Operator: Good morning. Welcome to Synlogic's Third Quarter 2020 Conference Call. [Operator Instructions]. Please be advised that this call is being recorded. I would now like to turn the call over to Daniel Rosan, Head of Corporate Finance and Investor Relations. Please proceed.

Daniel Rosan: Thank you, Operator. Good morning, and thanks for joining us on today's conference call. This morning, we issued a press release, which outlines our third quarter 2020 financial results and several other topics that we plan to discuss today. The release is available on the Investors section of our website at synlogictx.com. Joining me on this call are Dr. Aoife Brennan, President and Chief Executive Officer; Gregg Beloff, Interim Chief Financial Officer; and Dr. Richard Riese, Chief Medical Officer. Also joining us is Dr. David Hava, new appointed Chief Scientific Officer. During the call, Aoife will provide a brief outline of third quarter highlights and recent progress. Gregg will summarize our financial results for the quarter, and Richard will provide an update on our Metabolic portfolio. Following our prepared remarks, we will open the call for your 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 our press release or under the heading “Risk Factors” in our most recent 10-K filings or filings with the SEC. Synlogic cautions you not to place undue reliance on any forward-looking statements. And now I'd like to turn the call over to Aoife.

Aoife Brennan: Thanks, Dan. Good morning everyone and thank you for joining us. I am thrilled today to share with you our third quarter 2020 financial results and to highlight recent achievements including our newest candidate Enteric Hyperoxaluria entering the clinic this week ahead of schedule, and the initiation of our PKU SynPheny-1 Phase 2 study. To me awesome colors and back-to-school always feels like the real start of the New Year. And that has been especially true for us here at Synlogic. We’ve rapidly moved our clinical portfolio forward over the past nine months. And now we are gaining momentum as we head into one of the most data rich period in our history. Over the past few years, we have built a premier synthetic biology platform and today we are laser focused on establishing that platform as one that patients can rely on for life changing treatments. I know that we have the team, technology and portfolio to succeed. And I want to start today by discussing our team. Our recent research engine is one of the most productive amongst small biotech, bringing now 4 INDs into the clinic in short order. Each one of those INDs has come more rapidly than the one before. Yes, there is so much more we can do. Each day there is even more breaking sign and the power of bacteria therapeutics to change the course of human disease, something that Synlogic has realised and work towards since day one. We continue to execute strongly across Metabolic and Immunomodulation program, bringing the transformative power of synthetic biology to medicine. That is why I am pleased to welcome Dr. Dave Hava granting us our leadership team of Chief Scientific Officer. Dave is an experienced drug hunter who has brought multiple programs from ideation into and through the clinic and has led numerous successful partnerships. He is a microbiologist who is doing synthetic biology long before the field adopted that label. We look forward to Dave tuning our already prolific research engine. Dave, would you like to say a few words.

David Hava: Thanks, Aoife. Let me just say thank you for the top notch scientist who have welcomed me to Synlogic this past few weeks. The quality of the science and the rigor of the team here are second to none. This cannot be a better time to join Synlogic and advance synthetic biotic medicines as we launch our third clinical program this week. I am looking forward to deepening our work in Metabolic diseases, advancing our immunology efforts and partnering with the exception of clinical research and process development teams. Thank you for the warm welcome.

