Q4 2021 Synlogic Inc Earnings Call
Okay.
Today's conference will begin momentarily. Please continue to standby. Thank you for your patience.
[music].
Good morning, welcome to send logic fourth quarter and full year 2021 conference call.
At this time all participants are in a listen only mode.
There will be a question and answer session at the end of this call.
Please be advised that this call is being recorded.
I would now like to turn the call over to Andrew fund or breakup handle 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 fourth quarter and full year 2021 financial results and additional business updates.
The release is available on the investors section of our website at Www Dot sin logic, TX Dot com.
Joining me on this call are Dr. <unk>, Brennan, President and Chief Executive Officer, Molly Harper Chief Business Officer, Dave Harbour, Chief Scientific Officer, and Michael Jensen, Chief Financial Officer.
Other members of the management team will be available during the Q&A.
During the call equal will provide a review of fourth quarter highlights and recent progress, including an update on our lead program in PKU and Molly will share her perspective on the opportunity to address the medical need and provide a meaningful additional therapeutic option to patients with PKU.
We'll discuss our earlier stage programs and collaborations and Michael will provide a financial overview.
Following our prepared remarks, we will open the call for questions.
As we begin I'd like to remind everyone that comments made 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 and uncertainties, which change over time.
Actual results could differ materially from those contained in any forward looking statement as a result of various factors, including those described under the heading forward looking statements in <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 statements now I'd like to turn the call over to Eva.
Yeah.
Thanks, Andrew Good morning, everyone and thank you for joining us.
I'm thrilled to share with you today updates on our recent progress as well as our financial results from the fourth quarter and full year of 'twenty 'twenty button.
In 2021 this should not tech team achieved dramatic progress across the portfolio.
Proof of concept with our lead program for phenylketonuria or PKU.
And commitment to advance to phase III initiation this year.
Proof of mechanism, and then Carrie hydroxyurea, which shouldn't be a patient too.
A research collaboration with Roche inflammatory bowel disease.
And our second drug candidate for rare metabolic disease, which shouldn't be her team 53 for home, it's just been urea or H C U.
We are now advancing a pipeline of clinically differentiated already administered drug candidates for metabolic and immune diseases. All based on the advantages of a reproducible proprietary product engine.
We are continuing this momentum in 2022 with expected phase III initiation of our PKU program in the second half of this year.
Shouldn't be hurricane 53 is expected to have healthy volunteer data by year end.
And we're also looking forward to proof of concept patient data from our enteric Hyperoxaluria program.
Given our positive results in September 2021 we were able to compete a successful vanda financing with a strong balance sheet with 100, Turkey $6.6 million in cash and equivalents sufficient to carry us into 2024 and webcast <unk>.
<unk> upcoming milestones.
We strengthened this logic team to 2021 .
Today I'd like to welcome our new CFO Michael Johnson.
Michael brings an impressive financial and operational backgrounds from Biopharma and health care companies across therapeutic categories and through commercialization and.
As we progress our programs into late stage development and registration.
I'd also like to thank Gregg Beloff, who had served as our interim CFO during a critical stage for the company.
Let's ground ourselves innovation and breakthrough science, that's behind our recent progress.
From our inception, as Chengdu and Jim Collins as lab M I T.
Logic was founded on the premise of a new paradigm in biotherapeutics based on the application of some Patrick biology to Madison.
In just six years, we have created a product engine producing potentially transformative drug candidates.
On validated mechanisms for the treatment of metabolic and immune diseases.
These synthetic biotic share similar safety profile, each for lack of systemic absorption or call nidation.
<unk> oral delivery.
Flexible titration reversibility via rapid Gi Kieran.
And application across rare and common diseases.
I'd like to review our lead program in PKU, and we had as we advance into phase III and towards commercialization.
A majority of patients with PKU today remain untreated or under treated due to limitations of current options in both safety and efficacy.
With two FDA approved drugs PKU has derisked path to registration with fee reduction used is an acceptable endpoint for full approval.
Well, there's precedent for phase III study design and related considerations.
People with PKU in the U S and around the world are diagnosed at birth and treated by small specialist community.
<unk> and accessible patient population.
In September of last year, our phase two proof of concept data show the potential profile that could meet the PKU community needs for an efficacious safe oral option and one that could be used both as monotherapy and adjunctive treatments.
We are eager to continue to advance this program forward towards commercial pivotal studies.
I'd like to now hand, the call over to Molly to expand upon what makes our approach so potentially meaningful in PKU.
Thank you Ethan.
In the U S alone there are approximately 17000 patients with PKU, making it a large rare disease population.
