Q4 2019 Earnings Call
[music].
They will be a question answer session at the end of this call. Please be advised that today's conference is being recorded.
I'll now turn the call, obviously Dr. Elizabeth will head of Investor Relations Corporate Communications. Please proceed.
Thank you he and good afternoon, and thanks for joining us on today's conference call.
This afternoon, we issued a press release, which outlines our fourth quarter full year 29, chief financial results and several other topics. We plan to discuss today. The releases are available on the Investor section of our website www dumps and logic, TX Dot com.
Joining me on this call several members of Silajdzic senior management, including equal Brennan, President and Chief Executive Officer, Gregg Beloff interim Chief Financial Officer, Dr. Richard Reid.
<unk> medical office.
After he says introductory remarks, Greg will briefly summarize all financial results for the quarter I'm Rich will provide more details about on new programming and Keryx hyperoxaluria.
Following our prepared remarks, well open up the cultural question.
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 1995. These forward looking statements include without limitation statements other than statements of historical facts regarding the potential absent logics platform to develop several teaching.
To address a wide range diseases, including Kenisha metabolic disease, and inflammatory an infant immune disorders. The future do clinical development of synthetic biologic medicines. The approach than logic is taking to discover and develop novel therapeutics using synthetic biology, any expected timing of Silajdzic's clinical trials.
Availability of clinical trial data.
Actual results could differ materially from those can change in any forward looking statement as result of various factors, including those described under the heading forward looking statements and some logics press release Moody's today, we're under the heading risk factors Incent logics. Most recent form 10-K, which is also filed this morning.
So the logic cautions you not to place undue reliance on any forward looking statement.
Now I'd like to turn the call over to Eva.
The transfer.
<unk>.
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Hi, good afternoon tanks, Liz good afternoon, everyone and thank you for joining us on our quarterly update calls to discuss our financial results for the fourth quarter on full year for 29 team.
Provide an update on our programs and upcoming milestones.
Our mission is to develop a novel cost of living medicines Cogs synthetic biologic medicines.
You think synthetic biology to engineered non pathogenic bacteria to perform therapeutic functions.
We believe that synthetic biologic medicines have the potential to provide new solutions for patients who are currently underserved by conventional medicines.
We're pleased to be able to begin trend. He tried to you with notable progress in Austin, Texas biopic pipeline.
In December we announced data from our lead program for PK, you demonstrating that had solid oral form a and B 16, 18 could achieve a higher maximum tolerated dose compared to liquid I, just metabolic active consuming pheno Allen name or see any tea.
I track.
Based upon learnings from this program, we had better than new programs and metabolic disease, a second rare.
Heritage.
Metabolic.
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Yes.
Hello.
Hello.
He we can hear you Isa.
Operator.
Before we can hear you.
Okay.
Begin twentytwenty with notable progress you know synthetic biologic pipeline in December we announced data from a leap program for PK you demonstration was a solid awfulness shouldn't be 16, 18, 'cause cheap I am maximum tolerated dose compared to liquid and he's metabolic reactive consuming phenylalanine all fee in the G.
Attract based upon learnings from this program, we've advanced to new programs and metabolic disease.
Second rare inherited metabolic disease make sure you're in disease or I Miss you D. I know the client disease and Terry Claybrooks Gloria both of these programs will be built with poets. We've established previously Oh Sheffey E. coli missile promotions, we used to churn jeans on an oxo trophies that we know.
It would behave well in the fomento, so mentor and indeed.
We've asked Richard to provide an overview of all Hyperoxaluria program later in the cool and to explain why it's great reputation for synthetic biologic much.
In addition to Iran. Mitchell Boeing programs unimportant onto the strategy is to explore the Brett <unk> platform by evaluation of the potential of synthetic biologic medicines in broader indication.
Looting immune based diseases, such as inflammatory bowel disease, or IB D and oncology, we have a collaboration with abbvie to develop synthetic biologic medicines Ryaby do you know progressing our I O program.
In January we announced that we had treated the bush subjecting or open label Phase one clinical trial of intra Tumoral lean administered CNB 18, 91 in patients with advanced solid tumors with.
Oh collaboration with Gingko Bioworks enables rapid optimization of synthetic biologic candidates and complements our in house experience and strain design and engineering.
I think I was developed is kind of base, which is an extensive library of microbial sequencing data and use the software and automation to assemble and test new strain to enable and optimization of candidates the clinical development.
That technology provides us with access to a cutting edge synthetic biology base so programming stuff.
The collaboration is going very well with multiple projects underway. These projects have the potential to continued feed an exciting pipeline of program.
On the corporate site, we announced earlier this year the appointment to the new member to our board of Directors Dr., Mike Burgess, whose precedent of R&D. It turnstone biologics a clinical stage Bible Immunotherapy Council company, Mike is a physician scientists with over 20 years of drug research and development.
Experience and a track record of success in translational development, including Rolls Roche Bristol Myers Squibb Lilly, we're delighted to have him join the board and have already appreciate you disengagement an input as we develop on noble synthetic biologic nuts.
Our strategy from the start of the company wants to move initial programs quickly into the clinic to gain clinical and regulatory experience and an understanding of where our synthetic biologic medicines would be best deployed while continuing to invest and build the driving engine. It's possible, we learned a tremendous amount, particularly from a leap.
Okay, you program, which has provided nocioni practical experienced an engineering manufacturing and regulatory interactions, but in the volume of Pharmaco dynamic in vitro and preclinical modeling.
This program is also so just the guide for a strategic decisions, but pipeline development and the levels of potency that we need to cheat before advancing programs into clinical studies.
Summarize these lessons later in the cool However, first let me hand over to Greg to cover the financial support from full year 2090.