Aoife Brennan: Thanks, Dave. Let me turn now to an update on our business and portfolio progress over the past quarter. We are rapidly progressing our internal metabolic disease pipeline, which leverages the ability of our platform to safely deliver a synthetic biotic medicine into the human GI tract to consume toxic metabolites. Transforming toxic metabolites into the nine substances is something really no other platform can offer and would be clinically meaningful in a wide variety of disease states. The metabolic pipeline is entering a clinically exciting time with our Phase 2 study in PKU, which we call SynPheny now initiated as multiple clinical sites across the U.S. Even amidst COVID, patient interest in the study has been robust, and we're pleased with the progress thus far. We will speak in depth about that study in a moment. Our newest metabolic program, SYNB8802 in enteric hyperoxaluria has entered the clinic this week earlier than expected, because of the power of our reproducible platform. Relying on toxicology and CMC experience of our earlier products, we were able to follow an accelerated IND timeline and reduce the typical period from candidate declaration to first inhuman by more than six months. Our immunomodulation portfolio also continued to expand. The clinical team has done an exceptional job of shepherding the SYNB1891 Phase 1study through monotherapy dose escalation cohorts. The team remains on track to share an interim update on the monotherapy arm of the study by the end of the year. And we continue to expect initiation of the combination therapy on with SYNB1891 and the anti-PD 1 agent to centric early in 2021. I want to emphasize across an extraordinary amount we will learn about the potential of synthetic biotic medicines over the next year. Our team has done a tremendous job executing in the clinic, setting the table for multiple meaningful readouts. Thanks to our careful cash stewardship, all of those milestones occur well within our cash window. By the end of 2021, we will have proof-of-concept opportunities into patient populations. As those PKU patients unserved by current treatments where we will assess the feel or in potential of SYNB1618 and Roux-en-Y gastric bypass patients with impaired hyperoxaluria who have no options today for managing the dangerously high levels of urinary oxalate. We also continue to build our immunomodulation portfolio, which leverages our synthetic biotic platform to exploit the interaction between bacteria and the immune system in complex disease areas, including immunology and oncology. We're advancing our Phase 1 clinical trial of SYNB1891 in solid tumors. Despite the COVID-19 pandemic, enrollment in this study continues to track well. The monotherapy arm of SYNB1891 study is intended to demonstrate feasibility, safety and identify a maximum tolerated dose. SYNB1891 was designed to take advantage of the immunostimulatory properties of our bacterial chassis, as well as being specifically programmed to produce a STING agonists. By delivering a STING agonist directly into antigen presenting cells in the tumor using a synthetic biotic, we hope to avoid the t-cell apoptosis, which reduces the efficacy of traditional small molecules targeting the STING pathway. We continue to see data which supports the injection of SYNB1891 is feasible and that the strain is generally well tolerated. Todate, there are no dose-limiting toxicities or infection seen with SYNB1891 administration. We will share an update on the variance gathered from the initial monotherapy dose cohorts closer to the end of the year. In summary, we feel that we have great potential to bring new therapeutic approaches to patients. We have made exciting progress in our pipeline and are in a solid position to execute on our key upcoming milestones. Now, let me turn the call over to Gregg to briefly run through the financial results.

Gregg Beloff: Thank you, Aoife. And good morning, everyone. This morning, we released our financial results for the third quarter ended September 30, 2020. And I'm pleased to review those highlights with you now. Research and Development expenses were $10.5 million for the three months ended September 30 2020, compared to $10.6 million for the corresponding period in 2019. These costs were driven by Synlogic’s collaboration with Ginkgo for the optimization of synthetic bionic medicines, as well as clinical study start up activities associated with SYNB1618, and SYNB8802 as well as the on-going SYNB1891 Phase 1 study. General and Administration expenses were $3 million in the third quarter of 2020, compared to $3.9 million for the same period in 2019. For the third quarter of 2020, the company reported a net consolidated loss of $13.2 or $0.36 per share, as compared to a net loss of $13.3 million or $0.39 per share for the corresponding period in 2019. We had no revenues in the third quarter of 2020 compared to $305,000 for the same period in 2019. Revenues associated with the services performed under Synlogic's collaboration agreement with AbbVie to develop a synthetic biotic medicine for the treatment of IBD, an agreement which has since been terminated. Now, turning to the balance sheet, Synlogic ended the third quarter of 2020 with $102 million in cash, cash equivalents and other investments. Under our current operating plan, we expect that our cash will take us into 2022 and enable us to advance our clinical programs through important data readouts over the coming months. Thank you for your attention, and we look forward to keeping you updated on future calls. I'll now turn the call over to Richard to share progress with you on the metabolic portfolio.

