Q3 2020 Axcella Health Inc Earnings Call
Good morning, ladies and gentlemen, and welcome to accelerate <unk> third quarter 2020 conference call. Please be advised that todays conference is being run.
Got it and that all participants will be in listen only mode until the question and answer session.
After todays presentation, there will be an opportunity to ask questions to ask a question you May Press Star then one on your Touchtone. So.
To withdraw your question. Please press Star then two and.
And now for opening remarks.
I would now like to hand, the call over to Jason Fredette, Vice President of Investor Relations and corporate Communications at Accella. Please go ahead Sir.
Thank you operator, and thanks to everyone who's tuning in this morning, we would like to advise that certain remarks, we will make on today's conference call such as those relating to our planned R&D submissions.
And clinical trials include forward looking statements that are subject to various risks and uncertainties. These.
These risks and uncertainties are detailed in our form 10-Q for the most recent quarter and or other FCC filings, which can be accessed on our website Excela health dot com or on the Fccs web site.
All forward looking statements represent our.
Views as of today November 12, 2020, and should not be relied upon as representing our views as of any subsequent date.
We undertake no obligation to update these forward looking statements.
Please also note that the data we will reference on today's call stem from non <unk> clinical studies that were designed to evaluate product can.
Candidates for safety, Tolerability and effects on normal biological structures and function. These.
These studies were not designed are intended to evaluate the ability to treat or prevent diseases.
Our next clinical trials of axle 11 25.
And access 16, 65 will be aimed at the school.
On the call with me today are accelerates president and CEO Bill Hinshaw, our Chief Financial Officer, Laurence Chardan, <unk>, and Chief Medical Officer, Dr., Herman New truck of RP.
I'll now turn the call over to bill to kick off our discussion Bill.
Thank you, Jason and good morning, everyone we have.
Appreciate you joining us today.
2020, as a whole has been a period of significant advancement and validation for Accella and we're excited to share. The most recent and important examples of this on todays call.
I will update you. This morning on each of our three clinical stage programs, including some key details on our upcoming.
During trials in Nash and avert hepatic encephalopathy, OE Ci and Laurent will follow up with a brief recap of our financials. We'll then be happy to take your questions.
Before diving into the program specifics I would first like to ground you on our aim here at Accella.
Our platform focuses.
For use of endogenous metabolic modulators or are you, a mems specifically amino acids and their derivatives.
Leveraging these master regulators and signaling agents, we've compiled the portfolio of multi targeted product candidates that whole transformational potential.
Working with.
The body systems to tackle complex diseases, such as Nash and away G.
In September we were pleased to announce the publication of a manuscript in our science. There was lead authored by Axcelis head of research My count.
This paper elucidated the fundamental role that amino acids.
It's playing biology.
And it included many clinical precedents from others, who abuse single amino acids and simple combinations to treat diseases.
The manuscript also explains how excel is approaching things differently.
We are developing compositions of multiple mm.
Yes that have the potential to address complex diseases in a more comprehensive manner than a single targeted small molecule or biologic.
And since these mm.
Of course endogenous to all of us they have well established safety and Tolerability.
As a result, we.
And many of the key opinion leaders, we have spoken with believe our candidates are well positioned to be used chronically by both adults and children and to be used in combination with other agents as required.
Our two lead candidates are in the liver space X.
Axa 11, 25 for Nash and access six.
In 65 for O. HKG.
Let's begin with 11, 25, which is our multi targeted product candidate for Nash.
Following the readout from our successful 11, 25, 003 clinical study, which was presented as a late breaker at EASL, We recently engaged with the FDA and.
Completed a tight be pre AI in the meeting.
We are very pleased to report that this engagement allowed us to affirm our plan to proceed directly into a phase twob clinical trial in biopsy confirmed adult Nash patients the.
The agency confirmed that based on the significant.
Amount of safety information and human data, we have already generated.
We will be able to get this trial underway in a streamlined fashion without additional toxicology work.
As I mentioned this engagement followed topline data from our 003 clinical study earlier.
For this year, and which 11 25 showed meaningful and can cord and reductions in virtually all non invasive biomarkers measuring metabolism inflammation and fibrosis through 16 weeks and the overall population.