Great. Thank you Ms. good afternoon, everyone.
Earlier today, we filed a form 10-K that describes our financial results for the full year 2019.
And a corresponding press release that summarizes both the quarter, India and I'm pleased to review the highlights of both of those with you know.
Research and development expenses were $11.3 million in the fourth quarter of 2019 compared to $8.9 million for the fourth quarter of 2018.
This increase was primarily due to the use of synthetic biology services provided to understand silajdzic's collaboration with Danco.
An increased clinical study activities, including Cindy 16, 18, bridging study and the initiation of our Cindy 18, 91 phase one clinical study.
General and administrative expenses were $3.5 million in the fourth quarter 2019, compared to $4 million for that same period in 2018.
For the fourth quarter 2019, the company reported a consolidated net loss of $12.8 million or 37 cents per share as compared to a net loss of $11.9 million or 47 cents per share for the fourth quarter 2018.
Revenues in the fourth quarter, 2019 were $1.2 million as compared to $2.1 million for the same period in 2018.
Fourth quarter 2019 revenues were associated with the services performed under this in logic collaboration agreement with Abbvie to develop and synthetic biotic medicine for the treatment of inflammatory bowel disease.
The increase in revenue for the fourth quarter 2019 compared to the same carried into 2018 was as a result of revised estimates of time and effort required to reach certain milestones in this collaboration.
For the full year 2019, total operating expenses were $56.6 million in 2019 compared to $53.8 million in 2018.
The consolidated net loss for the full year, 2019 was $51.4 million or $1.70 per share as compared to a net loss of 48.4 million or $2.03 per share for 2018.
Revenues were $2.2 million as compared to $2.5 million in 2018, and again were associated with our collaboration with Abbvie.
Turning to the balance sheet Silajdzic ended the fourth quarter 2019, with $127.1 million in cash and equivalents.
And under our current operating plan, we expected this cash will allow us to continue operation into 2022.
In summary, we have the balance sheet strength to advance our ongoing clinical programs two important data readouts over the next 12 months and to accomplish our near and midterm goals as we continued to develop our platform and I bought.
We look forward to keeping you updated on our busy you're right.
Thank you and I'll now turn the call back to Eva.
Thanks, Greg and apologies for the technical difficulties earlier with my line everybody.
As far as you heard our solid cash position enables us to advance hidden be 16 18, our lead program in PK you.
The upcoming phase two clinical trial of our solid formulation in patients with Teekay you.
And should be 18, 91, our oncology program through phase one study in patients with advanced solid tumors or didn't feldman.
Importantly, we also expect to advance that's all of our 30 stage programs in our core area of focus rare metabolic disease.
As I mentioned earlier in the call. Our PK you program provides us with valuable information on the potential if I can tell the classic platform.
Data, we've obtained has reinforced our conviction around the net debt of therapeutic targets <unk> work is doing in rare metabolic diseases.
It's just the indication as well then be 16 18 for the treatment just PK you.
I can Patrick biotic Madison is designed to consume a tough toxic metabolites from the G. I tracked with the goal of lowering the levels of the metabolite into systemic circulation.
I cannot go data from this could be 16 18 program has deep enough confidence that this approach is safe and data engineered bacteria accomplish what they were programs to do into human body.
We know just finished chemtreat for my studies in both healthy volunteers and patients with PK you that shouldn't be 16, 18 is consuming see in the Gi tract.
The bridging study in which we evaluated the activity of the solid oral formulation in FY 16 18.
Has demonstrated that we can put you a solid oral form of our syntactic biotic medicines that would take good fidelity activity and stability onto refrigeration and at room temperature.
In addition, due to manufacturing process improvement.
That's your tolerated compared to the liquid formulation.
The next Gen <unk> program would be to advance it's solid oral material into a field ordering tried in patients with T.K., you, which we're on track to initiate into first half a day here.
As I've mentioned earlier, we demonstrated that the strain is consuming fee in the G. I tracked.
The next question, we would like I'm sure. It's credit strain is consuming sufficient me to change it didn't make levels in patients.
We continue to learn about the predictive value of in vitro preclinical and Pharmacodynamic modeling.
<unk> upcoming fielding trial will allow us to a valuation in the 16 18 is performing as predicted based on our modeling.
It's feedback loop between the clinic and preclinical assays in modeling is a key component of our research and development strategy.
For example, our experience in PK, you, it's helping us to say coating Pete criteria for advancement of new candidates can catch it biologic medicines into clinical development.
We've also gained used to experience into kind of on Rex clinical and regulatory development of synthetic biologic medicines.
Our interactions with regulatory agencies enough just the U.S., but in Canada and Europe also.
Good day regulators have been receptive to our approach and provide useful feedback.
Based on this experience for moving quickly to advance our new programs in enteric Hyperoxaluria an M. A C D.
Similar to PK U.N.S.T.D. is another inherited amino acids apathy.
Although indicates that this disease the defects in the metabolism of branch chain amino acid do scene I tell you seen unveiling.
Current standard of care is severe dietary restrictions Oh go different trends times can also helped.
There are no approved drugs.
Again as with PK you. There's reason to believe for the G.I. based consumption approach could be useful for patients.
We developed a prototype strain, but the multi enzyme pathways designed to come to bunch change amino acid and have been working with our collaborators gingko to improve the activity of the strain.
We have presented data from early collaboration that seat in 2019 and expect to have more Gazit you shared with you later this year.
In carry Hyperoxaluria isn't inquired metabolic disease, where we believe it or do you administered synthetic biologic medicine.
It has no impact on pushing slides.
