Q4 2020 Selecta Biosciences Inc Earnings Call
Good morning, and welcome to the Selecta Biosciences fourth quarter and full year 2020 financial results and corporate update conference call. Currently all participants are in a listen only mode should you need assistance. Please signal a conference specialist by pressing Star then zero after today's presentation.
Patient there'll be an opportunity to ask questions to ask a question you May Press Star then one on a touchtone phone to withdraw your question. Please press Star then two this call is being webcast live on the investors and media section of select does website at www Dot Selecta bio dot com.
And it is being recorded.
For opening remarks, I would like to introduce Brad Dahms, Chief Financial Officer of Selecta. Please go ahead.
Thank you and good morning, welcome to our fourth quarter and full year 2020 financial results and corporate update conference call.
The press release reporting our financial results is available in the investors and media section of our website Www Dot Selecta bio dot com and our annual report on form 10-K for the year ended December 31, 2020 will be filed with the SEC. Joining me today are Carsten Brunn, our president and Chief Executive Officer, Dr. Peter <unk>.
Traber, our chief Medical Officer, and K Keisha motto, our Chief Scientific Officer.
During today's call, we will be making certain forward looking statements, including without limitation statements about the potential safety efficacy and regulatory and clinical progress of our product candidates financial projections and future expectations plans partnerships and prospects.
These statements are subject to various risks, including those related to the COVID-19 outbreak that are described in our filings made with the Securities and Exchange Commission, including our most recent annual report on form 10-K, which will be filed with the SEC.
You are cautioned not to place undue reliance on these forward looking statements, which speak only as of today March 11, 2021, and selecta disclaims any obligation to update such statements, even if management's views change.
I would now like to turn the call over to Carsten Brunn, our president and CEO Carsten.
Thank you Brad.
I appreciate you joining us today.
Last year, we've made several advancements for our income platform to develop heterogenic therapies designed to selectively mitigate unwanted immune responses and have achieved several key clinical strategic and financial milestones and advance our pipeline and set the table for an exciting year ahead.
We believe our clinical and preclinical candidates have the potential to amplify the efficacy of biologic therapies, including re dosing of lifesaving gene therapies as well as restore the body's natural sales tolerance in autoimmune diseases, we will continue to advance our pipeline and build momentum in 2021.
I'll start with our enzymes therapies programs in 2020, we significantly de risked the company through strategic partnership with Shelby for Cielo to 12, and we've continued to make progress in getting our sales for 12 approved to treat patients with chronic refractory gout.
<unk> is comprised of <unk> co administered with our proprietary Uricase pediatric cases.
Remains a significant unmet medical needs in chronic refractory gout with only a fraction of the estimated 160000 patients in the U S receiving treatment with the currently approved Uricase.
It is often a good program kicked off in the fourth quarter of 2020 and consist of two double blinded placebo controlled trials of <unk> 12.
In September the first patient in these off one was dosed.
<unk> <unk> was initiated in December 2020.
In both trials.
12 will be evaluated at two doses of <unk> <unk>.
One milligrams per kilogram and 0.15 milligrams per kilogram and one dose of the GAAP. The case <unk> two milligrams per kilogram.
Each trial aims to enroll 105 patients with 35 at each dose and 35 on placebo.
Both trials have a six month primary endpoint of serum uric acid levels below six milligrams per deciliter at six months time points and only resolved one will have a six months extension for safety.
Secondary endpoints include Caldolor incidents tender and swollen joint counts Tophus burden patient reported outcomes of activity limitation and quality of life.
Top line data from the resolve program are expected in the second half of 2022.
Based on learnings from the phase II compare study, we intend to enroll a higher proportion of patients with visible tool fine.
As you will recall the Delta of 19 percentage points was observed on LCL to 12 versus pegloticase for patients with visible <unk> baseline from the primary endpoint and only 41% of patients and compare had miserable torrefy at baseline we believe the proportion of patients with.
Chronic refractory gout with visible profile is closer to 60% to 70% of the patient population in specialty care in the U S.
Our second indication in our enzymes program. This iga nephropathy, a kidney disease that occurs when immune complexes of an antibody called immuno globally, a one accumulates in the kidneys.
<unk> or environmental factors that caused this abnormal iga one and its accumulation in the kidney can result in the development of Iga nephropathy, one of the most common causes of kidney disease <unk>.
