Synlogic, Inc. Q3 FY2021 Earnings Call

Good morning and welcome to Synlogic’s Third Quarter 2021 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 that this call is being recorded. I would now like to turn the call over to Daniel Rosan, Head of Finance and Investor Relations. Please proceed.

Thank you, operator. Good morning and thanks for joining us on today’s conference call. This morning we issued a press release that outlines our third quarter 2021 financial results and additional business updates. The release is available on the Investors section of our website at synlogictx.com. Joining me on this morning are Dr. Aoife Brennan, President and Chief Executive Officer; and Molly Harper, our newly employed Chief Business Officer. Other members of the management team will also be available during the Q&A. During the call, Aoife will provide a review of third quarter highlights and recent progress including an update on our program in Phenylketonuria, and Molly will share her perspective on the unmet need in PKU and the opportunity to impact the patients. Aoife will then return to provide an update on our metabolic portfolio. Finally, I will summarize our financial results for the quarter. Following our prepared remarks, we will open the call for your questions. As we begin, I would 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 cautions you not to place undue reliance on any forward-looking statements. And now I would like to turn the call over to Aoife.

Thank you, Dan. Good morning everyone and thank you for joining us. I’m thrilled to share with you today an update on our recent progress as well as our financial results for the third quarter of 2021. When we began 2021, we set out to prove the clinical potential of our Synthetic Biotic platform. We have the opportunity to demonstrate proof of concept in Phenylketonuria in our Phase 3 SynPheny study. And we’re thrilled to report that we’ve done just that. Our lead asset SYNB1618 has demonstrated a robust and statistically significant reduction in plasma Phe levels, and clear alignment across a multitude of study endpoints. This is the first time in the history of PKU drug development that a therapeutic that is delivered locally in the GI tract has had an impact on systemic Phe levels. Furthermore, we believe our evolved Synthetic Biotic SYNB1934 may demonstrate even more Phe lowering activity. This is also the first example of a biotherapeutic generated by the Synthetic Biotic platform, demonstrating robust proof of concept in a disease population. But we do not intend to stop at PKU. We’re building a robust portfolio with significant progress over the past quarter in multiple metabolic indications. In Enteric hyperoxaluria, as we shared at the American Society of Nephrology Kidney week, our product candidate SYNB8802 has demonstrated robust consumption of oxalates in the GI tract as measured by both urinary and fecal oxalate reduction. SYNB8802 has the potential to be a meaningful therapy for patients suffering from Enteric hyperoxaluria who, as we also reported at Kidney week, are at substantially increased risk of incident chronic kidney disease as a result of the insidious damage oxalate does to renal function over time. We continue to prosecute the proof of concept study of SYNB8802 in patients and will report on that data in 2022. We’re also proud to have unveiled this week with our partners at Ginkgo Bioworks our third oral metabolic program, which we call SYNB1353. SYNB1353 degrades homocysteine in the GI tract for the treatment of homocystinuria or HCU. HCU is an inborn error of metabolism and a natural extension of our work in PKU. We’ll be speaking more about this program as we prepare to file an IND and advance into the clinic next year. Our immunology pipeline continues to advance as well. We’re excited that our collaboration with Roche to develop a Synthetic Biotic medicine for the treatment of IBD is off to a fast start with the first milestone already achieved, and we have also completed enrollment in the combination arm of a phase 1 all-comers immuno-oncology study of SYNB1891 with anti-PD1L1. We look forward to sharing updates from that study later this week. In order to focus our resources on our own programs, however, we will not be continuing further studies of SYNB1891 at this time. Synlogic is well-positioned to deliver on the promise of our platform and bring a meaningful new therapeutic approach to patients. We are executing on our strategy, focusing on rare and niche metabolic diseases, where a targeted approach restricted to the GI tract can treat patients in ways other modalities cannot. Now let me welcome Molly Harper to the team and give her a few moments to share her thoughts on the unmet need in PKU. Molly comes to us with a wealth of pre-commercial launch experience in both broad and rare diseases in the United States and globally, and we are thrilled to have her build our capability as we look at pivotal development in PKU. Molly, over to you.

