Synlogic, Inc.
Q3 2018 Earnings Call Transcript

Published: 14 Nov 2018

[Operator:]

Good afternoon, and welcome to Synlogic's Third Quarter 2018 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 Dr. Elizabeth Wolffe, Head of Investor Relations and Corporate Communications. Please proceed.

[Elizabeth Wolffe:]

Thank you, Andrew. Good afternoon and thanks for joining us on today's conference call. Earlier this afternoon, we issued a press release which outlines our third quarter 2018 financial results and several of the topics that we plan to discuss today. The release is available on the Investor Section of our website at www.synlogictx.com. Joining me on this call are several members of Synlogic's senior management team, including Aoife Brennan, President and Chief Executive Officer and Chief Medical Officer; Todd Shegog, Chief Financial Officer; Andrew Gengos, Chief Operating Officer and Head of Corporate Development; and Paul Miller, Chief Scientific Officer. Aoife will provide an update on our current programs and plans, and Tom will briefly summarize our financial results for the quarter. Following our prepared remarks, we'll open up the call for questions. As we begin, I'd like to remind everyone that the comments from today may include forward-looking statements made under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include without limitation, statements other than statements of historical facts regarding the potential of Synlogic's platform to develop therapeutics to address a wide range of diseases, including cancer in bone, areas of metabolism, liver disease, and inflammatory and immune disorders. The future clinical development of synthetic biotic medicines, the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology, and the expected timing of Synlogic's clinical trials and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statements as a result of various factors, including those described under the heading forward-looking statements in Synlogic's press release from earlier today or under the heading risk factors in Synlogic's most recent Form 10-Q or in the latest filings with the SEC. Synlogic cautions you not to place undue reliance on any forward-looking statements. Now, I'd like to turn the call over to Aoife.

[Aoife Brennan:]

