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spk00: Good morning, and welcome to Synlogic's first quarter 2022 conference call. At this time, all participants are in a listen-only mode. There will be a question and answer session at the end of this call. Please be advised this call is being recorded. I would now like to turn the call over to Andrew Funderburg of Kendall Investor Relations. Please proceed.
spk07: Thank you, operator. Good morning, and thank you for joining us on today's conference call. This morning, we issued a press release which outlines our first quarter 2022 financial results and additional business updates. The release is available on the investor section of our website at www.simlogictx.com. Joining me on this call are Dr. Aoife Brennan, President and Chief Executive Officer, Molly Harper, Chief Business Officer, Dave Hava, Chief Scientific Officer, and Michael Jensen, Chief Financial Officer. Other members of the management team will be available during the Q&A. During the call, Aoife will provide a review of first quarter highlights and recent progress, including an update on our lead program in PKU, and Molly will share her perspective on the PKU opportunity. Dave will discuss her earlier stage programs and collaborations, and Michael will provide a financial overview. Following our prepared remarks, we will open the call for questions. As we begin, I'd like to remind everyone that comments today may include forward-looking statements made under the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made as of the date hereof and are subject to numerous factors, assumptions, risks, and uncertainties, which change over time. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including those described under the heading Forward-Looking Statements in Synlogic's press release from earlier today or under the heading Risk Factors in Synlogic's most recent Form 10-K or in later filings with the SEC. Synlogic constitutes not to place undue reliance on any forward-looking statement. Now, I'd like to turn the call over to Aoife.
spk04: Thanks, Andrew. Good morning, everyone, and thank you for joining us. I'm happy to share with you today updates on our recent progress as well as our financial results from the first quarter of 2022. We've had a busy first quarter with significant progress. Michael Jensen joined us as Chief Financial Officer, bringing an impressive financial and operational background from biopharma and healthcare companies across therapeutic categories and through commercialization. This quarter also included a return to in-person presentations at scientific congresses. In the month of May, our congress presentations cover preclinical and clinical program data, as well as platform analytics from our manufacturing team, highlighting Synlogix's achievements across multiple domains. Looking ahead, while our Phase II program in PKU progresses, We, like others in the industry, have been affected by persistent and broad-based factors, most notably labor shortages impacting our clinical trial sites. For us, these challenges increased in parallel with implementation of the second arm of the symphony study for SYNB 1934. Given this, today's press release updated timelines for our PKU programs. with Phase II data now expected in the second half of this year and Phase III initiation in the first half of 2023. The milestones for HCU and enteric hyperoxaluria programs remain unchanged, with expected proof of concept in enteric hyperoxaluria and healthy volunteer days in HCU in the second half of 2022. Importantly, these PKU program updates do not reflect challenges with patient interest or trial competition. It has been the opposite. The more we engage with KOLs, clinicians and the PKU patient community, the more excited we are about the importance of and demand for a new treatment option and what our potential product profile could mean. As a disease, PKU presents both a significant medical need for a new treatment option and a relatively de-risked path from a regulatory and commercial perspective. Despite being a devastating disease with multiple FDA-approved treatments, a large majority, over 75% of patients with PKU today remain untreated or undertreated due to limitations of current options, both in safety and efficacy. At the same time, having two FDA-approved drugs provides us with regulatory precedents that are helpful and unusual in rare disease drug development. These precedents include a path to full approval based on the biochemical primary endpoint of plasma B reduction. They also provide precedents of approval based on one registrational study and without an advisory committee. These approved drugs also provide examples of Phase III study designs and related considerations that led to FDA and EMA approvals. Our interim Phase II proof-of-concept data last year showed a potential profile that is differentiated and well-suited for the patients who need a new option. A potentially efficacious, safe oral treatment that could be used as either monotherapy or as an adjunct to CUVAN or sepraterin. We look forward to providing an update on our phase two results in the second half of this year as we advance this program forward towards phase three and ultimately registration. I'd like to now hand the call over to Molly to expand upon our path to bringing the PKU program through to patients.