Richard Riese: Thank you, Gregg. I'd like to now walk you through our plans for the Phase 2 proof-of-concept study of SYNB1618, which we call SynPheny-1. This study will teach us a tremendous amount about the potential of our novel approach in PKU. PKU has attracted a wide range of new approaches, especially among drug developers advancing new modalities. This is a credit to the efforts of the PKU community. But as we talk with patients and caregivers, it is clear to us that both current and emerging treatment options continue to leave too many patients behind and a safe, tolerable, reversible and oral therapy would be welcomed. That is why we are progressing SYNB1618 through clinical development. Our initial program on PKU has shown promising activity. We have demonstrated the ability to consume Phe in the GI tract, most recently in our solid oral bridging study in healthy volunteers. The next step is to understand how the consumption of Phe in the GI tract in PKU patients would impact plasma Phe levels. To answer that question, we have initiated the Phase 2 SynPheny-1 study at multiple sites across the U.S. Inbound patient interest is robust, and the patients have the option of conducting all trial procedures at home or in the clinic. We plan to have all sites open by the end of 2020. Synlogic’s approach to PKU is simple and intuitive. It is well understood that reducing dietary consumption of Phe [Indiscernible] reduces plasma Phe levels in patients with [Indiscernible] PKU. Our approach is to build on our biology to introduce a synthetic product medicine into the GI tract, which is specifically designed to consume Phe and produce the measurable, measurable biomarkers TCA and HA. One of the benefits of this Synthetic Biotic platform is the ability to understand in healthy volunteers the way in which the strain behaves and whether it is performing as designed. In the recently completed Phase 1 solid oral study in healthy volunteers, we challenge healthy volunteers with label D5 Phe and saw that even in the context of endogenous Phe metabolism, we were able to generate a nice dose response of SYNB1618 on measures of D5 Phe consumption. This data gives us confidence as we move into Phase 2. The goals of the SynPheny-1 Phase 2 proof-of-concept study are to demonstrate the potential of SYNB1618 to lower blood Phe in adult PKU patients, and to validate our PD model in order to better understand the relationship between the production of strain biomarkers, and Phe lowering for SYNB1618. We have two opportunities to demonstrate blood Phe lowering, measurement that a plasma Phe lowering in a fasted state and measurement of label D5 Phe after meal challenge is designed very similar to the Phase 1 healthy volunteer study I just reviewed. The benefit of measuring label D5 Phe is that this endpoint is not impacted by dietary variations and Phe intake. Remember, the patients in SynPheny have no therapeutic options. They are ineligible, inappropriate for or unresponsive to cauvin [Ph] or pegvaliase. As you know, only approximately 30% of PKU population is Bh4 responsive. These patients are left behind by current therapies. Accordingly, we believe even relatively modest levels of Phe lowering would be clinically relevant for this population. Especially if we show consistent levels of Phe lowering across enrollees. The study is powered to detect 20% reductions in Phe. PKU patients and Investigators tell us that 20% Phe reductions in oral, tolerable and reversible therapeutic, which is effective for Bh4 non responders would be a competitive product profile. To ensure we can effectively carry out such a study in the midst of COVID-19. We are using a flexible design in which patients can participate in clinic or in their homes, a design directly in for by patient and investigative feedback. The response from the PKU community has been very welcoming, with significant inbound patient driven interest and a terrific spirit of partnership with the advocacy community. The willingness of advocates, caregivers and patients to engage with us and other sponsors is critical to advancing new treatment options for this devastating disease. We are looking forward to executing this study and sharing results in the middle of 2021. Now let me update you on our newest program, SYNB8802 in enteric hyperoxaluria. We are enthusiastic about the potential of this program to help patients with dangerously high urinary oxalate levels. Often these patients are living with other serious chronic conditions, such as obesity, inflammatory bowel disease, or short bowel syndrome. Since oxalate is present in many healthy foods enteric hyperoxaluria is almost impossible to control with diet alone. This means these patients are at risk for serious kidney complications, nephrocalcinosis, stones and chronic kidney disease. There are currently no available treatments. We are pleased to announce that the Phase 1clinical study has been initiated ahead of schedule, and our first cohort of healthy volunteers have been dosed. Our approach to enteric hyperoxaluria is informed by our learnings from PKU. The ability to consume a toxic metabolite in the GI tract is something which few modalities can accomplish. We are rationally designing our synthetic biotic medicines, to do just that. Building on validated biology, in which dietary oxalate levels are correlated with urinary oxalate and does kidney damage in enteric hyperoxaluria patients. SYNB8802, is moving into the clinic based on encouraging preclinical data, which we recently shared at kidney week. That data demonstrated a meaningful reduction in urinary oxalate and multiple animal models of hyperoxaluria as well as predictive in Silico simulations, suggesting a meaningful reduction in urinary oxalate of 20% to 50% is possible in patients. Our clinical development plan will give us the opportunity for a relatively rapid proof-of-concept readouts by focusing, capturing initial healthy volunteer MAD study on patients with enteric hyperoxaluria after Roux-en-Y gastric bypass surgery. Because the underlying bowel disease for hyperoxaluria patients can be quite heterogeneous, this post gastric bypass population provides an optimal cohort to clearly assess the ability of SYNB8802 to lower urinary oxalate. The regulatory and critical path in this indication is relatively straightforward with significant precedent set by sponsors in related diseases, such as primary hyperoxaluria. For the importance of urinary oxalate is one critical endpoint. We will continue to work closely with regulatory authorities as we develop our clinical strategy. Our initial efficacy assessment will evaluate clinically relevant reductions in urinary oxalate levels. And feedback from our key investigators suggests greater than 20% lowering would be meaningful. As we move forward with our Phase 1 proof-of-concept study in enteric hyperoxaluria and our Phase 2 proof-of-concept study in PKU, I will come back to you with details as both of these studies unfold. But now, let me hand the call back to Aoife to wrap up. Aoife?

