Synlogic Inc (SYBX) 2021 Q2 法說會逐字稿

Good morning, and welcome to Synlogic's Second Quarter 2021 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 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, which outlines our second 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 call are Dr. Aoife Brennan, President and Chief Executive Officer; and Dr. David Hava, Chief Scientific Officer. Other members of the management team will also be available during the Q&A. This morning, Aoife will provide a review of second quarter highlights and recent progress. Dave will share the latest advancements in applying our Synthetic Biotic platform to Phenylketonuria, and Aoife will then return to provide an update on our metabolic portfolio, including Enteric Hyperoxaluria. 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'd like to remind everyone that comments today may include forward-looking statements made under the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made as of the date hereof and are subject to numerous factors, assumptions, risks and uncertainties, which change over time. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including those described under the heading forward-looking statements in Synlogic's press release from earlier today or under the heading Risk Factors in Synlogic's most recent Form 10-K or in later filings with the SEC. Synlogic cautions you not to place undue reliance on any forward-looking statements.

Now I'd like to turn the call over to Aoife.

Thanks, Dan. Good morning, everyone, and thank you for joining us. I'm thrilled to share with you today updates on our recent execution and progress across the portfolio as well as our financial results for the second quarter of 2021. Before we dive in, and as I'm sure you're already aware, I wanted to first thank Dr. Richard Riese for all of his contributions over the last few years, serving as Synlogic's Chief Medical Officer. We wish Richard the best in his new endeavors. As our programs continue to build momentum, we remain in good hands with a highly experienced executive team. I'm personally excited to tap into my CMO Roots, as we initiate a search for a CMO who can lead our growing clinical development organization and shepherd our programs as they transition to later phases of development.

Now back to the business. We're executing on our plans to demonstrate the clinical potential of our Synthetic Biotic platform in 2021. With proof of mechanism established in our 2 lead metabolic programs, a strengthened balance sheet and an exciting new partnership, we are well positioned to deliver proof-of-concept in multiple high-value indications. Like all companies with ongoing clinical studies, we continue to watch the impact of the COVID-19 pandemic and particularly the delta variant carefully, especially on clinical sites in the Southeastern United States. We're pleased that our team continues to execute with the singular goal of developing Synthetic Biotic medicines, which provide meaningful treatment for patients with serious diseases.

Let me turn to those programs now. I'll begin with our PKU program. We believe patients living with PKU continue to need additional treatment options to manage this devastating disease, and we believe that an efficacious oral therapy regardless of genotype, remains one of the most attractive clinical profile. This is why we've been executing on our plan to evaluate our lead PKU candidate, SYNB1618 in a Phase 2 clinical study, we call SynPheny. We're thrilled to recently publish the compelling proof of mechanism results for our Phase I study of SYNB1618 in Nature Metabolism, and the SynPheny study is on track to deliver data later this year.

This quarter, we also took another important step forward by initiating the Phase 1 study of SYNB1934. SYNB1934 is an evolved strain of SYNB1618, and in a moment, Dave will tell you more about the science behind our PKU program. Let me tell you why we developed SYNB1934. It's because we never stopped asking the question, how much more efficacy can we deliver for patients? Synthetic biology tools are progressing rapidly, and our team had access to the best of those tools, both internally and through our network of collaborators. By deploying a new suite of directed evolution tools to SYNB1618, we were able to generate a candidate, which may have even more Phe-consuming capacity and move it rapidly into the clinic.

In Enteric Hyperoxaluria, we also see a significant opportunity to make a meaningful difference in the lives of patients. SYNB8802, our other lead metabolic program is designed to consume the toxic metabolite oxalate in the GI tract in patients with Enteric Hyperoxaluria, a leading cause of oxalate nephropathy and recurrent kidney stones, for which there are no approved therapies. As we previously communicated, SYNB8802 has demonstrated the ability to consume oxalate in the GI tract of healthy volunteers, exhibiting a robust and dose responsive urinary oxalate reduction. We are now evaluating the oxalate lowering potential of SYNB8802 in a Phase 1B study in patients with Enteric Hyperoxaluria, following Roux-en-Y gastric bypass surgery. This study gives us an opportunity to demonstrate a highly clinically attractive profile.