spk01: Thank you, Aoife. Building on Etho's description of the clinical and regulatory program, PKU and Synlogix approach in particular presents several advantages for commercialization. First, for a rare disease, this is a large population. And despite two approved treatments, a large majority of patients remain untreated due to the limitations of today's treatment options. The large untreated patient population reflects cuvan or sapropterin non-responders for whom the other approved therapy, Palanzeke, a daily injection, is not a viable option. The latter situation is usually due to safety concerns given the risk of anaphylaxis and allergic reactions. For those who do respond here and stay on Kuven, their fee levels are often remain above targets, presenting an opportunity for adjunctive treatment. In short, the vast majority of people with PKU need new treatment approaches. whether as a monotherapy or an adjunctive option. And as Ethan noted, we are thrilled to be advancing development of a potentially effective, safe, orally administered monotherapy and adjunctive treatment option for individuals with PKU. We designed our drug candidate to consume fee without risk of systemic absorption and the associated adverse events seen in other biotherapeutic approaches. The sachet product presentation being studied and expected for commercialization is an easily administered lyophilized powder taken with meals three times a day. The sachet format is familiar to this patient population as the same is used for Kuvan and often nutritional supplements. With this expected product profile, we are advancing a new treatment option for PKU with the potential for two distinct segments. the untreated monotherapy patients, and also as an adjunctive treatment to CUBAN or sepropterin. As laid out here, you can see that focusing just on the initial launch population with the greatest pent-up demand, these two segments provide an addressable patient population of more than 3,500 patients in the United States. With this clear clinical positioning, the way PKU is managed in the United States and many other countries presents several advantages for commercialization. First, PKU patients are diagnosed and well-connected starting at birth through newborn screening. There is a very active advocacy organization. The prescribing clinicians are concentrated at well-defined treatment centers. There are strong precedents for coverage and reimbursement via the pharmacy benefit and prior authorization processes. and we will use the well-established specialty pharmacy and distribution channel. Lastly, Synlogic will benefit from the streamlined and simplified patient support needs of an orally administered drug without the need to provide the support of injection training or infusion clinic setup so often seen in other rare disease therapies. With that, I'd now like to hand the call back to Aoife to discuss the PKU program's path forward to phase three.
spk04: Thank you, Molly. I'd like to review the ongoing phase two study of our PKU program and what we're looking for in our upcoming data. First, the drug candidates. The diagram on this slide illustrates our closely related drugs, CINB1618 and CINB1934. We developed CINB1934 starting from CINB1618 and using directed evolution to increase the productivity of the PAL enzyme that metabolizes feed. There are, in fact, only five amino acid changes needed to achieve that optimized activity, and the strains are over 99% genetically identical. You'll recall that in September, we announced phase one results from our head-to-head study in Healthy Volunteers between CINB 1618 and CINB 1934. This established a safety bridge between the two and confirmed that 1934 is greater potency based on multiple biomarkers of feed consumption in healthy volunteers. Based on that Phase 1, we made the decision to add a second arm to our Phase 2 Symphony 1 study to obtain data with SYNB 1934 in PKU patients. Meanwhile, at the same time, we announced our interim analysis of the Phase 2 Symphony 1 study in patients with statistically significant and clinically meaningful reductions in plasmaphe for SINB1618. The remaining data from the phase two study will indicate effects in PKU patients for the first time for both drug candidates, and also provide data regarding use as both monotherapy and adjunctive treatment, an important step as we proceed to phase three with the selected drug candidate. We anticipate data from the Symphony 1 study, a Phase 2 study in patients with classic PKU, for both drug candidates. This population has fee levels above 600 micromoles