Aoife Brennan: Thank you, Richard. I'm encouraged by the rapid progress the team has made in advancing our clinical portfolio across the board, with high quality execution leading to multiple opportunities for synthetic biotic to make meaningful changes to key disease endpoints in multiple indications over the next year. Together, we have built the premier synthetic biology platform, and together, we are at our strongest. I want to end by once again thanking the Synlogic team, employees and their families for their work and dedication in driving these programs forward with flying colors even through the challenges of COVID. The season is changing and with it brings abundant opportunities for success at Synlogic. It is energizing to be part of such a dedicated team. And we look forward to data-rich period to come. We will now open the call for questions.

Operator: [Operator Instructions] Our first question or comment comes from the line of Tom Shrader from BTIG. Your line is open.

Tom Shrader: Good morning. Thank you for taking the question. I'm kind of digging in a little bit on the 1891 data. Clinical Trials says 70 total. How many patients will we see at the end of the year? And it will be a full dosing cohort for monotherapy? Just what can you tell us about what we're going to see?

Aoife Brennan: Hi, Tom. This is Aoife. Thank so much for your question. So I think we haven't disclosed how many subjects have been enrolled in the study. But it will be most data from multiple cohorts in the monotherapy arm. Obviously, when we write the protocol and put postings on clinicaltrials.gov, we want to make sure that we set the outside number that we may enroll over the course of the entire study. But I think, we're making great progress, as I said in my prepared remarks, and we're very happy with how the study has been enrolling so far this year.

Tom Shrader: And just to set expectation, do you think monotherapy responses are on the table outside melanoma for a sting agonists, just your thoughts? And any hints? Does your preclinical data gives you a sense of where the active doses are?

Aoife Brennan: Yes. So I think, as we've said previously, to set expectations around the monotherapy group. First of all, it was a basket study. So we don't have -- we may enroll some melanomas. We may enroll different tumor types. So being able to parse our or guarantee a specific number of melanoma patients or non-melanoma patients is kind of beyond how we design the study. I think in terms of the objectives, and I'll get Richard to kind of weigh in here afterwards. But with our platform, our kind of philosophy has always been to evaluate initially in patients, is the bacteria performing as designed. And I think that's what we're hoping to evaluate as part of the monotherapy cohorts. And what we saw pre-clinically was that we saw some nice tumor shrinkage in consistent with some of the biomarker changes that we observed in our animal models. And we've published all of those data and are available publicly on the website for those who want to dig in. So we do kind of have some benchmarks in terms of what we sell for biomarkers and what we sell for activity in our preclinical models, and we're looking at similar biomarkers in the clinic. But as you know, you've been around this industry for long enough to know that lots of things can change when going from mice to humans. But we've tried to design the study with an eye to be able to look back at what we sell for efficacy pre-clinically and have a very robust biomarker plan. And that we've been successful in kind of executing and gathering the right kind of materials from the clinical trial patients. Richard, anything you'd like to add there? You're closer to the day-to-day than I am?