I see Endo, Richard wheat has extensive experience in rare disease imputing Hyperoxaluria I've asked him to provide an overview of the disorder and not rationales for selecting this program.
Richard.
Thanks, Eva and good afternoon, everyone.
Well that's way to calm commonly funding plan that humans are unable to materialize.
We primarily depend on excretion via your on Pcs to eliminate arc with from the body.
Hi, Burlington urea occurs when there are significantly elevated oxalate levels in the your do do either production overproduction of arts way for the liver as a result of a genetic defect.
No what Oh I'm sorry.
Yeah.
Well from over absorption walked away from the diet.
Well just close one secondary abroad.
Secondary has lots of urea can be further characterized into different types.
One floor isn't tour hyperoxaluria.
Would you as a consequence of certain certain intestinal diseases.
Including cool to see Joel balls.
As well surgical procedures, such as very Audrey we bolstered.
So just a little can lead to a range of conditions increasing suburb.
From record kidney stones, and you're correct that used to chronic kidney disease and potentially the need for kidney trends.
Their own estimated 80000 patients with severe into your Hyperoxaluria youre.
These are patients were experienced record kidney stones, and our at risk for kidney failure due to this disorder.
This is a patient group a rule that we will target.
Sure.
There's no approved pharmacologic therapy for the reduction of urinary oxalate excretion in patients with Hyperoxaluria either primary secondary.
Existing treatment options are nonspecific.
<unk> I wouldn't take to increase your no.
More than two or three liters per day.
Hello, Hello, Dolly diverse well insult Nox weight.
And oral situation calcium are big Museum supplementation.
Despite these strategies many patients continue to experience Hyperoxaluria would painful report kidney stones.
All right continued real long term kidney damage.
We have engineered synthetic well medicines that are designed to degrade actually mcgaha.
[laughter] absorption was about.
We have demonstrated a fishing honestly don't British in vitro you know doesn't really simulated got system.
In preliminary studies in mice.
All delivery of a prototype synthetic products drain led to a reduction of oxley into your own of treated animals.
Well, it's difficult to eliminate normal walks away from the diet. That's it is present in so many natural foods.
We do know that patient sort of synthetic well oxalate, though it for a period of time.
Lot of humor, oxalate levels fall and levels of urinary oxalate or core clearly would disease severity over the long term.
We also known as you averaged nine contains roughly 100 200 milligrams Boston way today.
So this gives us a range of local box, we've set our engineered bacterial strains need to consume.
And allows us to mamba potency.
Me too cheap.
We will need to energy to potentially having effect on urinary oxalate levels.
Based on our modeling and the Invivo therapeutic effect will observe.
Please turn to optimize its luster synthetic Plata lead candidate.
And advancement into R&D, enabling studies this year.
Potential therapy for patients wasn't sure Hyperoxaluria.
We look forward to updating you on our progress later this year.
I'll be able to take questions at the end of the cool.
Now, let me hand, you back to people.
Hi, Richard.
Parents.
With that program that we're very excited the guys.
As Richard mentioned this isn't acquired metabolic disorder that has significant unmet medical need and I can kind of biotic approach could provide meaningful therapeutic option for patients.
Working from our experience developing can be 16, 18, we've been able to move pretty quickly in the early development phases of our Hyperoxaluria program as there are many similarities with T.K. you.
Similarly, we are engineering bacteria to consume a topic metabolites, it's available in the G. I track.
We could also mobs and be average daily intake metabolite ego and just finding a therapeutic profile and the levels that box snake consumption that our bacteria have to achieve.
Unlike PK you the levels of Austin age that need to be consumed significantly lower than the legacy.
In addition, the metabolites its present throughout the GI track not just in the small intestine, which provides a greater exposure time to our bacteria and a longer window for them to work.
We had expected to be able to share more information with you about <unk> form in pipeline later this month and to provide okay well.
Patients point of view, we can invite speaker at an R&D events that we had scheduled for March 24.
However, given the cold 19 outbreak as you would expect going after discussion with our advisors. We've made it difficult decision to postpone this meeting until later this spring, whom we expected a clearer picture of the adds great progress.
Aside from delaying our R&D day trends were hopeful that the outbreak with minimal effect, an appropriate progresses I programs.
Clinical trial immaterial for both our ongoing phase one study 18 91 in patients with advanced solid tumors or lymphoma under upcoming phase two trial, it's been be 16 18, it's already manufactured.
We are able to manufacture adequate material for preclinical studies in our high for up to your E and M. A C D programs as our manufacturing is in has.
We have taken appropriate measures to secure surprises I raw materials or your this year when it looked as if they're making shortages.
Well the clinical sites involved in phase one study of our I O programs can be 18, 91 have all internet usage trends in the faces at break to limit exposure of patients to the Corona virus.
As limiting in person visits I kinda called tried mobs shrink.
As if this time all sites continue to clean and enrolled subjects. I mean, we remain on track to shared data from the monotherapy arm of the study and Twentytwenty.
That's far we also remain on track to initiate a phase two efficacy study of our solid oral formulation in patients with T.K. you in the first half is this year.
This study is designed to evaluate potential SNB 16, 18 nowhere systemic fee levels in patients.
And we'll provide important additional information about stability of our pharmacodynamic and pre technical and in vitro modeling.
With the new stable formulation patients will be able to go back their normal lives during the study, which will impute adult swim and stomach acid suffering with PPI.
Oh. This study is in progress. We will also continue to frighten us bodyweight different presentation of the solid couldn't be 16, 18 material it Chad entirely cogent caps to play pills.
I look forward to providing more details on the study and today said that we tend to collect at our R&D event and on future calls this year.
Well, we don't yet have a burn date for the rescheduled R&D day I go to host this event into first half of the year.