per liter at screening and is not adequately served by available therapies. Each patient functions as their own control. Subjects are placed on a strict diet that's designed to match their usual protein and fee intake, and each patient has a diet run-in followed by baseline assessments. We've included both patients currently untreated as well as those on sacroterin to assess the drug candidates as monotherapy and as an adjunctive option. Patients receive increasing doses of the drug over two weeks with repeat on-treatment assessments followed by a washout period. The diet management is maintained throughout the trial out to day 29. We measure label D5 fee prior to dosing and at day 14. As a reminder, because of our approach, we can utilize this highly drug-specific marker of activity that confirms our drug candidates are consuming fee in the GI tract independent of a placebo-controlled arm. Measures of fasting plasma C are taken at baseline, prior to dosing, after the end of the dose ramp at day seven, and after a week at the treatment dose on day 14. We also collect data on safety and tolerability throughout the trial. Again, it was our positive interim analysis last fall with Cindy 1618, and after establishing the Faith One Safety Bridge with both candidates and healthy volunteers and greater potency, with CINB 1934, that we added a second arm to the study for CINB 1934. We amended the inclusion criteria to enable evaluation of adjunctive use potential by allowing enrollment of patients who are on treatment with sacroterin but still have uncontrolled blood fee levels. This should allow us to review both monotherapy and adjunctive data. At this point, we demonstrated proof of concept with CINB 1618 and PKU patients, and for CINB 1934, have established the safety bridge to CINB 1618 and demonstrated greater potency in healthy volunteers. In addition, since last September, we've progressed our work on process development and stability, further de-risking the path to commercialization from a manufacturing perspective. Barring any inconsistencies with the profile already observed for CINB 1618 in Symphony, and SINB 1934 and Healthy Volunteers, we would advance SINB 1934 to Phase 3. Pending completion of Symphony 1 will conduct an end-of-Phase 2 meeting with the FDA, which will allow us to confirm specifics of the study plan, including timing and other considerations, prior to initiating Phase 3. In summary, we believe our path forward is clear as we advance our program into registrational studies and potentially towards commercialization. I'll now turn it over to Dave to discuss our other promising clinical and preclinical pipeline programs. Dave.
spk08: Thanks, Aoife. I'd like to review the additional programs we're advancing from our very active pipeline. We expect that CINB 1353 will be entering the clinic this year, and we'll share data from our phase one trial and healthy volunteers for homocystinuria in the second half of this year. CINB 1353 is highly synergistic with the PKU program in both its scientific approach and the high overlap of treating clinicians. Our program for enterokyproxyluria, CINB 8802, is on track for a proof-of-concept readout in 2022. We presented data last year from healthy volunteers that we view as promising proof-of-mechanism. The current portion of the ongoing study is in patients with Roux-en-Y gastric bypass surgery who have elevated absorption of oxalate to evaluate whether CINB 8802 can lower urinary oxalate in those patients. We've also added a second phase one study to the CINB 8802 program to continue to build our clinical data set in patients with Roux-en-Y gastric bypass. This study will be performed in an inpatient setting where we can collect diet data as well as high-quality 24-hour urine and fecal samples, and we expect to enroll 10 patients. The new Phase 1 study will evaluate a version of the CINB882 strain modified to remove the genes for colobactin synthesis. This modified strain and study are within the same CINB882 IND. and we believe can support the demonstration of proof of concept for SYNB 8802 in 2022. We're leveraging our platform to advance preclinical programs for other metabolic diseases, like gout, and for immunological conditions, such as inflammatory bowel disease. We look forward to sharing updates about these programs as they progress through development. We also have an ongoing collaboration with Roche to develop products for inflammatory bowel disease around a single target in parallel to our in-house efforts. I'll now turn things over to Michael to review our financial results.
