Synlogic, Inc. (SYBX) on Q1 2022 Results - Earnings Call Transcript
Operator: 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 Funderburk of Kendall Investor Relations. Please proceed. Andrew Funderburk: 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 Investors section of our website at www. synlogictx.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 our 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 statements 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 cautions you not to place undue reliance on any forward-looking statements. Now I'd like to turn the call over to Aoife. Aoife Brennan: 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 for 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 health care 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 Synlogic'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 time lines for our PKU program 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 data 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 derisked path from the regulatory and commercial perspective. Despite the devastating disease with multiple FDA-approved treatments, a large majority over 75% of patients with PKU today remain untreated or under-treated 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 Phe reduction. They also provide precedence of approval based on one registrational study and with as an advisory committee. These approved drugs also provide examples of Phase III study designs and related considerations that led to FDA at EMA approval. 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 auction, a potentially efficacious, safe oral treatment that could be used as either monotherapy or as an adjunct to Kuvan or sapropterin. We look forward to providing an update on our Phase II results in the second half of this year as we advance this program forward towards Phase III and ultimately registration. I'd like to now hand the call over to Molly to expand upon our path to bring the PKU program through to patients. Molly Harper: Thank you, Aoife. Building on Aoife's description of the clinical and regulatory program, PKU and Synlogic's approach in particular, presents several advantages for commercialization. First, for 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 Kuvan or sapropterin non-responders for whom the other approved therapy, Palynziq 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 Kuvan, their Phe 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 injunctive option. And as Aoife 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 Phe 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 as 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 Kuvan or sapropterin. 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 – for 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 set up 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 programs path forward to Phase III. Aoife Brennan: Thank you, Molly. I'd like to review the ongoing Phase II study of our PKU program and what we're looking for in our upcoming data. First, the drug candidate. The diagram on this slide illustrates our closely related drugs, SYNB 1618 and SYNB 1934. We developed SYNB 1934 starting from SYNB 1618 and using directed evolution to increase the productivity of the PAL enzyme that metabolizes Phe. There are, in fact, only five amino acid changes needed to achieve that optimized activity and the strains are over 99% genetically identical. You recall that in September, we announced Phase I results from our head-to-head study in healthy volunteers between SYNB 1618 and SYNB 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 I, we made the decision to add a second arm to our Phase II 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 II SYMPHONY-1 study in patients with statistically significant and clinically meaningful reductions in plasma Phe for SYNB 1618. The remaining data from the Phase II 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 III with the selected drug candidates. We anticipate data from the SYMPHONY-1 study, a Phase II study in patients with classic PKU for both drug candidates. This population has three 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 Phe 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 sapropterin to assess the drug candidate as monotherapy and as an adjunctive option. Patients received increasing doses of the drug over two weeks with repeat on-treatment assessment followed by a washout period. The diet management is maintained throughout the trial out to day 29. We measure label D5-Phe prior to dosing and at day 14. As a reminder, because our approach - because of our approach, we can utilize this highly drug-specific marker of activity that confirms our drug candidates are consuming Phe in the GI tract independent of a placebo-controlled arm. Measures of fasting plasma Phe are taken at baseline prior to dosing after the end of the dose ramp of day 7 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 SYNB 1618 and after establishing the Phase I safety bridge with both candidates and healthy volunteers and greater potency with SYNB 1934 that we added a second arm to the study for SYNB 1934. We amended the inclusion criteria to enable a valuation of adjunctive use potential by allowing enrollment of patients who are on treatment with sapropterin but still have uncontrolled blood Phe levels. This should allow us to review both monotherapy and adjunctive data. At this point, we demonstrated proof-of-concept with SYNB 1618 in PKU patients. And for SYNB 1934 have established the safety bridge to SYNB 1618 and demonstrated greater potency in healthy volunteers. In addition, since last September, we've progressed our work on process development and stability, further derisking the path to commercialization from the manufacturing perspective. Barring any inconsistencies with the profile already observed for SYNB 1618 in SYMPHONY and SYNB 1934 in healthy volunteers, we would advance SYNB 1934 to Phase III. Pending completion of SYMPHONY-1 will conduct end of Phase II meeting with the FDA, which will allow us to confirm specifics of the study plan, including timing and other considerations prior to initiating Phase III. 