Pretension Proteinuria and decrease estimated GFR at the time, Inc. 's diagnosis are associated with poor prognosis.
Can result in incremental loss of renal function and results in end stage renal disease in approximately 30% to 40% of patients.
We will be researching a novel combination therapy by combining in tour with an enzyme Iga 40 days.
Encouraged by published animal studies, and which has been shown to the bulk of the Iga one immune complexes in the kidney the root cause of Iga nephropathy.
Critical barrier to Iga Proteus development, you see immunogenic bacterial origin off the protease.
As demonstrated with <unk> 12 in tour has the ability to mitigate the formation of anti drug antibodies to immunogenic enzymes, we're moving forward.
Enabling work and we expect to have an IND filed by the end of 2021. So we can commence our first clinical study in 2022 within.
Within tour, we intend to develop a combination product candidate to treat the root cause of this disease in which there are currently no approved therapies.
A key objective of 2021 will be to generate our first human data for our gene therapy programs preclinical data of <unk> in gene therapy have demonstrated the potential to enable repeat dosing by preventing the formation of neutralizing antibodies. In addition to more durable and robust express.
<unk> off the Trans gene after the first dose.
We recently commenced the phase one first in human dose escalation trial of <unk> 399, which is the combination of an AAV eight caps at containing no trends seen with infor to further evaluate the ability of <unk> to mitigate the formation of antibodies to AAV eight caps it in used.
Gene therapies.
Trial plans to enroll 45 healthy volunteers randomized in a three to one ratio of <unk>, plus MTA AAV capsid to empty capsid alone.
Preliminary efficacy will get measured by assessing levels of specific neutralizing antibodies and topline data are anticipated in the fourth quarter of 2021.
The three.
399 study builds on extensive preclinical data that have demonstrated the potential benefits of the <unk> platform in AAV gene therapy in.
In the recent preclinical study in non human primates Selecta observed at co administration of AAV vector and interwar enabled higher and more durable transgene expression as well as robust inhibition of anti AAV eight ITG neutralizing antibodies.
The next day intends to percentage its findings at the annual meeting of the American Society of gene and cell therapy as GCT in May.
The observation that co administration of AAV vector and aimed tour leads to higher transient expression demonstrates the potential for dosing and lower levels of AAV gene therapies, when combined with <unk>, improving patient safety and lowering costs.
For the long term gene therapy data demonstrate that expression of systemic AAV gene therapies may vein over time limitation that <unk> has the potential to address.
Finally, AAV gene therapies cannot currently be re dose due to the formation from Jason.
And the bodies to the AAV vector.
In this study <unk> mitigated the formation of these neutralizing antibodies in non human primates, thereby potentially allowing for re dosing another key unmet need in the gene therapy field, our results along with previous studies supporting the in force and patent protected properties and liver injury.
Will move us one step closer to transforming the lives of patients and realizing the full potential of gene therapy.
In collaboration with <unk>, we plan to initiate our clinical trial in patients for the treatment of method malonic academia or MMA in the second quarter of 2021.
And then there is a rare monogenic disorder in which the body cannot breakdown certain proteins and fats.
This metabolic disease may lead to metabolic crisis, and its associated with long term complications, including feeding problems developmental delays intellectual impairment chronic kidney disease optic nerve atrophy.
The opinion and pancreatitis typically well managed patients have periods of relative health. The litany Pollack decompensation events that May result in multi organ failure triggered by into current infections or stressed episodes.
Symptoms of MMA, usually appear in early infancy and vary from mild to life threatening.
Treatment this disorder can lead to coma and in some cases per.
We expect to report data from the first cohort of patients by the end of 2021.
In November 2020, we announced that the FDA granted orphan designation to MMA Wonder woman, which previously received rare pediatric disease designation from the FDA in October 2020. This further underscores the significant unmet medical need it's Alexa and S value are seeking to address.
With M&A 101, and we look forward to advancing this program in the hopes of helping patients affected by this rare metabolic disorder.
Looking ahead, our proprietary gene therapy product candidate <unk> hundred 13 is being developed to treat ornithine <unk> or OTC deficiency and is expected to enter the clinic in 2022.