spk05: Thanks, Dave, and good morning, everyone. Early this morning, we released our financial results for the first quarter ending March 31st, 2022, and I'm pleased to review the highlights of those results with you now. Revenue was 0.2 million for the first quarter of 2022. There was no revenue for the same period in 2021. Revenue for Q1 of 2022 was due to our collaboration with Roche with the discovery of a novel synthetic biotic for treatment of inflammatory bowel disease or IVD. For the first quarter of 2022, the company reported a consolidated net loss of 15.7 million or 22 cents per share. compared to a consolidated net loss of $15 million of $0.36 per share for the corresponding period in 2021. Turning to the balance sheet, Synlogic ended the first quarter of 2022 with $120.5 million in cash equivalents and marketable securities, compared to $136.6 million as of December 31, 2021. On to our current operating plan. We expect that our cash will take us into 2024 and enable Synlogic to advance our clinical programs through multiple important data readouts across the metabolic portfolio. Thank you for your attention, and we look forward to keeping you updated on future calls. I will now turn the call back over to Aoife to wrap things up.
spk04: Thank you, Michael. This is an exciting period for Synlogic as we advance all of our clinical stage programs and look towards the series of data readouts, including PKU Phase 2 results, followed by Phase 3 initiations for that program. We're well positioned with a strong balance sheet to advance these important programs and are in the fortunate position of having funds available to support us well into 2024. I'm very pleased with all of our progress and the commitment of our entire team to advance promising therapies to patients in need of new treatment options. We will now open the call for questions.
spk00: If you'd like to ask a question at this time, please press the star then the number one key on your touch tone telephone. To withdraw your question, press the pound key. Again, that is star then one if you'd like to ask a question. Our first question comes from Joseph Schwartz with SVB Securities.
spk03: Hi, I'm Doree Dalyan for Joe. Thank you for taking our questions. First, you mentioned in your prepared remarks that labor shortages have affected your Phase II PKU trial, and based on the timelines, it seems like it's just affecting your PKU program. So I was just wondering if you could please provide additional details on how this impacts your PKU program but not your enteric hyperoxaluria, or homocystinuria program? And I have a follow-up. Thank you.
spk04: Yeah, thanks, Geri, for the question. So I think we were very unfortunate in terms of timing. Right around the December, January, February timeframe, we were implementing a major amendment to the study. We had assumed that that would go smoothly and follow the usual timelines. And what we found was that sites were having very difficult times as all businesses were around that time, dealing with Omicron and individuals being out of work and turnover there. So it really hit us at a time when we were making a big change to the study to implement the amendment to add 1934 to the trial, which really had a knock-on effect on all of the downstream activities. We had hoped that we would be able to make up for some of those delays as we went into the year, but unfortunately had to make the decision that... We need to change our guidance within the last couple of weeks. So that's kind of, I think, it was a perfect storm, if you will, of right at the time when the study was coming into an intense period, you know, we were seeing the effects of COVID and the Omicron variant that obviously we didn't anticipate last September. So I think that's why it had the disproportionate impact on the PKU program, less so the other studies that were already up and running at that time. Does that make sense?
spk03: Yes, that's helpful. Thank you. And then I guess I have two more questions. Could you provide additional color on the ordering or when we can expect the updates from your three programs in second half?
spk04: Yeah, so as you know, most of our studies are intense studies, but they're of short duration. So it's very difficult for us to tell when exactly or what the order of those studies is going to be. As we go on in the year, we may be able to tighten up the guidance a little bit. We remain confident that we'll have lead-outs from all three clinical programs in 2022. But in terms of which one's going to come first, second, and third, I really can't tell you at this point.
spk03: Okay, great. And then my final question is, I guess you've accumulated a fairly sizable amount of data so far with your platform. including data in PKU patients, enterococcal urea patients, and healthy volunteers. So I'm wondering if you could speak to a possible intrinsic variability associated with your technology. Do you think there is one? And if so, what do you think it is? Thank you so much.