We are taking the learnings from our co-lead metabolic programs and applying them to novel approaches to address other diseases, in which a GI based approach may be relevant, including inherited and acquired metabolic disorders as well as autoimmune conditions. We recently entered into a research collaboration agreement with Roche for the discovery of a novel Synthetic Biotic medicine for the treatment of inflammatory bowel disease or IBD. IBD remains an area of high unmet need in which new approaches are urgently needed. We're delighted to be working with an organization with unparalleled depth in immunology and look forward to exploring the potential of synthetic Biotic medicines in IBD.

Our team has done a tremendous job executing across multiple programs, during what continues to be trying times for all of us in 2021. This resilience and teamwork have set the stage for multiple meaningful readouts in 2021. Thanks to our careful capital stewardship, these milestones occur well within our cash window. In summary, 2021 has been an incredibly exciting year for the company. We now have demonstrated proof of mechanism in humans from both our lead metabolic programs in PKU and Enteric Hyperoxaluria. We initiated a Phase 1 study of a next-generation strain in our PKU portfolio, and initiated an exciting new partnership in Immunomodulation. We have the opportunity to demonstrate proof-of-concept in our co-lead programs and advance our mission to bring the transformative power of synthetic biology to medicine.

Now let me turn the call over to Dave to go deeper into our PKU program. Dave?

Thank you, Aoife. It's my role today to share the exciting science, which underpins our PKU program and our next-generation strain, SYNB1934. Before I do, let me remind you the challenges faced by PKU patients and caregivers. PKU is an inherited metabolic disease in which children are born without the ability to metabolize phenylalanine or Phe. Consuming even modest amounts of dietary Phe causes irreversible neurocognitive deficits in patients with PKU. Despite the availability of dietary management and approved treatments, a large proportion of patients struggle to maintain blood Phe levels in the target range required to avoid this irreversible damage. It is clear to us, that both current and emerging treatment options continue to leave too many patients behind, and so we have set as our target product profile, a safe, tolerable, reversible and oral therapy, which would reduce plasma Phe levels for PKU patients regardless of underlying setting.

The scientific hypothesis behind our approach is quite simple. It is well understood that reducing the dietary consumption of phenylalanine reduces plasma Pee levels in patients with PKU. Our team has built in that biology to introduce a Synthetic Biotic medicine into the GI tract, which is specifically designed to consume Phe and break it down to produce TCA and HA. TCA or trans-cinnamic acid is cinnamic, HA is a further breakdown product of TCA. Both are generally regarded as safe substances, which are harmlessly excreted from the body. These measurable biomarkers, TCA and HA are key because they allow us to determine the Phe lowering potency of our strains in a consistent manner, across in vitro, in vivo, healthy volunteer and patient studies.

As you know, our first-generation PKU candidate, SYNB1618 has shown promising activity with dose-dependent increases in TCA seen in healthy volunteers. This indicates that the strain is consuming Phe in the GI tract at escalating levels that correspond closely with how much SYNB1618 we are administering. Based on this observation, we have moved SYNB1618 into Phase 2 clinical development. However, our scientific team at Synlogic has continued to ask how much Phe consuming activity can we engineer into a Synthetic Biotic medicine. Especially as synthetic biology tools have advanced rapidly at the time since 1618 was engineered.

That curiosity led us to SYNB1934, a strain that has been evolved from SYNB1618, with the potential to provide increased Phe lowering efficacy for patients living with PKU. Preclinical in vivo and in vitro studies demonstrated a greater than twofold improvement and the ability of SYNB1934 to consume and break down Phe compared to SYNB1618. SYNB1934 was developed using a directed evolution approach, using a biosensor engineer into a tool strain, which was designed to respond to TCA. This allowed us to generate hundreds of variants of the Phe consuming enzyme [power], and to test our wholesale activity in a translationally relevant environment. After multiple rounds of selection, we chose the top candidate strains and confirmed their increased activity in simulated GI compartments in vitro and in vivo in non-human primates, which is the most predictive animal model for humans. This approach resulted in a doubling of Phe consuming activity between SYNB1934 and SYNB1618, which we are now seeking to confirm in Phase 1.