Despite two approved treatments a large majority of patients remain untreated.
This is surprising but understandable given the limitations of today's treatment options.
Taryn or coupon is a standard of care that is tried by all PKU patients age two.
It's response rate is approximately 20% to 30% of the PKU population responders tend to have mild forms of PKU. This leaves the more more severe majority untreated.
For those who do respond and take two than their fee levels, often remain well above targets presenting an opportunity for adjunctive treatment.
Note that with these limitations and 20% or less penetration globally Kuban was a $500 million business before it went generic in 2020.
The large untreated patient population.
The non responders to Q man for whom the other approved therapy policy is also not a viable option usually due to safety concerns.
Palin seek as a self administered injectable.
Risk of life, threatening anaphylactic reactions at any time.
And 10% of patients has limited uptake.
The boxed warning and restrictive Rems program require patients to carry auto injectable epinephrine at all times challenging given the neuro cognitive and executive functioning deficit of PKU.
In short the vast majority of people with pizza, you need new treatment approaches, whether as mono therapy or in adjunctive option.
It's in logics approach for PKU fits with these neat.
So in logic designed its drug candidate to consume fee in the Gi track without risk of colonization or systemic absorption and associated <unk>.
In September 2021, we announced that the phase two interim analysis for Cindy 16, 18 achieved the targeted mean fee reduction of 20% and in all comers analysis, which was twice what Kuban had achieved in its pivotal study.
We also saw strong 50% response rate as four of the eight patients met or exceeded the target for response.
In parallel we shared that the healthy volunteer head to head bridging study confirmed that Cindy $19 34 has potential for greater efficacy.
The product presentation being studied unexpected for commercialization.
<unk> powder provided in a sachet and taken with meals three times a day.
We are excited to be advancing a potentially effective safe convenient and oral monotherapy and adjunctive option. In summary, this is a tremendously exciting potential product profile for a patient population that has been waiting too long for new treatment options.
I'd like to hand, the call back to <unk> to discuss the PKU programs task forward to phase III.
Yeah.
Thank you Molly.
That's with you if I was going this year with our PKU program and how it reflects many of the specific advantages of the spin logic approach.
Last fall after achieving proof of concept with <unk> 16, 18, and an interim analysis of the phase two study.
We committed to advancing our program to phase III this year.
Happy with these data we made two important changes to the study to ensure that we had all of the information we needed from this study to initiate a phase III trial.
Firstly, we added a second arm person be 19, Turkey for based on the data from healthy volunteers, showing higher potency of that product candidates.
Secondly, we amended the inclusion criteria to allow patients who are on treatment with separate taryn, but continues to have uncontrolled blood fee levels to participate enabling evaluation of adjunctive use potential.
We set out to complete the first arm of <unk> 16, 18, and two enrolled the second arm and are looking forward to sharing that phase two data in the first half of this year.
So what are we hoping to see from that data set.
Already determined that our activity in PKU meets our criteria to advance into late stage development, but there is still a couple of questions to answer.
Number one candidate selection or which strain will be take forward.
<unk> seen in healthy volunteers shouldn't be 19, Turkey for had greater activity at a given dose compared to soon be 16 18.
Confirming that higher activity in PKU patients will help clarify the choice of strain.
Two the potential for adjunctive use how do patients who are on separate Karen but continue to have high blood fee levels responds to the addition of our therapeutic candidates.
This will help us understand whether these patients could be included in a phase III trial.
Currently what is the likely effect size, our efficacy profile ultimately for our product in PKU patients.
As a reminder, we were thrilled with the results seen in the interim analysis, just seeing the same or greater would of course be very positive.
We are particularly focused as we shared earlier on the response rates are the proportion of patients who have a meaningful reduction in blood fee levels.
And the mean reduction in that group.
Data from both arms of Symphony will help inform these expectations.
Pending answers to these questions will conduct an end of phase two meeting with the FDA, which will allow us to confirm the specifics steady plans, including timing and other considerations prior to initiating phase III.
It's important to note that needed bridging studies have been completed and arm to experience a simply shouldn't be 19, Turkey for in PKU patients represents the final step needed to advance to phase III.
We expect our timeline to be the same for either candidate.
As with all drug development, Great science, and data is necessary, but not sufficient to get new products to patients.
Regulatory path to a licensed product it's also critical.
In addition to the collaborative relationship we have established with regulators there are a number of other attributes in our favor and shooting in PKU. The precedent of two FDA approved drugs support use of a single Registrational study and fee reduction as an endpoint for full approval.