Thanks Liz. Good afternoon everyone, and thank you for joining us on our first quarterly update call. I would like to begin by expressing how excited I am about the opportunity to be at Synlogic at this important time in the company's development. We have two metabolic disease programs and ongoing clinical trials, we've just have carried a new candidate in immune oncology and we're making significant progress in understanding the potential of our therapeutic platform. For those of you who don't know me, I joined Synlogic in 2016 as Chief Medical Officer. A number of years ago, I moved from the role of practicing physician and academic into industry as I thought that developing new medicine would allow me to have greater impact on improving patients' lives. This mission is what drives me and the rest of the team here at Synlogic. I joined Synlogic from Biogen where I led the rare disease group and developed a number of drugs including Nusinersen for spinal muscular atrophy, and our Polexnalactic [ph] treatments for hemophilia B and A. As part of my role at Biogen, I evaluated many new technologies and so, in addition to my clinical development expertise, I gained a good sense of what's needed to make a new technology successful. When I was offered the opportunity to join Synlogic, I jumped at this. I believe that we have a platform that enables a whole new class of medicines that have broad applications from metabolic disease to cancer. The use of synthetic biology to modify microbes has been successfully applied in many different areas, particularly, in industrial microbiology. Synlogic leads the field in exploiting the science for this science for drug development. In 2014, the company was funded with technology from MIT and we treated our first subject with a synthetic biotic medicine in 2017. This is fast bringing technology and speaks to our focus on developing a translational foundation for our platform. We're using our proprietary platform to design and engineer beneficial microbes to perform critical functions, missing or damaged due to disease. We believe there are a number of distinct advantages to our approach in each of our early program indications, our synthetic biotic medicines are designed to act locally but to have systemic effect. We focused initially on engineering one strain of bacteria, a strain of E.coli called E. Coli Nissle, that was isolated from the gut microbiome of a human and has been widely used a probiotic. Apart from the safety records, we chose this organism as it's biology is well understood and it's easy to engineer and manufacture compared to other microbes. While we see broad potential for our platforms in and beyond metabolic and immune-based diseases, we've been focused on understanding the behavior of our bacteria in three different settings as a means to understand the application of our platform; the small intestine with the phenylketonuria, our PKU program, the colon with our hyperammonemia program, and an intratumor setting with our first oncology program. In addition, we have earlier stage programs in development for the treatment of more common diseases such as the liver disease and other inflammatory and immune-based disorders including an active collaboration with AbbVie to develop the synthetic biotic medicine for inflammatory bowel disease. So far we are improving this new technology. We have two orally-administrated programs currently in the clinic and SYNB1020 for the treatment of hyperammonemia and SYNB1618 which we're developing for the treatment of PKU. In both programs we've demonstrated activity in preclinical disease models and have proof-of-mechanism in healthy human volunteers. Across both programs, we've approximately 100 humans with our synthetic biotic candidates, including healthy volunteers and patients with liver disease and PKU. We've not observed any systemic toxicity and the bacteria have cleared within the expected time following dosing. Most recently we announced data from the healthy volunteer cohorts of our clinical trial of SYNB1618 for the treatment of PKU. A webcast a discussion of the initial clinical data and the paper describing our pre-clinical work which was published in Nature Biotechnology are both available on the Investor Section of our website; so I will only briefly summarize the program and our progress to-date here. SYNB1618 functions in the GI tract, specifically the small intestine, and has been engineered to consume phenylalanine, otherwise known Phe, which is an essential amino acid and the component of almost all proteins in food. In most people Phe is broken down by an enzyme in the live to produce another amino acid, tyrosine. However, patients with PKU have inefficient form of this enzyme and so are unable to effectively metabolize Phe. Phe can accumulate to harmful levels in the blood and brain of patients with PKU with severe consequences, including significant cognitive impairment, behavioral problems and convulsions. We've engineered SYNB1618 to express several different genes from other gut bacteria, including two enzymes that enable it to efficiently degrade Phe. In line with our published pre-clinical data and our first clinical trial from healthy volunteers, we observed a statistically significant dose-dependent effect of SYNB16 associated biomarkers which established proof-of-mechanism in humans. Currently we're enrolling patients with PKU and an additional single dose cohort of 4 subjects and a multi-dose cohort of 10 to 20 subjects. This study is designed to affect safety and pharmacodynamic in patients with disease. Top line data from this patient treatment arm of the study is expected in mid-2019 with presentation of full data and as an appropriate medical meeting thereafter. With these data in hand, we plan to conduct a Phase 2 study to determine the potential for Phe lowering in patients. We believe that SYNB1618 has the potential to address the needs of patients with PKU by providing at oral therapy that avoids systemic [indiscernible] that would be appropriate for all PKU patients including pediatric populations, and that would enable patients to control Phe levels who are potentially consuming a more natural protein containing diet. Our second orally-administered synthetic biotic medicine is SYNB1020 which we're developing to treat hyperammonemia. Ammonia is primarily produced in the colon as a byproduct of protein metabolism and microbial degradation of nitrogen containing compounds. Hyperammonemia is a metabolic condition characterized by the liver's inability to convert ammonia into urea resulting in accumulation of ammonia to levels that are toxic to the brain and can have severe consequences including neurological crisis requiring hospitalization, irreversible cognitive damage, and death. Hyperammonemia can occur as a result of liver damage or from rare genetic diseases such as urea glyco disorders. SYNB1020 is an engineered strain of E.coli Nissle designed to function in the colon, consume ammonia and convert it to arginine which is a beneficial amino acid. We have generated pre-clinical data that demonstrate dose dependent ammonia reduction and improved survival in several net modules of disease. In addition, this past weekend, at the Liver Meeting which is the annual meeting of the American Association