And even greater effects were noted in subjects.
Type two diabetes.
Also a meaningful proportion of subjects achieved thresholds of activity in markers that have been shown to correlate with histological outcomes.
Since we target all three biology's in this disease and various underline pathways simultaneously.
We believe there is a potential for even more profound benefits beyond 16 weeks.
Additionally, 11, 25 was well tolerated and no changes were seen in weight or limits. This is of particular importance given the profiles of other mechanisms in the Nash space and the fact that the typical Nash patients.
He is already on five to seven medications.
The potential to treat patients without additional interventions and complications is an important consideration for first line therapy.
We are gratified that these data were selected as an easel late breaker and we're looking forward to our two poster presentations.
And today, so Lee, which kicks off tomorrow.
One of these presentations will focus on the greater magnitude of effect that we're seeing among subjects with type two diabetes inner 003 study.
This is a potentially differentiating feature of 11 25 in a large sub population that.
We'll investigate further in our phase two b.
We are now in the process of preparing and I and the submission and we will provide the full trial details once it's accepted.
However, we are happy to share with you our thinking at this stage in terms of the phase Twob trial design.
His expect.
Acted to include a 48 week dosing period.
Two active arms versus placebo.
Standard histological in noninvasive endpoints, and we will again be stratifying by patients with and without type two diabetes to further inform our development plans.
The trial is expected.
It to include an interim analysis, and we look forward to giving that underway in the first half of 2021.
We believe in the acceptance and the trial initiation will demonstrate a few key advantages of excel as differentiated approach.
Firstly unlike.
Most phase one eye on the opening trials, we are proceeding directly into phase two b.
Secondly, we will be getting into this phase just four years after designing X 11 25 setting.
Setting the standard drug development timeline nearly in half.
And finally, and most importantly, we will be entering this next stage with far more human data that would normally be expected, helping to de risk our phase Twob trial.
So to summarize around 11 25, we believe this candidate is positioned strongly in the Nash space as a potential.
First line treatment based on the following.
The effects, we have seen and just 16 weeks in a meaningful percentage of subjects.
Its favorable safety and Tolerability to date.
The benign lipid profile and lack of effect on weight.
It's oral route of administration and.
So its modality that works with the body systems.
These same attributes also make 11 25, an appealing candidate to consider utilizing in combination with other agents when needed and.
And we believe it is also very well suited for early investigation in the burgeoning pediatric Nash population.
Now, let's move on to another important liver disease and access 16 65 access.
Axcelis product candidate for the prevention of recurrent Oh HKG.
He is a manifestation of cirrhosis in which patients are severely cognitively impaired the.
To the point, where they are unable to care for themselves and.
May ultimately become comatose.
It's estimated about a third of cirrhotic patients experienced at least one Oh 80 event during the course of their disease.
In many of these patients experienced repeated events, even while on todays approved medicines, namely latch lows and Rifaximin.
We believe that this is because these agents focus on only one of the disease drivers, namely elevated ammonia and.
And also because tolerability as a challenge and Thats compliance is limited.
The reality is that Oh, HCCI involves a vicious cycle in which amino acids become imbalance.
Once.
Ammonia levels increase and muscle tries to process the ammonia, but it does it poorly.
This then exacerbates muscle wasting and ammonia elevations.
The cycle ultimately leads to neuro cognitive impairment and oishi events.
16 65 holes.
The potential to improve the standard of care by addressing this disease more comprehensively.
In August results from our initial clinical investigation of 16 65 were published in clinical and translational gastroenterology.
And that same month, we were excited to share the topline data from our.
Our latest clinical study Axis 16, 60 500 to this.
This placebo controlled study enrolled 60 subjects in baseline characteristics were consistent with the population with mild to Pedic insufficiency and subjects were mostly non sarcopenia.
16 65.
I was again safe and very well tolerated in.
Encouragingly, we also saw a dose dependent activity across all measures of amino acid balance and narrow cognition in.
In fact for the high dose versus placebo.
We saw sustained and statistically significant improvement in the Fisher race.
Which is a measure of grants chain amino acids over aromatic amino acids as has been shown to correlate with outcomes.
And we saw statistically significant improvement in the P H EPS, which.