OTC deficiency is an excellent genetic disorder caused by genetic mutations in the OTC gene, which is critical for proper function of the urea cycle.
Individuals with OTC deficiency experienced accumulation of excessive levels of ammonia from the blood.
Your symptoms include inability to control body temperature and breathing rate seizures coma developmental delays and intellectual disability.
Most approved therapies are focused on reducing the amount of ammonia in the blood and are not curative.
Currently the only curative approach is the liver transplantation at an early stage H, which can be associated with severe side effects and complications of lifelong immune suppression.
Continue to work on the A&D, enabling activities and we'll share additional updates on this program later this year, including updates on our recently submitted pediatric investigation plan to the European Medicines Agency.
Overall into holds significant promise and has the potential to be revolutionary put a gene therapy field.
We're encouraged by the promising preclinical data and look forward to advancing these programs.
Before we wrap up on gene therapy. So raptor continues to conduct preclinical work looking at the combination of <unk> and certain neuromuscular disorders, including Duchenne muscular dystrophy, and limb girdle muscular dystrophy <unk> eastern.
<unk> exercises its option to enter into any commercial license agreements, we will be eligible for significant economics, including additional upfront development regulatory and commercial milestone payments as well as tiered royalties on net product sales. This agreement would further validate the potential.
Of intuit's platform to solve a critical hurdle in the gene therapy landscape, enabling re dosing and getting more patients access to these powerful medicines.
Our autoimmune program is advancing through IND, enabling studies with an initial focus on primary had been there collyn jaggers PBC is a chronic progressive autoimmune liver disorder that leads to inflammation damage and scarring of the smile small biotechs it.
It is a well defined target antigen significantly unmet medical need and it's well suited to the application of our <unk> immune tolerance platform.
<unk> expects to file an IND in PBC in 2022, and we look forward to providing additional updates from this program later this year.
Now I'll turn the call over to Brad to run through our financial results for the fourth quarter and full year ended December 31, 2020 breath.
Thanks Carsten.
We had $140 1 million in cash cash equivalents and restricted cash as of December 31, 2020, which compares to $147 6 million as of September 32020.
We believe our current liquidity position will be sufficient to meet our operating requirements into the second quarter of 2023.
Revenue recognition for the fourth quarter and fiscal year, 2020 was $12 million and $16 6 million, respectively, which compares with $6 7 million and $6 7 million for the same periods in 2019.
The increase in revenue was primarily driven by the license agreement with <unk>, resulting from the shipment of clinical supply.
As well as the reimbursement of costs incurred from the phase III dissolved clinical program.
<unk> expenses for the fourth quarter and fiscal year, 2020 was $15 1 million and $54 5 million, respectively, which compares with $15 2 million and $42 $7 million, respectively from the same periods in 2019.
During the quarter ended December 31, 2020, there was a reduction in expenses for the sales to 12 clinical programs due to the timing of the initiation of the phase III resolve program compared to the phase two compare program and the prior period.
And was offset by increases in expenses incurred under the <unk> collaboration combined with internal research and development to support our clinical programs. The annual increase reflects the initiation of the phase III <unk> clinical program.
These costs are subject to the cost reimbursement arrangement under the license agreement with <unk>.
General and administrative expenses from the fourth quarter and fiscal year, 2020 were $4 8 million and $18 $9 million, respectively, which compares with $4 1 million and $16 4 million for the same periods in 2019.
Quarterly and annual increase in expense was the result of increased patent and professional fees and facility and office expenses offset by a decrease in travel expense.
For the fourth quarter and fiscal year 2020, Selecta reported a net loss of $15 4 million or <unk> 14 cents a share at $68 9 million or <unk> 68 cents, a share respectively compared to a net loss of $14 9 million or 28 cents a share at $55 4 million or $1 22 per share for the same periods in 2019.
Yeah.
We have a well defined work plan ahead of us with a clear priority of deploying our financial and operating resources to advance our product candidates in multiple indications.
I'll hand, the call back over to Carsten Carson.
Thank you Brent as mentioned earlier 2020 was a transformational year for Selecta and we're extremely excited about the continued growth of our company and confidence in our platform.
I'd like to conclude by reiterating our gratitude to the many people who have been supportive along the way, including our patients and their families. Our investigators and our great team at select him with that we're happy to take questions.
We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone.