Summing up we have a strong cash position that look how are ya de <unk> in both clinical programs and I'm, making good progress as we build a pipeline of syntactic classic medicine in metabolic diseases.
I'd like to tank all of you for joining US. This afternoon, we will now open the call for questions.
Ladies and gentlemen, you'd be have a question at this time when you first part that the number one on your telephone keypad. If your question that's been answered for you wish to repeat yourself from the Q well use press the pound key.
Your first question is from Joseph Schwartz from <unk>, Inc.
Hi, I'm I'm jewelry park dialing in for Joseph Schwartz thinking for taking your question. My first question has to do with the knee 16 18 could you just remind us what you're hoping to see into phase two bridging study and with multiple PK. Your drug candidate development are you anticipating a difficulty and rolling peaking patients.
What are you doing to ensure you enroll in a timely manner.
Yeah. Thanks, so much jury for for that question I must start off a little bit maybe and then can do so for two to Richard trees that Chief Medical officer, and will be really leading the last of the books strategic but also the operational component of the study and if you can imagine with Covance 19 and.
Other changes to programs in development to at other companies, if it's an evolving landscape and but first off I think just to clarify you. I think you were asking a question about the phase two feet Loring trial and not necessarily the bridging study I mean, if that is that correct jury.
Yes, that's correct. Thank you, Okay, I think I make a few lowering.
If he likes that yet exactly yes, but that's the thing that we want to achieve from that study as I mentioned in his script. We've demonstrated that the strain is consuming seen loudly and were able to measure the product of the Biomarkers. We've made some estimates in terms of thought that was translate to fund the feeling pursue.
Yes, I think the big question no for this program is how activations are modeling and how when are we able to predict based on those biomarkers the level of feeling that we get in patients with PK you and that's we need the overarching goal of that study of course will be collecting biomarker days and we'll continue to collect.
Information about safety and Tolerability and PK you patients, but we really are our looking to address that and validate some of the modeling that we showed at a late last year from the program and Richardson team have been doing great job to add designed to try that and hopefully.
We'll be able to share kind of more information about specifically designed later this year, but we need the overarching goal is its to evaluate how well our modeling can predict feed ordering and PK patients.
I found it may be over to Richard to discuss you north tossed around I'm getting to study done I was curious if you'd like to take that part of the question that would be great.
Sure.
You know I think I think you brought some yeah.
Certainly some joint points said, we're not really only.
Oh, probably doing studies in PK, you and I think as well. So you know speaks to the unmet medical need in in the need out there for.
Ultra Medusa field people don't use.
You know I think we only sumatriptan <unk>.
We do you usually that's in logic is quite a bit of experience doing studies in rare diseases and one of the big points is to do your homework in terms of feasibility assessment, where are you go where the competition like.
And you, where we think we can recruit patients and working hard on on all those.
I think one good thing for Walter could we do have some experience from or is there was a one study in recruiting.
PK you patients included 11 became Asians and for a woman's Roes are one studies from you know some experience where to go on in terms of <unk> academic and in other sites.
So I need you species, and we're hoping to junior work harder.
Feasibility funding slides I'm in for in finding patients than maybe you know the other aspect is making it easy for patients to well just things you could easy and convenient.
In making the.
Those studies its limiting the number of in whole study reserves.
And complexity you've drawn we're taking all the stuff into consideration as we move aggressively to surface true.
Okay. Thank you and then if I could just ask one more question. So he's on thoughtfully executing studies and the Internet of matter to you know systematically build your platform and you briefly talked about this in your opening remarks, but I was just wondering if you could you kind of expands on her learning so far in new lessons that you plan to integrate.
No whether it be manufacturing or strain optimization techniques into your new you know enteric Hyperoxaluria program.
Yeah, I'm. So you know like interest costs on in terms of your characterization jury about how we're really building. This platform I'm you know hopefully in enough talk sold it purchase manner, where things that we learn from a lead program can be rapidly applied to programs that are going behind I think that was a bit.
Big driver in terms of the kind of focus around these rare metabolic diseases, where you know this a lot of similarities in terms of the biology and turns if the formulation into their free and as you know you followed the company carefully for it for some time no onto our ability to manufacture and deliver.
That's a product that was stable at room temperature in refrigeration that was well tolerated and we could be scales up and manufacturing, which was a key challenge for us that weve been kind of able to me Colossus progress on we're certainly not done yet and I'm they'll continue to work on that because it's such a key and a key success factor.
For us and for our platform in terms of how we've been thinking about applying those learnings to the next that's just programs. One thing for sure is that you'll be applying a loss of the assays and the manufacturing methodology that we've established with PK you to those next programs I think the second component that we're able to do.
It's really not stats kind of what dose and back calculate how much potency you need Purcell ask you haven't jokes in order to achieve our target product profile. So it really does allow us that you start to push a framework around go no go criteria for preclinical programs and to.
Hi, good it's good to know her program to move forward into clinical development. So I think we've we've learned a tremendous amount in the last year, an 18 month and have built to last of foundational capabilities that too we're hoping to leverage with this next wave those programs that we lead time.
Okay, great. Thank you that's very helpful. That's it for me.
Your next question is from Mark Breidenbach from Oppenheimer.
Okay, good afternoon, and glad to have your Nike.
I know on social dispensing and it's not working that so so far.
[laughter] might try <unk>, let me start worth maybe very quick ones on 16, 18, and then one follow up on 80 91 [laughter]. Maybe this is related to the first question I'm wondering is it reasonable to expect that enrollment criteria in the lowering.
While we'll be very similar to the patients who were enrolled in your previous study and where are you going to be targeting in any specific oh levels of serum the offer for picking the right patients for this trial and another question on on 16 18 is on.