Which is considered the gold standard for diagnosing minimal hepatic encephalopathy.
In fact, even in this population with mostly mild hepatic insufficiency, a majority of subjects receiving the high dose of 16 65 achieved a placebo adjusted two point improvement in the Phds score this.
This is a clinically relevant change that is in the range of other approved.
Proof therapies in the field.
Plasma ammonia also tended to decline in subjects with minimal hepatic encephalopathy, and finally, a greater proportion of subjects in the active arms versus placebo tended to show an improvement in muscle function as measured by the liver Frailty index.
These results in our past interactions with the FDA regarding 16, 65 provide us with confidence and excitement as we prepare I'd submission and design our planned phase two clinical trial.
We are now able to share some initial details of the trial.
Our phase two is expected to be a placebo controlled six month trial that enroll cirrhotic patients who have experienced at least one prior oishi event.
Since we already have investigated four doses of 16 65 in prior clinical studies, we believe it may be more streamlined.
In terms of the number of arms then.
Similar to 11 25, we plan to share further details once our R&D is accepted.
And then get the phase two underway in the first half of 2021.
So now that we've covered our liver programs, let's shift to another clinical stage product can.
Candidate 40 10.
In the hematology space.
40, 10 is currently being investigated in an initial non I in the clinical study enrolling subjects with sickle cell disease. This.
This candidate was designed to target multiple pathways involved in red blood cell metabolism.
Vascular function and inflammation.
The basic design of our 001 study enables us to efficiently investigate a first cohort of subjects to determine if 40 10 is safe and well tolerated and if it appears to be influencing the targeted biology's.
We complete.
Did enrollment of this first cohort a few months ago and will receive data on these subjects in December.
If we see results consistent with impact on Biology's and appropriate safety. We will proceed with the enrollment of two additional cohorts one in adults and the other in adolescence with sickle cell disease.
We expect to report back to you on our decision to enroll additional subjects by early 2021.
So we certainly have a great deal of work in front of us and our excitement continues to build as we approach important milestones for accella and for its shareholders.
Now, let me turn the call over to our CFO.
But the rot chardan.
To review our financials for the third quarter Rob.
Thank you Bill and good morning, everyone. As Bill mentioned this that two months were very productive with multiple data readouts and DMD is a submission that we can proceed into phase two clinical trials underlying.
This morning, we settle overview by discussing our cash position.
We ended the third quarter with $170 million in cash and marketable securities as compared to $92 million at the end of 2019.
The increase is primarily the result of net proceeds from a follow on stock offering that was completed.
That's funny enough thoughtful management of expenses.
Our cash balance as of September Thirtyth was sufficient to meet our operating needs well into 2022.
We plan to provide more expensive cash when get gain on putting the completion of a trial designs NEXMET densifying the known between 21.
Now turning to our research and roaming expenses.
We just did you have announcement of our portfolio. We continue to invest actively now drug development program.
Our research and development expenses were seven half million and $26.4 million for the three and nine months ended September Thirtyth 2020.
This is Dan.
From 12.2 and $29.1 million for the same period of 2019.
The decrease primarily due to the completion of our 11 25 zero that three clinical study.
And the wind down of costs for 660 502 clinical study.
We are expecting that R&D cost.
Well, if we begin to increase again in the coming quarters as we prepare to go into later stage clinical trials.
Expenses were $4.2 million and $12.9 million for the three and nine months ended September Thirtyth 2020. This.
This is roughly flat with a 4.8 million.
$13 million for the same period of 2019.
We expect expenses to remain and change in the near term.
Excellent net loss for the third quarter of 2012 was 12.4 million or 34 cents per share and our net loss for the nine months ended September Thirtyth was 41 point premium.
Margin or dollar 39 per share.
Included in this net losses were 1.4 and $4.9 million, respectively in noncash expense related to stock based compensation.
So with 170 million cash in hand, we are very well positioned to continue to advance our pipeline.
With.
That operator will please open the line for questions.
Thank you we will now begin the question and answer session.
You asked a question you May press Star then one on your Touchtone phone. If you are using a speakerphone. Please pick up your handset before pressing the keys.
To withdraw your question please.
Just press Star then too.
At this time, we will pause momentarily to assemble our roster.