for The Study of Liver Disease, our collaborator, Dr. Chris Rose, presented confirmatory ammonia lowering data in a rat model using our synthetic biotic strain; this rat model maybe more suitable for testing benefits on cognitive functions. Based on our pre-clinical data we moved into single and multiple ascending dose Phase 1 clinical trial in healthy volunteers which demonstrated proof-of-mechanism based on dose dependent production of biomarkers, in this case, plasma and urinary nitrate, a final product of arginine metabolism. To determine the effect of SYNB1020 on blood-ammonia levels, we initiated a Phase 1b/2a trial in patients with cirrhosis and elevated ammonia. The primary goal of this study is safety and tolerability in the patient population with a secondary endpoint being pneumonia lowering. Earlier this year the FDA asked us to treat an initial open-label cohort of 6 subjects which Myers [ph] disease to ensure that SYNB1020 was safe in patients with liver disease who often have impaired barrier function and might be susceptible to infection. This part of the study is complete and after review of the data by Study Safety Committee we were given the green light to treat patients whose cirrhosis had progressed to the stage where they have elevated ammonia at baseline. Measurements of ammonia in blood is notoriously variable, and so we've worked with our clinical sites to ensure that they have a reproducible assay, and that they have defined standards at each site for a normal range of blood ammonia. Data were also presented this past weekend AASLD meeting from a cross-sectional study that we conducted to establish a normal range for each of our sites, and to compare the reproducibility of ammonia measurements in fresh versus frozen samples. Based on these data, each site must measure ammonia in fresh samples within 60 minutes of collection. The site that we can use for such studies must have assay capabilities in place onsite. We've also designed a protocol to ensure that only patients with elevated ammonia enter the study. In the first 5 days subjects receive a standard diet and only expect elevation in ammonia at the end of it's running period can they enter the study proper. We now have a total of 5 sites open and screening subjects, several of which were added in the last month and we expect to add an additional two sites by the end of the year. However, we believe it will take longer to enroll our initial cohort of subject than initially predicted; we now expect to have data in mid-2019 rather than at the end of 2018. I should also mention that when we design the trial, we made certain assumptions as to the variability of ammonia measurements. Using an independent monitor, we'll be reviewing variability in the study and have the ability to enroll additional subjects, if needed, in order to meet our objectives. With ammonia lowering data enhanced, we'll determine how to proceed to develop SYNB1020 and for which indications. Our strategy was to move from concept to clinic very expeditiously, and to use an early formulation of our synthetic biotic medicine in order to obtain clinical experience and better understand the predictive value of our animal models. In parallel, we've been exploring manufacturing options and investing in process development and formulation to improve our products and to enable us to move from liquid to solid formulation. As part of it's effort, we're also gaining a better understanding of how to maximize activity and tolerability of our engineered bacteria, and I hope to be able to give you a fuller picture of these advances in the first half of 2019. Which brings me to our initiative in immuno-oncology which we believe is another therapeutic area in which our synthetic biotic platform could have significant advantages over other approaches. While great strides have been made in immune-based approaches to cancer treatments, one of the problems is that not all patients respond to immune checkpoint inhibitors even where indicated and there are significant numbers of tumors that don't respond to treatment. Our goal is to expand the benefits of immunotherapy broadly across tumor types. Tumors have multiple mechanisms to evade the immune system; the flexibility of our syntactic biotic platform enables us to engineer strains that can overcome tumors resistance to treatments and leverage both, DNA and adaptive immune systems turn a tumor evading the immune system into one that can be targeted by, and is susceptible to immune system appearance. In addition, our locomotive delivery into the tumor via bacteria chassis can provide additional immune stimulation by reducing other risks. This past weekend we presented supporting pre-clinical data and held an investor and analyst event at the annual meeting of The Society for Immunotherapy of Cancer or SITC. At which we announced our first immuno-oncology candidate, SYNB1891. This acts as a dual innate immune activator, the presentation and the webcast of the event which provided a comprehensive review of our data and rationale, as well as commentary by experts, Dr. Philip Jenkins, from M.D. Anderson, and Dr. Dimitris [ph] from Memorial Sloan Kettering Cancer Center, are available on our website, and so I will only covered it briefly today. SYNB1891 is an engineered strain of E. coli that produces cyclic di-AMP or CDA, a potent agonist of the sting pathway which plays a critical role in the production of Type I interferon and initiation of anti-tumor responses by activation of antigen presenting cells or APC, and the presentation of tumor antigens. There are several key differences between our approach and others, particularly small molecule teams agonist approaches. SYNB1891 can deliver directly into the tumor where it remains active for several days to stimulate a local immune response. This is in contrast to make it's T-agonists that tend to have short half-life. CDA is delivered directly into the tumor residents APCs when they engulf SYNB1891; as these innate immune cells naturally sense and engulf bacteria. This process results in a highly efficient activation of distinct pathway and Type I interferon response in APC sparing while sparing other cell types such as T-cells where sting activation might be detrimental for efficacy. We believe this delivery feature is unique to our synthetic biotic platform among all other modalities. In addition, the bacterial chassis [ph] used in Synlogic's synthetic biotic approach is also be able to stimulate the immune system via several other mechanisms, potentially adding to the magnitude of the overall immune response. These two key features STING activation within and only in APCs, an activation of additional immune pathways make SYNB1891 a truly differentiated first-in-class immuno-oncology agent. Our goal is to file an investigational new drug application or IND for SYNB1891 in the second half of 2019 and to move as quickly as possible into a clinical study. We looked forward to providing more details as to the design and scope of the study on future calls. As you can see, it's been a busy period. We've made significant progress in advancing our program and we have a lot to look forward to in 2019. Now, I'd like to turn over the call to our CFO, Todd, to summarize our financial results for the quarter.