Secondly, our platform sits within the F D. A framework for live biotherapeutic products.
S T. A S also familiar with E coli missile the chassis for our drug candidates.
<unk> got over 100 years of safety in humans.
Turkey. In addition across our programs our manufacturing is based on fermentation and Lyophilize Asian, well established manufacturing approaches. Unlike those of other new modalities and finally from a product perspective, both strains have been extensively studied in healthy volunteers with multiple.
Strain specific biomarkers.
Interim analysis of the Symphony Trust B Biomarkers confirm the mechanism of action in PKU patients and resulted in a meaningful and significant reduction in blood fee.
In summary, the path ahead is both Derisked unexciting as we advance our PKU biotherapeutic put those who need it most.
I'll now turn it over to Dave to discuss our other promising clinical and preclinical pipeline programs Gabe.
Thanks Eva.
I'd now like to talk about our program for homeless a scenario <unk> 13 53.
Cindy 13, 53 same logic second rare metabolic disease targeted drug candidates.
Entering the clinic this year for almost a scenario or <unk>.
<unk> patients have a deficiency in the metabolism of another amino acid homocysteine.
As a result of elevated blood almost cystine levels.
This can cause intellectual disability and also can result in thromboembolism, presenting as strokes in individuals and their teams and <unk>.
There is a need for treatment new treatment options for which our approach could be a strong fit.
Our approach was to be $13 53 is to consume assigning a precursor to homelessness theme.
We have promising preclinical data from nonhuman primates, and mouse models, showing that we're able to lower blood homeless cystine levels.
We expect to enter the clinic this year with results in healthy volunteers by the end of this year.
That will be another important milestone for us as a company.
As we build a pipeline of assets in diseases caused by inborn errors of metabolism.
Cindy $13 53 is highly synergistic with the PKU program.
In addition to leveraging our platform people with HCA you are treated at the same sites by the same clinicians as PKU patients.
We apply learnings from the PKU program and build upon the relationships that we've established.
Through that work for <unk> patients.
Moving beyond the rare metabolic portfolio, our next program with milestones this year as Cindy <unk>.
Being developed for <unk> Toric Hyperoxaluria.
And toric Hyperoxaluria is a chronic progressive disease caused by underlying Gi disorder.
Causes patients to absorb too much oxalate from their diet.
That buildup of oxalate crystallizes in the kidneys.
<unk> Crystal and stone formation.
Which manifests severe pain and may require intervention to Paas yourself.
There is an established and linear relationship between oxalate levels and stone formation.
Over time, the oxalate crystals and stones damage, the kidneys, leading to irreversible kidney damage with major implications for morbidity and mortality.
There is no FDA approved treatment for this disease.
The drug candidates and be able to go to consumes actually and produces a harmless metabolite called formats in the Gi track lumen.
Our specific approach enables oxalate could be consumed throughout the Gi tract.
Pending the duration of activity and efficacy potential compared to other modalities addressing the same target.
We presented data last year that we view as promising proof of mechanism.
Showing that we can reduce urinary and fecal oxalate levels in a dose dependent manner in healthy volunteers that works at a high oxalate diet.
To model and tariff Hyperoxaluria.
Given the established relationship between oxalate levels and stone formation, we expect this to translate into a clinically meaningful benefit.
We are now moving forward with a portion of the study in patients with Rune Y gastric bypass surgery, who have elevated absorption of oxalate.
To evaluate whether it be easier to kind of lower urinary oxalate in those patients.
Turning now to our early stage in house pipeline.
The progress of both the PKU and Hawks programs have Derisked our platform.
Especially when focused on consuming Gi based metabolites.
This allows us to expand our focus to other areas, including metabolic diseases like gout.
And also to larger diseases, such as IBD.
We look forward to sharing updates about these programs as they advance through development.
We have two collaborators, which reflect the strength of our product engine.
The ginkgo bio ups collaboration resulted in the SNB $13 53 clinical candidates.
We also established a collaboration with Roche last year to develop products for inflammatory bowel disease.
We've already achieved the first pre specified research milestone within this collaboration.
I'll now turn things over to Michael to review our financial results.
Thanks, Dave and good morning, everyone earlier. This morning, we released our financial results for the fourth quarter and full year ended December 31 2021.
I'm pleased to review the highlights of those results with you now.
Revenue was <unk> 6 million for the fourth quarter of 2021, there was no revenue for the same period in 2020.
Revenue in 2021 was due to the recently initiated collaboration with Roche for the discovery of a novel synthetic biotic for treatment of inflammatory bowel disease or IBD.