spk04: Yeah, so I think you make a very good point. We have dosed, at last count, I think over 350 humans across all of the studies comprised of healthy volunteers as well as patients with disease. And I think what we see consistently across all of the studies that we've done is that the bacteria, they perform as designed. So we design them not to colonize. They don't colonize. We don't see any systemic toxicity across any program. We see consistently that the bacteria switch on the function that they've been engineered to perform in vivo in the human GI tract. in a way that's very predictable. So when you look back at some of our preclinical modeling, I think we've gotten better and better at predicting what kind of efficacy we see on average in humans. So I think for me that's very gratifying. It means the science is working and some of those translational questions that we had really early on as a company have really been de-risked at this point, so I think that's wonderful. I think the intrinsic variability question you're getting to is around the PKU program, and we saw some patients in the interim data set who had a really remarkable response in terms of phyloring, and then other patients who had a less impressive response, so there was some variability there. We don't understand exactly what the driver of that variability is as we go forward and dose more patients, we may get additional insights. My best guess at this point in time is that there are differences in all of us between our GI physiology. Some of us have lower pH in our stomach. Some of us have faster small intestinal transit times. And that variability results in, you know, the normal biological variability you see with any drug, where there are some patients who, you know, respond more optimally than others. But as we continue to learn from our studies in patients, I think we'll get better at informing and predicting. The nice thing across all of our programs is that we have these biochemical biomarkers that really give us a nice early readout, so we can really determine whether you know, which patient subsets are going to do well based on the actual endpoint pretty early on in the trial. You don't have to follow a patient for two years to work out whether or not they're going to respond. So I think that's an attribute that's very favorable based on the diseases and the indications we've chosen that we'll certainly be taking advantage of as we move forward into late-phase development across all the trials.
spk03: That's very helpful. Thank you again.
spk04: Thanks, Geri.
spk00: Our next question comes from Kay Nakai with Chardon.
spk06: Thanks. So when we get to the point where you're going to decide which PKU candidate to take forward, how much better would 1934 need to be for that to be the one you take forward? Yes.
spk04: So that's a great question, Kay. So just to take a step back, what we've already demonstrated with the PKU program is that 1618 achieves our kind of go forward as a strain for Phase 3. We had pre-specified some criteria that needed to be met, and what we've seen across the program is that 1618 achieves those criteria. The question now is, Which strain do we take forward? Is it 1618 or 1934? And across all of the studies that we've done to date, be they in vitro animal studies or a healthy volunteer crossover study, we've seen that 1934 is consistently 2x better in terms of activity, particularly around some of the biomarkers and the D5P lowering that we've seen in plasma. Our expectation is that 1934 will be the strain that we take forward into phase three. We're just looking for some confirmatory evidence in the second arm of symphony that there's nothing unanticipated with regard to safety and that that kind of biomarker strain activity pulls through what we've seen up to this point. So I think, you know, based on everything we know today, the likelihood is that 1934 will be the go-forward strain.
spk06: Okay, and then can you give us some more color on the process development improvements you implemented?
spk04: Yes, yeah, I think Tony Awad is on the call. He's been leading that effort here. So I'll pass you over to Tony to describe some of the work that his team have been doing to prepare for a Phase III study initiation. Okay.
spk10: Yeah, great. Thanks, Yves. As was mentioned earlier, we have made concrete progress in currently executing on our plans. There's so much that goes into, again, ready for phase three, obviously. But to highlight and call out a couple of the critical paths or important paths, we finalize our formulation, which is key, and we finalize our presentation, which you heard about a little bit ago from Molly. This presentation is very patient-friendly. To give an example, it's like taking a vitamin C sachet, which everyone's familiar with, pouring it in a glass of water, mixing it, and drinking it. It's very easy to take orally. We've also optimized and scaled up our manufacturing process to allow for higher production and yield. That's really the process that would go forward into Phase 3 and commercial. In addition, We've completed renovation expansion of our GMP manufacturing suite to support the scaled-up process and the production that we will need moving ahead. And to tie it all together, of course, into the diverse path, we've had some very positive support of CMC regulatory correspondence with the agency. We're seeing eye-to-eye and we understand what they're requiring of us and we're happy with where we stand. So pulling this all together and knowing that our process of scale will meet the demands for phase three in commercialization, we really believe that we've de-risked the CMC path and we're driving well towards phase three initiation. Does that answer your question? Can I tell you?
spk06: Yeah, so just in terms of avoiding any possible delays due to comparability, you feel like your conversations with the FDA, that's not going to be any kind of issue. Okay.