And the first question will be from Yasmeen Rahimi with Piper Sandler. Please go ahead.
The team congrats.
Yeah.
Continued progress you're making.
The number of questions one related to 11 25, and 16 65, So maybe lets get started on 11 25. So the first question for you is directed on.
Can you give us a little bit color on what you're gonna be powering in terms of the histological endpoint you see.
Benefits, both the Nash resolution and potentially Piper said, if you could shed light on the histological endpoint.
Would be important secondly, you pointed out that there will be an interim analysis that will be conducted can you tell us if the interim analysis would be the typical MRI pdfs or other non.
On an invasive biomarkers and what the size of the interim analysis will include and then in regards to 16 65, we would be very much interested and understanding what the primary endpoint of that study would be under.
And thank you again for taking our questions.
Great. Thanks, guys great.
I want to speak with you. This is bill and yeah. We're very excited about the progress. We've made here in terms of your specific questions. What I'll share with you is this is we plan to communicate specifics and I'll say detailed specifics on both of the protocols and trials post AI and the acceptance, which we expect in the first half of.
Great to anyone and then carrying forward into the study what I can tell you on the two trials are some pretty detailed information. So let me start with 11 25. The type of patients will be biopsy confirmed Nash and were very excited that the agency with the data that we generated supported going into a 48 week dosing.
I've treated in that paired biopsies study the endpoints there are going to be standard Nash histological end points and noninvasive markers that you're used to seeing in a phase two study.
We're going to have the two active arms and placebo.
We are going to be looking likely in the low hundreds of patients in the trial that.
It will be finalized in the near term and we expect to run the trial globally.
And we'll share again additional details about that following I and the acceptance which is similar on the interim analysis. I know you guys would want all the details right now we'll share that once the idea is accepted we plan to look at interim analysis to help provide.
Good information for ourselves as well as a public update and then in terms of 16 65, a were in a position there where again, we'll share the details beyond this at the at the acceptance of AI and the types of patients there are going to be at least one prior away. She event. So these are going to.
B patients, who have more advanced liver disease there'll be coming in on co medications have latched flows or less plus rifaximin. We're looking at a six month dosing dosing period. There in terms of your question on endpoints. We expect those to include elements around Phds score oishi events and other outcomes, while we'll finalize.
Communicate those post I, India acceptance.
Here, we are excited to have to submit and then follow up because on the number of arms as you're familiar we've already dosed four different dose regimens here and we expect this to be a little more streamlined than typical in a phase two trial and then the number of patients similar.
Lastly, we plan to be in the low hundreds to be finalized similar approach on site selection and number of sites globally and then additionally on the interim we're examining an interim and or futility approach thats optimal for this patient population and we will communicate again all the details upcoming.
In the first half when we both have the acceptance, which we're very excited about and confident and then move forward with the trials.
Thank you Bob Thanks for the color.
Yes.
Q.
And the next question will come from Michael We're a veto with Shire Dan.
In capital markets. Please go ahead.
Hi, Jane Thanks for taking the questions.
Can you please give us a little bit more color on what you plan to announce for each trial in the first of next year between when you finish the file the R&D versus when you subscribe to the versus when you begin.
Initiating enrollments of those trials.
But you know plant amounts for us.
And secondly.
On.
The both trials, how many clinical sites do you anticipate enrolling in each trial.
Of those how many do you expect had been previously used for your clinical.
Ladies.
Yes.
Thanks, Michael for your interest in your questions here in terms of the approach on the announcement, we will certainly announced the acceptance of the India, which is a fairly standard practice in our cases, you're familiar our R&D opening is not typical.
We're not going into an initial first in human study, we're going into a phase two and phase two b study. So we I outlined that because we will definitely communicate the acceptance and then we will have the initiation of the trial when patients are enrolled will be will take longer than a quote typical I Andy.
Spinning setting because we have all of the normal screening process et cetera, and we will be communicating that appropriately with you all in terms of how many sites are again, we'll finalize that and communicate with that post the India acceptance. We are planning on working with a number of the sites that we have collaborated with.
Before and we're very confident on our ability to continue a strong execution on that piece and one of them of course that you're familiar with his doctor Harrison and the summit network in 11, 25, who we continue to collaborate with in this setting. So we're very excited as are the opinion leaders both with Nat.