Richard Riese: Sure. Just reinforce a couple of points. The primary endpoints in the Phase 1 study are safety and tolerability. So of us would be very interested in that. And as Aoife mentioned, we're really interested in the monotherapy. I'm looking for target engagement at doses that are relatively tolerated. Understanding that we are going to have a heterogeneous patient population in this all kind of studies. So that's our overall goal for the monotherapy.

Tom Shrader: Great. Okay. Exciting stuff. Thank you very much.

Aoife Brennan: Thanks, Tom.

Operator: Thank you. Our next question or comment comes from the line of Mark Breidenbach from Oppenheimer. Your line is open.

Unidentified Analyst: Hey guys, it's Matt from our Mark.

Aoife Brennan: Hey, Matt. How are you?

Unidentified Analyst: Good Thanks for the update on the SynPheny design, particularly the powering assumptions. I was wondering in those assumptions, if you could tell us, what's the degree of natural variability that you're assuming in patient Phe levels over time?

Aoife Brennan: But I might pass that one over to Richard to answer. Matt, is that's okay. Richard, do you want to take Matt to some of the powering assumptions?

Richard Riese: Yes, sure. I mean, we know in our asset, there's about a 15% variability for just measuring Phe in and of itself. And there's is also at least equal amount of variability in into a patient variability from day to day. And the variability is driven by your changes in Phe levels over time and patient up and down diet, and our ability to ask them to quantitate Phe. So we have taken all those into -- we have evaluated all those and came up with the appropriate size so that we could detect at least a 20% decrease in Phe in this patient population.

Aoife Brennan: Yes. Quite a lot there as well, Matt, as we're not the first ones to do a study and PKU. So we have the benefit of being able to look back at those prior trials, and to evaluate their variability was and to incorporate some of that into our kind of powering assumptions. So we do have the benefit of some of that prior days from studies in patients with PKU.

Unidentified Analyst: Right. Yes. That sounds like a reasonable cushion. So maybe turning to the 1891 study. Can you just remind us if you're taking paired biopsies, maybe looking at things like tail [ph] induction? Or I guess, what are some of the other PD biomarkers that we should be expecting from this data set?

Aoife Brennan: Richard, do you want to take Matt on that one.

Richard Riese: Yes. So we are looking at per biopsies. And as you mentioned, we're looking at tails as well as interferon beta, interferon dependent gene expression. That's the mRNA in paired biopsies, tumor biopsies. We're also looking at kinetics of SYNB1891 itself, our preclinical data suggests that the bacteria can stay alive in the tumor and be present for four to six days. So we think that would be very interesting. And then systemically, we're looking at serum cytokine levels, as well, if -- seeing if we detect SYNB1891 in the pot. So that -- and we think we have a pretty good complete set of PD biomarkers to really assess tumor engagement, which is our big goal here.

Unidentified Analyst: Cool. Thanks for the update.

Operator: Thank you. Our next question or comment comes from the line of Ted Tenthoff from Piper Sandler. Your line is open.

Ted Tenthoff: Great. Thank you. Thanks for the update. I wanted to get a sense of what your plans might be with the returned inflammatory bowel disease asset from AbbVie. Again, I know you have a lot going on with PKU. I know you have a lot going on with 8802, and also IO. But that seems like a pretty natural approach for this technology. And I'm wanting to get a sense for what you were thinking? Thank you.

Aoife Brennan: Hi, Ted. Its Aoife here. I'll make a couple of general remarks and then maybe pass it over to Dave Hava, who is on the call as our new Chief Scientific Officer. And I think, certainly he has plans to continue to evaluate IBD as they application for our platform, because you're absolutely right, it makes very a lot of sense. And I think kind of expands on what would probably be able to do in the metabolic care therapeutic area. So what I say is that we got the assets returned, but we didn't need to regenerate some data from the collaboration. So we're now in the process of kind of regenerating some of that data and evaluating kind of which of those assets to take forward in terms of generating additional data package around them. But I think we agree 100%, it's completely consistent with our company's strategy to focus on metabolic diseases internally and to continue to leverage the breadth of the platform in immunomodulation in the context of partnerships and collaborations in the future. Dave, anything you want to add there as you started to dig in?

