 patients bogey that we had been targeting but simply debating.
Yeah, we haven't really given specifics I can tell you that it's up and running we have patients enrolled we have numerous sites across the company. We've tried to strategically place them so that patients.
Patients can access the site, regardless of where they are and we'll look forward to giving you more information in the future, but we haven't really been specific on numbers yet.
And thank you that's really helpful. And then maybe a real quick question on the SER 155 program.
I know that when we've talked about previously you'd said that the cohorts you can begin enrolling before COVID-19 one initiative.
Is there a certain level of efficacy that would be required to begin enrolling cohort. Two and then also are there any plans to expand the number of sites for this trial is being conducted or is it just going to be a Chicago and N S. K.
Yes.
Yes, Lisa maybe you can comment on both I think the one is the protocol structure and progression and the others maybe the.
In terms of size, yes, we're at two sites right now and we are intending to increase those so.
So I think what you're referring to with the first part of your question is that there is a pretty long safety follow up over the course of actually over an entire year, we don't need to wait for that entire year to start the second cohort.
The first has to finish the first set of patients through an initial safety assessment and at that point, we're free to go into the second sector without waiting that entire year.
Safety follow up I think that's what you're probably referring to.
That's exactly it alright, thank you so much.
Sure Thanks for the questions.
Thank you Andrew.
Question comes from the line of Christian Chabot, Tony with Goldman Sachs.
Hi, This is Steven on for Chris. Thank you for taking our question.
I had one on the 301 program.
Do you expect that your label would include language for how many recurrences of patients.
Prior to going on a tier one.
And then just if you could comment on that gets who youre seeing in these patients with fresher karnes versus.
Kind of the.
Phase III trial population. Thank you.
So Stephen I want to make sure that we've got on our numbers are our programs right. The question was 301 around recurrences do you mean, one O nine.
Oh, yes, sorry, sorry about that okay, alright, no problem, yeah. So look I think what we said before is that.
The you know the label of course will be part of a negotiation that will happen with the FDA as part of the BLA process.
We don't want to get ahead of that at the same time, we absolutely think that the.
Medically and Lisa pads, and certainly can again speak to our view of why we think that that recurrent C. Diff patients is that sort of where that is appropriate for that.
That patient population.
And maybe Lisa let me hand, it to you on that yeah, I think both from a pathophysiology as a basis as well as how our interactions with physicians are indicating they think about recurrent disease. It's it pretty much just falls into primary disease primary current and everything else.
And from a pathophysiology standpoint that Rick first recurrence is the marker and happens because the microbiome is unable to suppress the germination of those spores and that's the point that we're at which it makes sense to start restructuring.
And as well physicians in practice tend to.
C a C diff in.
Section as either the first bout or everything else. So for those reasons, we we really see this as an appropriate therapy, but as for all of our current patients.
As Eric said the label will reflect the negotiations with it with the agency.
And maybe just to follow I think you had asked about the percentage of first occurrence that we had seen in the in the <unk>.
And labeling we haven't disclosed that data, but as Lisa mentioned, we're kind of type of rise on on opportunities. Once we're past the follow.
Follow up period to disclose those those data.
Got it thank you for taking my questions.
Sure. Thanks for the question.
Thank you and our next question comes from the line of John Newman with Canaccord.
Oh, Hi, there Tim good morning.
Thanks for taking my question.
Just had a question about the SER 301 data.
I noticed in your press release as well as in your prepared remarks.
You mentioned that.
SER 301.
Did modulate.
Short chain and medium chain fatty acids, which interesting is.
Many patients actually will take.
Those types of products.
Off label, but just curious if those types of changes for a relatively consistent across the patients.
In that.
In that first quarter, you did mention that baseline metabolic state.
Did the changes and partly by 301, but just curious specifically on the short to medium chain trading assets, if that was somewhat consistent across the patients that you looked at thanks.
Yeah, John Good morning, and thank you for the question I'm going to I'm going to hand, it to Matt, but I'll do so just with the first.
No qualification that.
You have to remember we're talking about 15 subjects right. So so it's a pretty limited dataset that said, it's interesting and we think we're going up quite a bit from it and where we are in the process of analyzing some of the some of the data sets that have come from it but maybe without it can hit a demand.
Yeah. So a couple of good morning, John .