The enteric coated capsules I'm wondering if any of these will make it into cohorts in a few lowering well worth it would have to be tested in healthy volunteers first.
Yes, I think to answer your first question Mark I think a fair assumption you. We do think that they you know the project. If we can achieve our product profile has broad applicability across.
Multiple different patient types in patient segments, but we think that doesn't best place to start something the adult population the elevated baseline sea level and once we demonstrate that to you know we can predict the lowering faith in our modeling and that we're kind of moving the needle there in terms to the female plus we're seeing then we can start to see.
Okay, that's expanding and looking at other efficacy endpoints in different populations for instance, in you know patients who may be partially controls with diet and can be bring those patients into the target range, but you know for now we're very much starting up and sticking with the adult population who has elevated sea level.
So you know I think your assumption around the patient population being broadly similar.
Patients that we enrolled in the phase one study is absolutely correct I think I think that's the right making capacity in terms of the formulation work and on the second part of your question you know, it's always challenging to keep guests studies done first is way too it seems to be able to enroll.
Add on cohorts with different formulations are assessment and put we're hoping to show is if we can show that the biomarkers in healthy volunteers modeling we've done maybe just predicts wells what happens in patients with T.K. you. The huge advantage that gives us from a development perspective is that we can actually do allow.
Cost of development work in healthy volunteers and a move a lot more quickly and with with the program compared to having to do allow shows evaluation of different formulations in patients with PK you. So that's really an advantage. If this program that we're hoping to leverage in order to be maximally mission as we go through.
Kinda somebody psychosis situation and different formulations I would anticipate that that was that's what we'll do which I'm you know in carry co said to capsules <unk>. When we have the development work done, but we haven't formalize that plan, yes, but it it it's a it's a good advantage for us being able to us.
Some work in healthy volunteers, particularly if we show that we can accurately predict what's going to happen from the field owning perspective in Teekay you patients.
Does that make sense.
Yeah, Yeah got it that's very helpful and money when we do a quick one on 18 91, given that we have some some data coming in a they're not too distant future I was wondering if we could get your thoughts on what would be.
Early indicators of differentiated activity for for 18 91 versus the naked stick with a nucleotide classes compounds.
Is there something more granular and type one interferon response to look for that would be a an early indicator that that that you're probably is behaving differently in tumors that and yeah. Oh, there's thing Agnes we've seen in the clinic, yes, yes. So I think it's as you know from that program to Street.
Ways that we think for fun too many different from the small molecule Sting agonist.
Number one is that we didn't meet at multiple different pathways me immune response, and certainly based on our preclinical models in some work we've done with human quite blood cells in vitro, what we see very sweet stimulated type one interfere in response, that's greater in magnitude compared to see doses that have b note the comparable.
This is if the naked Sting agonist, but we also stimulate other immune pathways and so the when did the endpoints that we'd be looking at from a T.D. perspective in this phase one study it's not just the type one inch friend pathway, but some of those other additional pathways as well I'm really hoping to see that we are able to enjoy.
A robust type when it here in the sponsors well tolerated dose what that we're also seeing evidence of some of those older. You know pathways that that that could be BD importance in terms of that and then you respond but that's the first thing I think the second to two ways with your friends are you know the second one is that we have this longer.
Profiles as the naked Sting agonist that are given into tumor they have been very short half life. Our bacteria are designed to be able to justify for up to a weak in the tumor microenvironment. So we'll be also looking at that spend undeterred. One if these T cell apoptosis, that's going to be difficult for me to think about how weak.
And.
Measure that in vivo in in human to human clinical trials, but certainly ex vivo, we've looked at that with and showed that he sting agonist is actually in in intra cellular already in the bacteria I know he gets to each one dose at bacterial cells are in Gulf by Apc's.
You know how did that currently in India can Nick I think it is gonna be challenging and until we get to an efficacy study and then an efficacy study we're going to want to see that you know higher doses are more efficacious and that we've avoided it's kind of inverted U shaped dose response curve it seems to and in fact some.
The other sting agonist based approaches.
Okay, well thanks, Thank you for that and congrats on the progress.
Hi, Thanks Mark.
The next question is from Giggling become ovitz from Citi.
Hi, This is nothing at all thanks very much for taking the question.
Hi, I appreciate all the detail the prepared remarks about you mentioned that the hyperoxaluria.
Biotic, it's able to be used all throughout the got that's where they look to consume all right I Wonder if you could maybe expand upon that and how they're using or anything he.
20 here sort of investigate is there a part of the got that maybe work that's or is it truly active throughout the whole got maybe you could maybe going up and information as well about the mobile Sarkozy biotic along that line.
Yeah, I'm. So I think the one of the reasons that we're very excited to decide says he and his hair cut Brooks of urea is that as you mentioned Smith said that it works to I see the G. I track and we know that this approach is validation to others have done studies with export enzyme based approach showing that's working you know in the Gulf.
You can reduce here in the oxalate levels you know our approach.
I was the best you really need that's consumed that all the way along the G. I Trust, we know that there's available <unk> place in the G. I tracked in both the small intestine and the coal on what we know as of today based on the preclinical work that we've done if that's the bacteria are active in the stimulated upper Gi environment as well as it's been related nowhere G.
Fireman's, that's and aerobics, we know that work in vivo in the preclinical Mezz model.
We happen yes.
Any you know doctor on my model, but would you intend to do that base run. This year. So I think based on on the day said that we've seen in <unk>, we know what that is physiology of oxalate.
We think that there's a nice opportunity for it bacterial based approach that will work both into small intestine like the PK program, but that also we'll have some activity in in the colonic environment and in the large and testing as well I think you referred to the and seen 18, <unk> and 10 20 program.