If youre using a speakerphone please pick up your handset before pressing the keys.
At any time. Your question has been up just and you would like to withdraw. Your question. Please press Star then two at this time, we will pause momentarily to assemble our roster.
The first question comes from Kristen <unk> with Cantor Fitzgerald. Please go ahead.
Hi, good morning, everybody and thanks for taking my questions.
The first question is how might the initial trials you are conducting this year for gene therapy help you determine when might be the most appropriate time to potentially re dose is successful do you think this is going to be viewed as more of an indication by indication basis or more of a patient by patient basis, especially if patients are dosed that.
Different agents, considering the benefits we've seen across the field when treated earlier.
Thanks Christian.
Excellent question.
So I think what we're trying to address initially it's really.
Ability.
To re dose and that's defined as are we able to prevent the formation of neutralizing antibodies and obviously that varies very much by indication, but also patient to patient.
If you look at specifically.
I think indication we believe there's a significant need there.
Especially in liver based applications, we know that deliver growth gross up to 40 fold actually from birth to adulthood.
Obviously high likelihood that you have to re dose in other indications it might be a couple of years before re dosing and we always reference.
The <unk> data.
It is out there and what we saw after three to four years of decline of transgene expression.
So it really varies by it by indication age of the patients in individual patients.
Thank you and then in your recent science advances publication, you highlighted that even a two fold decrease in vector dose could have a meaningful impact both to safety and cost, but I wanted to ask how you and your partners are thinking about these potential advantages from a manufacturing standpoint.
Yes. So obviously, we're excited about our publication science advances and indeed, we believe if this translates into humans.
Be a.
Benefit on various fronts, a lower dose obviously.
Brings lower safety concerns, which I think is a key driver in gene therapy, but also a potential lower doses as well and gene gene therapy manufacturing is a bottleneck and a key cost driver and associated lower cost of goods will be quite meaningful, but obviously, we would have to see where the translate.
From the non human primates into humans, but we're definitely encouraged by the data we have seen in non human primates.
Obviously the.
The increase from <unk> expression is is very relevant.
Great. Thanks, and then a question for Brad could you remind us whether your cash guidance is that factoring in any potential milestone payments across your collaborations.
Yes. So it does not include any potential milestone payments, which would serve to extend our run it.
Six serviced on a run way non non dilutive basis.
Okay, great. Thanks, everyone.
The next question comes from Raju Prasad with William Blair. Please go ahead.
Thanks for taking the question and congrats on the progress on the pipeline.
Just wanted to see if you could provide a little more color on.
On the dosing regimen for <unk> gene therapy can you talk a little bit about the need to dose.
And tour at the first dose of AAV <unk> and <unk>.
There is some discussion.
A discussion.
Some of the papers on.
The potential to increase transduction on the initial dosage and then maybe.
Carson that you could also comment on.
<unk>.
The potential to dose re dose patients that have already received the gene therapy and any other clinical trial.
So down the line.
Thanks.
Yes, maybe I'll take the last question.
That's a quick one so if you have been previously.
Exposed to an AAV gene therapy, and you have not been dosed with <unk> or we don't address this patient population. So you have to give him score with the initial dose.
In terms of some color on the dosing.
You're right.
We saw a strong first dose benefit so in tour always has to be given with the first dose of AAV and we're obviously looking now.
With the empty capsid study to do a dose escalation to retesting. So no rush three doses in tour.
We're starting with one 5.3 and 0.5 to see what the appropriate dose is and obviously, we feel very confident.
With with these doses since we've had almost dose 300, almost 300 patients.
Within <unk> in our gout program. We've also seen in the non human Primate study.
Net.
Monthly three monthly doses are a value as well and obviously you would take all this into consideration.
For the the first human approach.
With MMA.
Great.
Just a quick follow up.
On the MMA program have you disclosed the tour dose that you'll be taking forward in the clinical trial.
Yeah, we haven't filed the IND. So we don't want to give guidance before the R&D.
<unk> has been accepted.
So we'll have to hold off from that but.
It's the.
The dose range. We've previously discussed nothing I can say as much.
Got it and it'll be the dose selection was independent is independent of the phase one study results I assume or will you be able to look at that yes, yes, yes, that's correct yes.
Yes, they are.