This rapid progression of SYNB1934, which went from candidate selection to first-in-human dosing in less than 8 months, demonstrates the speed and power of our Synthetic Biotic platform. While we evaluate SYNB1934, we also continue to progress the SynPheny-1 Phase 2 proof-of-concept study with utmost care and attention. Our goals in this study are to demonstrate the potential of SYNB1618 to lower blood Phe in adult PKU patients and to validate our pharmacodynamic model to better understand the relationship between the strain biomarkers we have spoken about and plasma Phe lowering in a disease setting.

Patients in SynPheny have no therapeutic options. They're ineligible, inappropriate for or unresponsive to existing therapies. These are patients left behind by today's limited treatment options. The study is powered to detect 20% reduction in plasma Phe. PKU patients and investigators tell us that 20% Phe reductions in an oral, tolerable and reversible therapeutic, which is effective for KUVAN nonresponders would be a welcome treatment option.

In summary, the Phase 1 multiple ascending dose study of SYNB1934 will evaluate the safety, tolerability and Phe consumption activity of SYNB1934, including a head-to-head comparison with SYNB1618 in healthy volunteers using biomarkers of Phe consumption. Based on the data from the head-to-head comparison as well as results of the ongoing Phase 2 study of SYNB1618 in patients with PKU, Synlogic plans to select one therapeutic strain for late-stage development. Data from both studies are expected by the end of 2021. 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 want to thank them for their partnership.

Let me now turn the call over to share progress in Enteric Hyperoxaluria.

Thank you, Dave, and congratulations to your team on the tremendous progress in bringing potential new treatments to patients with PKU.

Now let me turn to our co-lead metabolic program, SYNB8802 in Enteric Hyperoxaluria. Enteric Hyperoxaluria, which we just call HOX, is a devastating condition with no treatment option in which dangerously high levels of urinary oxalate lead to progressive kidney damage. It often occurs as a result of the primary insult to the bowel, leading to fat malabsorption, such as in Inflammatory Bowel Disease, Short Bowel Syndrome or as a result of surgical procedures such as bariatric weight loss surgery. If left untreated, the 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 health and foods, Enteric Hyperoxaluria is almost impossible to control with diet alone. That means these patients are at risk for serious kidney complications. For most patients, Enteric Hyperoxaluria isn't a stand-alone problem. The increase absorption of oxalate is a result of an underlying bowel disorder. This means in clinical practice, it is patients who already have the complexity of living with Short Bowel Syndrome, Chronic Pancreatitis, IBD or who have undergone bariatric surgery, who now have to face the devastating challenge of the current and chronic kidney stones.

In this patient population, the pain and disruption of recurrent kidney stones is a significant challenge in their overall care. There are approximately 75,000 to 90,000 patients with Enteric Hyperoxaluria and recurrent chronic kidney stones, a high-risk of significant kidney damage in the United States. They have no treatment options today, and we believe the Synthetic Biotic platform could provide a meaningful new approach. Meeting the needs of this population led us to develop SYNB8802, an oral Synthetic Biotic medicine, which metabolizes the toxic substance oxalate in the GI tract and convert it into format, which is harmlessly excreted from the body.

As you may recall, we have demonstrated 8802 proof of mechanism in a Dietary Hyperoxaluria study. We have now moved to Part B effect study in which SYNB8802 will be evaluated for the potential to lower urinary oxalate in Enteric Hyperoxaluria patients. Let me walk you through both parts of this study. The primary outcome of Part A of the Phase 1 study with safety and tolerability, which would be used to select a dose for further study in patients with Enteric Hyperoxaluria in Part B of the trial. We completed dosing of 5 cohorts in Part A of the study. In the efficacy analysis, the percent change from baseline urinary oxalate level was 28.6% compared to placebo at the 3e11 live cell dose, a clinically meaningful level of oxalate degradation. This dose was well tolerated and is being used in Part B of the study.