And some of the learnings there and of course, those learnings have absolutely been and integrated into this program you know where we're using a lot with the modeling that we've developed PK you program to conservatively model the activity of the strain assuming doesn't really active into small intestine based on <unk>, we know around kind of yours.
Nation of activity from the PK you program. So that that's currently being being informative and then from the Tentwenty perspective, as we were designing the strain realizing that you know the and it's not to get to technical but the bacteria Wendy Hutchinson origin test and they switched anaerobic metabolism. So you need.
To have circuits that don't require ATP under circuit that we engineered for the prototype strain of the Hawk program doesn't actually require quite ATP. So you know we're learning is we're going to log and pointing at work best to apply this platform and just based on the data that we have today.
Hi brought to you are you seeing second it could be a really nice opportunity for us.
Yeah.
<unk>.
Yeah. You did this is Richard just what you're doing a little bit that we believe in her remarks, we rubicon is very important.
Please quickly for these patients so you're getting to the coal and [noise].
To me obsolete.
We believe will be real benefit too.
You know platform.
Treating these patients with him really.
<unk>.
Great. Thank you for all that additional detail.
And maybe sort of thinking is the theme.
Let's say you know you're just starting the phase to see lower betting down, but you know if I could maybe look forward and make some assumptions and assume that you know everything comes up positive in your modeling is validated and it sounds like you said that earlier prepared remark that oxiclean, you don't need to necessarily consume it.
Much if you do occur that you heard me.
Is it fair to say that there maybe a lower our broccoli potentially and then if you're modeling is validated the Bakken.
All that every for your alkaloid program at Centralia than other programs on your pipeline.
Yes, I think you know two month is what we're really trying to build this is credits and the secret the platform. So I think anything that that we can do to show clinical meaningfulness, particularly needs where metabolic diseases. I think makes us feel more confident than in programs that that are coming along behind us. So we certainly.
Interpret it that way and there are I'm kind of moving logically with with the platform and I'm trying to develop similar types of programs. So that there is that maximal learnings that can be applied to the pulls on sets that are going be for but I think you know your assumption around the level of substrate.
<unk>.
Without really are correct I think as Richard mentioned in his script you our daily the average daily intake of Avastin nave is about 200 milligrams. Your average daily intake. He is about five grams. So just from a pure math perspective, there's a lot less.
Late <unk> in the dice has a lot less off late in the G. I trust that needs to be consumed.
Yes.
Great. That's helpful. Thanks, very much for taking my question.
The next question is from Fred and Paul from Piper Jaffray.
Great. Thank you very much and I'm thinking for all of them up it could be carried Cuzzort thing [laughter], Oh, Oh questions of women Firstly Ruth.
Turning to come to you.
Yep, Yeah, you existing therapies is this something worked with up to go on top of funnel Cougar Workover rig works out their work because they're not you know ubiquitous will use.
Is there still the opportunity to demonstrate well in Serbia activity and hopefully get monotherapy activity, maybe just a quick follow on to the dark.
Is you know what do you ultimately because of the mechanism of action for their TV with other approved being turned out there.
So those are two questions. The live a quick housekeeping if I back.
Yes, Hey, Pat how you I'm good actually ask Richard to address that question around the clinical development plan I'm you know so far what we've been proposing is and as a monotherapy a indication and we've had a you know a losses of regulatory interactions around the program and.
That's certainly it's a path that we continue to pursue and I say into confessed first line indication Richard has been in the last of those meetings and since joining the company. So I pass you wanted him to maybe add some additional color there in terms of the feedback and guidance that we've received.
Yeah, I think they can be for yeah. So when we were bad discussions with the right.
So what is most of the U.S. and actually work and most of the discussions have been you're wrong into at least Guinea. The initial Google wasn't as a monotherapy and yours is as you said yeah you know.
Dan is you efficacious in Brooklyn, <unk>, no patients was not not educational operations and.
No no because now for everybody here youre doing with before for adults.
Oh, you mean, a generic issues issues with that so you're most of our regulatory interactions I've been around as monotherapy or you bring up from interesting questions or could it be used its combination Derby, there's no slightly different reason why.
No I wouldn't helping or totally different mechanisms of action.
No I wouldn't use words synergy I certainly would extent.
They have you ever give you will be added due to other.
She such as.
Well, let's see.
Mhm currently available in the U.S. and other markets.
Good day, and then other parts of the World, we want to rotors. They don't have access to <unk>. Once they can so we're really interested in any alternative therapies that come along with them.
Very productive discussions.
Excellent. Thank you I appreciate that perspective, Greg you heard me just a quick question over revenues Hart with <unk> early recognition, a 1.2 million in the quarter does that kind of exhaust the amortization was that a separate upon.
You know.
Does this sort of a zero out the revenues going forward, how many of the going thanks very much.
Sure. So generally when we don't do his comment on how revenues will be coming in in the future, but the way to look at this is.
Just typical of oral Briatore research just isn't collaborations there are periods and intensity and then there are levels in periods of intensity. So as you know as part of the collaboration were or efforts were underwritten and so that's really where you see the spike in the revenue in the quarter.
Okay. Thank you.
Your next question news from like who simpler from H.C. Wainwright.
Good afternoon. This is Ed remarks on for Rob I. Appreciate you taking my question.
For the 16 18 study just wondered real quick with a timeline is to deliver top line data.
They do you want to address that question.
So.
I'm, sorry, I missed it could you could you say it again.
Guidance on topline data from the feeling study.
We've not given guidance on the we've given guidance on the initiation of the study and at this point a you know until we get things up and running particularly with the current situation, where we're not giving guidance on a when we expect to have data we're moving as quickly as we can we have.
