Q3 2021 Synlogic Inc Earnings Call

Ladies and gentlemen, your conference call is scheduled to begin shortly please continue to standby. Thank you for your patience.

Yeah.

[music].

Good morning, welcome to send logic third quarter 2021 conference call. At this time all participants are in a listen only mode. There will be a question and answer session at the end of this call.

Please be advised this call is being recorded I would now like to hand, the call over to Daniel Roseanne 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 third quarter 2021 financial results and additional business updates. The release is available on the investors section of our website, that's the logic, TX Dot com.

Joining me this morning, our Doctor, if O'brien, President and Chief Executive Officer, and Molly Harper, our newly appointed Chief business Officer.

Other members of the management team will be available during the Q&A.

During the call <unk> will provide a review of third quarter highlights.

<unk> progress, including an update on our program and casino Ketonuria and Molly will share her perspective on the unmet need in PKU and the opportunity to impact patients.

<unk> will then return to provide an update on our metabolic portfolio. Finally, I will summarize our financial results for the quarter.

Following our prepared remarks, we will open the call for your questions.

As we begin I'd like to remind everyone that comments today may include forward looking statements made under the private Securities Litigation Reform Act of 1095. These forward looking statements are made as of the date hereof and are subject to numerous factors assumptions risks uncertainties, which may 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 <unk> press release from earlier today or under the heading risk factors in <unk>. Most recent Form 10-K or in later filings with the SEC.

<unk> cautions you not to place undue reliance on any forward looking statement.

And now I'd like to turn the call over to Eva.

Thanks, Dan Good morning, everyone and thank you for joining us I'm sure.

To share with you today updates on our recent progress as well as our financial results for the third quarter of 2021.

When we began 2021, we set out to prove the clinical potential of asking Patrick biotic platform.

We have the opportunity to demonstrate proof of concept in phenylketonuria in our phase two study.

Thrilled to report that we've done Jeff back.

Lead asset <unk>, <unk> demonstrated a robust and statistically significant reduction in plasma feed apples.

I'm clear alignment across a multitude of study end points.

This is the first time in the history of PKU drug development, that's a therapeutic.

Delivered locally in the GI tract has had an impact on systemic feed Apple.

Furthermore, we believe our evolves synthetic biotic strain can be 19, Turkey floor may demonstrate even more feed lowering activity.

This is also the first example of the biotherapeutic generated by the synthetic biotic platform demonstrating robust proof of concept in a disease population.

But we do not intend to stop at PKU.

We are building a robust portfolio with significant progress over the past quarter and multiple metabolic indications.

Yeah.

And then tech Hyperoxemia area as we shared at the American Society of Nephrology kidney week.

Product candidate <unk> <unk>, two has demonstrated robust consumption of oxalate in the Gi tract.

As measured by both urinary and fecal oxalate reduction.

<unk> <unk> two has the potential to be a meaningful therapy for patients suffering from empiric hypoxia, you're yet to.

Faith as we also reported at kidney week, a substantial increase risk of incident chronic kidney disease.

As a result of being serious damage oxalate dead to renal function over time.

We continue to prosecute the proof of concept study of <unk> in patients.

We'll report on that data in 2022.

Okay.

We're also proud to have unveiled this week with our partners that ginkgo bio works.

Heard oral metabolic program, which we call <unk> be hurricane 53.

Shouldn't be Turkey, 53, degrades Mackay and <unk> in the Gi tract for the treatment Tacoma Cystinuria, our H C M.

<unk> is an inborn error of metabolism and a natural extension of our work in PKU.

It will be speaking more about this program as we prepare for and file an IND.

And advanced into the clinic next year.

Our immunology pipeline why more nascent also continues to advance well.

We're excited that our collaboration with Roche.

Develop a synthetic biotic medicine for the treatment of IBD is off to a fast start with the first milestone already achieved.

And we have also completed enrollment in the combination arm of the phase one all comers immuno oncology study I've seen be 18, 19, one with anti PD one album.

We look forward to sharing data on that steady at 50. They said this week.

In order to focus our resources on our oral programs. However, we will not be continuing further studies of CB 891 at this time.

Didn't like it today is well positioned to deliver on the promise of our platform and bring a meaningful new therapeutic approach to patients.

We are executing on our strategy focusing on rare and niche metabolic diseases, where a targeted approach restricted to the Gi tract can treat patients in ways other modalities cannot.

No let me welcome Molly Harper to the team and give her a few moments to share her thoughts on the unmet need in PKU.

Molly comes to us with a wealth of pre commercial launch experience in both broad and rare diseases in the United States and globally.

We're thrilled to have her build our capabilities as we look to pivotal development in PKU.

Molly over to you.

Thank you Eva is incredibly exciting to join us in logic team, particularly at this.

Momentum time, I'm delighted to share some initial observations regarding the remarkable opportunity that some logic has before us as we advance our program with the potential to transform the lives of those living with and it was affected by PJM.

As a disease and for their community affected by the disease PKU presents something of a paradox.

So on the one hand P. J was a well characterized disease with a community that has seen tremendous progress. It is a sizable population for a rare disease and has been extensively researched the.

Diagnosis is straightforward and it is universally implemented that'd be a newborn screening in many countries and the United States every person born since the 19 sixties Charles P. J you have been diagnosed at some point in their lives.

There had been ICD nine and ICD 10 codes there are dedicated clinic.

There is a vibrant and well networked advocacy community, who provide clear links to those specialists and clinics.

There are both well defined medical sub specialists as well as dietitian specialists, who are clinical as well as research experts who are passionate about taking care of and advancing research. This population.

On the therapeutic side multiple drugs have been approved there is regulatory precedent there are clear protocols for reimbursement one of these therapies is now generic facilitating and pure trial periods to determine response.

And yet.

Well, we perhaps are not heard enough about is that despite these attributes PKU is a disease that continues to be devastating for those affected and for their caregivers.

The burden of living with P. J here is often extraordinary on every level medically psychologically socially economically much of this burden as well documented such as the large claims based analysis that showed that even among those diagnosed and while I'm sure. There remains an eight fold greater risk of intellectual disabilities.

We're a different study, which is focused on patients patient populations, who are connected to specialized clinic and still show the 70% has significant neuropsychiatric comorbidities with 50% of those with multiple comorbidities.

Reflecting these disease complications and the limitations of a truly transformative treatment for most patients. One study found that 70% of adults living with PKU, we're disconnected and despite these drug approvals are not receiving treatment through the establishment of all clinics.

So with multiple FDA approved drugs, it's hard to understand why this would be the case.

Looking closer these advances while important have unfortunately left the majority of those living with PKU in need of additional option.

So, perhaps sharon's utility generally limited to people living with Covid mild.

Mild PKU who may.

Maintaining some ph enzyme functionality does respond to that mechanism of action.

This group represents a minority about 30% of patients. This renders fee reduction for all comers that is relatively modest at just a negative 10% decrease.

With this the burden of approximately 10 pills a day on top of required dietary restrictions and needed to supplement the treatment.

Experience can be conducive to internet in compliance and risk and just discontinuation.

This is the classic or the more severe PKU population, which makes up the majority of people living with PKU and the population who have been most significantly underserved by options today take valleys injection those offer efficacy for those adults.

Adults, who can persist through the titration, which can extend over one calendar year daily injections and those were both the capacity and the vigilance to manage the risk of anaphylaxis at any moment, which is thousands characterized in this box warning.

It is important to note that even for those who adhere to both dietary requirements and drug therapy, there's a great desire for a treatment.

That can provide additional feed lowering or something closer to what most of us take for granted at a normal eating and social life.

So looking to the split on the res side of the screen the well controlled segment represent those with more mild underlying disease, who are able to respond and inherited treatment as well as those children, whose diets are closely managed by their caregivers.

The larger part of this population outlined here include people living with PKU, who are in need of a novel treatment that provides significant reduction of plasma see regardless of their treatment status.

So for several years now there's some logic team has been actively listening to and learning from the PKU community, who have been consistent in sharing their wish list for a new treatment option.

That would be one that would be orally administered can.

Convenient.

Safe and efficacious.

Designed with these exact needs in mind to synthetic biotic approach to PKU has the potential to address these needs.

The mechanism could not be more intuitive.

People would pique you cannot metabolize dietary fee, which enters predominantly via dietary protein.

Some logic design bio therapeutics with the potential to metabolize dietary fee in the GI track with decent bet. If biotic is orally administered conveniently package with a locally delivered mechanism without systemic absorption and the associated potential AE.

And we recently were able to share an early view of how this has worked and those with the greatest need.

So now let me ask you tried to take you through the clinical data that we've been able to share today.

Thank you Bonnie.

Earlier this quarter, we presented two dataset, which gives us confidence in advancing our PKU program.

Firstly and Symphony a phase two study in patients with PKU, we achieved our target reduction in blood fee levels and an interim analysis of eight patients with available data.

And secondly in a head to head comparison shouldn't be 16, 18, and shouldn't be 19, Turkey for our optimized strained for PKU and healthy volunteers. We found that the fee consuming activity can be 1934 is approximately two fold basch of can be 16 18.

This suggests shouldn't be 1934, and they provide an even more attractive clinical profile.

Based on these highly encouraging data, we will be adding shouldn't be 1934 to phase two symphony study and preparing to advance our PKU program into a pivotal phase III study.