spk10: Yeah, absolutely. I mean, so to back up a little bit, you know, our technology, we're very big on single-use technology, so nothing is really tied to the facility. Our scale-up is going 10x, which is very reasonable within regulatory acceptance criteria. And like I mentioned, the feedback from the agency has been very positive. We know the path ahead. We know what we need to do from a comparability standpoint to move forward into this process that we're taking forward to phase three. So we feel very comfortable where we are.
spk06: Okay, thank you. And then just finally for 8802, can you talk about the modifications in the strain?
spk04: Yes, sure. I think Dave is on the line, and Dave's our chief scientific officer, and I think probably best place to describe some of the small tweaks we've made to 8802.
spk08: Yeah, sure. I'm happy to do that. So the change that we've made is to delete a set of genes that synthesize a product called colobactin. So colobactin preclinically in animals has been associated with some genotoxicity or risks for genotoxicity. Whether there's a long-term risk to that in humans is really unknown. There's really not a lot of great data to support that, so it's somewhat controversial if it would be a concern. But rather than try to prove the negative, and given the fact that we're able to manipulate the strains pretty readily, we decided just to remove it from our strain, take that risk off the table, and move forward with a strain that doesn't synthesize those genes. That's true for the 802 strain, and that's also true for other strains in development.
spk06: Okay. And then with respect to that inpatient study that you'll do, you know, you talked about the advantages of getting samples, but anything else about that patient population that would help to make it more homogeneous in any way?
spk04: No, so I think the patient population are patients with Roux-en-Y. The big piece by, you know, we can't control biologic variability by bringing people into a unit, but what you can control is their diet, and you can make sure that the 24-hour urine collections are complete. So I think those are obviously, you know, potential sources of variability when you're looking at a urine reoxalate endpoint. So understanding those potential sources of variability, I think, is really important for us. particularly given how important urinary oxalate measurements are going to be for this program going forward. So we thought it was prudent to invest in that now, particularly given the strong data we've seen in healthy volunteers with this strain. So we're really looking forward to seeing some data from that trial when it reads out later this year.
spk06: Okay, very good. Thank you.
spk00: Our next question comes from Mark Breedenbach with Oppenheimer.
spk02: Hey, good morning, and sorry to hear we'll have to wait a little bit longer for that Symphony 1 update. Just a couple questions from me. First, with respect to your respective modeling of phenylalanine reduction in PKU patients using the healthy volunteer data, I'm just wondering if baseline plasma fee factors into the predicted phenylalanine lowering In other words, do you think the magnitude of the treatment effect could potentially be skewed simply by selecting patients who start out with either very high or very low baseline serum fee? And then a second question is just maybe on the regulatory front. I'm wondering what your current plans are for engaging with the EMA with respect to regulatory path at Europe, and if we could expect the planned phase three trial to include XUS clinical sites. Thanks.
spk04: Yeah. Yeah, two great questions, Mark. On the biology one, first of all, What we predict based on our modeling is that the absolute fee lowering will be naive to the baseline levels, and certainly that's what we've seen to date in the, you know, small number of patients from the Symphony study that we've looked at. We have, to be included in the study, patients need to have a blood fee level of greater than 600 micromole per liter. We have patients, obviously, who are, you know, just above that cut point, and then we have patients who are coming in well into the thousands in terms of their baseline fee levels. And we seem to see consistent results regardless of where patients come in. So to date, the clinical data and the modeling seem to be very consistent. As we learn more, obviously, from Symphony, we'll continue to look at that. But to date, it seems like there is potential for the strain to be active and to deliver efficacy regardless of where patients are coming in in terms of baseline levels. The second question of EMAs is a great one. Molly has done a lot of great work in the last couple of months to really understand for us the potential commercially outside of the U.S. for a product, and we believe actually there's a significant commercial opportunity and a significant opportunity to bring a new treatment to patients with PKU around the world. As you know, there are about 17,000 patients in the U.S. with PKU, When you look at globally the addressable population, we're talking about 55,000 patients. So engaging with regulators outside of the FDA in the U.S. is absolutely something that we're focused on. We've already started that work and we'll understand what the regulatory requirements are, but assuming that it's not onerous and that it makes sense from a business and an investment perspective, I'm certainly very committed to advancing treatments for PKU patients globally, and I think we have something that could really bring a lot of value to patients outside of the U.S., so we'll be looking to do that as quickly as possible as we think about our Phase 3 plans.