[Todd Shegog:]

Great, thank you Aoife, and good afternoon everyone. As you know, after the close of market today we released our financial results for the third quarter ended September 30, 2018, and I'm pleased to review the highlights of those results with you now. Revenues in the third quarter of 2018 were $1.8 million compared to $0.1 million for the same period in 2017. The revenue from both periods is associated with Synlogic's collaboration with AbbVie to develop a synthetic biotic medicine for the treatment of inflammatory bowel disease. The increase in revenue is primarily the result of the achievement of a $2 million milestone under a September 2018 amendment for the AbbVie agreement of which $1.8 million was recognized in revenue in the quarter-ended September 30, 2018. Total operating expenses for the third quarter of 2018 were $13.3 million compared to $12.2 million for the same period in 2017. Research and development expenses were $9.9 million for the third quarter of 2018 compared to $9.0 million for the third quarter of 2017. General and administrative expenses were $3.4 million in the third quarter of 2018 compared to $3.2 million for the same period in 2017. For the third quarter of 2018, the company reported a consolidated net loss of $10.7 million or $0.43 per share, compared to a net loss of $11.9 million or $1.66 per share for the third quarter of 2017. I'll refer you to today's press release for a summary of the 9 month year-to-date results. Turning to the balance sheet; Synlogic ended the third quarter of 2018 with a $132.6 million in cash, cash equivalents and short-term investments. In summary, we have the balance sheet strength to advance our ongoing clinical programs, for important data readouts in 2019 and to accomplish our near-term and mid-term goals as we continue to develop our platform and pipeline. Thank you. I will now turn the call back over to Aoife.

[Aoife Brennan:]

Thanks, Todd. Operator, we're now open for questions.

[Operator:]

[Operator Instructions] And our first question comes from the line of Joseph Schwartz with Leerink Partners.

[Joseph Schwartz:]

I wanted to ask some things on SYNB1891; what remains to be done there before you file the IND in the second half of next year? And can you talk about the design of the study or studies you're thinking of undertaking once it enters the clinic, things like dosing and tumor types that you have in mind?

[Aoife Brennan:]

So, in terms of the work seen between now and opening the clinical trial, finding the IND -- I think there are three buckets. Number one is our manufacturing and manufacturing clinical trial material which obviously undergoes several stages. The second component is completing our pre-clinical package with the clinical candidate which includes the INR enabling toxicology program. And then third component of that IND is the final clinical plan in terms of Phase 1 study design will look like. Obviously all three components will require alignment with the FDA prior to filling the IND to give us the best potential for new sailing [ph] as we experienced with our first two INDs. So that work is ongoing, and we'll be making great progress. In terms of the second component of your question; and -- I think our plan is, we're continuing to work on the clinical trial design and strategy, and as soon as we have that finalized with the various stakeholders we'll provide additional details on that in the early part of next year.

[Joseph Schwartz:]

And then, what do you think about the potential for repeat dosing of 1891 if enough of an effect isn't seen from a single administration? Is there any thought about whether the immune system would accommodate that in tolerable manner?

[Aoife Brennan:]

So, the data that we presented pre-clinically from safety and I'll turn over to Paul after I kind of get the first line answer. The data that we presented there included a sequence of three injections, and that were a couple of days apart in the pre-clinical mess [ph] model of what we send is that that's the optimal kind of sequence of injections that leads to the best response rate in the pre-clinical model and we're -- basing our clinical plan around that. So that's the plan right now, no reason to believe that that won't be successful clinically based on what the others have done injecting live bacteria into tumors and experience from other clinical learning's, and so that's the time there. Anything else Paul you want to add?

[Paul Miller:]

I think that's quite accurate and I think we have quite a bit of confidence that we will see an immunological response from the initial dose, but we -- our safety data and our experience so far supports exploring additional doses.

[Operator:]

And our next question comes from the line of Ram Selvaraju with H.C. Wainwright.

[Robert Burns:]

This is Robert Burns on for Ram. So just three questions if I may, congrats on all the data that you are full-leased [ph] over the weekend. So the first one; so how should we really be thinking about the data presented at AASLD regarding them enter an intrapatient variability in ammonia levels. Now what kinds of challenges do these variations pose for controlled clinical trials with probiotic agents time to consume ammonia in the gut?