As you recall, our ongoing phase two symphony is a single arm study in patients with classic PKU.

This population has fee levels above 600 micro most producer at screening and is not served by available therapies.

The more severe population than the BH for responsive population enrich coupon has been studied.

The interim data we shared from the first eight patients to complete the study which remains open to enrollment.

And important design element of this study is that each patient function at their own control.

Subjects were placed on a strict diet that was designed to match their usual protein and food intake and had a diet run in followed by baseline assessments.

They then received increasing doses of <unk> B 16, 18 over two weeks with repeat on treatment assessment, followed by a washout period.

Diet management was maintained throughout the trial to the day 929 assessments.

There were two critical endpoints in this study.

First and B O Challenge test, which were performed with a standardized breakfast containing labels fee here called D. Five fee at the beginning and end of the dosing period to determine SNB 16, 18 prevent dietary feet absorption.

Second we evaluated fasting plasma fee.

This was measured prior to dosing after seven days again on day 14, and at the end of the wash out period on day 29.

Let's begin with the meal challenge yourself.

And these tests the subjects receive a standard breakfast containing five feet.

They received their first meal challenge on day minus one and then underwent the same test on day 15, after a dose or two each wildlife cells, which is the highest dose studies.

The purpose of this test was to look at whether it be 16, 18, with metabolically active and metabolizing feat in the Gi tract and preventing it from being absorbed and increasing blood fee levels.

On the left hand panel is shown to increase and blood TCA, a biomarker a strained activity because it's a byproduct of feed breakdown by the strain.

As expected, we can observe that it increases significantly with dosing.

On the right hand panel is the area under the curve of blood five feet.

Compared to baseline, we observed a reduction of 40% and the advent of the five feet absorbed from that Neal.

The combined production of TCA and lowering of blood fee indicates that shouldn't be 16, 18 is actively metabolizing feat in the Gi tract before it can be absorbed by the cuts.

The next key question with whether treatment with <unk> B 16, 18 over two weeks with impact fasting fee levels in patients.

Fasting blood fee is a critical endpoint in PKU and what's the basis of FDA approval of the product previously approved in this indication.

It's also the measure of which physicians and patients think about the most as they manage their disease and used to assess whether or not they're in feed controls.

Suddenly compared levels on treatment to dose at baseline, we observed a dose dependent reduction in blood fee level.

The mean percent change from baseline was 14% after the dose titration periods.

Which went up to three E L F and lifestyles.

This is represented in the graph by the first blue bar with 95% confidence intervals.

The second Blue bar on this graph represents the Winnie 12 go pro we observed a mean, 20% blood fee reduction compared to baseline.

Importantly, the confidence intervals here do not cross the arrow, indicating that this decrease was statistically significant.

Finally on this slide you will see what happens when patients stop taking shouldn't be 16 18 represented by the Pink bar.

Despite continuing steady procedures, including diet management blood fee levels increased indicating that the observed decline in blood feet on treatment is likely a response to be 16 to 18.

One thing that's particularly exciting to me is that this data matches very well, our prospective biomarker modeling, which increases our confidence that our synthetic biotic parakeet doing what we expected to do and that we can predict its effect in patients.

Also critically it compares favorably to prior clinical research in the field.

And then all comers analysis at the coupon phase III trials, the mean blood flooring was 10% with approximately 30% of patients showing a reduction in black sea levels sufficient to be defined as responded to coupon.

In our interim data set of Symphony. The all comers analysis demonstrated a mean, 20% reduction with half of the patients achieving a turkey percent Black Sea Laurie.

What does this mean it means that for the first time, an intervention and PKU, which is I think from the gut lumen to break down fee has been shown to have an impact on systemic plasma fee levels are clinically relevant endpoints in a disease population.

In short it means this approach could be therapeutically relevant for the treatment of PKU.

Finally, and importantly safety can be 16, 18 acted in a gut restricted manner. There were no serious adverse events and no treatment related discontinuation.

The adverse events, we did observe for predominant T. G I related advice moderate in severity and consistent with the gut restricted action of our strain and that prior experience in healthy volunteers.

No as you know we've also been developing it evolves more potency consuming product candidate, which we call it couldn't be 19, Turkey for.

It wouldn't be 1934 was developed using advanced synthetic biology techniques, which we recently published in nature Communications.

Through the first three dose cohorts in healthy volunteers in the phase one study of shouldn't be 1934, we have demonstrated two things.

First that can be 1934 metabolites fee and dose dependent manner.

And secondly that it does so at approximately twice the rate of activity SNB 16 18.

We think this has been exciting indication for both the PKU program and the broader mass abolished portfolio I've said logic.

When we calculated the ratio of <unk> five P production between <unk> 1934, and shouldn't be 16 18 before.

We find it shouldn't be 1934 activity was approximately two fold greater than that of shouldn't be 16 to 18.

This was consistent across both Biomarkers TCA in plasma and H, a urine and also consistent with findings in preclinical studies.

With these data in hand, and the important question becomes how will it be improved shouldn't be 19, Turkey for activity translate to fiori in PKU patients.

One way to assess its potential is to compare the activity in healthy volunteers based under controlled meal challenge to inform activity in patients.

We couldn't be 16, a T me previously observed a 7% reduction in labor speed in healthy volunteers, which has translated to a 20% lowering in fasting fee in PKU patients.

Of note the post Mi and assessments between can be 16, 18 and shouldn't be 1934 is a cross study comparison with the usual caveat.

After seeing a 27% reduction in D five feet post meal, which shouldn't be 19 tests before we expect an improved clinical profile in PKU patients, which is why we rapidly advanced shouldn't be 1934 into a new arm of the symphony study to confirm its efficacy.

Upon conclusion of the Symphony study, we intend to select the strain, which will advance into pivotal development.

Because couldn't be 16 18 meet their minimum product profile, we are in the enviable position of having potentially multiple viable assets.

We will advance only the asset with the greatest potential for a differentiated profile based on the clinical data.

Validation of our platform for this groundbreaking datasets in PKU is exciting implications for our other metabolic diseases.

Let me briefly provide an update on our efforts in enteric hyperoxaluria.

And tech Kyprolis, Saudi area, which we often call Hawk is a devastating condition with no treatment option in which dangerously high levels of urinary oxalate lead to progressive kidney damage.

Often occurs as a result of a primary himself to the leading to fat Mal absorption such as inflammatory bowel disease short bowel syndrome, or as a result of surgical procedures, because she's bariatrics weight loss surgery.

If left untreated dangerously high levels, if you're already off place caused recurrent kidney stone formation macro calcinosis and progressive damage, resulting in chronic kidney disease.

Tim Oxley its presence in many healthy food and tech Hyperoxaluria, it's almost impossible to control with diet alone.

Means that patients are at risk for serious kidney computation.

For most patients enteric hyperoxaluria isn't just standalone problem, because the pathologic absorption of activity is the result of an underlying disorder.

Means in clinical practice is patients who already have the complexity of living with short bowel syndrome, chronic pancreatitis or IBD.

We also have to face the devastating challenge of recurrent in chronic kidney stone.

In this patient population to pain and disruption of recurrent kidney stones is a significant challenge in their overall care.

There are approximately 75000 to 90000 patients with enteric hyperoxaluria and chronic recurrent kidney stones.

And 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.

Our approach is simple and intuitive and oral synthetic biotic medicine, which metabolize toxic substance oxalate in the Gi tract and converts it into for me switching Carnoustie excrete it.

This approach is able to consume oxalate throughout the Gi tract. The only one currently in development, which can do so.

As you May recall, we demonstrated shouldn't be a phase two proof of mechanism and a dietary hyperoxaluria study earlier this year.

We previously showed that in the efficacy analysis part of the phase one phase of the study the percent change from baseline urinary oxalate level with 28, 6% compared to placebo at the three year laughing lifestyle dose with a robust dose response relationship.

We reported at ASN kidney week earlier this month, the other measures of oxalate reduction, including fecal asked me to confirm these findings.

This is significant because consistent reduction of oxalate excretion in both urine and feces demonstrates it shouldn't be a J. So too is metabolizing oxalate in the Gi tract in a dose responsive manner at levels consistent with our translational modeling.

The amount of oxalate consumption is significant with greater than 60% lowering of fecal oxalate concentration I said 311 dose.

Lowering dangerously high levels of oxalate is the only way to reduce the risk of disease progression and reduce or eliminate oxalate nephropathy.

Shouldn't be a patient two has demonstrated the potential to do great athletes are clinically meaningful right.

I I think progressive program in patients with enteric Hyperoxaluria area. We are looking forward to providing additional data in 2022.

Now, let me hand, the call over to Dan to briefly run through our financial results.

Don.

Thank you Eva and good morning, everyone.

This morning, we released our financial results for the third quarter ended September 30th 2021.

To review the highlights of those results with you now.

Research and development expenses were $13 $4 million for the three months ended September 30th 21, compared to $10 5 million for the corresponding period in 2020.

R&D expense consisted primarily of clinical study activities associated with it shouldn't be 16, 18 and to be a little too as well as the sudden be itchy 91 phase one study and the initiation of the soon to be like 234 phase one study.

As well as other costs related to our collaboration with Ginkgo bio works for the optimization of synthetic biotic medicines.