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? Dave Hava: Thanks, Aoife. I'd like to review the additional programs we're advancing from our very active pipeline. We expect that SYNB 1353 will be entering the clinic this year, and we'll share data from our Phase I trial in healthy volunteers for homocystinuria in the second half of this year. SYNB 1353 is highly synergistic with the PKU program in both its scientific approach and the high overlap of treating clinicians. Our program for enteric hyperoxaluria, SYNB 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 SYNB 8802 can lower urinary oxalate in those patients. We've also added a second Phase I study to the SYNB 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 I study will evaluate a version of the SYNB 8802 strain modified to remove the genes for colibactin synthesis. This modified strain and study are within the same SYNB 8802 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, blackout 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. Michael Jensen: Thanks, Dave, and good morning, everyone. Earlier this morning, we released our financial results for the first quarter ending March 31, 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 IBD. For the first quarter of 2022, the company reported a consolidated net loss of $15.7 million or $0.22 per share compared to a consolidated net loss of $15 million or $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, cash equivalents and marketable securities compared to $136.6 million as of December 31, 2021. Under 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. Aoife Brennan: Thank you, Michael. This is an exciting period for Synlogic as we advance all of our clinical stage programs and look towards a series of data readouts, including PKU Phase II results, followed by Phase III initiation 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. Operator: First question comes from Joseph Schwartz with SVB Securities. Unidentified Analyst: Hi. I'm Julie dialing in 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 time line, it seems like it's just affecting your PTU program. So I was just wondering if you could please provide additional detail on how this impacts your PKU program, but not your enteric hyperoxaluria or homocystinuria program? And I have a follow-up. Thank you. Aoife Brennan: Yeah. Thanks, July, for the question. So I think it was - we were very unfortunate in terms of timing and right around the December, January, February time frame we were implementing a major amendment to the study. We had assumed that, that would go smoothly and follow the usual time lines. And what we found was that sites were having very difficult time, 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, have 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, right at the time when the study was coming into an intense period, 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 and less so the other studies that were already up and running at that time. Does that make sense? Unidentified Analyst: Yes. That's helpful. Thank you. And then I guess I have two more questions. Could you provide additional color on ordering or when we can expect the updates from your three programs in the second half? Aoife Brennan: Yeah. So as you know, most of this - our studies are short, they're in 10 studies, but they are 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, and we may be able to tighten up the guidance a little bit. And we remain confident that we'll have readouts from all three clinical programs in 2022. But in terms of which one is going to come first, second and third, I really can't tell you at this point. Unidentified Analyst: 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, enteric hyperoxaluria patients and healthy volunteers. So I'm wondering if you could speak to a possible intrinsic variability associated with your technology. Is there - do you think there is one? And if so, what do you think it is? Thank you so much. Aoife Brennan: 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 derisked 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 some - we saw some patients in the interim data set who had a really remarkable response in terms of Phe lowering 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 it have faster small intestinal transit times, and that variability results in the normal biological variability you see with any drug where there are some patients who 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 which patient subsets are going to do well based on the actual endpoint pretty early on 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. Unidentified Analyst: That's very helpful. Thank you, again. Aoife Brennan: Thanks, Julie Operator: Our next question comes from Keay Nakae with Chardan. Keay Nakae: Yeah, 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? Aoife Brennan: Yeah. So that's a great question, Keay. 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 III. We had set - prespecified some criteria that needed to be met. And what we've seen across the program is that 1618 achieve 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 CE D5-Phe lowering that we've seen in plasma. Our expectation is that 1934 will be the strain that we take forward into Phase III. 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 kind of biomarker strain activity pulls through what we've seen up to this point. So I think based on everything we know today, the likelihood is that 1934 will be the go-forward strain. Keay Nakae: Okay. And then can you give us more color on the process, excuse me, development improvements you implemented? Aoife Brennan: 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. Tony Awad: Yeah. Great. Thanks, Aoife. 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 III, obviously. But to highlight call out a couple of the critical paths are important paths. We finalized our formulation, which is key. And we finalized our presentation, which you heard about a little bit ago from Molly. This presentation is very patient-friendly. It's to give you an example, it's like taking the vitamin C, which sachet, which everyone is familiar with, pouring in glass and water, mixing and drinking it. So very easy to take orally. We've also optimized and scaled up our manufacturing process to allow for higher production and yield, and that's really the process that would go forward into Phase III and commercial. And in addition, we've completed renovation expansion of our GMP manufacturing suite to support the scale-up process and the production that we will need moving ahead. And to tie it all together, of course, into the rest of the path, we've had some very positive support of CMC regulatory corresponds 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 scale will meet the demands for Phase III and commercialization, we