You know experience with some of the centers there in academic centers. So they take a little while to get going and as we said the situation as it is its little hard to know, but once we get things up and running and and stopped enrollment we will certainly be trying to give you is close an estimate this weekend so.
Excellent what does the likelihood that future development and Peter you would be pursued with a different strain and if this pretty Peter Keith how much more bridging work do you think you'd have to do.
Yeah, I think you know that's that's certainly a great question, it's as Weve.
Discussed on previous calls we are working on years since we initiated the gingko collaboration we're working on optima strain optimization and when it the first projects that they worked on with US was that optimizing the PK you strain you know we're in new territory with our platform and in terms of how regulators I think it by saying.
Yes first is different than us if you will really important thing from a time nine perspective is how much of our preclinical work can be cross reference to any future interaction. If we work to make changes for instance that involved to sequence of the strain you know I think at that point when we think we have some.
I think that's an interesting and viable we would need to go back to regulators and to make the cases that our preclinical work was was it pick a bowl depending on what that strain looked like and would obviously look to move as aggressively as possible, but I will say today, you know bank matrix has been very flexible with us we take.
In a very site based approach, but that they have appreciated tend to I have given us lots of flexibility and obviously because this is is a rare disease. We also got lots of opportunity to interact with the agency I'm afraid Pernod, that's that's about it as much as we can say you know we.
We think could be a new sufficiently but until we kind of get into it with regulators is gonna be hard to say exactly what that data package need to look like.
Okay that makes sense I just two more quick ones. Just wondering if you intend to assess 18 91, a in additional regiments beyond that double a combo with centric or is this all that plant.
Yeah that said do you want to speak to this one Richard can given that you are leading the technical program for 18, 91 and have had some thoughts about specific indication.
It was so the question whats wrong, a different indications on different than all the major Jordan.
I am.
Okay total broker.
Did you get done is.
Different combinations.
Ah yes.
Additional regimens beyond the double of coupled with the centric.
Okay.
Oh, yes, right now we are.
Conducting a phase one study was in the first arms monotherapy, which will lead.
Determining the emptied American polluted goes for monotherapy anti smoking home you once once we get the M.T.D. will be in combination with <unk> to <unk>. Thank you.
[laughter], we have no plans to do right right right now that's the extent of our plans for I'm. Just wondering you know just one inhibitor combination, but you know I think the so whatever questions. We have is.
If we show a casino combination you cannot be used in June or other combinations. So in the future.
Yeah.
Total one of them out there we heard on it.
[laughter].
And finally, you mentioned a lot on this call about inter copper oxide.
But I'm wondering when you might slip candidate for people Therapure in disease, and you know how might this program computer get something I guess sodium phenobarbital you are right sorry.
Yeah. So for both programs, we have set potency criteria in terms of how good they need to be to be and ready for kind of prime time. She will declare candidate start 90, enabling work you know, we're making significant progress towards that goal. This year, whether we'll get the potency that's required during our.
Not we're still working on it we're hopeful that we can at least for one of them <unk> chief of apart potency and move forward.
Mm <unk>, we think both are great indications M. A C. D. Obviously very similar to PK you in terms of being in the meeting last adopter CNN is it you mentioned dirtier interconnect rock. So your E beam similar to Teekay, you, but also having at a slightly different opportunities that yeah. We think that the AMITS UTI program can be very compelling.
Because at the field abuse for eight days had that that's out there. It is a little marginal to us, but you know we think that they could be if we can achieve our product profile to really interesting approach effort that you see I did you see that has had no and you're correct. The other than liver transplant 10 and strict die.
Very controlled so yeah, we think bokor, a real programs and very interesting programs with promising data from prototype strains. It's really just im not sure. He chasing the potency that weve pre specified for each and I'm, just very accommodation and moving forward into the idea enabling phase.
Okay perfect I appreciate all detail. Thank you.
Thank you. The next question is for Chris Howerton from Jefferies.
Hi, everyone. Thanks for taking the questions and addressing a lot of the I think most of the questions.
For the topline one I think you know one thing that I did just stands out to me is done relatively strong balance sheet that you have currently and.
Obviously in in these tumultuous times getting capital on your balance sheet could be challenging so kind of given that perspective, what are kind of the key value, creating milestones or catalyst that you. You know thing can be transformative to your company over the next 12 months or so that we as outsiders should pay attention to.
Yeah. So you know where you're right. We're in we're in an enviable position, particularly given some of the uncertainty that that we're seeing right now and that we can be knuckled down and execute and that's really caught where we've been focused on doing and what will continue to do.
I think what were you know it's still guiding to went and bought we're excited about is showing in the feeling studies that we can lower fee and that we can do that based on our prediction and in line with our prediction I think well give us that on the outside world confidence that you know our biomarkers are actually predict is that we can do something.
That has potential clinical meaningfulness. So I think that's going to be you know what unimportant one milestone for us I seek advancing additional programs into the pipeline and being able to demonstrate that we're able to move quicker with higher quality strains and bash. It kinda call candidates based off of our Kinda Foundation okay.
The business. He said, they're learning from PK you I think is also going to be really important and then I think the oncology program, where we'd have monotherapy data this year and that and then combination therapy. You know thereafter, well really demonstrate that weakening engineered these bacteria administer them into the tumor microenvironment and update.
Hey, as behave as designed that this approach is feasible that says the regulatory path forward that we're engaging the mechanisms that we've designed into the bacteria and when I think for me that's going to really opened up and it kind of an alternative or collagen opportunity for the platform and you know we ultimately see.
On college in Immunomodulation is at partnership opportunities.