General and administrative expenses were $3 $6 million in the third quarter of 2021 compared to $3 million for the same periods in 2020 for the third quarter of 2021. The company reported a consolidated net loss of $16 million or 29 cents per share compared to a net loss of $13 $2 million or 36 cents per share.

<unk> for the corresponding periods in 2020.

Revenue was $9 million for the third quarter of 'twenty, one compared to no revenue for the same period in 2020.

Revenue was due to the recently initiated collaboration with Roche for the discovery of a novel synthetic biotic medicine for the treatment of <unk>.

For adult disease.

Now turning to the balance sheet.

<unk> ended the third quarter of 2021 with $150 1 million ton cash equivalents and short term investments.

<unk> to a 100.4 million as of December 31, 2020.

This was buttressed by our recent financing.

Under our current operating plan, we expect our cash and cash equivalents will be sufficient to fund the company into 2024.

This will enable corelogic to advance our clinical programs through important data readouts crossed the metabolic portfolio.

Thank you for your attention we look forward to keeping you updated on future calls.

I will now turn the call over to Eva to wrap up.

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

I'll now open the call for questions.

Thank you if you have a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.

And my first question comes from the line of Kay Mackay with Chardan. Your line is open. Please go ahead.

Sure.

Yes. Thank you I'm just wondering.

If you could comment a little bit further on your newest compound once refractory for HBU and specifically can you characterize the size of the market opportunity here.

Yeah, Thanks K M.

I'm going to turn you over to Dave to talk about just the compound and.

The work that we've done in research to get us to this point because I think it exemplifies how we are leveraging our collaboration with ginkgo to rapidly advance high quality programs to the stage of being ready to move into an I N. D. So I think that's a very exciting element of that program and then I'll I'll ask Molly to make.

Couple of comments on that decided that the market opportunity. Obviously early days there in terms of you know.

Not saying gosh out, but we do believe there's a substantial unmet need and a sizable population of patients in need of treatment. So I'll ask Molly to make some comments on that so first over to Dave just to give a couple of the highlights I'm on the research side.

Yeah sure happy to happy to do that.

<unk> is a disease, where patients have elevated homeless cystine levels.

Systemically that drives a lot of peso pathology.

That we think we can address with our Gulf based approach. So almost 15 is generated from our society.

So what we have and shouldn't be $13 53, It's Australia, it's engineered to consume society never got as a way to prevent the absorption of the finding and its ultimate conversion tahoma assisting them. So.

Sounds familiar it's very similar to the approach that we're taking with PKU and phenylalanine and we've certainly been able to leverage a lot of our understanding in the advancement of our platform from the PKU program.

Towards the development of shouldn't be 13 53.

As Eva mentioned this is also a program where ginkgo and we've collaborated to ultimately land on the clinical candidate.

And so the ginkgo was involved in kind of discovering and.

<unk> some of the molecular components that went into that strained, namely.

Transporter in the enzyme components that were using to transport methionine into the bacteria.

Break it down.

Putting that into our kind of base chassis and kind of the base organism that we've developed so we're looking forward to advancing that.

Into IND, enabling studies, and then into the clinic and we.

We think it's a really nice kind of extension of what we've been doing in PKU and kind of building upon that story. So.

Molly you can speak a little bit more to the market and the disease.

Yeah sure thing and I think building on Dave's comments about associates from the technical side or the.

Our therapeutic development side its similar on the in terms of the commercial opportunity. So we think it's really interesting in terms of both synergies and comparisons as well as distinctions from the PKU market in some ways I think first point to consider her perspective is that as a market is the synergies and the opportunity is for a company that's already.

<unk> in PKU are are really attracted to these doctors call points. These vaccine prescribing base.

Very similar challenges in terms of lifestyle and crank burden and in some cases, even greater due to the government either current therapies, but in contrast with interesting as opposed to PKU, where the market has been fairly defined in terms of diagnosis.

The underlying prevalence diagnosis rate is.

He was the general area is really the very dynamic situation right now and it's particularly interesting that the you know the.

Historic assumptions in terms of market size.

Increasingly we're learning are quite different but the other opportunity to sometimes you just see the therapeutic potential and so similar to PKU. We're also hearing very clearly from this community.

<unk> for a therapy that could be efficacious safe convenient orally administrated is.

Tremendously, there's quite a bit about and.

Very much looking forward to so we're really thinking about it that way in terms of if there is a ton of.

The market size and potentially it's a very dynamic situation driven by diagnosis and awareness, but at the same time, there's a lot of opportunity for us or rather is really attractive synergies from us given our current.

Kind of investment and development in the PKU.

Yeah.

Yeah, and just to clarify this is easier just to clarify what Marty said because it may not for those familiar with PKU may not be familiar with this element to peak for you in that you know a proportion of patients are diagnosed at birth, but newborn screening for H C was not 100% so they're actually a substantial proportion of the <unk>.

<unk> could tell me cystinuria, who were diagnosed when they have their first stroke in their teens early twenty's. So for that reason there is you know a little bit of variance around the PKU prevalence estimates in epidemiology is very precise because patients are diagnosed at birth based on the heel prick test H C.

Lifting barbarian in terms of the prevalent because of those kind of late later diagnosed patients because of newborn screening test is not 100% at catching dose those patients. So that's just for those not familiar with the disease just wanted to provide that additional clarity.

Sorry, you had a follow up question as well.

Yes, just wondering with respect to the Roche collaboration you mentioned you'd give cheap [laughter].

First research milestone so for for that program or others under the collaboration what is the next step once you've reached this first milestone.

Essentially how far do you take it.

Before you hand, it over to Roche to pursue further clinical development.

Yeah. So this is a discovery phase collaboration with the single target and inflammatory bowel disease similar to other similar collaborations and there are a number of milestones followed by a option an option exercise fee that that has been disclosed in our in our filings.

What happened subsequently, it's still very much open to negotiation as we progress, but you know I think both sides both ourselves and Roche are very pleased with how things are going be achievement took the first milestone. So quickly having you know initiated the collaboration earlier. This year I think has been a real positive and.

Where we're getting some excitement there is as we think about using our platform in inflammatory bowel disease. So I think a great Testament to the work Dave and his team have done and I think a great relationship being established between both companies.

Okay, well, let me jump back in queue. Thanks.

Uh huh.

Thank you and our next question comes from the line of Joseph Schwartz with SVP Leerink. Your line is open. Please go ahead.

Hi, Angela dialing in for Joe. Thank you for taking our questions. My first one was on the PKU program.

As you mentioned in your prepared remarks, the PKU market appears to be under penetrated you know there are many patients who are diagnosed but are not treated.

In your opinion, what do you believe are the key drivers for adoption, maybe you could talk a little bit more about.

Hershal potential commercial strategies, you could employ to penetrate the PKU market. That's currently dominated by one sponsors.

Awesome, Yeah that sounds like a perfect question for Molly So jewelry I'm, just going to pass the call tomorrow to provide additional color around some of the commercial strategy, obviously violate the perfect person with her extensive experience in rare disease to I think meet meet this challenge and I'll ask her to provide some color around that.

Her plans and how she sees the opportunity sure.

Sure. Thanks CFO.

Yeah.

He is really interesting compared to a lot of other recent launches in rare diseases in the sense that there's a really high degree of awareness and Theres also.

Even described earlier are very strong and consistent in the United States and with most countries diagnosis rate. So it's actually unlike a lot of other situations not an area, where there needs to be of course, a tremendous uplift in terms of disease awareness lift and things like that.

So what's in it and where you picked up on is really interesting is was very low treatment rate right. So you know and why is that and.

Because as you know how long that she wants to go to the oval and really what we hear consistently and it makes a lot of sense is that while there are two approved therapies as we described there.

Apparently you know the first.

Smartcard are inherently limited basically do the mechanism. So there's a minority it's a finite minority group of patients based on the mechanisms are underlying b that there'll be will work out for but it's important to note that basically every person diagnosed with P. T was universally Ah trial.

Our parents around age two or so so it's not for lack of awareness testing inclusion of awareness in the market, but really the availability of a viable treatment option that can work for us.

A wide range of patients, but also can be seen.

It's convenient.

Orally Administrated all of those points and it's really remarkable how consistent both the clinicians and patients when you've been describing exactly what you point out you know why is this.

Treatment and it's really just fundamentally about the options that have been available today, and and where that's left the community in terms of her meeting medical need for new options.

Okay, Great. Thank you and then my second question is on.

Your collaboration with Ginkgo, how many more programs can we expect from your collaboration and then maybe more broadly you know how is their friend.

You know and 13 53 their friends from your other programs in the clinic now what does it mean that the time in the preclinical development stage that out.

Or do you think that you know through the ginkgo platform you could develop more potent drugs.

The first time, thank you very much.

Tracy I jewelry that sounds like a perfect question for Dave because I can keep the person most closely.

And in the research and the Ginkgo collaboration so Dave do you want to comment on this.

Yeah for sure Yeah. So in terms of the similarity between the 13 53 program and some of it in the PKU progression box program.

We're leveraging a lot of understanding and a lot of the molecular tools and parts that we built as part of our platform right. So you know we're using the same chassis organism were using the same types of promoters in molecular switches. The same types of genetic manipulations that we're making for regulatory purposes.