Thank you, Aoife. It’s incredibly exciting to join the Synlogic team, particularly at this momentous time. I’m delighted to share some initial observations regarding the remarkable opportunity that Synlogic has before us as we advance a program with the potential to transform the lives of those living with and affected by PKU. As a disease, PKU presents something of a paradox. So on the one hand, PKU is a well-characterized disease with a community that has seen tremendous progress. It is a sizable population for a rare disease and it has been extensively researched. The diagnosis is straightforward and universally implemented via newborn screening in many countries. In the United States, every person born since the 1960s who has PKU has been diagnosed at some point in their lives. There have been ICD9 and ICD-10 codes. There are dedicated clinics. There’s a vibrant and well-networked advocacy community providing clear links to those specialists and clinics. There are both well-defined medical sub-specialists as well as dietitian specialists who are clinical as well as research experts and who are passionate about taking care of and advancing research for this population. On the therapeutic side, multiple drugs have been approved. There is regulatory precedent. There are clear protocols for reimbursement. One of these therapies is now generic, facilitating empiric trial periods to determine response. And yet, what we perhaps have not heard enough about is that despite these attributes, PKU is a disease that continues to be devastating for those affected and for their caregivers. The burden of living with PKU is often extraordinary on every level; medically, psychologically, socially, and economically. Much of this burden is well documented, such as a large claims-based analysis that showed that even among those diagnosed and well-insured, there remains an eightfold greater risk of intellectual disabilities. One study which focused on patient populations connected to specialized clinics still showed that 70% have significant neuropsychiatric comorbidities, with 50% of those having multiple comorbidities, reflecting these complications and the limitations of truly transformative treatment for most patients. One study found that 70% of adults living with PKU were disconnected; and despite these drug approvals, many are not receiving treatment through established clinics. With multiple FDA-approved drugs, it’s hard to understand why this would be the case. Looking closer, these advances, while important, have unfortunately left the majority of those living with PKU in need of additional options. Utility is generally limited to people living with mild PKU, who maintain some functionality that responds to the mechanism of action of these treatments. This mild group represents a minority, about 30% of patients. This renders Phe reduction for all comers relatively modest at just a negative 10% decrease. With this, the burden of approximately 10 pills a day on top of required dietary restrictions and needed supplements can lead to intermittent compliance and risk discontinuation. For the classic or more severe PKU population, which makes up the majority of people living with PKU, the population who has been most significantly underserved by existing options today, injections do offer advocacy for those adults who can persist through the titration, which can extend over one calendar year with daily injections, and who have both the capacity and the vigilance to manage the risk of anaphylaxis at any moment, which is characterized in this boxed warning. It's important to note that even for those who adhere to both dietary requirements and drug therapy, there's a significant desire for a treatment that can provide additional Phe lowering or something closer to what most of us take for granted as a normal eating and social life. So looking to the split on the right side of the screen, the well-controlled segment represents those with more mild underlying disease who are able to respond to inherited treatment, as well as those children whose diets are closely managed by their caregivers. The larger part of this population includes those living with PKU who are in direct need of a novel treatment that provides significant reduction in plasma Phe, regardless of their treatment status. For several years now, the Synlogic team has been actively listening to and learning from the PKU community, who have been consistent in sharing their wish list for a new treatment option. That would be orally administered, convenient, safe, and efficacious. Designed with these exact needs in mind, the Synthetic Biotic approach to PKU has the potential to address these needs. The mechanism cannot be more intuitive: people with PKU cannot metabolize dietary Phe, which enters predominantly via dietary protein. Synlogic designed biotherapeutics with the potential to metabolize dietary Phe in the GI tract, delivering them orally, conveniently packaged, with a locally delivered mechanism and without systemic absorption and any associated potential risk. We recently were able to share an early view of how this has worked in those with the greatest need. Now let me ask Aoife to take you through the clinical data that we’ve been able to share today.