For the fourth quarter of 2021, the company reported a consolidated net loss of $15 1 million or 21 per share compared to a consolidated net loss of $14 6 million or <unk> 39 per share for the corresponding period in 2020.
Turning to the balance sheet and logic ended the fourth quarter of 2021 with $136 6 million in cash cash equivalents and marketable securities compared to $100 4 million as of December 31, 2020.
Under our current operating plan, we expect that our cash will take us into 2024 and enables <unk> to advance our clinical programs with important data readouts across the metabolic portfolio.
Thank you for your attention and we look forward to keeping you updated on future calls I will now turn the call back over to igo to wrap things up.
Michael I'm extremely pleased with all the progress we've made across our programs. Our team is pushing forward with great urgency to advance the therapies with the goal of bringing meaningful new treatments to patients.
2022 will be a busy year for us with several important milestones across our expanding portfolio.
We're looking forward to read as if our Symphony one study in PKU in the first half of the year, which will help inform the final candidate selection for our phase III study that we expect to initiate in the second half of this year.
We also expect to have the first human data for our <unk> program in the second half of this year as well and we are anticipating patient proof of concept data for our <unk> program.
In addition, we're fortunate to be well funded to break all of these milestones to fruition with the strong balance sheet to support our work we will now open the call for questions.
If you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone telephone.
To withdraw your question press the pound key.
Our first question comes from Joseph Schwartz with SBB Leerink.
Hi, Andrew dialing in for Joe. Thank you for taking our questions.
In your opening remarks, you mentioned that you were more focused on a responder analysis any overall gain reduction for your PKU program.
But unlike other approved drugs that makes sense to look at a responder analysis because the mechanism is likely to have a greater degree of response among a subset of patients with PKU program seems like it should work more uniformly. So just wanted to get your thoughts on why you why you have a more focus on our response.
Under analysis.
Overall mean reduction.
Yeah. Thanks, Jerry.
I'll make some remarks, and then hand it over to Molly because I think the response to your question is really looking forward to commercialization and the label on the product profile, which is really defined by the category and what physicians and what information they use about products to determine whether or not.
Prescribed by products for different patient of course, we will continue to report all days as we have but I think as we look forward to kind of the commercialization and hopefully following a successful phase III to launch its important that we start to talk and speak in language, that's familiar to the prescriber and patient.
Sure and I think this is very much ingrained in this category that is really the percent responders in the percent reduction within those responders that really define.
This class on these products, then I'll hand, it over to Molly speak from the commercial perspective, and why that's the case and quite we think it's important from a benchmarking perspective to use similar endpoints and language to outline the results of our trials Molly.
Thanks Hooper.
Thanks for the question. So it's a great question and it's interesting because.
As the EBA outlined we do have two approved drugs.
In this category, which is a real advantage from a precedent setting but also in terms of looking to existing labeling and to your point, it's really interesting that the two approved drugs, while a completely different mechanisms.
Couldn't be further apart.
But they do have quite a similarity in terms of how they're registrational in pivotal studies were done to set up for promotion and then what's seen in the labels. So both of the <unk>.
Both of those approved drugs.
Have been studied and are outlined in the U S. P is in terms of responder analyses. So that's independent of mechanism and its a precedent that was sad and I think it just speaks to the importance in this category of you know given the unmet need and given the.
The individual needs of each patient just to really understand when a drug works.
For a given patient how well does it work. So it's really about following that precedent from a regulatory standpoint, and a promotional standpoint, which obviously.
I had gone through a lot of consideration and deliberation.
Yes.
Okay, great. Thank you and then we noticed a change a change in the threshold for your responder analysis in your corporate Tech I think it now reach at least 20%, which is down from 30% you referenced previous so would just love to get your thoughts on the change in one of the reasons for their paint I think if we can just put it into context for us.
Yes, so we have.
Oh, I don't remember that we had ever defined responder based on export 2% no.
During my and I may be wrong here and someone else on the call can correct me, we had always defined responders at least 20% blood fee reduction there isn't a quebec is variability across different products in PKU in terms of how responders is determined.
But the 20% is the number we kind of pre specified as clinically meaningful based on discussions with patients and with prescribers.
And that's to my memory has been consistent throughout so apologies if we caused any confusion there, but that 20% has always been kind of what we call it outsized chemically meaningful.
Okay, Great and then if I could just squeeze one more and based on what you've seen so far can be 1934 appears to be.
More active than 16 18 I was just wondering if you could just elaborate on the trajectory of the two agents overtime relative to each other you know for example did you see 1934 to be consistently more active than 16 18 or did you see you know the reduction accelerate overtime. Thank you very much.