So that that threads through everything we're doing and that's a core part of our platform and the pipeline that.

We're building out behind the clinical stage programs.

A lot of that learning also helps us speed up how we started the organism start how we predict their potential activity in humans right. So all of the translational capabilities that we've built to predict strain activity to model that activity in humans, and therefore predict the types of <unk>.

Impact it might have.

Right and as applicable so that does allow us to go.

Slightly faster pace than we might have with some earlier stage programs.

The thing that is really different across the programs are the molecular components that drive the biology that we're interested in right. So the types of specific transporters for phenylalanine. For example, then the enzymes that break down.

And so this is where the collaboration with ginkgo has been very fruitful for shouldn't be $13 53, and we think will continue to be so.

Railway that we're working effectively with them as you know they have the capabilities to both street in New York deep databases to find components that might allow us to improve the activity of streams right different transporters different enzymes enzymes with better activity as.

Some examples and so.

With 13 53, they were able to through a screening approach identify some of those components transfer those components to us for engineering into our strains in and ultimately building the clinical candidates. So.

It's a great thing for us and that we don't need to build that out internally right. We can leverage their expertise and kind of what they've built we can focus on constructing the clinical candidates translating the activity of those candidates.

Into the clinic, and then really focus on the biology underlying mechanisms that we're going after so.

It's been a really great collaboration to date and we're working on them with them on a number of other earlier stage programs and that we would look forward to updating you all on that as those emerge and get to a similar level of maturity. This shouldn't be 30 53 program.

Okay, great. Thank you very much.

Thank you and our next question comes from the line of from some of our U with H C. Wainwright. Your line is open. Please go ahead.

Good morning. This is minus one for Ron Thanks for taking my questions. Three quick timing. So you previously observed this kind of dose dependent effects can be 60 maintain on fee reduction so.

We've seen data, 20% versus 40% reduction with the $1 12 dose compared to the 2012.

As you continue to analyze data are you able to provide any color on perhaps widen maintenance dose range towards higher doses. When you go into your pivotal study.

Yeah. Thanks, that's a great question, you're absolutely correct, we have a nice dose response relationship across all of our programs in fact that we've taken into the Kinect, which really gives us confidence that we're hitting the right biology and that we're seeing consistent effects and that we've really achieved what we set out to achieve was making this fact.

Cereals base pack for them, you know like a traditional drug development platform with the pharmacology and predictable dose response. So I think that's a really strong attribute of our underlying platforms. In terms of you know I think you're absolutely right. We're constantly looking how can we do better for patients and but we've focused on for the PKU program.

It's actually to work with the strain that has more enzyme activity per scout rather than continuing to increase the dose of cells. So that's what we've done with 1934, so dose by apples to apples 19, Turkey for actually get to ex the amount of activity.

What we see for 16, 18, and I think in healthy volunteers that.

Behaved exactly as we predicted we see about <unk> in terms of the amount of Biomarkers developed and in healthy volunteers, we're able to see this really nice reduction in blood fee levels. After a meal after that meal challenge. So we believe that that will also translate into PKU patients. So while it's kind of increasing.

The dose from a potency perspective, its maintaining the same number of cells.

You know I think the second comment I would make is in terms of our strategy around kind of making sure. We're optimizing the clinical profile of the project and.

The likelihood is that are in phase.

Phase III study will look at you know allow patients to individualize based on both their tolerability and their response to the treatment. So it's likely that there might be a single dose, but there'll be a starting dose and then it dose range, where physicians and patients can adjust the dose based on their technical response.

We believe that that's the best way that we can achieve the optimal outcome for each individual patient recognizing that each patient will have different needs and so that you know that there's likely to be some flexibility there in terms of getting patients onto the right dose for them. So we think both 19, Turkey for as well.

This flexibility and individualization around dosing will both achieved a really interesting profile and at the end of our phase III program.

Does that make sense of that nature, yes, absolutely that's great.

Shifting gears to can be seen 53 are the kind of that generated in collaboration with ginkgo I was interested in the high throughput high throughput testing code base.

They were able to advance but really relatively quickly.

Using this code base for all future lead candidate selection.

Are you going to look to develop similar capability yourself.

Yeah, Great question David.

Yes, I mean I.

We're happy with what has come out for $30 53.

We would look to replicate that for as many programs as we can into the future. I mean, I think there is really there is no need for us to do it internally I mean, I think the capabilities that ginkgo has built both with the codebase and that kind of database of genetic material to us.

With which we can search for and identify enzymes and proteins and other component of interest is really valuable.

Other approaches like a specific protein engineering and building libraries and databases around that is also something that we haven't played with them and so the expectation would be removed continue to operate in that fashion and again really focus our internal efforts on the underlying biology, the construction of the clinical candidates and really the translational ASP.

Opex of.

Leading the strains in their activity into a into early clinical development. So we.

We would expect it to be very similar.

Going forward.

And just finally are you able to reveal news of any further partnerships are any opportunities in the near term. In addition to the Roche ginkgo partnerships.

I think you already know the answers to that question.

If we hadn't done the partnership we absolutely would disclose that.

Disclose anything that wasn't finals so.

The answer to that is no, but we are our strategy we've been very consistent in overt about our strategy, which is we're pursuing these metabolic programs internally. We continued to advance really interesting candidates built on our experience in PKU and then the second component of our strategy is to leverage our platform to pursue.

Sue opportunities outside of that core focus in metabolic diseases I think the progress we've made with Roche exemplifies that you know some of the recent publication exploring other opportunities for our platform and high profile.

Journalists exemplifies that strategy. So the strategy hasn't changed our ability to execute hasnt changed and we'll continue to pursue opportunities that make sense.

Okay brilliant thanks for the comprehensive update.

Hi.

Thank you and again, ladies and gentlemen, if you have a question at this time. Please press Star then one and our next question comes from the line of Jack Lu with Oppenheimer. Your line is open. Please go ahead.

Hi, This is Jack Hogan for Mark from Oppenheimer, Oh, you just have a few questions. The first one is regarding your.

616, 18, and adult PKU I know you've been able to demonstrate safety are you considering pediatric trial run in parallel with apparel with our plant pivotal studies next year.

Yeah. That's a great question I think as Marty nicely outlined earlier in her prepared remarks, it really is a big opportunity here for an oral product.

Pediatric population, who you know if you don't respond to coupon and you have no opportunity for therapeutic intervention. So we see that as a key market for us and we'll be pursuing pediatric development just as soon as we get regulatory alignment.

On that and until you be hearing more about our plans there as those regulatory discussions progress.

Okay. Thank you and also I'm, assuming you can demonstrate clinical proof of concept for Oh, two in the Hawk next year, what would be the most likely next steps for the program would you want to go right into a pivotal study in the gastric bypass population.

Yeah. So I think the key question, we have there for the Hawk program would be expanding into you know we've chosen and bariatrics.

Bariatric surgery population for a proof of concept opportunity, but we do plan to expand into other underlying etiologies. So I think making sure that the product is similarly efficacious across a range of underlying etiologies is something that we will pursue I mean, our goal is to have as broad as possible and <unk>.

Indications statements at lunch.

You know I think whether we proceed to a phase two will go directly to a phase two three is still kind of under discussion internally and will of course depend on how clear the data is coming out of that the proof of concept study. We also have some work going on with kind of generating real world evidence that.

I think we'll inform the clinical development plan, we had a really nice presentation at the ASN kidney week meeting last week, just that kind of demonstrates how we're using real world evidence to make sure we're making the best possible decision for the program going forward. So I think both the data from the proof of concept readouts as well as our <unk>.

<unk> understanding of the natural history of the disease and the opportunity in the patient segmentation will really inform the next step on the program, but we will absolutely keep the investment community apprised as we make some of those key decisions.

Don't get and also on our last question.

Regards to Q.

34, I think the answer is no but can you remind us if the 1934 falls under the umbrella of your all collaboration with Genco and if so is there any milestone for a while.

Royalty obligations to genco.

1934 makes it to the market and eventually it gets commercialized.

Yeah. So 1934 was not it was developed with technology that is it actually we started a collaboration with and evolve who subsequently become zymogen before we had signed the ginkgo collaboration and the enzyme Pal enzyme that's inside 19, Turkey for it was actually developed.

By Zymogen.

And so we are that's the kind of provenance of that strain I just to remind you our collaboration with ginkgo does not involve any milestones or royalties.

It's really a you know they have an equity stake in the company and I think are very incentivized to make sure. We're getting the best possible candidate to their ownership stake into logic, but you know we have the rights and there's no.

Further our commercial obligation downstream to ginkgo as part of that collaboration.

Okay. That's that's all the questions unless I'm. Thank you for taking our questions.

Thank you and we have a follow up question from.

Kay Mackay with Chardan. Your line is open. Please go ahead.

Just a question about the.

Oral presentations coming up at ICR.

Is that.

Just going to include perhaps more more detail but.

Not any new patient data.

Correct, Yeah. It will be the end of eight that we presented in the press release them at the interim but there would be I.

I think you're more data obviously, it's a it's an academic presentation, it's been prevented by Jerry Rocky one of her.

The investigators on the trial.

Just to be more detail and color but.

Key conclusions remain the same and that the number of patients that are included it is consistent with our press release earlier this year.