Okay, because they see the profile of this agent as a potential differentiated program in terms of the patient population as well as the profile profile itself with its unique multi targeted mechanisms working with the body systems with the safety and Tolerability, we've demonstrated to date with.
Nash the lack of impact on lepage and on weight and the oral convenient dosing profile and then the opportunity population wise not only to be a first line agent, but potentially be differentiated in type two diabetics as well as pediatrics and then of course, where there is a need in this very large market place.
With a generic place for combinations, we believe are profiles well suited there.
Thanks for your questions.
[laughter].
And the next question is from Julien Harrison with BTI Ji. Please go ahead.
Hi, good morning, Thank you for taking.
And your questions and your discussions on the path forward for 11 25, I'm curious if for Cirrhotics have come up at all is this a subset that might make sense in the future to explore as a cohort or is it safe to say you are focused on earlier stages of Nash for now.
Yes.
Hi, Julien this is Atlanta, and Chicago Becky Thanks for the question.
So our first phase.
I used to be is of course going to be focused on further guidance in non cirrhotic Nash using the guidance that that has on this one still has to be delivered alluded to earlier, our standard histologic criteria. After three NASCAR Haven for.
Question about potentially considering other things.
Of course, that's always on our minds.
We believe our platform is applicable widely across the disease spectrum.
And as you know we already have a program in 16 65 at the more advanced liver disease patients.
Okay. Great. Thanks, that's helpful and then on your presentations at ESMO, the sorry, if I missed it but should we be expecting any incremental.
Data or new us new analysis of prior data is that something you could possibly comment on now.
So as you know we have to do posted a presentation.
Focusing on the overall population from the dealers are three and as well as I'm very excited to talk about the the subgroup of type two diabetic I would've had a different.
Frank will impact and consistent impact on all of our key markers. So those are the two key once that out we'll be presenting there.
And so the diabetic population gives you a little bit of additional color and up.
Versus what you've seen previously doing.
Specific.
Great. Thank you.
And the next question is from Jessica Fung with JP Morgan. Please go ahead.
Hey, there good morning. Thanks for taking my question I was wondering if you could share a little bit more about the pre R&D meeting for 11, 25, and well what were some of the kinda suggestions that yet.
And.
You're able to incorporate into your spending plans.
So we had just as always we spoke by phone as well as any written correspondents. Obviously, we cannot share with you all of the fine details on this but.
Well I think what we can share is the fact that.
The path that bill outlined before.
For which is that we can go into a street biopsy study. So serial biopsy study that is focused on histological endpoint 48 week duration in the standard population again, if two of three typically with a natural even for a standard criteria.
So thats streamlining was really helpful.
Hi, there, except insofar a proposal suggests to us that the the package that we have so far generated from zero zero to end user three studies, which were all.
Characterizing noninvasive markers, certainly seems to be to patient to get us to this very streamlined path.
And just this is bill good morning. Thanks for the question I would just pull it back up even from 11 to 25 for a minute and say between 11 25, and 16 65, we've now had a series of interactions with both the FDA and other regulatory agencies and I just want to rest on the fact that.
There.
I've been questions about how can we proceed what's the best path and what can we do and what I can tell you is consistently we have been able to move inside of design to phase two and phase to be inside of four years, which is quite remarkable when you step back and think about it. Additionally, we are very clear that we don't have to do getting toxicology.
Allergy work, we don't have to worry about a number of aspects related to how we formulate how weve placebo, how we execute our programs whether in the non I in the Oregon now going into the eye Andy setting.
That the safety is well understood and characterized and that the FDA is supporting us moving forward.
Into a biopsy confirmed trial in this case a phase to be level. So we're extremely excited about this in terms of what it validates for our platform and our approach and the fact that it puts us in a position to be well informed in a highly efficient way and this also bodes well for our future.
Your programs.
Okay great.
And then just.
60 65.
Hey, I know, you're inventing indices to analogy, but what's what's your latest thinking on that cirrhotic sarcopenia opportunity with that asset.
Yes, so we will continue.