Thank you, Molly. Earlier this quarter, we presented two datasets which give us confidence in advancing our PKU program. Firstly, in SynPheny, a phase 2 study in patients with PKU, we achieved our target reduction in blood Phe levels in an interim analysis of eight patients with available data. Secondly, in a head-to-head comparison of SYNB1618 and SYNB1934, our optimized strains for PKU in healthy volunteers, we found that the Phe-consuming activity of SYNB1934 is approximately two times that of SYNB1618. This suggests that SYNB1934 may provide an even more attractive clinical profile. Based on these highly encouraging data, we will be adding SYNB1934 to the phase two SynPheny study and preparing to advance our PKU program into a pivotal phase 3 study. As you recall, our ongoing phase 2 SynPheny is a single-arm study in patients with classic PKU. This population has Phe levels above 600 micromoles per liter at screening and is not served by available therapies. It’s a more severe population than the BH4 sponsor population in which earlier treatments have been studied. The interim data we shared from the first eight patients to complete the study remains open to enrollment. An important design element of this study is that each patient functions as their own control. Subjects were placed on a strict diet designed to match their usual protein and Phe intake with a dietary run-in followed by baseline assessments. They then received increasing doses of SYNB1618 over two weeks, with repeat on-treatment assessments followed by a washout period. The diet management was maintained throughout the trial up to the day 29 assessment. There were two critical endpoints in this study. First, we performed an unveiled challenge test with a standardized breakfast containing labeled Phe at the beginning and end of the dosing period to determine if SYNB1618 prevents dietary Phe absorption. Second, we evaluated fasting plasma Phe, which was measured post-dosing after seven days, again on day 14, and at the end of the washout period on day 29. In these tests, the subjects received a standard breakfast containing D5 Phe. They received their first meal challenge on day 1 and then underwent the same test on day 15 after a dose of 3e11 cells, which is the highest dose studied. The purpose of this test was to determine whether SYNB1618 was metabolically active and metabolizing Phe in the GI tract and preventing its absorption. On the left panel, we can observe that it increases significantly with dosing. On the right panel is the area under the curve of blood D5 Phe compared to baseline, showing a reduction of 40% in the amount of D5 Phe absorbed from that meal. The combined production of TCA and lowering of blood Phe indicates that SYNB1618 is actively metabolizing Phe in the GI tract before it can be absorbed by the gut. Moving on to the next question of whether treatment with SYNB1618 for two weeks impacts fasting Phe levels in patients. Fasting blood Phe is a critical endpoint in PKU and the basis for FDA approval of products previously approved in this indication. It’s also the measure that physicians and patients consider the most as they manage this disease and use to assess whether or not they’re in control of Phe levels. When we compared levels on treatment to those at baseline, we observed a dose-dependent reduction in blood Phe levels. The mean percentage change from baseline was 14% after the dose titration period which reached up to 3e11 live cells. The second analysis observed a mean 20% blood Phe reduction compared to baseline, with the confidence intervals here indicating that this decrease was statistically significant. Finally, on the slide, you will see what happens when patients stopped taking SYNB1618, represented by the pink bar. Despite continuing study procedures, including diet management, blood Phe levels increased, indicating that the observed decline in blood Phe during treatment is likely a response to SYNB1618. One thing that’s particularly exciting to me is that this data matches well with our prospective biomarker-driven modeling, which increases our confidence that our Synthetic Biotic therapy is doing what we expect it to do, and that we can predict its effect in patients. Also, crucially, it compared favorably to prior clinical research in this field, demonstrating a mean blood Phe lowering of 10% in an all-comers analysis of the previous phase 3 trial, with 30% of patients showing a reduction in blood Phe level sufficient to be defined as a response to earlier therapies. In our interim dataset of SynPheny, the all-comers analysis demonstrated a mean 20% reduction, with half of the patients achieving a 30% blood Phe lowering. What does this mean? It means that for the first time an intervention in PKU, which is acting from the gut level to break down Phe has been shown to have a significant impact on systemic plasma Phe levels, a clinically relevant endpoint in this disease population. In short, it means that this approach could be therapeutically relevant for the treatment of PKU. Finally, and importantly, in terms of safety, SYNB1618 acted in a gut-restricted manner; there were no serious adverse events, and no treatment-related discontinuations occurred. The adverse events we did observe were predominantly GI-related and mild to moderate in severity and consistent with our prior experience in healthy volunteers. Now, as you know, we’ve also been developing an evolved, more potent Phe product candidate, which we’ve called SYNB1934. SYNB1934 was developed using advanced synthetic biology techniques, which we recently published in Nature Communications. Through the first three dose cohorts in healthy volunteers in the phase 1 study, we have demonstrated two things. First, that SYNB1934 metabolizes Phe in a dose-dependent manner. Secondly, that it does so at approximately twice the rate of activity compared to SYNB1618. We think this has exciting implications for the PKU program and our broader metabolic portfolio at Synlogic. When we calculated the ratio of D5 Phe production between SYNB1934 and SYNB1618, we find that SYNB1934 activity was approximately two times greater than SYNB1618 across both biomarkers, TCA and plasma, consistent with our findings in preclinical studies. With these data in hand, the important question becomes how will the improved SYNB1934 activity translate to PKU patients? One way to assess its potential is to compare the activity in healthy volunteers based on the control meal challenge to inform activity in patients. With SYNB1618 we previously observed a 7% reduction in labeled Phe in healthy volunteers, which translated to a 20% lowering in fasting Phe in PKU patients. After seeing a 27% reduction in D5 Phe post-meal with SYNB1934, we expect an improved clinical profile in PKU patients, which is why we are rapidly advancing SYNB1934 into a new arm of the SynPheny study to confirm its efficacy. Upon conclusion of the SynPheny study, we intend to select the strain that will advance into pivotal development. Because SYNB1618 meets our minimum product profile, we are in the fortunate position of having potentially multiple viable assets. But we will advance only the asset with the greatest potential for a differentiated profile based on clinical data. Validation of our platform from this groundbreaking dataset in PKU has exciting implications for our other metabolic diseases. Let me briefly provide updates on our efforts in Enteric hyperoxaluria. Enteric hyperoxaluria, often called HOX, is a devastating condition with no treatment option, wherein dangerously high levels of urinary oxalate lead to progressive kidney damage. It often occurs as a result of a primary insult to the bowel leading to fat malabsorption, such as inflammatory bowel disease, short bowel syndrome, or as a result of surgical procedures such as bariatric weight loss surgery. If left untreated, dangerously high levels of urinary oxalate cause recurrent kidney stone formation, nephrocalcinosis, and progressive damage, resulting in chronic kidney disease. Since oxalate is present in many healthy foods, Enteric hyperoxaluria is almost impossible to control with diet alone, putting patients at risk for serious kidney complications. For most patients, Enteric hyperoxaluria isn’t a standalone problem since the pathologic absorption of oxalates results from an underlying bowel disorder. This means, in clinical practice, it is patients who already have the complexity of living with short bowel syndrome or chronic pancreatitis or IBD who also face the challenge of recurrent and chronic kidney stones. There are approximately 75,000 to 90,000 patients with Enteric hyperoxaluria and chronic recurrent kidney stones at high risk of significant kidney damage in the United States, who currently have no treatment options. We believe our Synthetic Biotic platform could provide a meaningful new approach. Our approach is simple and intuitive: an oral synthetic biotic medicine that metabolizes the toxic oxalate in the GI tract and converts it into harmless byproducts that can be excreted. This approach has the potential to consume oxalate throughout the GI tract, and SYNB8802 is the only one currently being developed that has shown consistent efficacy. As you may recall, we demonstrated SYNB8802 proof of mechanism in a dietary hyperoxaluria study earlier this year. We previously showed that in the efficacy analysis part of the phase 1 trial, the percent change from the baseline urinary oxalate level was 28.6% compared to placebo with robust dose-response relationships. We reported at ASN Kidney week earlier this month that other measures of oxalate reduction are significant. This is significant because consistent reduction of oxalate excretion in both urine and feces demonstrates that SYNB8802 is metabolizing oxalate in the GI tract in a dose-responsive manner, with levels consistent with our translational modeling. The amount of oxalate consumption is significant, with a greater than 60% lowering of fecal oxalate concentration at the 3e11 dose. Lowering dangerously high levels of oxalates is the only way to reduce the risk of disease progression and minimize the risk of oxalate nephropathy. SYNB8802 has demonstrated the potential to degrade oxalate at a clinically meaningful rate as we progress the program, and we look forward to providing additional data in 2022. Now, let me hand the call over to Dan to briefly run through our financial results. Dan?