Got it fixed.

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

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

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

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Good morning, welcome to send logic third quarter 2021 conference call. At this time all participants are in a listen only mode. There will be a question and answer session. At the end of this call. Please be advised this call is being recorded I would now like to hand, the call over to Daniel Roseanne 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 third quarter 2021 financial results and additional business updates. The release is available on the investors section of our website, that's the logic, TX Dot com.

Joining me this morning, our Doctor you for Brendan President and Chief Executive Officer, and Molly Harper, our newly appointed Chief business Officer.

Other members of the management team will be available during the Q&A.

During the call if I will provide a review of third quarter highlights and recent progress, including an update on our program in phenylketonuria and Molly will share her perspective on the unmet need in PKU and the opportunity to impact patients equal will then return to provide an update on our metabolic portfolio. Finally, I will summarize our financial results for the.

Quarter.

Following our prepared remarks, we will open the call for your questions.

As we begin I'd like to remind everyone that comments today may include forward looking statements made under the private Securities Litigation Reform Act of 1095. These forward looking statements are made as of the date hereof and are subject to numerous factors assumptions risks uncertainties, which may 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. It's logics press release from earlier today or under the heading risk factors in <unk>. Most recent Form 10-K or in later filings with the SEC.

<unk> cautions you not to place undue reliance on any forward looking statement.

And now I'd like to turn the call over to Eva.

Thanks, Dan Good morning, everyone and thank you for joining us.

I'm thrilled to share with you today uptake on our recent progress as well as our financial results for the third quarter of trying to trying to buy.

Let me began 2021 we set out to prove the clinical potential of our synthetic biotic platform.

Have the opportunity to demonstrate proof of concept in phenylketonuria interface to Symphony study.

We're thrilled to report that we've done Jeff back.

Our lead asset shouldn't be 16 18.

Administrated, a robust and statistically significant reduction in plasma feed apples.

I'm clear alignment across a multitude of study end points.

This is the first time in the history of PKU drug development, that's a therapeutic that's delivered.

Luckily in the GI tract has had an impact on systemic feed I thought.

Furthermore, we believe our evolves synthetic biotic strain shouldn't be 19, Turkey for may demonstrate even more feed ordering activity.

This is also the first example of a bioterror pubic generated by the synthetic biotic platform demonstrating robust proof of concept in a disease population.

But we do not intend to stop at PKU.

We are building a robust portfolio with significant progress over the past quarter and multiple metabolic indications.

Yeah.

And then Terry Kai crux of urea as we shared at the American Society of Nephrology kidney week, a product candidate that can be a day. So too has demonstrated robust consumption of oxalate in the Gi tract.

As measured by both urinary and fecal oxalate reduction.

Shouldn't be a tito two has the potential to be a meaningful therapy for patients suffering from empiric hyperoxaluria.

Who face as we also reported at kidney week, a substantial increase risk of incident chronic kidney disease.

As a result of being serious damage oxalate does to renal function over time.

We continue to prosecute the proof of concept study is simply a J so too impatient.

And we'll report on that data in 2022.

Okay.

We're also proud to have unveiled this week with our partner that ginkgo bio works.

Heard oral metabolic program, which we call it shouldn't be hurricane 53.

Shouldn't be Turkey, fifty-three degrades Mackay inning in the Gi tract for the treatment at home at 15 area are H C M.

<unk> is an inborn error of metabolism and a natural extension of our work in PKU.

Will it be speaking more about this program as we prepare for and file an IND.

And advanced into the clinic next year.

Our immunology pipeline why more nascent also continues to advance.

We're excited that our collaboration with Roche is to develop a synthetic biotic medicine for the treatment of IBD is off to a fast start with the first milestone already achieved.

We have also completed enrollment in the combination arm of the phase one all comers immuno oncology study I've seen be 18, 19, one with anti PD one album.

We look forward to sharing data on that study later.

And they said this week.

In order to focus our resources on our oral programs. However, we will not be continuing further studies of CB 891 at this time.

And logic today is well positioned to deliver on the promise of our platform and bring a meaningful new therapeutic approach to patients.

We are executing on our strategy focusing on rare and niche metabolic diseases, where a targeted approach restricted to the Gi tract can treat patients in ways other modalities cannot.

No let me welcome Molly Hartford to the team and give her a few moments to share her thoughts on the unmet need in PKU.

Molly comes to us with a wealth of pre commercial launch experience in both broad and rare diseases in the United States and globally and we are thrilled to have her build our capabilities as we look to pivotal development in PKU.

Molly over to you.

Thank you Eva is incredibly exciting to join us in logic team, particularly this momentous time I'm delighted to share. Some initial observations regarding the remarkable opportunity. That's in logic has before us as we advance our program with the potential to transform the lives of those living with and it was affected by PJM.

As a disease and for their community affected by the disease PKU, because that's something of a paradox.

On the one hand P junior was a well characterized disease with a community that has seen tremendous progress and it's a sizable population for a rare disease and has been extensively researched the diagnosis is straightforward and it is universally implement JV in newborn screening in many countries and the United States every person born since the 19 sixties Charles P. J.

Your husband diagnosed at some point in their lives.

There have been ICD nine and ICD 10 codes. There are dedicated clinics, there's a vibrant and well networked advocacy community, who provide clear links to those specialists and clinics. There are both well defined medical some specialists as well as dietitian specialists, who are clinical as well as research experts who are passionate about taking care of and advancing research.

This population.

On the therapeutic side multiple drugs have been approved there's regulatory precedent there are clear protocols for reimbursement one of these therapies is now generic facilitating empiric trial period to determine response.

And yet.

Well, we perhaps are not heard enough about is that despite these attributes PKU is a disease that continues to be devastating for those affected and for their caregivers.

The burden of living with P. J here is often extraordinary on every level.

Medically psychologically socially economically.

Much of this burden as well documented such as the large claims based analysis that showed that even among those diagnosed and while I'm sure. There remains an eight fold greater risk of intellectual disabilities or a different study, which is focused on patients patient populations, who are connected to specialized clinic and still show that 70% has significant neuropsychiatric comorbidities.

It is with 50% of those with multiple Comorbidities what's.

Reflecting these disease complications and the limitations of a truly transformative treatment for most patients. One study found that 70% of adults living with PKU, we're disconnected and despite these drug approvals are not receiving treatment through the establishment of all clinics.

So with multiple FDA approved drugs, it's hard to understand why this would be the case.

Looking closer these advances while important hub. Unfortunately left the majority of those living with PKU in need of additional options.

So perhaps sharon's utility is generally limited to people living with Covid mild.

Smiled PK you maintain some ph enzyme functionality it does respond to that mechanism of action.

This group represents a minority about 30% of patients. This renders fee reduction for all comers that is relatively modest at just a negative 10% decrease.

With this the burden of approximately 10 pills a day on top of required dietary restrictions and needed to supplement the treatment.

Experience can be conducive to internet in compliance and risk and just discontinuation.

It is the classic or the more severe PKU population, which makes up the majority of people living with PKU and its population who have been most significantly underserved by options today take valleys injection does offer efficacy for those adults, but those adults who can persist through the titration was kind of spend.

For one calendar year daily injections and those were both the capacity and the vigilant to manage the risk of anaphylaxis at any moment, which is the ASIC characterized in this box warning.

It is important to note that even further to adhere to both dietary requirements and drug therapy, there's a great desire for a treatment.

<unk> can provide additional CMO rang or something closer to what most of us take for granted a normal eating and social life.

So looking to the split on the res side of the screen.

Well controlled segment represent those with more mild underlying disease, who are able to respond and inherited treatment as well as those children, whose diets are closely managed by their caregivers.

The larger part of this population outlined here includes people living with PKU, who are in need of a novel treatment that provides significant reduction of plasma see regardless of their treatment status.

So for several years now there's some logic team has been actively listening to and learning from the PKU community, who have been consistent in sharing their wish list for a new treatment option.

That would be one that would be orally administered <unk>.

Convenient.

Safe and efficacious.

Designed with these exact needs in mind, the synthetic biotic approach PKU has the potential to address these needs.

The mechanism could not be more intuitive.

People with PKU cannot metabolize dietary fee, which enters predominantly via dietary protein.

Similarly, designed bio therapeutics with the potential to metabolize dietary fee in the Gi tract.

Synthetic biotic is orally administered conveniently package with a locally delivered mechanism without systemic absorption any associated potentially risk and we recently were able to share an early view of how this has worked and those with the greatest need.

So now let me ask you if I could take you through the clinical data that we've been able to share today.

Thank you Polly.

Earlier this quarter, we presented two data sets, which gives us confidence in advancing our PKU program.

Firstly and Symphony a phase two study in patients with PKU, we achieved our target reduction in blood fee levels and an interim analysis of eight patients with available data.

And secondly in a head to head comparison can be 16, 18, and shouldn't be 19, Turkey for our optimized strained for PKU and healthy volunteers, we found that the fee consuming activity of <unk> 1934 is approximately two fold dash of soon be 16 to 18.

This suggests shouldn't be 1934, and they provide an even more attractive clinical profile.

Based on these highly encouraging data, we will be adding shouldn't be 1934 to phase two symphony study and preparing to advance our PKU program into a pivotal phase III study.