Can you believe that both hepatic and muscular metabolism are important aspects related to this program and our opportunity to differentiate we will be continuing to measure and the more advanced patient population muscle function and and structural measures as well.
Our core focus of course is on the existing regulatory endpoint prevention of recurrent oahe, we will be measuring these and see whether there are in addition to the differentiated mechanism that allows us to support additional claims and then potentially in the future additional populations our core focus right now is.
Getting the regulatory approval in the in the core platform the new as anything you'd like to there knocking the cover they really love building.
Great. Thank you.
Thank you.
The next question is from Thomas Smith with.
The Leerink. Please go ahead.
Hey, guys. Thanks for taking the questions first just on the planned phase Twob trial for 11 20 private Nash can you just clarify the patient population you are targeting here like are you looking exclusively at the F. two or three population or is there potential that you could enroll some F. One patients with co morbidities as well and then.
He also mentioned taking two doses of 11 25 into this seems to be how are you thinking about which doses that take forward here relative to this years here three study.
[noise] get tied down.
This is Mike so so again to reiterate though that population that you're going to focus on for the phase two b is the standard <unk>.
Yes, the guidance from the FDA. So we just typically.
After three patients, which signifies more advanced disease.
Natalie.
Activity score or Nasacort, thats, typically greater than or equal to four. So these are pretty standard guidance is at this point. So this is certainly a core population that we will be testing into phase two b trial.
While the broader question of course as I think was asked earlier can you go earlier can go later. So these are all possibilities that we will evaluate and certainly our modality allows us to interrogate those earlier population as well as the more advanced population. So those are all considerations for us operating the interface do at this point.
And we are planning to do the standard guidance, but again once we finalize the protocol and these except we can share with you more precise details of the breakdown.
Now your second question about the.
The two doses.
So again these are also being discussed and we and we do need to wait for the final finding acceptance to share.
The final details with you, but I think it's suffice to say based on ideas. There are three and does your two trials.
Where we tested if you recall in zero to 72 grams per day and then the second one was 48 grams per day, we believe that we have.
Enough information from a dosing perspective that we that we do think that up to two to three doses.
This will be the doses that we were taking the place to be.
And a final is of course decision on what the doses are well, we'll have to wait until we actually finalize the protocol and get behind excepted.
Okay got it and then just a quick follow up on 40 tenants sickle cell you're going.
To get the initial results here from the the first cohort in December and then sounds like you're going to decide whether or not to open up the subsequent cohorts kind of a go no go decision on the program can you just.
Talk a little bit or maybe give a little more color around what you need to see from this first dataset to guide that decision on whether or not to move forward.
Sure.
We're excited for this readout coming up in beyond our core liver programs and lean programs. There because as you are familiar with we are looking at three major biology is their red blood cell metabolism vascular function in inflammation and were looking of course at safety and Tolerability that's to answer your question.
And we're what we're looking for is the right directional impact on the Biology's as well as the appropriate safety and Tolerability in which has a population that has a number of co morbidities.
This was a basie in design, which means you have a relatively small number of subjects. It allows you to make a binary decision and then move forward.
Into additional cohorts, we're optimistic we'll wait eagerly to see the data and then we'll communicate our decision and then we will be expanding into additional cohorts next year, assuming that thats positive.
Got it got it okay. Thanks for the color and thanks for taking the question.
Of course thanks.
Thank you.
Again, if you have a question. Please press Star then one.
The next question is from Mayank.
Tony with B. Riley Securities. Please go ahead.
Hi, good morning team, thanks for taking our questions and again, congrats and unproductive here so far so needy.
It's like in Big on you know this is Ellie update next week and really in the context of your choice of patients boy face to be good could you maybe touch on the type two diabetes cohort.
What proportion of that you know you are.
Thinking about in place to be and if if at all your line for.
Some background therapies like GLP ones being greater than that in that study and then I have a follow up.
Sure Mike Hi.
This is my name again, so very excited about the diabetes subgroup or.
As you can tell you know very partly because of an endocrinologist and I'd like to have somebody some therapies here to help.
These patients who really don't have many options right now so.
In terms of the diabetes subgroup and what we can share with you is the fact that the based on the epidemiology.
40% to 60% of the Nash cohort typically ends up being diabetic and people with diabetes certainly have more advanced liver disease. So this is.