But given the novelty if the platform. We felt it was worth of making you know the investment to take some looks that regulatory safety and kind of feasibility risk off the table and then 10. She gets the right kind of partnership it's really going to allow us to develop <unk> farm in potentially an interesting and.
Additional opportunity on top of our focus on rare metabolic diseases. So you know we think.
All of that is is within grass based on our current resources and our execution plan and that we're going to have that unexciting tough months ahead.
Sure. Okay that makes sense, Okay, and then I guess shifting gears to enter type or actual area. That's just because I'm familiar with this you know what watch is kind of your regulatory path or you're envisioning because you know one of your competitor.
Others had spent a fair amount of time negotiating with the of D.A. on a clinical registrational path, which they've kept largely to themselves. So you know just kind of what are your thoughts with respect to the registrational path moving forward and particularly as it relates to any kind of clinical endpoint that may or may not be.
Required.
Yeah, I'm, so you're right, Chris you a lot of experience habits in the syndication and sometimes it's nice to be second Gen. Obviously, we're learning you know everything from a lean I think they've done a great job those kind of thinking through at the development path I'm used to raise a consorted effort right now and in Tehrik Hyperoxaluria where power.
Our child, if they academic F.D.A. industry consortium that specifically designed around understanding the epidemiology of the disease understand if physiology of the disease and then working on Registrational endpoint and in the indication and we can we love. The indication is you know I think there's lots of strong evidence that you're in.
The oxalate really does predict subsequent and more good to see from a current stones that I'm progressive and kidney failure. So I think it's one of these diseases and indication that's on the cost of having a really nice approvable endpoint. If we can build the package direct to support a urinary oxalate lowering yet as an up.
Horton to surrogate endpoint, but you know there is this construction efforts now so we need to find clinical endpoint and in this indication and certainly based on what you've learned from the public disclosures of of Alina others. It seems that you know, even if a clinical endpoint over and above.
You are in the opposite lowering his requires that that can be done at prestea judiciously with <unk> with a modest at trial sites. So we think it's a nice indication for companies our size it and resources and that you know the kind of evidence base supporting your me oxalate and we'll move quickly.
Not that there's good kind of stakeholder engagement and the good appreciation of the unmet needs in this indication, but you know I thought I'd be opened here yourself also given given your background and expertise in the area.
Sure I'm happy to have that discussion I think.
Maybe that's something that we should have off line, but I I know the particular, the the clinical endpoint. It's been a sticking point I think for for a lean is certainly very much look forward to how these discussions revolve overtime with the regulators and yourself.
Yep.
We are too.
Okay. That's all for me so thank you so much.
Thanks, Chris.
Your last question is from Palm Friedman from BTG.
Hi, there this is drilling on for Tom Thanks for taking my questions and hope you all doing well first just on 80 91 I know the primary objective for the monotherapy trial is safety, but do you think of Sting agonist and it back to your chassis could be enough to generate.
He profound immune response and by extension, maybe early efficacy signals without a checkpoint inhibitor. Thanks.
Yeah. So you I think the were just couldn't be phase one populations always important to kind of set expectations at the very oncology trials and it was going to be phase one year heavy treated at population with advanced 10 malignancy, you know we're going to be looking at Biomarkers will obviously.
He'd be measuring clinical response, we'd be doing staging and imaging during the study, but you know where we're really and designed study to optimize for the Biomarkers and on the safety learnings into quickly into the combination arm. So certainly internally the company there's no.
Expectation that we would see you know complete responses are a partial responses in the monotherapy arm of the study, but we are looking for us and of course would be delighted to.
Sure reports that that we're seeing something but that's not our expectation.
Okay. Thanks, that's helpful and just to piggyback on the Los Angeles question I know this is far down the road, but just curious if you have a good sense for what the registrational endpoint or end points might be for and that's Judy.
There's a surrogate measurement like Lucien and around the possibilities or.
Something more functional like cognition is likely need it.
Yes. So I'm you know I think it's going to be subject to negotiation with with regulators. Yeah. We haven't had any of those discussions with regulators yet you know obviously, we would be.
Much more favorably inclined to use you seen lowering as as an endpoint for the study and I think based on kind of analogies and parallels to PK. You were feeling is the principal endpoint. In addition to the fact that it's a pretty rare disease, and I think likely to be kind of subjected to two flexibility enterprise.
Chisholm in terms of what's really going to take two to develop the treatment for did you see we would be and certainly making a strong case for somebody seen then do seem doring being the endpoint, but where were lifted special waste from not having that conversation, yes, but as soon as as we have piracy, we'll we'll update you and anything else mature.
With that you'd like to address that I left out there.
Yeah, No I think I think you you're just talking points.
And I do want to sort of reinforce what is a rare disease and talking between her <unk> 4500 patients in the U.S. in in the past when we report you regulators with a pragmatic sort of solution and point out there not a clinical endpoints such as neurological function along with.
Hey, too.
Measure to assess as well just number of patients depending on the variability <unk> session, which is quite high neurological.
It's not really feasible.
So our expectation is would be going in with the losing weight important either lorimer or or stabilization independence. When we presented those type of argument to regulators and the new stuff doesn't is very rare disease.
Arena.
Okay, great. Thanks, that's very helpful.
I'm showing no further questions at this time I would like to turn the conference back to Dr. Britain Preclosing.
Thank you so much operator, we'd like to thank you for joining us on today's call and we look forward to updating you on on progress across our developing pipeline in the coming among untapped will be available later today. If there any follow on question hopefully one stays healthy bye bye.
Ladies and gentlemen, the two groups with based conference call and webcast. Thank you for your participation that can have wonderful thing you me all disconnect.
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