As you recall, our ongoing phase two symphony is a single arm study in patients with classic PKU.

Its population has fee levels above 600 micro most producer at screening and is not served by available therapies.

It's a more severe population than the BH forest sponsors population enriched coupon has been studied.

The interim data we shared from the first eight patients to complete the study which remains open to enrollment.

And important design elements of this study is that each patient function at their own control.

Subject to a case on a strict diet that was designed to match their usual protein and food intake and had a diet run in followed by baseline assessments.

They then received increasing doses of <unk> B 16, 18 over two weeks with repeat on treatment assessment, followed by a washout period.

The diet management was maintained throughout the trial to the day 929 assessments.

There were two critical endpoints in this study.

First and B O Challenge test, which were performed with a standardized breakfast containing labeled fee here called D. Five fee at the beginning and end of the dosing period to determine SNB 16, 18 prevent dietary fee absorption.

Second we evaluated fasting plasma fee.

This was measured park dosing after seven days again on day 14, and at the end of the wash out period on day 29.

Let's begin with the meal challenge yourself.

And these tests the subjects receive a standard breakfast containing five feet.

They received their first meal challenge on day minus one and then underwent the same test on day 15, after a dose or two each wildlife cells, which is the highest dose studies.

The purpose of this test was to look at whether it can be 16, 18, with metabolically active and metabolizing feat in the Gi tract and preventing it from being absorbed and increasing blood fee levels.

On the left hand panel is shown to increase in blood TCA or biomarker strained activity because it's a byproduct of feed breakdown by the strain.

As expected, we can observe that it increases significantly with dosing.

On the right hand panel is the area under the curve of blood the five fee.

Compared to baseline, we observed a reduction of 40% and the advent of D. Five feet absorbed from that Neal.

The combined production of TCA and lowering of blood fee indicates that shouldn't be 16, 18 is actively metabolizing feat in the Gi tract before it can be absorbed by the cuts.

The next key question with whether treatment with Cindy 16, 18 over two weeks with impact fasting fee levels in patients.

Fasting blood fee is a critical endpoint in PKU unless the basis of FDA approval of the product previously approved in this indication.

It's also the measure of which physicians and patients think about the most as they manage their disease and used to assess whether or not they're in feed controls.

Suddenly compared levels on treatment to dose at baseline, we observed a dose dependent reduction in blood fee level can.

The mean percent change from baseline was 14% after the dose titration periods.

Which went up to three E L F and lifestyles.

This is represented in the graph by the first blue bar with 95% confidence intervals.

The second Blue bar on this graph represents the Winnie 12 dose, while we observed a mean, 20% blood fee reduction compared to baseline.

Importantly, the confidence intervals here do not cross arrow, indicating that this decrease was statistically significant.

Finally on this slide you will see what happens when patients stop taking some b 16 18 represented by the Pink bar.

Spike continuing study procedures, including diet management blood fee levels increased indicating that the observed decline in blood feet on treatment is likely a response to be 16 to 18.

One thing that's particularly exciting to me is that this data matches very well our prospective biomarker, just modeling, which increases our confidence that our synthetic biotic parakeet doing what we expected to do and that we can predict its effect in patients.

Also critically it compares favorably to prior technical research in the field.

And then all comers analysis at the coupon phase III trials, the mean blood see lowering was 10% with approximately 30% of patients showing a reduction in blood fee levels sufficient to be defined as responded to coupon.

In our interim days effect of Symphony. The all comers analysis demonstrated a mean, 20% reduction with half of the patients achieving a 30% Black sea Laurie.

What does this mean it means that for the first time, an intervention and PKU, which is acting from the gut lumen to breakdown fee has been shown to have an impact on systemic plasma fee levels are clinically relevant endpoints in a disease population.

In short it means this approach could be therapeutically relevant for the treatment of PKU.

Finally, and importantly safety can be 16, 18 acted in a gut restricted manner. There were no serious adverse events and no treatment related discontinuation.

The adverse events, we did observe for predominantly Gi related advised moderate in severity and consistent with the gut restricted action of our strain and that prior experience in healthy volunteers.

No as you know we've also been developing an evolved more potency consuming product candidate, which we've called couldn't be 19, Turkey for.

<unk> 1934 was developed using advanced synthetic biology techniques, which we recently published in nature Communications.

Through the first three dose cohorts in healthy volunteers in the phase one study of Symbian 1934, we have demonstrated two things.

First that shouldn't be 1934 metabolites fee and dose dependent manner.

And secondly that it does so at approximately twice the rate of activity SNB 16 18.

We think this has an exciting indication for both the PKU program and the broader message Polish portfolio I'd say logic.

When we calculated the ratio of <unk> five P production between <unk> 1934, and shouldn't be 16 18.

We find that shouldn't be 1934 activity was approximately two fold greater than that shouldn't be 16 to 18.

This is consistent across both biomarkers TCA in plasma and H, a urine and also consistent with findings in preclinical studies.

With these data in hand, and the important question becomes how will it be improved shouldn't be 19, Turkey for activity translate to fiori in PKU patients.

One way to affect the potential is to compare the activity in healthy volunteers based on the controlled meal challenge to inform activity in patients.

But shouldn't be 16, a T me previously observed a 7% reduction in labor speed in healthy volunteers, which has translated to a 10, 2% lowering in fasting feet in PKU patients.

Of note the postman assessments between can be 16, 18 and shouldn't be 1934 is a cross study comparison with the usual caveat. Nonetheless, after seeing a 27% reduction in <unk> five feet post meal, which shouldn't be 19 care support we expect an improved clinical profile in PKU.

Patients, which is why we rapidly advance shouldn't be 19, Turkey for into a new arm of the Symphony study to confirm its efficacy.

Upon conclusion of the Symphony study, we intend to select the strain, which will advance into pivotal development.

Because then be 16 18 meet a minimum product profile, we are in the enviable position of having potentially multiple viable assets, but we will advance only the asset with the greatest potential for a differentiated profile based on the clinical data.

Validation of our platform.

Breaking datasets in PKU is exciting implications for our other metabolic diseases.

Briefly provide an update on our efforts in enteric hyperoxaluria.

And tech Hyperoxaluria, which we often called Hawk is a devastating condition with no treatment options in which dangerously high levels of urinary oxalate lead to progressive kidney damage.

It often occurs as a result of a primary himself about leading to fat Mal absorption.

Jazz inflammatory bowel disease sharp out syndrome, or as a result of surgical procedures, such as bariatric weight loss surgery.

If left untreated the dangerously high levels, if you're already off place caused recurrent kidney stone formation macro calcinosis and progressive damage, resulting in chronic kidney disease.

Tim Oxley is present in many healthy food and Carrick Hyperoxaluria, it's almost impossible to control with diet alone.

The patients who are at risk for serious kidney complications.

For most patients entire kyprolis of urea isn't just standalone problems because the pathologic absorption of oxalate is a result of an underlying battery disorder.

This means in clinical practice it is patients who already have the complexity of living with short bowel syndrome, chronic pancreatitis or IBP.

I also have to face the devastating challenge of our current and chronic kidney stone.

In this patient population to pain and disruption of recurrent kidney stones is a significant challenge in their overall care.

There are approximately 75000 to 90000 patients with enteric hyperoxaluria and chronic recurrent kidney stones.

And 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.

Our approach is simple and intuitive and or a synthetic biotic medicine, which metabolizes to toxic substance oxalate in the Gi tract and converts it into four maze, which is harvesting excrete it.

This approach is able to consume oxalate throughout the Gi tract. The only one currently in development, which can do so.

As you May recall, we demonstrated shouldn't be a phase two proof of mechanism and a dietary hydroxyurea study earlier this year.

We previously showed that in the efficacy analysis part of the phase one phase.

Study the percent change from baseline urinary oxalate levels with 28, 6% compared to placebo at the 311 lifestyle dose with a robust dose response relationship.

We reported at ASN kidney week earlier this month that other measures of oxalate reduction, including fecal asked me to confirm these findings.

This is significant because consistent reduction of oxalate excretion in both urine and feces demonstrates it shouldn't be a J. So too is metabolizing oxalate in the Gi tract in a dose responsive manner at levels consistent with our translational modeling.

The amount of oxalate consumption is significant with greater than 60% lowering of fecal oxalate concentration after 311 dose.

Lowering dangerously high levels of oxalate is the only way to reduce the risk of disease progression and reduce or eliminate oxalate nephropathy.

Wouldn't be a phase two has demonstrated the potential to do great athletes, a clinically meaningful rates I think progressive program in patients with enteric Hyperoxaluria area. We are looking forward to providing additional data in 2022.

Now, let me hand, the call over to Dan to briefly run through our financial results Dan.

Thank you Eva and good morning, everyone.

This morning, we released our financial results for the third quarter ended September 30th 'twenty, 'twenty, one and I'd like to review the highlights of those results with you now.

Research and development expenses were $13 $4 million for the three months ended September 30th 21, compared to $10 5 million for the corresponding period in 2020.

R&D expense consisted primarily of clinical study activities associated with shouldn't be 16, 18, and can be either too as well as the sudden be itchy 91 phase one study and the initiation of this shouldn't be like 234 phase one studies.

Well as other costs related to our collaboration with Ginkgo bio works for the optimization of synthetic biotic medicines.