Thank you, Aoife, and good morning everyone. This morning we released our financial results for the third quarter ended September 30, 2021, and I'd like to review the highlights of those results with you now. Research and development expenses were $13.4 million for the three months ended September 30, 2021, compared to $10.5 million for the corresponding period in 2020. R&D expense consisted primarily of clinical study activities associated with SYNB1618 and SYNB8802, as well as the SYNB1891 phase 1 study and the initiation of the SYNB1934 phase 1 study, along with other costs related to our collaboration with Ginkgo Bioworks for the optimization of Synthetic Biotic medicines. General and administrative expenses were $3.6 million in the third quarter of 2021, compared to $3 million for the same period in 2020. For the third quarter of 2021, the company reported a consolidated net loss of $16 million or $0.29 per share, compared to a net loss of $13.2 million or $0.36 per share for the corresponding period in 2020. Revenue was $0.9 million for the third quarter of 2021 compared to no revenue for the same period in 2020. Revenue was due to the recently initiated collaboration with Roche for the discovery of a novel Synthetic Biotic medicine for the treatment of inflammatory bowel disease. Now turning to the balance sheet, Synlogic ended the third quarter of 2021 with $150.1 million in cash, cash equivalents, and short-term investments, compared to $100.4 million as of December 31, 2020. This was supported by our recent financing. Under our current operating plan, we expect our cash and cash equivalents will be sufficient to fund the company into 2024. This will enable Synlogic to advance our clinical programs through important data readouts across the metabolic portfolio. Thank you for your attention. We look forward to keeping you updated on future calls. I will now turn the call over to Aoife to wrap up.