Yeah. So how we determined the superiority from an activity perspective of 1934 versus 16 18.
And with defined here back in vitro pre clinically in vivo there was a consistent two X greater activity at a similar dose of 1934 compared to 16 18. We then went one step further and we evaluated it in a head to head study in healthy volunteers, where the same patient.
Received a dose of 16 18, and then washed out and receive the same dose of 1934 and in every single patient in that healthy volunteer cross over 1934 resulted in greater biomarker production and the mean you know when we compare the ratio at each individual patient level. The mean of that ratio was it.
To X. So across every piece of data that we've collected preclinical or clinical and help he volunteers, we've seen a consistent finding and back to X greater activity based on biomarker production. We've absolutely no reason from a biological perspective to think that that would change over time.
Believes that it's based on the underlying changes that we've made to the Pal enzyme to make it more active.
And certainly it's been consistent and can we expect to see consistent data in the PKU patients I want to be evaluated later in the first half.
Does that makes sense.
Yes, thank you very much.
Our next question comes from Mitchell Kapoor with H C Wainwright.
Hi, everyone. Thank you for taking the questions today.
The first one just wanted to ask how much better you think 1934 could potentially look versus 16 18 with respect to the reduction in blood <unk> levels, and what would constitute a meaningful difference.
So I think first of all I'd say that we were really happy with with 16 18 pardon me looked at the first data from the first eight patients with PKU being that we got to mean, 20% reduction which is to ask the standard of care based on the all comers analysis. We believe really showed that this mechanism is.
Working the strain is consuming phenylalanine in the Gi tract, and it's resulting in a significant reduction in blood fee levels now around the same time, we had this healthy volunteer data is showing that that was too ex activity. So we know that 90 <unk> for us is only going to be better than 16 18 based on the activity in biomarker data.
So we think we're in a very good position in terms of having two candidates that are potentially viable to move into phase III. It's really at this stage a decision on which of those candidates were taking forward more than it kind of a binary decision about whether or not we're moving forward into phase III. So you know.
I think when look at the data that we're expecting to see more activity for 1934 similar to what we saw in healthy volunteers and the expectation is that that would be the strain going forward, but until we see the biomarker data is going to be you know hard to make that decision.
Okay, and then have you received any formal feedback from the FDA that no additional development work.
Would be necessary with the newer strength.
And if not when would you expect to get that that formal confirmation.
Yeah. So we have not had our end of phase two meeting yet, but we have seen working very collaboratively with the FDA threat development of both product.
And when we moved forward with 1934 into the clinic and based on the fact that there's really only five base pair differences at 99, 9% identical we used the same chassis. It's really the same enzyme. It's could you see the same product we were able to move 1934 very rapidly without doing any preclinical toxicology.
For instance, based on the fact that it really has a very very similar safety profile. So you know based on that we're able to move forward into a healthy volunteer study and generated some head to head data very very quickly and.
Once we have our end of phase two meeting obviously that will define what the phase III study looks like but our expectation is that we have completed all toxicology work and have a very robust human data access once we've completed the second arm of symphony, but until we have that end of phase two meeting as you know it is.
You know what.
Where it is it's not 100% guarantee but we feel we're in a very good position based on our conversations to date.
Thank you very much I appreciate it.
As a reminder, if you'd like to ask a question at this time that is star then one.
Our next question comes from Keay <unk> with Chardan.
Yes. Thank you.
For each.
Are you experiencing any challenges.
Patients in that study.
So the thanks for your question because the studies enrolling we are on track to meet our guidance, which is to establish proof of concept for that stream. This year. You know it's been a challenging time for all clinical studies I think it can be hard to adapt but.
But we are seeing good activity at the sites and our piece with our progress and at this stage you don't feel that we're in a good position to meet our guidance for the trials.
You know I think it's a credit to the team that we've been able to push through some of the external challenges with COVID-19 and other things.
Tough year to be in clinical research as you can imagine.
Okay. That's all I have.
Great. Thanks, Keith.
I'm showing no further questions in queue at this time I'd like to turn the call back to Eva for closing remarks.
Great well, thanks, so much everyone for joining us this morning on the call and that it would be remiss. If I ended without wishing everyone. A happy St. Patrick's day. Thank you all bye bye.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
Okay.
Sure.
[music].
Okay.
[music].
Okay.
Yes.
Okay.
[music].
Okay.
Okay.
Yes.
[music].
Yes.
Yes.
Okay.
Okay.
<unk>.
Hum.
[music].
Mhm.
Hum.