General and administrative expenses were $3.6 million in the third quarter of 2021 compared to $3 million for the same period in 2020 for the third quarter of 2021. The company reported a consolidated net loss of $16 million or 29 cents per share.

<unk> net loss of $13 $2 million or 36 cents per share for the corresponding period in 2020.

Revenue was <unk> $9 billion for the third quarter of 'twenty, one compared to no revenue for the same period in 2020.

Revenue was due to the recently initiated collaboration with Roche for the discovery of a novel synthetic biotic medicine for the treatment of <unk>.

Towards all disease.

Now turning to the balance sheet.

<unk> ended the third quarter of 2021 with $150 1 million in touch cash equivalents and short term investments.

<unk> to a 100.4 million as of December 31, 2020.

This was buttressed by our recent financing.

Under our current operating plan, we expect our cash and cash equivalents will be sufficient to fund the company into 2024.

This will enable some logic to advance our clinical programs through important data readouts across the metabolic portfolio.

Thank you for your attention we look forward to keeping you updated on future calls.

I will now turn the call over to Eva to wrap up.

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

I'll now open the call for questions.

Thank you if you have a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.

And my first question comes from the line of Kay Mackay with Chardan. Your line is open. Please go ahead.

Oh, yes. Thank you.

Just wondering if you could comment a little bit further on your newest compound 1353 for HBU and specifically can you characterize the size of the market opportunity here.

Yeah. Thanks Kay.

I'm going to turn you over to Dave to talk about just the the compound and then.

The work that we've done in research to get us to this point because I think it exemplifies how we are leveraging our collaboration with ginkgo to rapidly advance high quality programs to the stage of being ready to move into an I N. D. So I think that's a very exciting element of that program and then I'll I'll ask Molly to make.

Couple of comments on that besides the market opportunity obviously early days there in terms of.

Not paying that out, but we do believe there's a substantial unmet need and a sizable population of patients in need of treatment. So I'll ask Molly to make some comments on that so first over to Dave just to give a couple of the highlights I'm on the research side.

Yeah sure happy to happy to do that.

<unk> is a disease, where patients have elevated homeless cystine levels are systemically that drives a lot of peso pathology and Oh.

We think we can address with a GAAP based approach. So almost 15 is generated from our society.

So what we have and can be $13 53, it's Australia, it's engineered to consume beside it never got as a way to prevent the absorption of the fine Ya man its ultimate conversion up to whole assisting them. So that probably sounds familiar it is very similar to the approach that we're taking with PKU.

Phenylalanine.

We've certainly been able to leverage a lot of our understanding in the advancement of our platform from the PKU program.

The development of shouldn't be $13 53.

As Eva mentioned this is also a program where it ginkgo.

We have collaborated to ultimately land on the clinical candidate.

And so.

Ginkgo was involved in kind of discovering and identifying some of the molecular components that went into that strength, namely.

Transporter in the Amazon components that were using to transport beside him into the bacteria.

It down.

Putting that into our kind of base chassis and that kind of a base organism that we've developed so we're looking forward to advancing that.

Into IND, enabling studies and then into the clinic and we think it's a really nice kind of extension of what we've been doing in PKU and kind of building upon that story. So.

Molly you can speak a little bit more to the marketing and the disease.

Yeah sure thing and I think building on Dave's comments about associates, and the technical side or the.

Our therapeutic development side its similar on the in terms of the commercial opportunity. So we think it's really interesting in terms of both synergies and comparisons as well as distinctions from the PKU market in some ways I think the first point to consider our perspective is that as the market is the synergies and the.

The opportunity is for a company that's already in PKU are are really attracted at the exact same call point the vaccine prescribed Arbor base, a very similar challenges in terms of lifestyle and crank burden and in some cases, even greater due to the government either current therapies, but in contrast with interest.

As opposed to PKU, where the market has been fairly defined in terms of diagnosis.

The underlying prevalence diagnosis rate is in Hmm scenario is really in a very dynamic situation right now and it's particularly interesting that the you know the historic assumptions in terms of market size.

Increasingly we're learning are quite different but the other opportunity to sometimes you just see the therapeutic potential and so similarly, the PKU. We're also hearing very clearly from this community.

The opportunity for a therapy that could be efficacious safe convenient orally administrated is.

Tremendously excited about and.

Very much looking forward to so we're really thinking about it that way in terms of the bears the tons of the market size and potentially it's a very dynamic situation driven by diagnosis and awareness, but at the same time, there's a lot of opportunity for us or rather easily tracking synergies given our current.

Kind of investment and development in the PKU.

Yeah.

Yeah, and just to clarify this is easier just to clarify what Marty said because it may not for those familiar with PKU may not be familiar with this element. It takes you in that you know a proportion of patients are diagnosed at birth, but newborn screening for H T was not 100%. So they were actually a substantial proportion of PAH.

<unk> Tacoma Cystinuria, who were diagnosed when they have their first stroke in their teens early twenty's. So for that reason there is you know a little bit of varian to rent the PKU prevalence estimates in academia as he's very precise because all patients are diagnosed at birth based on the heel prick test H C.

Lifting more variance in terms of the prevalent because of those kind of late later diagnosed patients because of newborn screening test is not 100% at catching dose those patients. So that's just for those not familiar with the disease just wanted to provide that additional clarity.

Sorry, you had a follow up question as well.

Yes, just wondering with respect to the Roche collaboration you mentioned Jimmy Choo.

First research milestone.

For for that program or others under the collaboration what is the next step once you've reached the first milestone.

Essentially how far do you take it but before you hand, it over to Roche to pursue further clinical development.

Yeah. So this is a discovery phase collaboration with a single target in inflammatory bowel disease.

Similar to other <unk>.

Similar collaborations and there are a number of milestones followed by a option an option exercise fee.

See that that has been disclosed in our in our filings I'm quite happy and subsequently it's still very much open to negotiation as we progress, but you know I think both sides both for ourselves and Roche were very pleased with how things are going achievement of the first milestone so quickly having initiated the collaboration earlier this year.

Here I think has been a real positive and where we're getting some excitement there is as we think about using our cut for them in inflammatory bowel disease. So I think a great Testament to the work Dave and his team have done and I think.

Great relationship being established between both companies.

Okay, well, let me jump back in queue. Thanks.

Thank you and our next question comes from the line of Joseph Schwartz with SVP Leerink. Your line is open. Please go ahead.

Hi, Angela dialing in for Joe. Thank you for taking our questions. My first one is on the PKU program.

You mentioned in your prepared remarks, the PKU market appears to be under penetrated you know there are many patients who are diagnosed but are not treated so in your opinion. What do you believe are the key drivers for adoption, maybe you could talk a little bit more about commercial potential commercial strategies, you can employ to penetrate the PKU market. That's currently Dom.

Needed by one sponsor.

Awesome, Yeah that sounds like a perfect question for Molly So jewelry I'm, just going to pass the call to Mali to provide additional color around some of the commercial strategies obviously.

He is the perfect person with her extensive experience in rare disease to I think meet meet this challenge and I'll ask her to provide some color around her plans and how she sees the opportunity.

Sure. Thanks CFO.

So yes.

I was here is really interesting compared to a lot of other recent launches in rare diseases in the sense that there's a really high degree of awareness and Theres also.

I described earlier are very strong and consistent in the United States. Most countries diagnosis rate. So it's actually unlike a lot of other situations not an area, where there needs to be of course, a tremendous efforts in terms of disease awareness lift and things like that so what's in it and when you picked up on is really interesting. It was very low treatment rate right. So.

And why is that and.

Given you know how long that she wants to enter the oval and really what we hear consistently and it makes a lot of sense is that while there are two approved therapies as we described there.

Currently you.

The first.

For clarity are inherently limited basically do the mechanism. So theres a minority it's a finite minority group of patients based on the mechanism of the underlying b that there'll be more work elsewhere, but it's important to note that basically every person diagnosed with PKU is universally tries to pop time around.

Two or so.

So it's not for lack of awareness testing inclusion of awareness in the market, but really the the availability of a viable treatment option that can work for.

A wide range of patients, but also can be space convenience.

Orally Administrated all of those points and it's really remarkable how consistent both clinicians and patients when you've been describing exactly what you point out you know why is this low treatment rate is really just fundamentally about the options that have been available today and where that's left the community in terms of her meeting medical need.

Need for new options.

Okay, Great. Thank you and then my second question is on <unk>.

Your collaboration with Ginkgo, how many miles program can we expect from your collaboration and then maybe more broadly you know how different.

You know and 13 53 their friends family or other programs in the clinic now does it mean that the time in the preclinical development stage.

Or do you think that you know through the ginkgo platform you could develop more potent drugs.

The first time, thank you very much.

Tracy I jewelry that sounds like a perfect question for Dave because I can keep the person most closely.

And in the research and the Ginkgo collaboration so Dave do you want to kind of comment on this.

Yes for sure.

Yeah. So in terms of the similarity between the 13 53 program and some of it in the PKU progression box program.

We're leveraging a lot of understanding and a lot of the molecular tools and parts that we built as part of our platform right. So we're using the same chassis organism were using the same types of promoters in molecular switches. The same types of genetic manipulations that we're making for regulatory purposes.

So that that threads through everything we're doing and that's a core part of our platform and the pipeline network.