Similar to our prior programs, we did not observe any systemic toxicity, and there were no SAEs or Serious Adverse Events at any dose. Adverse events were generally mild to moderate GI related and transient. We found that a dose ramp significantly improved the tolerability profile. SYNB8802 is a non-colonizing, non-reproducing strain and cleared from subjects after cessation of dosing. We were thrilled to see substantial urinary oxalate lowering across multiple dosing cohorts. This consistent and dose responsive results is very encouraging.

In Part B of the study, patients with Enteric Hyperoxaluria post Roux-en-Y gastric bypass surgery, who have dangerously high levels of urinary oxalate will be assessed in a crossover design. We have chosen a dose of 3e11 live cells for Part B of the trial. We believe this dose could provide a clinically meaningful reduction in urinary oxalate levels in this population. In parallel, we will also continue to evaluate SYNB8802 in additional cohorts with healthy volunteers as we explore further optimization of dose and dose frequency. Overall, this study will inform an enormous amount, as we progress in the 8802 through clinical development. We will better understand not only the activity of SYNB8802 in Dietary Hyperoxaluria disease model, but also in patients with Enteric Hyperoxaluria itself as well as the degree of colonic activity and the potential for less frequent dosing.

Moving forward, we believe the regulatory and clinical path in this indication is relatively straightforward, with significant precedent by sponsors in related diseases such as Primary Hyperoxaluria for the importance of urinary oxalate as one critical endpoint. Our initial efficacy assessment will evaluate clinically relevant reductions in urinary oxalate levels and feedback from our key investigators suggest greater than 20% lowering in patients would be clinically meaningful. Lowering dangerously high levels of urinary oxalate is the only way to reduce the risk of disease progression and reduce or eliminate oxalate nephropathy. We're pleased that SYNB8802 has demonstrated the potential to lower urinary oxalate levels in healthy volunteers with Dietary Hyperoxaluria. We're looking forward to advancing the program rapidly into patient and providing additional data later this year.

As we move forward with both of our lead metabolic programs in PKU and Enteric Hyperoxaluria, I will come back to you with more information as the studies unfold.

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 second quarter ended June 30, 2021, and I'd like to review the highlights of those results with you now.

Research and development expenses were $10.7 million for the 3 months ended June 30, 2021, compared to $12.9 million for the corresponding period in 2020. The R&D expense for the 3 months ended June 30, 2021, consisted primarily of costs related to our collaboration with Ginkgo Bioworks for the optimization of Synthetic Biotic medicines as well as clinical study activities associated with SYNB1618 and SYNB8802, the ongoing SYNB1891 Phase 1 study, and the initiation of the SYNB1934 Phase 1 study.

General and administrative expenses were $4.1 million for the second quarter of 2021 compared to $3.5 million for the same period in 2020. For the second quarter of 2021, the company reported a consolidated net loss of $14.5 million or $0.28 per share compared to a net loss of $15.5 million or $0.44 per share for the corresponding period in 2020.

Revenue was $0.2 million for the second quarter of 2021 compared to $0.4 million 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 IBD.

Now turning to the balance sheet. Synlogic ended the second quarter of 2021 with $115.5 million in cash, cash equivalents and short-term investments, compared to $100.4 million as of December 31, 2020. Under our current operating plan, we expect our cash and cash equivalents will be sufficient to fund the company through the second half of 2023. This will enable Synlogic 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 back over to Aoife to wrap up.

Thank you, Dan. Our team has made tremendous progress across all of our programs, both in and outside the clinic. We're executing effectively and with a sense of urgency. We look forward to demonstrating proof-of-concept in our co-lead programs in PKU and Enteric Hyperoxaluria later this year.

We will now open the call for questions.

(Operator Instructions) Our first question comes from Ram Selvaraju with H.C. Wainwright.