Dave Hava: Yes. I mean, I kind of just reiterate some of those things. I mean, it's certainly a space that we remain committed to. And I think we certainly see the potential of our platform to make an impact there. And we think there's some biology that we can unlock using the platform and our learnings both from the previous work we've done in the space as well as the metabolic portfolio. So we're working on some discovery stage programs and are excited about the potential there.

Ted Tenthoff: And then, one quick follow up to that. Is it something where maybe the Ginkgo Alliance could be applied to potentially seek advanced products? Thank you.

Aoife Brennan: Yes. So, how would the collaboration with Ginkgo works is, we will come up with a concept for a strain that we'd like to design us and we'll build a prototype, and then we work with Gingko, to optimize. And so I think you're exactly right. They do have access to a broad array of synthetic biology tools that really allow us to do new things from a synthetic biology perspective. And I think one of the challenges for IBD is that it's a very competitive space, the studies are large and often complex. So I think while we use Gingko, as kind of the very early end of our platform, certainly for mid and late stage development in Crohn's and ulcerative colitis, which are the kind of big chunks of the IBD market, and we'd be looking to collaborate with the right big pharma partner to bring these programs all the way through development. So I think there's kind of two ends of the spectrum with Ginkgo being very involved early on. But then with I think IBD generally, kind of requires that big pharma muscle to take it all the way through commercial. So I think that would be the strategy as of today. Now, , in the future, can we carve as a niche? Is there a sub population maybe that we could see pursuing ourselves right to secure development path forward? Sure. Right. But -- so we identify that. Yes, yeah, exactly.

Ted Tenthoff: Yeah. Okay. Great. Thank you so much for the answer, and keep up the good work. Thanks.

Aoife Brennan: Thanks, Ted.

Operator: Thank you. Our next question or comment comes from the line of Gbolahan Amusa from Chardan. Your line is open.

Unidentified Analyst: Hi, this is Sam in for Gbolahan. First, congrats on progress. Just couple questions from me. For 8802, can you just provide us an update on the enrollment and dosing status for Part B of the Phase 1 study, that is the patients with the entiric hyperoxaluria?

Aoife Brennan: Yes. Maybe I'll ask Richard to answer that question. Richard, do you mind providing an overview of kind of plans for Part B to Sam?

Richard Riese: Sure. So right now we have just an issue as mentioned in Part 1. And following a dose of the MAD in part one, we'll move on to part two, which is looking at the patients with enteric hyperoxaluria. And these are patients with hyperoxaluria secondary to Roux-en-Y. And our plan is just going to be a crossover design to enable rapid proof-of-concept. We plan to enroll approximately 20 patients with hyperoxaluria after Roux-en-Y gastric bypass surgery. And the idea here is we wanted to in our initial foray into entiric hyperoxaluria. We want to use a patient population that was not as diverse as the overall enteric hyperoxaluria patient to get a cleaner signal of our proof of concept study. And these page [ph] where we are going to enroll patients with urinary oxalates levels above 70 milligrams a day. So we'll certainly start that as soon as we get data from the healthy volunteer MAD cohort, which is ongoing right now.

Unidentified Analyst: Got it. So the data -- so the enrollments I should say, is contingent or you're going to wait for the data from Part A first before thinking about dosing the Part B?

Richard Riese: Well, now we're going to move ahead with Part B. But we need to determine a dose, maximum tolerated dose, we need to get safety data in healthy volunteers before we move on to patients with enteric hyperoxaluria area. And then when we get the dose in tolerability, we'll be moving on to the second part of this study.

Aoife Brennan: And just to add on to what Richard said there. We're able to start out the proprietary work as we're enrolling the healthy volunteers getting the sites up and running. And right now we're on track to meet the guidance that we've provided, which is to have data in the disease patients mid year next year.

Unidentified Analyst: Got it. Great. And then one more question. So you have quite a few readouts in 2021 with in 1618, 8802, and the immuno oncology 1891. Assuming positive readouts across the board, do you expect to prioritize one asset over another for pivotal studies? And how do you see the best path moving forward?