Thank you, Dan. Our team has made tremendous progress across all our programs, both in and outside the clinic. We're executing effectively with a sense of urgency. We look forward to continuing to advance meaningful therapies for patients with PKU and other serious metabolic diseases. We will now open the call for questions.

Thank you. And our first question comes from Keay Nakae with Chardan. Your line is open. Please go ahead.

Yes. Thank you. Just wondering if you could comment a little bit further on your newest compound SYNB1353 for HCU? And specifically, can you characterize the size of the market opportunity here?

Yes, thanks, Keay. I'm going to turn you over to Dave to talk about just the compound and the work that we've done in research to get us to this point because I think it exemplifies how we are leveraging our collaboration with Ginkgo to rapidly advance high-quality programs to the stage of being ready to move into an IND. So I think that's a very exciting element of that program. And then I'll ask Molly to make a couple of comments on the size of the market opportunity, obviously, it's early days in terms of mapping that out, but we do believe there's a substantial unmet need and a sizable population of patients in need of treatment. So I'll ask Molly to make some comments on that. So first over to Dave just to give a couple of the highlights on the research side.

Yes, sure happy to do that. So HCU is a disease where patients have elevated homocysteine levels that drive a lot of pathology, and we think we can address this with a gut-based approach. Homocysteine is generated from thiamine, so what we have in SYNB1353 is a strain that's engineered to consume thiamine in the gut as a way to prevent the absorption of thiamine and its ultimate conversion to homocysteine. So that probably sounds familiar—it's very similar to the approach that we're taking with PKU and phenylalanine. We've certainly been able to leverage a lot of our understanding and the advanced state of our platform from the PKU program towards the development of SYNB1353. As Eva mentioned, this is also a program where Ginkgo and we have collaborated to ultimately land on the clinical candidate. So Ginkgo was involved in discovering and identifying some of the molecular components that went into that strain, namely, the transporter and enzyme components that we're using to transport thiamine into the bacterium, and then break it down into our kind of base chassis and the organism that we've developed. So we look forward to advancing that into IND-enabling studies and then into the clinic. We think it's a really nice extension of what we've been doing in PKU, building upon that story.

Yes, sure, Dan. I think building on Dave's comments about synergies from the technical side of our therapeutic development, we see that similar in terms of the commercial opportunities. So we think it's really interesting in terms of both synergies and comparisons, as well as distinctions from the PKU market in some ways. The first point to consider is that the synergies and the opportunity for a company that is already in PKU are really attractive. It's the exact same call points, the same prescribed base sharing very similar challenges in terms of lifestyle, and in some cases, even greater due to the unmet need of current therapies. But in contrast, it's interesting, as opposed to PKU, where the market has been fairly defined in terms of diagnosis, the underlying prevalence and diagnosis rate in the homocysteine area is really a dynamic situation right now. The historic assumptions regarding prevalence are increasingly being revised. But the opportunity also comes down to just the therapeutic potential, as similarly to PKU, we are also hearing very clearly from this community that the opportunity for therapy that could be efficacious, safe, convenient, and orally administered is something they're very excited about and looking forward to. So we’re really thinking about it that way: there is potential for market size, and it's a very dynamic situation driven by diagnosis and awareness. At the same time, there are a lot of attractive synergies given our current investment and development in PKU.