This is [Miles] speaking on behalf of Ram at H.C. Wainwright. So in terms of the SynPheny-1 Phase 2 trial for 1618 and the Phase 1 for 1934, can we expect a combined data release at the same time later this year, together with your announcement of your selection for one of the compounds for development?

Yes. It's very difficult for us to predict exactly when those readouts will come. We know that they're both on track for the second half of this year. I think it really will depend on how exactly the timing falls, whether we can make a single announcement or would have to do 2 separate announcements. So I can't give you a straight answer to your question other than to let you know that they will fall within the second half of this year if all continues to plan.

And if 1934 is indeed selected, what kinds of bridging studies would need to be done to move to a pivotal status? And is the formulation of 1934 day for already optimized or not?

Yes. So the nice thing about 1934 is it is very similar to 1618. We use the same enzyme pathways. It's just with an optimized version of the gene for path. So we were really able to leverage a lot of the work that we had done for 1618 as we were developing 1934, and I think that's evidenced by how quickly it moved from clinical candidate to IND to being in the clinic. And we anticipate that it will continue to benefit from kind of having a lead program that's very, very similar. Right now, the Phase 1 study is being done by -- with a lyo formulation of 1934, so we were able to go into the clinic with already kind of having you taken that big step to lyo. And we anticipate that it will move very, very quickly thereafter. In terms of what we would need to do before initiating the Phase 3 study, should we decide to switch to 1934. We haven't provided a lot of guidance in terms of the specific steps, suffice to say that we think that it can move very, very rapidly because it's been able to take advantage of all of the learnings we've had with 1618. And of course, any regulatory plan would be subject to agreement with the FDA and other regulators. So that's kind of all we can say at this time.

Okay. And just finally, regarding business development. The recent gastroenterology collaboration with Roche, has this triggered any interest and momentum for further partnership opportunities?

Yes. So the Roche agreement is -- was very exciting for us. We're absolutely thrilled. It's exactly the kind of deal that we want to do in Inflammation and in Immunomodulation generally. As we've disclosed, the Roche collaboration was around a single specific target that organization are interested in based on their research in immunology. Obviously, we will continue to advance our own programs that Dave's group are working on and continue to have discussions with potential partners around the same kind of area broadly. Dave, anything you want to say about the immunology strategy, just more broadly, to add to my comments there?

Yes, sure. I mean I think you've summarized it well. I mean I think we still believe there's a lot of biology that can unlock using the platform. We have a number of internal programs that we're working on at the pre-clinical stage, and those will be opportunities to explore either additional partnerships or to advance our own pipeline as those mature. So I think it's all pretty consistent with the strategy we've been following, and we're excited about the Roche agreement, and that is a highlight of kind of that strategy going forward.

Congrats on the exciting developments in the pipeline.

Our next question comes from Joseph Schwartz with SVB Leerink.

I'm Joori down in for Joe. My first question is on SYNB8802. I was wondering if you could help frame how we should be thinking about the Phase 1 Part B data in patients with EHOX resulting from Roux-en-Y gastric bypass surgery when it becomes available. How representative is this group from other manifestations with EHOX, such as Inflammatory Bowel Disease and Celiac disease? Are there any biological considerations we should be taking into consideration about this group? Or is this a fairly good representative of the overall EHOX population.

Yes. And number one, I'd say that our goal is to develop a product for patients with severe Enteric Hyperoxaluria regardless of their underlying GI disease or condition. So that's -- our target is that segment of patients with Enteric Hyperoxaluria, recurrent stones that are really having a very high burden of disease for whom there's currently no treatment. Based on the precedents and others who have done work in this area, we don't believe that there's going to be a difference based on the underlying GI insults that has occurred. When we've looked at prior studies that have been done in this indication, what we see is very similar and consistent treatment effects across all of the underlying GI kind of conditions. We made a decision to focus it on a kind of a relatively homogeneous group to get proof of concept. I think that was kind of a development tactic. It doesn't necessarily indicate that we'll be pursuing a very narrow group or a narrow underlying GI etiology as we move forward in development. In fact, I think the next step in the development program would be for us to evaluate efficacy in a much broader population, including patients with some of the diseases you just mentioned there, Joori, like Inflammatory Bowel Disease, Short Bowel Syndrome, chronic pancreatitis. I think there's a lot of diseases that can result in Enteric Hyperoxaluria, and we plan to pursue all of them.