Not necessarily sequence. So we yes, we plan to run this in parallel so it's independent of that yeah. I mean, obviously, we have some guidance from long wavelength incorporate them, but right now they run in parallel basically our plan in parallel.
Great. Thanks for the question.
Thanks Raj.
The next question comes from John Newman with Canaccord. Please go ahead.
Hey, guys. Good morning, Thank you for taking my question.
I also had a question on the.
Excuse me the work that Youre doing.
In the MMA with Alan.
101.
I'm just curious.
What you would be looking to potentially present.
In terms of preliminary data would you focus on.
Hopefully the lack of formation of neutralizing antibodies to choose.
Sensitive, let's talk a little bit about.
I don't know if you could get an initial efficacy read that quickly, but just curious as to what types of things that you might be thinking about sort of preliminary data for that program.
Yeah. That's a good question John obviously, I mean, we're always trying to address the underlying disease with gene therapy. So we're looking at at least the initial biomarkers.
Off of the disease, such as <unk> and MAA levels.
But as a platform company of course, we are extremely interested in the neutralizing antibodies because we think that's an indicator.
For the ability to be able to re dose.
Okay.
And.
<unk>.
The <unk> one.
On one program.
Would you potentially look to explore.
Re dosing with this program initially or would that be something that perhaps you would look at in the subsequent trial.
Yeah. That's a good question as well, we get a lot as well I mean, I think we would initially look at.
The first day efficacy off after gene therapy, obviously, that's the key driver we're trying to treat those kits.
And then we would see if we're able to prevent the formation of antibodies as a good indication that we are able to re dose, but it wouldn't be necessarily a part.
Off the first approach off the trial.
Between.
When you have to re dose and it would be a fairly lengthy lengthy trial.
Okay.
I just had one additional question, which is a broader question on that is.
Just wondering if you could talk about the existing partnership with Espial and whether that.
Would preclude you.
From.
If you would if you choose to excuse me.
To enter into additional partnerships. Obviously, you have the partnership with <unk>, which is very interesting, but just curious if theres anything.
With the <unk> partnership that would perhaps maybe to a small extent limit other partnerships you can enter into.
Yes, that's a good question as well obviously as you know John we can very selective in our partnerships.
And we are we don't see any limitations.
Having additional partnerships just to kind of remind everyone. We have two partnerships with <unk> bio we have a true strategic a 50 50 collaboration where we plan to co development co commercialize gene therapies. The first indication is in.
And then we've also licensed in tour to ask volume per lead indication in Pompe disease.
And then we have a research partnership.
With <unk>, which is really focused on neuromuscular disorders. All the work we have done John.
Based diseases.
But yes, I mean, there I'm not sure there's like three 400 different.
Gene therapy monogenic diseases that can be addressed so there's plenty of room.
For both inbound and outbound partnerships as well.
Okay, great. Thank you very much.
Thank you John.
The next question comes from the Ipi Young with Mizuho Securities. Please go ahead.
Hi, good morning, and thanks for taking my question and congrats on all the progress on gene therapy side.
A couple quick ones.
For.
The pediatric and adolescent gene therapies.
Do you have a general sense throughout the patients life, how many times you mind me too or the patients like me to get treatment.
Yeah, I'll I'll hand, this question to our CMO Peter.
Okay.
Thank you Carsten.
That's very that's a very astute question.
Because.
The need for re dosing really is quite going to be quite variable, depending as you say on the age of the subjects patients as well as the.
As the disease indications.
And I think one needs to.
Look at <unk>.
Different indications as to what re dosing might be required.
So for instance in.
Neuromuscular disease say like most killer dystrophy.
What are you going to be treating young boys.
Whose muscles will continue to develop and.
You, presumably will have to re dose got it.
Certain interval, which remains to be determined also.
Getting high levels of expression.
In say muscles might require a couple initial doses, which could be considered if we were able to read those.
Using <unk>.
In other disorders, like metabolic disorders, like MMA or OTC deficiency.
It's really going to depend on.
How.
The liver grows and what the.
Continued expression of the transgene is going to be and how that's reflected in their metabolic syndrome. So they.
They are metabolic syndrome could be improved for a year or two and then require re dosing or it could be longer.
It's really going to depend on the indication the disease.
And the individual patient with regard to the.