Yes, just to clarify, this is Aoife here. Just to clarify what Molly said, for those unfamiliar with PKU, a proportion of patients are diagnosed at birth, but newborn screening for HCU is not 100%. There are actually a substantial proportion of patients with homocystinuria who are diagnosed when they have their first stroke in their teens or early 20s. For that reason, there is a little bit of variance around the PKU prevalence estimates; epidemiologists are very precise for PKU because all patients are diagnosed at birth based on the heel prick test. HCU has a little more variance in terms of prevalence because of those later diagnosed patients since the newborn screening test is not 100% effective at catching these patients. So that's just for those not familiar with the disease; I wanted to provide that additional clarity. Sorry, Keay, you had a follow-up question as well.

Yes. Just wondering, regarding the Roche collaboration, you mentioned you achieved the first research milestone. For that program or others under collaboration, what is the next step once you reach this first milestone? Essentially, how far do you take it before you hand it over to Roche to pursue further clinical development?

Yes. So this is the discovery phase collaboration with a singular target in inflammatory bowel disease. Similar to other similar collaborations, there are several milestones followed by an option exercise that has been disclosed in our filings. What happens subsequently is still very much open to negotiation as we progress. Both sides—Roche and ourselves—are pleased with how things are going. The achievement of the first milestone so quickly after initiating the collaboration earlier this year has been a real positive, and we're getting some excitement as we think about the application of our platform in IBD. I think this is a great testament to the work Dave and his team have done and a great relationship established between both companies.

Thank you. And our next question comes from the line of Joseph Schwartz from SVB Leerink. Your line is open, please go ahead.

Hi, I'm Julie for Joe. Thank you for taking our questions. The first one is on the PKU program. As you mentioned in your prepared remarks, the PKU market appears to be under-penetrated. There are many patients who are diagnosed but are not treated. So in your opinion, what do you believe are the key drivers for adoption? Maybe you could talk a little bit more about commercial potential and commercial strategies you could employ to penetrate the PKU market that's currently dominated by one sponsor.

Awesome. Yes, that sounds like a perfect question for Molly. So Julie, I'm just going to pass it to Molly to provide additional color around some of the commercial strategies. Obviously, Molly is the perfect person for this, given her extensive experience in rare diseases, to meet this challenge. I'll ask her to provide some color around her plans and how she sees the opportunity.

So yes, this is really interesting compared to a lot of other recent launches in rare diseases in the sense that there’s a really high degree of awareness. And as you described earlier, there’s a very strong and consistent diagnosis, right? So it’s actually unlike a lot of other situations—not an area where there needs to be tremendous efforts in terms of disease awareness, but what you’ve picked up on is really interesting: a very low treatment rate. Given how long the treatments have been available, we hear consistently that while there are two approved therapies, they’re inherently limited due to their mechanisms of action. The majority of patients, based on the mechanism of their underlying disease, will not be responsive to those therapies. It’s important to note that every person diagnosed with PKU is universally diagnosed around age two, so it’s not for lack of awareness or testing, but really the availability of a viable treatment option that works for a broad range of patients. What this leaves is the community in terms of remaining medical need for a new option.

Okay, great. Thank you. And then my second question is on your collaboration with Ginkgo. How many more programs can we expect from your collaboration? More broadly, how different is SYNB1353 from your other programs in the clinic? Will the time in the preclinical development stage get sped up? Or do you think that through the Ginkgo platform, you could develop more potent drugs on the first try? Thank you very much.

That sounds like a perfect question for Dave because I think he’s the person most closely involved in the research and the Ginkgo collaboration. So Dave, do you want to comment?

Yes, for sure. In terms of the similarity between the SYNB1353 program and some of the PKU programs, we're leveraging a lot of understanding and a lot of the molecular tools and parts we've built as part of our platform. So we’re using the same chassis organism, the same types of promoters and molecular switches, the same types of genetic manipulations for regulatory purposes. That threads through everything we’re doing, and it's a core part of our pipeline. A lot of our learning also helps us speed up the start and predict the potential activity in humans. So all of the translational capabilities we've built to predict strain activity and model that activity in humans translate and are applicable. This does allow us to go at a slightly faster pace than we might have had in some earlier stage programs. The thing that is different across the programs are the molecular components that drive the biology we are interested in, such as specific transporters for phenylalanine, for example, than the enzymes that break down it. For SYNB1353, we are able to have a screening approach to identify some of those components, transfer those components for engineering into our strains, and ultimately build the clinical candidate, so this has been a fruitful collaboration, and we are working with them on several other earlier-stage programs. We look forward to updating you all as those emerge and reach a similar level of maturity as SYNB1353.