Aoife Brennan: Yes. A great question, Sam. So, I think here, we yet to reiterate our strategy, because I think everything that we've done and discussed today on this call is very consistent with our strategy, which is to focus on rare or niche metabolic diseases internally for our internal pipeline. We really like those diseases, because they're often very much informed by early development, biomarkers. They have biomarker readouts that can be either the basis of full approval or the basis -- you know, or critical endpoints in terms of regulatory approval. They tend to have very efficient kind of Phase 2, 3 development paths that are doable for a company of our size. And then, from a commercialization perspective, there is a very defined subgroup of prescribers that we could see certain taking those programs all the way out through commercialization. For diseases that have potentially bigger opportunities, but maybe more late phase complexity, larger trials, requiring bigger commercial infrastructure than we would envision building ourselves. Our intent has always been to partner those opportunities, and certainly, that will be the case in a disease area, like melanoma or oncology. So I think for 1891, we've been consistent that, that's something that ideally we would love to partner at the right time once we have de risked the safety and efficacy profile, similarly, IBD. So, I think we will continue to execute in line with our strategy, with the focus for our internal pipeline, Visa, being on these metabolic diseases. But then, with the immunomodulation programs, really providing an opportunity to broaden the pipeline, to seed potential collaborations, and to continue to build value for the company and it bring important therapeutics for patients. Does that make sense.

Unidentified Analyst: Got it. Thank you. It does. Thank you so much. And congrats again on the progress.

Aoife Brennan: Thank you.

Operator: Thank you. Our next question or comment comes from the line of Joseph Schwartz from SVB Leerink. Your line is open.

Unidentified Analyst: Hi. I'm Julie dialing for Joe. Thanks for taking our question. My questions on SYNB1618. I was wondering if you could talk about your NexGen, PKU 2.0 strain? What additional optimization tools are you planning to implement? Assuming you transition to your next strain in the clinic? Could you provide some color on how easy or difficult it would be to swap out the strain? You know, are you just anticipating a simple bridging study? Or is there something more extensive than that?

Aoife Brennan: So maybe I'll answer part to your question, then hand over to Richard to talk about the regulatory strategy and how we see these programs kind of moving forward. So, in terms of the optimization, I think we shared some data earlier this year, Julie, as you're aware, our R&D data just showing some of the progress that we've made. We've been very pleased with the progress we've made. We've been working with Ginkgo and with enEvolv, to evaluate a number of different technologies that can help us really make sure that we have gotten the optimal potency from a next generation strain. And that work continues, and we continue to make very good progress. I think the one thing that we've learned from 8802 experience is that the regulators have actually allowed us to be able to cross reference the toxicology and preclinical data that we had for earlier programs. So the reason that we raised those two, bring that IND in so quickly moved from clinical candidate to IND, is because we did not have to perform any GRP toxicology. And we would anticipate that we would be able to follow a similar path for certainly, the metabolic programs where we're producing a benign metabolize and using the same chassis organism and some of our reusable parts. So we think that that really -- that experience really enables us to go very, very quickly with future programs, but also with some of our Next Gen programs as well. And so maybe I'll stop there and hand over to Richard in terms of kind of how he sees the first Gen and second Gen opportunity and PKU and how those might play out as part of the clinical development plan.

Richard Riese: Sure. Thanks Aoife. Some of the some of the thoughts we've had is we would want to gain clinical experience with the second generation product in healthy volunteers and one of their really big advantages. We have with the PKU program in general as we can measure a biomakers and get a good idea of our activity of the second gen versus 1618, which data we already have. So, and the healthy volunteer study would be for two purposes to flying the dose, maximum tolerated dose as well as to look at activity in humans which I think will be based on biomarker work which will vital as we develop our clinical and regulatory strategy. And then, I think is likely we would want to get some evidence of CLA in PKU patients with second-gen product and some idea of comparison prior to kicking off a pivotal study. All this -- whether 1618 versus second-gen will determine the timing of it and relative potencies of each strains. But I think that's in a high level is the way we would approach it.

Unidentified Analyst: Okay, great. That's it from us.

Operator: Thank you. I'm showing no additional questions in the queue. At this time, I'd like turn the call back over to management for any closing remarks.

Aoife Brennan: Great. I just like to thank everyone for joining us today. And we're looking forward to keeping you updated regarding our progress going forward.

Operator: Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.