[Aoife Brennan:]

I think we're -- our plan is to execute a study that determines the impact on ammonia lowering and a foundational component of that is how you set yourself and how you understand the optimal way to perform the sampling for ammonia. I think the data that we presented at AASLD kind of underlines the care and attention we've put in designing and executing this study, and we did normal ranges at each individual site, we set up specific infrastructure to support doing a study that has the lowest possible variability to give us the most power to see an effect. So I think we're moving ahead in a very logical way by creating a foundation at each site, it's been a challenging area for many others, we've learned from studies that have gone before us and done extensive -- in intel gathering before initiating the study, and I think that's kind of underscored by the data that we released at the AASLD. And I will say that moving forward; certainly in liver disease population after the early phase studies we'd be posting to more of a clinical endpoint for subsequent Phase 2 and 3 trials; so I think we would hope to move past ammonia as an endpoint as quickly as we can as we further develop the programs. So I don't think that would be kind of a re-through in terms of up Phase 3 and would look like there. So I know you had two other questions Rob; does that answer your first one?

[Robert Burns:]

Yes, this is my first one; so you actually answered a second one with your response. So I guess just one additional one; and that's really, really -- can you provide any extra granularity as to what specifically within the sample processing introduces that variability within the readings?

[Aoife Brennan:]

So I think we haven't discovered that, not only is very difficult to analyze to measure, I think it's been well known, and the ammonia is very difficult, it's very labile, and the samples can't be taken with truncate, it has to be taken on ice; we've gone one step further and we're establishing a very protocol-based assessment from the same way every time but I certainly know from my years working as a physician it was kind of a notoriously difficult analyte to run accurately, so I think it's just the nature of the molecules and the analyte and resulting loss of the difficulty [indiscernible] hemolysis in the sample will force to elevate the ammonia, it's just a very fickle analyte to measure and that's well known in the field. I think what we've done is try to establish an infrastructure to do that in the most precise and accurate way possible, but you know, I think notwithstanding it continues to be a challenge.

[Operator:]

And our next question comes from the line of Mark Breidenbach with Oppenheimer.

[Mark Breidenbach:]

A couple of questions on the ongoing trial in liver cirrhotics; I'm wondering if there is any repercussions for the initiation of the trial in UCD based on the sort of delayed or slow enrollment in the cirrhotics trial; can you comment on that first?

[Aoife Brennan:]

So I think our plan remains the same and mark in terms of staging initiation of the UCD trials based on our experience in the liver disease population. A lot of the -- I think there is a lot of read-through there in terms of some of the technical challenges we've had to solve for this trial would equally apply based on the fact that ammonia is even more important being the approvable endpoint for UCD indication. So I think there is some synergy there and we can absolutely apply our earnings around the infrastructure and what we have to do and through to UCD but they continue to be in our strategy that continue to be staged, so we would proceed with UCD only following kind of learning and some data and readout from the Haiti [ph] study.

[Mark Breidenbach:]

And would you say the slower than expected enrollment in this trial is primarily coming from screening failures in terms of the patients don't have high enough baseline ammonia or has it been just more of a challenge in getting a standard guidance among your assay set-up across all of your sites?

[Aoife Brennan:]

So the real challenge right now is initiating the site in terms of getting them up and running, there is generic reasons in terms of just getting the contracting paperwork and budgets done, and then, there is reasons that are specific to the trial in terms of what we had to do to get the ammonia ranges established at each site before they enroll their first patient; a combination of that and the fact that the FDA asked us to do kind of a run-in cohorts before we were able to start the study proper are the two main drivers of the delay right now. So it's not necessarily related to screen sales.

[Mark Breidenbach:]

And I think you mentioned in a response to one of the earlier questions that you would ultimately want to move into a more clinically relevant endpoint in liver cirrhotics specifically; what do you see is an approvable endpoint in this population?

[Aoife Brennan:]

So this [indiscernible] they were approved on the basis of reduction in episodes of hepatic encephalopathy or worsening of hepatic encephalopathy that we for sure have the precedent of back to follow, and I think we're also open to exploring other kind of cognitive or functional endpoints that might be relevant in this population, and obviously, lot of work to do before we're able to enhance our Phase 3 plan is for the indication but I think there a number of options that could provide us with a path to approval in the indication if the data continue to have positive.

[Mark Breidenbach:]

Can you comment on what triggered the $2million milestone for AbbVie?

[Aoife Brennan:]

I think I'll ask Paul to cover that one, and Marquee [ph] is leading the AbbVie collaboration and can give you some more color.

[Paul Miller:]

So we have a staged partnership with AbbVie and in inflammatory bowel disease which we haven't really talked about what all of the components of that are but suffice it to say, we're executing successfully against that program and we're able to show progress in developing strains against pre-clinical models of inflammatory bowel disease that merited that award [ph].

[Mark Breidenbach:]

So no candidates have advanced in for the clinic yet under that collaboration?