And then my second question is kind of building on our earlier one. So wondering if you had any color on the order in which we will see your HOX program relative to your PKU program?

Yes. Unfortunately, we get asked that frequently, and we don't have sufficient line of sight to be able to provide guidance around the specific order. Both are on track for results in the second half of this year. In terms of which way they'll fall from a sequence perspective, we just don't know.

Your next question comes from Mark Breidenbach with Oppenheimer.

Just looking at the SynPheny protocol, I'm remembering that you ramped up to dose levels that are about an order of magnitude higher than the previously established MTD for 1618. And I'm just wondering if you can remind us what's giving you confidence that you can safely dose up to those levels in SynPheny. And with respect to the upcoming 1934 data later this year, will that be inclusive of both healthy volunteers and PKU patients or healthy volunteers only?

Yes. Great, Mark, thanks so much for giving me the opportunity to clarify the first point. So I think you'll remember that we did an early study with a liquid formulation of 1618, where we studied small cohort of patients with PKU. The doses that we're currently using in the SynPheny study are log higher than the doses that we previously used approximately in the -- with the liquid formulation in patients with PKU. So I think that's where the log piece comes, but they're not a log higher than the maximum tolerated dose. In fact, when we did the bridging study with the LYO formulation in healthy volunteers, the maximum tolerated dose there with 2e12. So they're absolutely still within the tolerated dose range that we established in healthy volunteers with the LYO formulation. They're just a log higher than the dose we used in the prior PKU cohort with the liquid formulation. So that's just a clarification there in terms of the safety and the dose that we're using in SynPheny. In terms of the second part of your question around 1934, no, the current study is designed to evaluate 1934 head-to-head with 1618 in healthy volunteers. And we look at the production of the strain specific biomarkers to make a determination around whether 1934 is actually more active in humans compared to 1618. It will not include any data in patients with PKU.

Our next question comes from Ted Tenthoff with Piper Sandler.

I really appreciate you guys laying out sort of the efficacy bar for SynPheny in terms of what you're seeing as sort of a win. And I'm wondering what would next steps be assuming positive data?

Yes. So I think in the second half of this year, we have data from SynPheny as well as from 1934. I think the first step is going to be determining which strain of those 2 that we're going to take forward into the next phase of development. And I think then the next step from there will be planning and getting regulatory alignment around our Phase 3 plan as we would with any program. So starting that conversation with regulators in the regions globally that we would intend to commercialize the product and starting to plan for that kind of confirmatory phase of development as we move forward with the program. So that's the kind of the 2 steps. Obviously, a lot of work going into that second step, preparing to move to Phase 3 is not for the faint at heart, but in kind of the logical flow would be making a decision on which strain and then starting to kind of lay out the Phase 3 plan and get engagement with the various stakeholders. Does that make sense, Ted?

Our next question comes from Keay Nakae with Chardan.

So Aoife my question is for EH. Recently, we saw another company who's developing a drug for Primary Hyperoxaluria, show a failed result in the Type 2 patients, and you guys have done a great job in prior presentations in explaining the differences in pathology and metabolic pathways for EH versus PH. But I guess the takeaway from that failed study in PH is just a lack of understanding of what they thought the pathway was prior to -- versus prior knowledge. So how confident are you that you understand the pathway for EH and just building on that prior question in the different patients with different underlying insult.

Yes, Keay, So I'm assuming you're referring to the Dietary results, which...

That's correct.