spk02: Okay, but too early to say whether or not the Phase 3 trial would include ex-U.S. sites?
spk04: Well, as you know, Mark, the first step is you engage with the regulators to understand what the paths and what they're going to require. We're obviously not going to wait if You know, the most important thing for us from a business perspective is to get the PKU product approved as quickly as possible. So until you understand a little bit more from regulators exactly what that path to opening sites outside the U.S. is, it's very difficult to give a commitment that you're absolutely going to do it because it just may not make sense from a business and timeline perspective to do so. But certainly as a company, we intend to do that and we want to do that and assuming that it doesn't, you know, that there are no big delays we would intend to enroll the Phase III study as quickly as possible, which is definitely aided by having more sites outside of the U.S. So that's certainly our intent. Until we have a clear regulatory path and agreement, it's very difficult to say for certain that that's going to happen.
spk02: Does that make sense? Okay, thank you so much. Yeah, it does. Thank you.
spk00: As a reminder, if you'd like to ask a question at this time, that is star, then 1. Our next question comes from Ram Selvaraju with H.C. Wainwright.
spk09: Hi, this is Mitchell Ambaram. Thank you for taking our questions. The first question I have is, you know, for the PKU readout, could you just kind of elaborate on the breadth of data we can expect to see and how much will the data go into both strains?
spk04: Yeah. So the Symphony study was designed initially to have 12 patients dosed with 1618s. These patients had to be classic PKU. They weren't able to be, you know, we excluded patients who were on any currently available pharmacotherapy for PKU. We announced data last September from the first eight patients to complete the study. It looked really promising, and as we started to think about, okay, moving forward into phase three, we made the decision to make two amendments. Number one was to add an additional arm with 1934 up to 12 patients, And number two was to allow patients who were on saproteran or cuvan but had a blood fee level of over 600 to participate. So those are the kind of two changes we made. We anticipate that the next readout would include, you know, complete data from the first arm. We announced data from the first eight in September. as well as data from the second arm and some small amount of data in the combo setting where we're administering either strain on the background of saproteran. So that's kind of the breadth of what's anticipated in the second half of the year, and we're certainly really looking forward to continue to build that data set and continue to build our understanding in PKU and sharing it externally as soon as we can.
spk09: Okay. Okay. And what would constitute the key driver of a go, no-go decision for the 8802 program in teric hyperoxylyria?
spk04: So that program is being developed for patients who have increased dietary oxalate absorption. We're really compelled by the unmet need in this indication. We continue to hear that there are patients who have you know, really severe recurrent stone disease where they're having multiple episodes of kidney stones per year. And we just did some data and shared some data externally at Kidney Week last year showing that these patients also have a very significant risk of chronic renal failure. So it really is a big unmet need. Based on our feedback, a 20% urinary oxalate lowering would be significant and would result in a lowering of the incidence of stones in these patients. So that's really what we're looking for is a 20% urine reoxalate lowering to achieve proof of concept and to give us confidence that we really do have a product that can address that unmet medical need. So that's kind of our goal criteria from an efficacy perspective.
spk09: Great. Thank you very much for taking the questions.
spk00: I'm showing no further questions in queue at this time. I'd like to turn the call back to Dr. Aoife Brennan for closing remarks.
spk04: Thanks so much, Liz, and thanks so much, everyone, for joining us this morning. We look forward to keeping everyone updated as we progress through this very exciting year for Synlogic. Thanks so much.
spk00: This concludes today's conference call. Thank you for participating. You may now disconnect.
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