Thank you. And just finally, are you able to reveal any news of further partnerships, any opportunities in the near term, in addition to the Roche and Ginkgo partnerships?

I think you already know the answer to that question. If we hadn't done the partnership, we absolutely would disclose that, but the answer to that is no. Our strategy, as we've been very consistent and overt about, is to pursue these metabolic programs internally. We continue to advance really interesting candidates that build on our experience in PKU, and the second component of our strategy is to leverage our platform to pursue opportunities outside of that core focus on metabolic diseases. I think the progress we've made with Roche exemplifies that, along with our recent publications exploring other opportunities for our platform in high-profile journals—this exemplifies that strategy. So our strategy hasn’t changed; our ability to execute hasn’t changed, and we will continue to pursue opportunities that make sense.

Thank you. Our next question comes from Jacqueline with Oppenheimer. Your line is open. Please go ahead.

Hi, this is Jacqueline for Mark from Oppenheimer. We just have a few questions. The first one is regarding the SYNB1618 in PKU. I know you've been able to demonstrate safety. Are you considering pediatric trials running in parallel with the study next year?

Yes, that’s a great question. As Molly rightly outlined earlier in her prepared remarks, there is a big opportunity for an oral product in the pediatric population that doesn’t respond to previous treatment. So we see that as a key market for us, and we'll be pursuing pediatric development as soon as we get regulatory alignment on that. So you'll hear more about our plans as those regulatory discussions progress.

Thank you all, and also, assuming you can demonstrate clinical proof of concept for SYNB8802 next year, what would be the most likely next steps for the program? Would you want to go right into a pivotal study in the gastric bypass population?

Yes. The key question for HOX program would be expanding our chosen proof-of-concept opportunity in the bariatric surgery population. We plan to expand into other underlying etiologies. So making sure the product is similarly efficacious across a range of underlying etiologies is something we will pursue. Our goal is to have as broad a launch indication as possible. I think whether we proceed to a phase 2 or go directly to a phase 2-3 is still under discussion and will depend on how clear the data is from our proof-of-concept study. We have some work happening to generate real-world evidence that will inform the clinical plan, and we recently had a nice presentation at ASN Kidney week discussing how we're using this evidence to make the best possible decisions for the program going forward. The data from our proof-of-concept study, along with our understanding of the natural history of the disease and patient segmentation will inform the next steps, but we'll keep the investment community apprised as we make these key decisions.

Alright. Sounds good. And our last question is regarding SYNB1934. Can you remind us if SYNB1934 falls under the umbrella of your collaboration with Ginkgo, and if so, will there be any milestone or royalty obligations to Ginkgo if SYNB1934 makes it to market internationally?

Yes, SYNB1934 was not developed under the collaboration; we started our collaboration with Ginkgo, which subsequently became Zymogen, before we had signed the Ginkgo collaboration. The enzyme inside SYNB1934 was developed by Zymogen; so that’s the provenance of that strain. And just to remind you, our collaboration with Ginkgo does not involve any milestones or royalties. They have an equity stake in the company and are incentivized to ensure we're getting the best candidates for their ownership stake in Synlogic, but we have full rights; there are no further commercial obligations downstream to Ginkgo as part of that collaboration.

Thank you. And we have a follow-up question from Keay Nakae with Chardan. Your line is open. Please go ahead.

Yes. Just a question about the oral presentation coming up at ICIEM. Is that just going to include more detail, but not any new patient data per se?

Correct. Yes, it will be that we presented in the press release as part of the interim; but there will be, I think, more data. Obviously, it’s an academic presentation. It’s being presented by Jerry, one of our principal investigators on the trial, and it will include more detail and color, but the key conclusions remain the same based on the number of patients that are included, which is consistent with our press release earlier this year.

Thank you. And I'm showing no further questions at this time. I would like to turn the conference back over to Aoife for any closing remarks.

Great. Well, thanks everyone for joining us this morning. It's been a pleasure to share the updates that we've had across all our programs, and we look forward to keeping you informed as we go into next year.

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.