[Paul Miller:]

Not at this point.

[Operator:]

And our next question comes from the line of [indiscernible] with Citigroup.

[Unidentified Analyst:]

Could you speak a little bit more about the relative contribution of the STING activation and the bacterial chassis with regard to the immune phenotype that you're seeking in this product?

[Aoife Brennan:]

In the slide I didn't discuss it in a lot of detail today but we can certainly provide you more information, the sum on the website as you go. But the bottom line is, when we do side-by-side comparison of the naked STING of various doses versus the STING expressed in bacteria, we see quite a significant difference in terms of the Type I interferon response, and then we can further start to kind of pull that apart by looking at TLR-4 knockouts and some other kind of cell model systems to really understand what the contribution of bacteria chassis is to that difference. The bottom line is that delivering STING in the context of bacteria potentiates the increase in Type I interferon that injects compared to when you deliver the same dose of STING as a naked agonist, and we think that's the combination of the fact that bacteria gets into antigen presenting cells through a natural engulfment that that just happens by way of how those cells function; so the STING actually is getting closer to the site of action. And the second component is the fact that we stimulate multiple other TLR-4 and TLR-5 pathways within those antigen presenting cells and both of those contribute to a much greater magnitude of Type I interferon releasing an activation then you get with just a small molecule of agonist alone. And we have some data, in vitro showing head-to-head how the STING compared to our bacteria expressing STING. Does that make sense?

[Unidentified Analyst:]

Yes, it does, thank you. And then on the 1618 program for PKU; based on what you've seen so far from the healthy volunteer work and then the Phe biomarker data that you're seeing in the single dose and multiple dose cohorts; is it fairly clear to you that in the Phase 2 that you expect to be well within the normal range for phenylalanine when you do that study?

[Aoife Brennan:]

I think what we know right now is the bacteria are already acting as we designed them to do, they are consuming a significant amount of Phe, based on our calculation we think the amount of Phe that they are consuming has potential to be clinically meaningful in patients with PKU. What we don't know yet is how the bacteria is going to behave in patients with PKU, that part of the study is currently ongoing. And in terms of our -- what we want to see in Phase 2, what we're looking for as a significant reduction in blood Phe levels, and that would be the approvable endpoint for the program. Obviously, we'd love to be able to completely normalize Phe, we may or may not get there, we don't know yet; but I think if we continue with the program we'll learn more and more in terms of what the magnitude of the effect is in patients with PKU Does that makes sense?

[Unidentified Analyst:]

Yes. Thank you.

[Operator:]

And our next question comes from the line of [indiscernible] with Piper Jaffrey.

[Unidentified Analyst:]

It was great to see you all, and sine here with the weekend, really interesting progress on those program; I was impressed by the immune response that you saw. Just a quick follow-up question, rest of mine have been asked and answered, but specifically, just to confirm; whether the number of patients that you're treating in this PKU cohort and what are kind of the doses that you're exploring? Thank you.

[Aoife Brennan:]

For the PKU cohort, if you know, we did single and multiple dose cohorts in healthy volunteers and our plan is to do a single cohort of 4 patients with PKU of whom 3 would get active drug at a dose of 7/10

[Unidentified Analyst:]

Thank you very much.

[Aoife Brennan:]

Are there any other questions, operator?

[Operator:]

I'm showing no further questions. [Operator Instructions]

[Aoife Brennan:]

Thanks, operator. So I think I'll just sum up; this an exciting time for Synlogic, this year we've built on our understanding of the pharmacodynamic in the GI tract. We look forward to a date in 2019 which will give us insights and potential and future directions of our platform. We expect our current clinical studies, Phase 1b/2a to evaluate 1020 in patients with cirrhosis and elevated ammonia, and 1/2a to evaluate SYNB1618 in patients with PKU to both yield data around the midpoint of 2019. We've nominated our first clinical candidates in IO since the 1891 and expect to find an IND application in the second half of 2019. We're also making good progress in our collaboration with AbbVie and Gingko [ph], and in our activities to develop solid oral formulation of our synthetic biotic medicines. And with the cash position of approximately $133 million at the end of the third quarter, we have a solid financial position to execute on all of our planned activities in 2019. In the year ahead we believe we'll gain additional insights into the potential of our program to treat human disease and the promise of our platform across metabolic and oncology indications. I'd like to thank you all for joining us this afternoon. We'll be available later today if there are any follow-up questions. Thank you, operator.

[Operator:]

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone, have a wonderful day.