The effect that they get from the initial dose of gene therapy. So it's very clearly going to be complex, but the the main issue is that if we have the opportunity to read those individuals it's going to be a huge.
Vantage to treating these.
Genetic diseases.
Thank you Peter.
Hum for that information.
Just moving onto from strategic standpoint.
We have been hearing or the AAV, especially in a kind of a situation durability.
Hum.
Current construct.
Losing durability over time pretty quickly.
Do you would.
Would you consider getting into using the entire platform.
Yeah.
Right.
It was just a therapy that to remind everyone that we actually do have an existing partnership with spark an extra spark has exclusive rights to.
Two he may.
Thank you and I think that this can be either never based diseases that have interest as well so.
The next question comes from Chad Messer with Needham <unk> Company. Please go ahead.
Great. Thanks, good morning, and non thanks for taking my question.
Can we maybe revisit the the.
Now for for dosing in gene therapy, as we're kind of get ready to get the clinical data later this year I know, we learned a lot from the <unk> program in all of the patients we dosed there, but how confident are you in the translate ability of that data, which is an enzyme over two antiviral back.
And the dosing there was sub chronic dosing for gene therapies, obviously as we've discussed.
Different and potentially more complicated just.
Wondering why and how confident you are in the transit lead ability of that clinical data and obviously I'm sure you've got other evidence from from preclinical studies and things too.
Yeah, that's a great question, Chad and obviously I mean, one of the key drivers and I said, we have almost 300 patients dosed with the large safety database that we have with them tour with up to six months now and in the phase III dosing up to 12 months, so that definitely gives us confidence.
On the safety side of things, we had significant interactions with the FDA around in tour, which gives us confidence.
And then obviously were building on the on the on the preclinical data we've seen so far and most recently the non human primate data. We're very encouraged we're able to prevent the formation of interest.
The anti bodies.
One of the key differences as you said.
Hey, guys hanging.
Almost like a chronic intermittent.
[noise] treatment approach.
Gene therapy will be obviously.
Much fewer treatments, which means you can potentially.
With the dose of <unk>, which we're exploring with the empty capsid study, where we're looking at three doses.
Off of in tour.
And then just to remind you I mean, we have demonstrated in a number of different <unk>.
Indications approaches that <unk> is pretty much agnostic to the antigen. So.
But obviously the proof will be in humans in the human studies and that's really our key focus for 2020 wanted to demonstrate that.
Yeah.
Alright, great. Thanks.
The next question is from Ram <unk> with H C. Wainwright. Please go ahead.
Hi, This is <unk> dialing in from a run from Roger and Thanks for taking my question.
Could you please comment on the enrollment status of the dissolved triangle and do you plan doing interim analysis sometime in 2000 and Taiwan.
Yes, that's a great question. So as mentioned we are we have started both studies we started us off one in September.
Is off two in December of last year, we are on track enrolling those studies.
And we will be releasing top line data in the second half of 2022, and we don't plan to have any interim analysis at this point.
Yeah.
Alright.
Understood. Thank.
Thank you up operations at icon Biosciences. So once all the gating items that are remaining to advance the candidate to the human trials and specifically what metrics will be.
As to your process.
In addition to.
Validating the candidate list.
You may now diversity.
Yeah, I'll, let I'll, let clay addressed this and obviously, we guided that we are currently doing.
On the IND, enabling studies.
<unk>, yes.
The key driver, but I'll, let Alex comment in more detail.
Sure happy to.
Just repeat the question I didn't catch the first part of it.
With respect to the collaboration with <unk> Biosciences, So I'm curious, what's gating items from the remaining advanced candidate to the human trials.
And what metrics do you plan to do in the due process. In addition to elevating the candidate but not.
Immunogenicity.
Sure.
Yeah.
Now for.
Finally, the R&D we.
We need to produce.
R&D, enabling pharmacology and toxicology studies.
So that will involve combinations of the Iga protease with with total molecule.
Ultimately, though I think our our goal is to get into the clinic as quickly as possible because I think theres. Good pharmacological rationale based on published studies showing that.
Iga protease can the bulk iga immune complexes in animal models.
And.
As you know we have a lot of clinical experience using <unk>. So I think that's the key.
Combination.
Sense, because right now the main limitation of Iga using Iga protease toward the treatment of Iga nephropathy is the immunogenicity.