So I -- yes. It showed nice activity in the Type 1, but not the expected activity in the Type 2, 3. So #1 thing I'll say is we don't believe that, that has any bearing on our program. I think the Primary is, as you mentioned, very different disease due to a genetic liver defect over production of oxalate, a number of different mutations that result in that kind of over production there, but we think it's a very, very different disease, a very different etiology, very different underlying pathophysiology. What I will say about Enteric Hyperoxaluria is, we have a pretty good understanding that it's due to over absorption of oxalate. We know that these patients have fat malabsorption that results in a lot of free oxalate being available in the GI tract that then continue to be absorbed at a much higher rate than individuals who have a normal GI pathophysiology would be. So across all of the diseases, what they all have in common, Pancreatitis, IBD, Short Bowel Syndrome, is that they have this linking kind of underlying pathophysiology of having a lot of free fatty acid in GI tract lumen. And based on our understanding of the pathophysiology of Enteric Hyperoxaluria, that appears to be the kind of unifying component of driving the elevated urinary oxalate levels. So I think that gives us confidence that we'll be able to kind of address the broader population regardless of underlying GI insults. But obviously, the proof of the pudding is going to be in the clinical study once we -- assuming that we get nice results in Part B of the current study. Our next step would be to broaden to include some of those other GI diseases and to start to evaluate whether we get similar efficacy in that broader patient population. But as I said, based on what we know today about the pathophysiology and the precedent from prior studies in the Enteric Hyperoxaluria population, we believe that there's a substantial chance we'll be able to address that broader group of patients.

And then just in terms of the homogeneousness of the bypass patients, is something specific about that population that makes them more consistent versus some of the others within disease state?

Yes. So the bariatric patients have all had similar surgery, right? So that's a nice component in that they'll be quite -- you try in early development, you're trying to do a smaller study and get as much information as you can as a limited treatment numbers. So the more homogeneous, they are often the cleaner the signal is. As you go out into different groups of patients, your -- for instance, you're going into IBD, could some of those patients have active inflammation within their GI tract. Could there be other con-meds that you worry about? So there's different things that you need to take into consideration as you look across broader patients population. So it was really around keeping it homogeneous as well as be able to execute a relatively straightforward study that led to that decision. But I think the next test, as I've mentioned, would be to broaden out and to look at different patient types as we move forward in development.

Our next question comes from Tom Shrader with BTIG.

This is [Zhong] dialing in for Tom. Just one question regarding the PKU program. So I know you have power for a 20% reduction in phenylalanine. So regarding like patients, like what does that mean for patients? Is a 20% reduction based on the low phenylalanine meals that a patient inject?

Yes. So thanks for the opportunity to clarify that. Our current study is being done in patients who have blood Phe levels that are greater than 600 millimolar. So there are patients who are not on a controlled diet or maybe they're semi-controlled but have elevated blood Phe at baseline. We believe in those patients being able to reduce blood Phe levels by 20% is meaningful. It may bring some of them into the less than 600 range. But really importantly for us, we think that this is a gateway to moving into other patient segments, including patients who are maybe on diet, but not achieving their goal, or patients who are on a very strict diet, but would really like to be able to eat additional protein, that's a particularly important consideration in the pediatric patients. We consistently hear from parents that in the pediatric group managing protein intakes such that kids are getting enough so that they feel full, they're satiated and they're growing normally, it's a real challenge with a very, very restricted diet that these kids have to be on. And when we kind of extrapolate what 20% Phe lowering in adults who are un-controlled could mean for pediatric patients in control. We estimate that, that could been able to double the amount of natural protein that, that kid is able to eat on a given day, which I think would be a huge boost to that kid from both a clinical and a quality of life perspective. So we really do see being able to demonstrate 20% Phe lowering in the current population as kind of a step to further evaluation across patients with different kind of different clinical scenarios, and we'll continue to build that value story as we move forward in development and execute additional studies.

And there are no further questions in the queue. I'd like to turn the call back to Aoife Brennan for closing remarks.

Great. Thank you, operator, and thank you, everyone, for joining us today. A very exciting year for us at Synlogic, and we look forward to keeping you up-to-date. Thank you.

This concludes today's conference call. Thank you for participating. You may now disconnect.