Couple of a couple of points. So first let me start with saying that I said is this 15 subjects in 301, so we need to we need to be cautious in terms of the extrapolation of of those results, but I think it's clear that SER 301, certainly demonstrated the pharmacological properties that it was designed to inhibit it certainly short chain fatty acids in medium chain fatty acids or <unk>.
One particular.
Tablet that the SER 301 is designed and optimized to produce a there are multiple others as well.
And.
Does he see patients are certainly a heterogeneous patient population.
And you certainly can see variations in the short and medium chain fatty acids amongst patients at baseline I will tell you that that is not the biomarker that we are focused on.
With respect to our patients and in the population that we've identified but that is certainly an important functional parameter that we continue to assess and evaluate.
And know that modulating that can be one important mechanism in the context of <unk>.
Reducing inflammation.
Got.
In the gastrointestinal tract.
There are multiple others as well that we are while we are focused on the second part of your question.
Comment on on that.
Another part of your question, which is your comment that you made that folks taking these are sort of.
Compounds. If you will off label, what's important is that and I think what's important about our drugs is that it's the bacteria that are producing these and while you have not seen success with patients previously taking things like bile acids are short chain fatty acids are then metabolized to.
<unk> vitamins et cetera, because of course, these things need to get to the site of activity and where they need to be and I think that's one of the clear benefits of our technology is that we are using the bacterias drugs in the bacteria naturally and have evolved to be at the site.
Whereas most where it's most relevant to have those effects. So the bacteria produce need metabolites at the site that.
We want them to.
Okay, great. Thank you.
Thanks for the question John .
And our next question comes from the line of Golden Sea with JMP Securities.
Okay.
Our questions and congrats on a partner if I could dig a little bit more into the grid.
That's true.
Is it is there.
Is it possible and would it be accurate to say that the positive metabolic changes seen with 301, where were meaningful compared to with the changes that we've seen with 287 or the lack thereof.
And since we're talking about metabolic profile.
Just wanted to confirm that and graph net profile with 301.
Presumably robust and I don't know if theres any way to talk about the quantitative.
If there was any compared to 287, and how that could maybe and towards independent metabolic changes that you guys are seeing.
This would be a positive indicator and.
And if there's any feedback or comments that you could share around.
Metabolic profile.
At baseline or otherwise and optimizing that tend towards clinical remission.
Maybe on a general level or just from data out there I know, there's only 15 patients here that would be great. Thank you.
Yes, gobin good morning, and thank you for the question, there's a lot there in terms of.
In your questions around some of the depth of our microbiome analysis.
Again, I'm going to I'm going to pass it to Matt, but I'll do so with just the caution that we.
We are.
Continue to be in the process of analyzing this data.
We are striving to put ourselves in the best position to help patients and of course return Hum.
In return for shareholders based on our efforts and Youll see and we're Iterating and we're learning and there's a number of data sets that we think put ourselves in a position to have.
More visibility, perhaps than others as it relates to maximize our chance of success and you can see but but there's a lot for us to do and maybe Matt can can take at their forward.
Yeah.
And I think I heard two questions in.
In your comments. So one was a question about the Grafman of SER 301 bacteria in patients post treatment and the second was the magnitude of metabolic changes in the SER 301 cohort one.
Population versus your 287 population so.
With respect to an Grafman, yes, we did see both rapid and durable and Craftsman of SER 301 bacteria into patients post treatment you may recall that.
One reason we had this first cohort was that we were testing a novel formulation of the drug where we had bacteria in the drug formulated both in the form of scores as well as in the form of vegetative bacteria and we wanted to evaluate that formulation.
In the cohort one study and I can tell you that we sell Paul Congrats on a spore form spore formulated bacteria as well as vegetative Lee formulated bacteria, which I think is important because it speaks to the strength and the breadth of our manufacturing capabilities.
At the company.
<unk>.
Excuse me in Grassman as we have consistently observed across our studies can have variability from patient to patient.
But we certainly.
Consistently get bacteria onboard and importantly, what we are sort of shifting to the second.
Second question, you had the magnitude of the metabolic changes.
We certainly were able to observe.
Trends and changes and as well as significant differences in.
Multiple pre defined the tablets that we think are important and relevant for.
The treatment of D C and for which SER 301 is designed to do in terms of the magnitude of that.
As we noted in the phase two study of SER 287, we did not observe these predefined metabolic changes that we had anticipated two and that was a surprise.
Whereas in the context of SER 301.
Good.
And a good number of those were also significantly changed at multiple different time points in the course of the study so.
We saw more meaningful change in the context of history.