Okay.
So moving forward with your M&A program. So I'm curious what is the current standard of care for MMA.
How much it cost per treatment MMA patient, the United States, United States, and what unique futures of MMA, one will accelerate its clinical development and market adoption.
Yeah, I'll, let I'll, let Peter speak about this but really right now the treatment options are fairly limited and free.
Really it's.
Liver transplantation.
Only approach right now and that oftentimes.
There has its own risks and limitations since you have two immune suppressed.
For lifetime basically.
But I'll, let Peter talk that addresses question Peter.
Sure.
The approach to MMA, but at this point is really diet dietary restrictions.
So reducing the amount of <unk>.
Intake of foods that can be.
That need to be metabolized by the pathway.
And then intermittently treating the the episodes of metabolic crises that these children have.
In general care.
Beyond.
Well, a liver transplant, which.
Although it doesn't completely cure the disorder is markedly improved.
There their outcomes.
So those that's really the approach at this point in terms of the cost of care.
I really can't give you a number for that but I will say that.
These children are basically in intensive.
Observation and care almost their entire lives.
With.
Often stays in the hospital.
Up to months when they have metabolic crises. So the cost of care is is enormous I just can't put a.
Particular number on it at this point.
That's understood and one final from me do you think in pillar will be equally effective in mitigating <unk> bingo Genesee, regardless of the stereotype of AAV vector being used.
Yeah, I'll, let Alex K answered. It's obviously, we have done quite a bit of work and looking at various stereotypes king.
Sure Yeah. So we've looked at multiple thorough types, including a V. A baby bye baby core.
And Katy.
And really.
Consistent with our other preclinical data that in cars.
Agnostic to the antigen, so whether it's an enzyme or capsid or from other therapeutic protein or autoantigen.
We are seeing good preclinical data to support the mitigation of indigenous city.
Alright, that's it from me thanks for your time and congrats on the progress.
Yeah.
As a reminder, if you have a question. Please press star then one to be joined into the queue.
The next question comes from Derek <unk> with Stifel. Please go ahead.
Is your line muted can you hear us.
So I guess, thanks, Hey, guys. This is Jack on for Derik, Thanks for citizens fitting us in here and taking our questions I guess.
On your gene therapy programs first on M E. One O one.
One how many patients worth of data should we expect and then.
What in the biomarker data could we look to signs of activity for the therapy and then if I may on your ongoing mm 399 study.
Other than antibody formation, what else are you looking.
To go from this study that could help us further derisk the technology.
Yes. Thanks.
For the question.
Peter once again, a handful this one could get more color on on the MMA study.
Okay. Thank you Carsten so for the for the MMA study.
The.
Efficacy endpoints that we're going to be looking at are as Carsten mentioned earlier, we're gonna be biomarkers of enzymatic activity. So one of the obvious ones is MMA levels in the serum.
But there is a very specific and a.
Test called <unk>.
Appropriate ionic acid metabolism.
Which has been developed by our clinical collaborators at the NIH that will be used to measure activity of the enzyme.
It's a very sensitive and a validated test for for looking at the enzymatic activity.
And it's the enzymatic activity that is going to determine the.
The clinical outcomes in the patients so we'll be measuring both of those as endpoints in the initial trial.
The other aspect of course.
The initial trial was safety.
We're going to be focused on on that as well as the neutralizing antibodies and other immunologic T.
T cell markers and so forth that might be affected by import treatment. So it'll be a.
From an extensive evaluation of both the disease as well as the Immunogenicity.
And in terms of the empty capsid study.
In addition to the neutralizing antibodies will also be looking at other.
Immunologic Biomarkers that we believe that we'll be looking at in an exploratory way and then of course, a key aspect of that trial will be safety.
First time that a.
B.
Vector has been administered with him tour.
And so.
That safety analysis will be we'll kind of setup future human trials as well.
Okay.
Great. Thanks, guys and congrats on the progress.
This concludes the question and answer portion of the call.
I'll now turn the call back over to select does CEO Carsten Brunn for closing remarks Carsten.
Thank you operator, and thank you to everyone who joined US. This morning, please stay safe and healthy and this concludes today's call. Thanks again.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Okay.
Right.
Yes.
Yes.
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