really believe that we've derisked the CMC path and we're driving well towards Phase III initiation. Does that answer your question? Keay Nakae: 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. Tony Awad: Yeah, absolutely. I mean so to back up a little bit, our technology, we were 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 comparable standpoint to move forward into this process that we're taking forward to Phase III. So we feel very comfortable where we are. Keay Nakae: Okay. Thank you. And then just finally for 8802, can you talk about the modifications in the strain? Aoife Brennan: Yes, sure. I think Dave is on the line and Dave is our Chief Scientific Officer, and I think probably best place to describe some of the small tweaks we've made to 8802. Dave Hava: 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 colibactin. So colibactin preclinically in animals has been associated with some genotoxicity or risks for genotoxicity. Whether there's a long-term risk to that 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 schemes. So that's true for the 8802 strain, and that's also true for other strains in development. Keay Nakae: Okay. And then with respect to that inpatient study that you'll do - 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? Aoife Brennan: No. So I think the patient population are patients with Roux-en-Y. The big piece by - 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-urine collections are complete. So I think those are obviously potential sources of variability when you're looking at a urinary oxalate 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 the strain. So we're really looking forward to seeing some data from that trial when it reads that later this year. Keay Nakae: Okay. Very good. Thank you. Operator: Our next question comes from Mark Breidenbach with Oppenheimer. Mark Breidenbach: Hey, good morning. And sorry to hear we'll have to wait a little bit longer for that SYMPHONY-1 update. Just a couple of 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 Phe 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 B And then the 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 in Europe and if we could expect the planned Phase III trial to include ex-U.S. clinical sites? Thanks. Aoife Brennan: Yes. Yeah, two great questions, Mark. On the biology one, first of all, what we predict based on our modeling is that the absolute Phe lowering will be naive to the baseline levels. And certainly, that's what we've seen to date in the 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 Phe level of greater than 600 micromole per liter. We had patients, obviously, who are just above that cut point and then we have patients who are coming in well into the thousands in terms of their baseline Phe 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 EMA 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 is 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., it's absolutely something that we're focused on. We've already started that work. And understand what the regulatory requirements are. But assuming that it's not onerous and that it makes sense from the business and an investment perspective, I'm certainly very committed to advancing treatment 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 III plans. Mark Breidenbach: Okay. But too early to say whether or not that the Phase III trial would include ex-U.S. sites? Aoife Brennan: Well, as you know, Mark, you first step as you engage with the regulators to understand what the path and what they're going to require. We're obviously not going to wait if 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 time line 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 - 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 an agreement. It's very difficult to say for certain that, that's going to happen. Does that make sense? Mark Breidenbach: Thank you so much. Yeah, it does. Thank you. Operator: Our next question comes from Ram Selvaraju with H.C. Wainwright. Unidentified Analyst: Hi. This is Mitchell on for Ram. Thank you for taking our questions. The first question I have is 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? Aoife Brennan: Yeah. So the SYMPHONY study was designed initially to have 12 patients dosed with 1618. These patients had to be classic PKU. They weren't able to be - we excluded patients who are 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 III, 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 are on sapropterin or Kuvan, but had a blood Phe level of over 600 to participate. So those are the kind of two changes we made. We anticipate that the next readout would include complete data from the first arm. We announced data from the first eight in September, as well as data from the second arm and the - some small amount of data in the combo setting where we're administering either strain on the background of sapropterin. So that's kind of the breadth of what we anticipate 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. Unidentified Analyst: Okay. And what would constitute the key driver of a go, no-go decision for the 8802 program enteric hyperoxaluria? Aoife Brennan: So that program is being developed for patients who have increased - 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 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. And based on our feedback, a 20% urinary oxalate lowering would be significant and would result in a lowering of the instance of stones in these patients. So that's really what we're looking for is a 20% yearly oxalate 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 go criteria from an efficacy perspective. Unidentified Analyst: Great. Thank you very much for taking the questions. Operator: 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. Aoife Brennan: 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. Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.SYBX Ratings Summary
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Synlogic Reports Q4 Results, Shares Down 3%
Synlogic, Inc. (NASDAQ:SYBX) shares were trading 3% lower Friday afternoon following the company’s Q4 results.
The company has several clinical updates on deck for 2022— starting with initial results for SYNB1934 in PKU in the first half of the year—which is expected to inform a product candidate selection for a planned pivotal trial in the second half of the year.
With shares trading near cash, analysts at Oppenheimer see an attractive buying opportunity ahead of upcoming readouts.