Yeah, So maybe I'll just close by saying.
The we will continue to think about as you often do with a phase one study.
Optimize them dose.
Continuing to analyze the biomarker data that we think is intriguing and especially given the heterogeneous disease like do you see thinking about patient segmentation, where we can have an impact on the right patients patient groups. So those are the pieces that we are currently continuing to iterate on.
I appreciate you guys are making advancements in the state.
Thanks for the question.
Yeah.
Thank you and our next question comes from the line of burden Bernardino with H C. Wainwright.
Hi, everyone. Thanks for taking my questions and congrats on the process looking forward to the BLA midyear.
So with SER 109.
The results showed a high sustained clinical response rate about 88% are yet.
Yes.
In a survey conducted.
There's still a significant number or a percentage rather of.
Prescribers.
Who.
Definitely not.
Prescriber Ceragon online what does.
The driver of their hesitancy in what kind of efforts do you think you are in commercialization of <unk>.
Think you could implement to perhaps target.
The perhaps significant patient population that may not receive so in my mind.
Vern and good morning, and thanks for the question I'm going to ask Terry to comment, but I would say that.
The conclusion based on the question is we have a very different point of view.
From from what you I bought the size based on the analysis that we did in fact, we felt extremely favorable favorable in terms of what we heard back from our primary research, but Terry maybe you can take that one forward.
Yeah. Thanks, Eric I mean, it's a great question and I would refer you to a slide that is in our current corporate deck to actually illustrate feedback that we've obtained recently from both HCP and payers and <unk>.
What you'll see is if you look at the HCP response, it's actually quite remarkable in the positive direction, we have a what I would call a see a green and this is likelihood to prescribe data right. So the vast majority of physicians, saying that they are probably or definitely will use tier one of nine within their patient population.
For something that's it's transformative and such a new approach to care like here one of nine that's actually quite unusual. So I imagine your question is more in the smaller gray percentage on that.
Of label, but I thought yeah, it might or might not so this is actually very typical.
And a new category you get what I call defense centers. So they tend to you know you're showing them the profiling research right and you're asking them.
Based on one piece of paper.
Would you use this in your patient population and they're just more cautious physician sat so they want to for example here from their specialist down the street they want to wait for FDA approval, they want to understand the data in a little bit more depth. So.
These pet sitters don't tend to sit for very long.
But that's typically the dynamic that you're dealing with so how do you how do you deal with it back it's through the the approaches we're taking today around market education from the medical affair standpoint, and of course that approval, we can deploy our broader field forces well publications conferences and of course, the BLA approval.
Alright I implied.
Yeah.
There's a C agreement I'm, sorry, I implied.
There was a greater hesitancy.
Seems like there'll be a low bar Ansari, Eric go ahead.
I was just going to say so.
I appreciate the clarification and.
I'd just say.
We feel we're starting commercially from a very good squad based on the data and it really comes down to the data more than anything else right.
We couldnt be more pleased with the data set that we have we think it resonated.
We've talked about in the past and the momentum that we saw as the open label study was conducted even amidst the pandemic.
We saw it with the acceptance of the manuscript into the New England Journal of Medicine.
Lisa has commented earlier and can maybe comment again just in terms of the Med affairs side, which we think is really important work that we have to do.
With our partners and ensuring that that people know about this technology. They know about this profile and maybe Lisa can come in.
Yeah, No I I think I I can't overstate really the impact from the New England Journal paper in in and really solidifying the position of the data for so many of the physicians.
I think not only within folks who had been watching and wanted to see the whole dataset I think I can also say that we've heard from people who were still somewhat skeptical and.
Still hanging on to FMT or other potential alternatives, who have now contacted us and said now that I've seen that data set in a peer reviewed and this particular peer review journal.
And I've seen the data for myself I really I'm, just blown away and I can't I can't wait to be able to use it. So I think we're well positioned to be able to.
Through the education that we need to do.
I guess you are and thanks.
Thanks for taking my question looks like.
Publication, you, Joe Metz, and some going to help with the fences. Thank you and congrats.
Congrats on the progress.
Thanks for the question.
Thank you I'm showing no further questions so with that I'll turn the call back over to management for any further remarks.
So thank you and I want to thank everyone for joining our call today and for your continued interest in the series. We look forward to keeping you updated on our progress and with that we'll conclude hope everyone has a great day, thanks very much.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating and you may now disconnect.
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Yes.
Okay.
Yes.
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