Well no.
Owned by directional pathway.
That has been studied and understood for many years.
So what.
Proportionately obviously cannot.
Say, what it is but I think it's suffice to say, 40% to 60% basically epidemiologists and as I think bill already outlined the trial design. We are stratifying people on diabetes. So this is the same thing that we did.
In the 003 study, we expect to do the same.
In terms of the question around.
The background Meds again. These are fine details that we'll have to wait until we finalize a protocol but.
But certainly standard.
Standard of care therapies are something that we're very familiar with and again you will recall from zero to two or three we had a very.
Did similar patient population similar management, and we anticipate the same or as well.
And Mike as Bill I would just add that this next phase to be as an opportunity to follow up or two studies that included type two diabetics, both 002, and 003, where we replicate.
Located the findings and really determine at a greater degree the potential differentiated benefit for this important population and we will also have the data on the broad population without type two diabetes. So this sets us up very well to understand and then guide our next steps in development post though.
That's very helpful color Zillow Kuala gunboats also.
The next question.
Good thing about the blood from broadly what color you know I'm, just curious that drug drug interaction.
Earlier stage clinical work you have to do I'm also thinking about.
What do you study. The you know there are bad going therapy. So they can you can you just walk us through some learnings you might have had in the type B meeting and maybe you have another type b meeting for LTE.
What are those considerations on the dark side or on the pretty quick on the earlier stage phase one that do you.
Oh, effectively moving parts very quickly to get to a phase three study.
Across different indications.
Yes, So I'll start my bank and then ended some of the new for the second part of the.
The answer here, so I'll reinforce something that you brought up here that I'm very excited about witches.
We now have two consecutive program interactions with the agency, where there are no gating toxicology studies or work that's required and that's because not just of the modality of our studies, but the amount of data and information we are able to provide and our submissions and dossiers. So that is something we feel very confident about on a go.
Forward basis for our platform. Additionally, we have other steps whether its DMP K related whether it's related to our compositions et cetera that we again can move faster and more efficiently than traditional models in terms of drug drug interactions there are some aspects.
I'm sorry, we got a call there there are some aspects in any case that the agency requires you to do the question is is it you know in what context and so we feel very good about our potential to not have significant drug drug interactions based on our overall mechanism and I'll have.
A new quickly expand on that and then what you should know is there are no gating aspects related to Didi eyes in work that's necessary prior to starting the studies. So yes, so just to build on that line.
So yes, the modalities in diagnosis metabolic modulators rate so.
Latin biology in general do not share the same clearance pathways enzymes transporter mechanisms as xena Biotics. So this is a unique distinguishing feature of our platform.
Weve, obviously showcase that and this is the reflection of what we got from the agency feedback while many of the usual things that are guilty.
Like talk CMT DMP K related things are not factors here. So I think that should be a testament to.
The the intrinsic.
If you have to have the modality. The other is you know weve since the very beginning from the dealers or to try to study that here's your three studies we've allowed the con.
It depends on which are typical of the comorbidities. These patients have.
People typically typically have hypertension hyperlipidemia diabetes. These are all polypharmacy diseases that have many concomitant meds and so we have clinical experience.
Already under our belt on these on these meds so going into.
The 101 study, we do feel quite confident that again, because we've already done. These studies to some extent where essentially following the same principles. The same management guidelines and still feel confident that these are not going to be issues, but again I would emphasize that we would have to wait until we've formalized Oliver protocols.
On Maui and have the R&D acceptance in order to share with you to find details.
I think your second question was how potential interactions with the agency on 16 65, if I recall correctly.
So I would just remind everybody that what 16 65.
Actually had several agency interactions including.
Both us and ex us.
We had very productive meetings with them on.
Over the course of the last year.
As well as this year.
Along with Xcede with agencies, where we've been able to come to.
Fairly good understanding of what the protocol looks like so we're not anticipating any further interactions.
I think we are going to submit the Indy and anticipated approval in the first half of 21.
Machine to face do also in the first half of 21.
Okay.
Yes, yes appreciate the comprehensive Galore My final one is just.
Quickly minded on where you are with the pediatric indication.