We're building out behind the clinical stage programs.

A lot of that learning also helps us speed up how we started the organism started how we predict their potential activity in humans right. So all of the translational capabilities that we've built to predict strain activity to model that activity in humans, and therefore predict the types of <unk>.

Impact it might have a trend like right and as applicable so that does allow us to go.

Slightly faster pace than we might have with some earlier stage programs.

The thing that's really different across the programs are the molecular component to drive the biology that we're interested in right. So the types of specific transporters for phenylalanine. For example, then the enzymes that break down.

And so this is where the collaboration with ginkgo has been very fruitful for shouldn't be $13 53, and we think we will continue to be so.

The real way that we're working effectively with them as you know they have the capabilities to both street and deep databases to find components that might allow us to improve the activity of streams right different transporters different enzymes enzymes are better activity as.

Some examples and so.

With $13 53, they were able to through a screening approach identify some of those components transfer those components to us for engineering into our strains in and ultimately building the clinical candidates. So.

It's a great thing for us and that we don't need to build that out internally that we can leverage their expertise and kind of what they've built we can focus on constructing the clinical candidates translating the activity of those candidates.

Into the clinic, and then really focus on the biology underlying mechanisms that we're going after so.

It's been a really great collaboration to date and we're working on it with them on a number of other earlier stage programs and we would look forward to updating you all on that as those emerge and get to a similar level of maturity that they shouldn't be searching 53 program.

Okay, great. Thank you very much.

Thank you and our next question comes from the line of from several are you with H C. Wainwright. Your line is open. Please go ahead.

Good morning. This is Mike on for Rob. Thanks for taking my questions three quick timing. So you previously observed.

A dose dependent effect.

<unk> maintained onto your reduction so we.

We've seen data, 20% versus 40% reduction with the 112 dose compared to the 2012.

Continuing to analyze data are you able to provide any color on perhaps why maintenance dose range towards higher doses. When you go into your pivotal study.

Yeah. Thanks, that's a great question, you're absolutely correct, we have a nice dose response relationship across all of our programs in fact that we've taken into the Kinect, which really gives us confidence that we're hitting the right biology and that we're seeing consistent effect and that we've really achieved what we set out to achieve was making this bacteria.

Base pack for them, you know like a traditional drug development platform with pharmacology and predictable dose response. So you know I think that's a really strong attributes of our underlying platforms. In terms of you know I think you're absolutely right. We're constantly looking how can we do better for patients than what we've focused on for the PKU program.

Actually to work with the strain that has more enzyme activity per scale, rather than continuing to increase the dose of cells. So that's what we've done with 1934, so yeah dose by apples to apples 1934 actually get to ask at the amount of activity.

That we see for 16, 18, and I think in healthy volunteers that behavior.

Behaved exactly as we predicted you see about two X in terms of the amount of Biomarkers developed and in healthy volunteers, we're able to see this really nice reduction in blood fee levels. After a meal after that meal challenge. So we believe that that will also translate into PKU patients. So while it's kind of increasing.

The dose from a potency perspective, its maintaining the same number of cells.

You know I think the second comment I would make is in terms of our strategy around kind of making sure. We're optimizing the clinical profile of the product.

Will the likelihood is that our and phase.

<unk> III study will look at you know allow patients to individualize based on both their tolerability and their response to the treatment. So it's likely that there might be a single dose, but there'll be a starting dose and then a dose range, where physicians and patients can adjust their dose based on their technical response.

We believe that that's the best way that we can achieve the optimal outcome for each individual patient recognizing that each patient will have different needs and.

And so that's you know that there's likely to be some flexibility there in terms of getting patients onto the right dose for them. So we think both 19, Turkey for as well as this flexibility and individualization around dosing will both achieved a really interesting profile and at the end of our phase III program.

Does that makes sense that makes sense, yeah, absolutely that's great.

Shifting gears to some beef 53 candidate generated in collaboration with Ginkgo.

I was interested in the high throughput high throughput testing code base.

They were able to advance of comes at really relatively quickly.

Would you be using this code base for all future lead candidate selection.

Or are you going to look to develop similar capability yourself.

Yeah, great questions there David.

Yeah.

Yes.

We're happy with what has come out for $2 53, and we would look to replicate that for as many programs as we can into the future I think.

There is really there is no need for us to do it internally I mean, I think the capabilities that ginkgo has built both with the code base and that kind of database of genetic material to us.

With which we can search for and identify enzymes and proteins and other components of interest is really valuable.

Other approaches like a specific protein engineering and building libraries and databases around that is also something that we have employed with them and so the expectation.

Spectation would be removed continue to operate in that fashion and again really focus our internal efforts on the underlying biology, the construction of the clinical candidates and really the translational aspects of.

Leading the strains in their activity into into early clinical development. So I think we.

We would expect it to be very similar.

Going forward.

And just finally are you able to reveal news of any further partnerships are any opportunities in the near term. In addition to the Roche ginkgo partnerships.

I think you already know the answer to that question.

If we hadn't done the partnership we absolutely would disclose that.

We wouldn't disclose anything that wasn't final so.

The answer to that is no but you know we are our strategy. We've been very consistent handover to about our strategy, which is we're pursuing these metabolic programs internally. We continued to advance really interesting candidates that builds on our experience in PKU and then the second component of our strategy is to leverage our platform to pursue.

Sue opportunities outside of that core focus in metabolic diseases I think the progress we've made with Roche exemplifies that some of the recent publications exploring other opportunities for our platform and high profile.

Journalists exemplifies that strategy. So the strategy hasn't changed our ability to execute it hasnt changed and we'll continue to pursue opportunities that make sense.

Okay brilliant thanks for the comprehensive update.

Uh huh.

Thank you and again, ladies and gentlemen, if you have a question at this time. Please press Star then one and our next question comes from the line of Jacqueline Lu with Oppenheimer. Your line is open. Please go ahead.

Hi, This is Jack Mcglinn for marks from Oppenheimer I'll just have a few questions. The first one is regarding your.

616, 18, and about PKU I know you've been able to demonstrate safety are you considering pediatric trial run in parallel with apparel with our planned pivotal studies next year.

Yeah. That's a great question I think is Molly Nike outlined earlier in her prepared remarks. It really is a big opportunity here for an oral product in the pediatric population, who you know if you don't respond to coupon you have no opportunity for for therapeutic intervention. So we see that as a key market for us and we'll be pursuing pediatric developed.

But just as soon as we get regulatory alignment on.

That and until you be hearing more about our plans there as those regulatory discussions progressed.

Okay. Thank you and also I'm, assuming you can demonstrate clinical proof of concept for Oh, two in the Hawk next year.

What would be the most likely next steps for the program would you want to go right into a pivotal study in the gastric bypass population.

Yes, So I think the key question, we have there for the Hawk program would be expanding into you know we've chosen the bariatric.

Baby electric surgery population for proof of concept opportunity, but we do plan to expand into other underlying etiologies. So I think making sure that the product is similarly applications across a range of underlying etiologies is something that we will pursue I mean, our goal is to have as broad as possible and <unk>.

Acacias statements at lunch and I think whether we proceed to a phase two would go directly to a phase two three is still kind of under discussion internally and will of course depend on how clear the data is coming out of that the proof of concept study. We also have some work going on with kind.

Generating real world evidence that I think will inform the clinical development plan, we had a really nice presentation at the ASN kidney week meeting last week, just that kind of demonstrates how we're using real world evidence to make sure we're making the best possible decision for the program going forward. So I think both the data.

The proof of concept readouts as well as our continued understanding of the natural history of the disease and the opportunity in the patient segmentation will really inform the next step on the program, but we will absolutely keep the investment community apprised as we make some of those key decisions.

Okay sounds good and also on our last question.

Regards to.

34, I think the answer is no but can you remind us if the 1934 falls under the umbrella of nor all collaboration with Genco and if so is there any milestones or royalty our royalty obligations to genco. If it's 1934 makes it to the market and eventually it gets commercialized.

Yeah. So 1934 it was not it was developed with technology that is it actually we started a collaboration with and evolve who subsequently become zymogen before we had signed the ginkgo collaboration and the enzyme Pal enzyme that's inside 19, Turkey for it was actually developed.

Zymogen and so we.

That's the kind of provenance of that strain.

Just to remind you our collaboration with ginkgo does not involve any milestone or royalties.

It's really a you know they have an equity stake in the company and I think are very incentivized to make sure. We're getting the best possible candidate to their ownership stake into logic, but we have full rights and Theres no.

Further our commercial obligation downstream to ginkgo as part of that collaboration.

Okay. That's that's all the questions from us Thank you for taking our questions.

Thank you and we have a follow up question from.

Kay Mackay with Chardan. Your line is open. Please go ahead.

Yes, just a question about the.

Oral presentations coming up there.

Yeah.

Is that.

Just going to include perhaps more more detail.

But not any new patient data.

Correct, Yeah. It will be the end of eight that we presented in the press release.

I parked interim but they would be.

Thank you more data obviously, it's a it's an academic presentation, it's being presented by Jerry Rocky one of our principal investigators on the trial a number just to be more detail and color, but you know keep completions remained the same and that the number of patients that are included it is consistent with our press release earlier this year.

Got it thanks.

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

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

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