Yes. So again this is one of our exciting opportunities just like the diabetes subgroup is.
Unfortunately, the pediatric Nash is a significant.
Health burden medical burden that is unmet because of the epidemic of obesity and diabetes has also happening to our kids.
We did raise this topic with the FDA.
However, the agency primarily focused.
Their interactions with us on the adult developing program and understandably. So since we had a lot to get through we of course plan to re engage them with our pediatric development program. Once we have the face to be in adults underway.
Thank you for taking my question.
Thank you.
Once again, if you have a question. Please press Star then one.
The next question is from Andreas our garage with.
Bush Securities. Please go ahead.
Good morning, Tim. Thank you for taking our questions I am also liana.
Most.
My questions have actually been answered so I'll just start to brief ones right now.
With regard to the Phds score.
I know, it's the gold standard for minimal hepatic encephalopathy.
So how do you plan to use it.
Albert population.
Hi, Thank you for your question.
So the Pts is indeed, a battery of five different tests are pretty rigorous to have a pretty comprehensive psychometric evaluation assessing various cognitive domains from executive function to memory to coordination visual spatial.
Aspects.
It has been used boats.
And from an M&A standpoint, but also to actually prognosticate only cheap.
So it.
It is in fact used in that setting us up 80, and we believe that given our results from the dealers are too we are able to not only look at of course, the amici subgroup population, but also how does.
Both the impact of future achievements.
And then maybe speak about the.
Population that MHG predisposes for Ritchie Scottie, yes, that's a great point.
So the risk of a future OTI event.
It's really predicated upon two main factors right one is of course.
Zero each event, which is why we our population is going to have that and the other equally important is a prior MACI.
If that studies so far have shown that if you have it.
Hey, Amici at baseline or prior Amaechi episode, which again is best diagnosed with the mph. He has those people are going to have.
Five to six for higher risk of a future overachievement, so very very pertinent for us.
And hence one of the key assessments in our study.
Okay, great. Thank you for the color on that matured afforded sand and then you provide too much color on the previous question, but maybe.
Okay.
Briefly discuss.
The proposed mechanism based on the composition. So some of the key things to look out.
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Uh huh.
Yes, I think the question. Please yes. So what do you asked was basically the proposed mechanism.
For 40 10 in terms of just a little bit more depth offshore the red blood cell Mattel yeah patient.
And kind of some measures that we look at that are important yeah, great. Yeah. So in terms of the mechanism is very similar to the way that weve approached our aspects in the liver space. So its a multi factorial given that SCD is.
Indeed, a very complex disease.
And one of the key aspects there is for us to look at their disease from a more comprehensive standpoint to address its equally so specifically focusing on Threed biology is one is red blood cell physiology. The other is vascular biology or vascular function and then the third of course is inflammation.
Each one of those things contribute ultimately to basal occlusive crisis, which are ultimately.
Currently the current thinking on how the drugs are getting approved for LCD, but certainly from a clinical standpoint, an outcome standpoint visa because the prices are indeed, a big burden for patients. So we believe our comprehensive.
His approach of really tackling this in a multi factorial way similar to all of our other acts of products here vacant.
Very consistent with that so the measures of course are also multi factorial into address each of those by allergies. So we have specific markers for each of those four vascular function RBC physiology.
Of those information.
And Andreas we see a couple of important biology read throughs here of course, you're also familiar with JBT is approval on or Hematological endpoint in sickle cell disease, but there are also important other.
Health and disease areas, where these biology is.
Play an important role so we're excited to see this read through and the continued opportunities that we see for our design platform that's very efficient.
Yes, great looking forward to the update as well.
For me, Thank you guys and congrats on the progress.
Thank you.
Okay.
Ladies and gentlemen, this concludes our question and answer session.
Like to turn the conference back over to CEO Bill Hinshaw for any closing remarks.
So thank you all for tuning in with US today, everyone. We're very pleased and proud of the progress that the company has made in 2020 and we're excited about what lies ahead.
Good for Accella, and we look forward to seeing many of you on the virtual circuit in the weeks ahead. So this concludes our call operator, thanks, everyone be well and be safe.
Yes. Thank you Sir the conference has now concluded. Thank you for attending today's presentation you may now disconnect.
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