Q2 2021 Provention Bio Inc Earnings Call
Yeah.
[music].
Good morning, everyone. My name is Jamie and I will be your conference operator today.
This time I would like to welcome everyone to the prevention bio call.
There will be a question and answer to follow.
Please be advised that this call is being recorded at the company's request.
At this time I would like to turn the conference call over to Mr. Robert Doody, Vice President of Investor Relations for prevention bio.
Sir you may begin.
Thank you operator, and thank you all for joining us on prevention Bio's second quarter 2021 financial results Conference call.
Joining todays call from the prevention bio team as Ashleigh Palmer, Chief Executive Officer, and cofounder and Andrew Jackson, Chief Financial Officer, and other members of the prevention bio leadership team.
Before we begin let me remind you that the various remarks, we will make today constitute forward looking statements.
These include statements about our future expectations clinical results regulatory and other developments and timelines related to our product candidates, including our plans to work with the FDA to address the RL deficiencies.
<unk> their PK comparability and product quality considerations and the delivery of significant catalysts over the next 24 months.
For the potential safety efficacy and commercial success of <unk> and our other product candidates.
The potential COVID-19 impact on our clinical studies and business plans.
Financial projections, including our anticipated use of cash and our cash runway.
Our business plans and prospects, including with respect to any potential approval of <unk>.
For clarity map and projected timing for the same.
Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent quarterly report on form 10-Q, which we filed with the SEC. This morning and in other filings that we may make with the SEC.
In the future.
Any forward looking statements represent our views as of today only.
While we may elect to update these forward looking statements at some point in the future. We specifically disclaim any obligation to do so even if our views change except as required by law. Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today.
There is more complete information regarding forward looking statements risks and uncertainties and the report prevention filed with the SEC. These.
These documents are available on prevention web site at Www prevention bio dot com under the investors section.
We encourage you to review these documents carefully.
With that I will now turn the call over to Ashley.
Thank you Bob and good morning to everyone joining us on the call today.
It has now been just over 3 years since prevention <unk> initial public offering.
I think its worth taking a moment to reflect on a remarkable accomplishments on the evolution of our disruptive and paradigm shifting company in a relatively short period of time.
When we acquired the rights to Pep lithium from Macrogenics in May of 2019 on.
Our plan was to develop this novel immuno modulator agent for the treatment of new onset of clinical stage type 1 diabetes.
This is Kent was based on our understanding from prior trials.
Getting a newly diagnosed <unk> patients precious remaining beta cells from ongoing autoimmune destruction cash.
And then potentially lead to better clinical outcomes.
Today, we find ourselves rapidly approaching the completion of target enrollment for our phase III newly diagnosed protect trial.
And we are on the verge of evaluating data from a PK PD sub study to.
To potentially address the fda's remaining consideration.
For what we hope will become <unk> first approved indication to delay the onset of clinical stage type 1 diabetes.
At risk individuals.
This breakthrough therapy indication was not even under consideration when we first day quiet type lithium ion in 2019, let alone contemplated to become the basis for potentially commercializing the first ever disease modifying therapy for <unk> well.
In advance of receiving topline results from our protect trial.
Also let's not forget that the successful progression of type lithium up on.
Lead therapeutic candidate targeting the intersection of T cell mediated disease.
Validates this company's foundational strategic intent and distinctive core competence.
Throughout these 3 years, we've been a public company, we have expanded and progressed our pipeline of conceptually related therapeutic candidates targeting a diversified portfolio of serious autoimmune diseases, including P. R V.
279 for lupus and other b cell mediated diseases.
<unk> 5 targeting the innate auto immunity driving diseases, such as severe disease.
P. R O B 1 O 1 to prevent what we believe to be a viable trigger of both T..1 day.
Celiac or 2 immunity.
This progress sets the stage for a series of significant catalysts over the next 24 months.
These catalysts are in addition to the ongoing progress of Pep lithium map not only with respect to the potential approval of our 14 day course of therapy to delay the onset of T..1 day.
Individuals.
On the topline results of the protect study in new onset T..1 b patients.
But also the potential for label expansion.
Repeat dosing and combination therapy, including in conjunction with beta cell transplantation therapy in established type 1 diabetics.
As well as the prospect of a subcutaneous formulation and just for tile portfolio of potential lifecycle opportunities.
Including targeting other T cell mediated diseases, such as Crohn's, celiac and rheumatoid arthritis.
Throughout 2020, despite the unprecedented challenges of a global Covid pandemic.
Our team worked diligently to prepare package and present data from a trial of 76.
T 1 day subjects.
It over more than 7 years by an NIH sponsored academic consortium.
Using <unk> drug substance made by Eli Lilly more than 11 years ago.
Every piece of data had to be Reformatted compiled a meticulously analyzed to present the T. N 10 study as a pivotal trial in a breakthrough therapy designation BLA submission.
We further supported this BLA with the submission of come from Atria evidence in the form of a meta analysis of C peptide decline.
Across other studies previously conducted in U T..1 day patients.
These studies, we're also integrated into a database for the purposes of safety analysis.
Meanwhile, we accelerated the manufacturing technology transfer process originally scheduled to take place over 3 years.
Stocking up commercial scale GMP production in less than half that time on successfully completing 3 P. P. Q validation runs over the summer of last year.
As a result, we completed our rolling BLA submission last November to meet an ambitious and highly challenging self imposed timeline.
As a result, the FDA accepted and filed our BLA at the outset of the share setting of July 2nd to do for date and scheduling of May 27 at the Advisory Committee meeting.
As many of you witnessed the endocrinology divisions Advisory committee seem them familiar with immuno modulator reagents and more used to reviewing phase III trials approaching at times in patients or more in diseases, such as type 2 diabetes in osteoporosis.
Nevertheless, with the help of supportive briefing documents from the FDA and then incredible outpouring of support from Tijuana D patients families clinicians advocacy organizations and the broader community.
We ultimately received a vote in favor of approval.
And then I have a complete response letter issued on July the second without any deficiencies related to the efficacy and safety data packages, we submitted 2 happy L. A.
This progress towards potentially bringing the first ever disease modifying therapy to type 1 diabetics in the centennial year of Insulins Lifesaving discovery is truly pioneering are nothing short of amazing for a company barely for years old.
But July 2nd C. O L. Also clearly set out what we believe to be the remaining substantive hurdle to obtaining approval for the commercialization of Texas the Mab for.
Risk T on the patients.
Yeah.
While there were no physicochemical comparability issues for the manufacture of our to be commercialized product batches.
As we reported back in April.
The FDA considers a single low dose PK PD bridging study conducted in healthy volunteers.
I hope to show adequate PK comparability.
Relative to product originating from drug substance manufactured by Eli Lilly for prior clinical trials.
Specifically in its advisory Committee briefing document USDA reported its extrapolation of the mean zero to infinity area under the curve or AUC for ought to be commercialized product to be approaching half that of the levy source material.
On the attributed this this difference to fast the Cleveland.
However from our perspective, Prespecified rules determined that the zero to infinity AUC could not be reliably estimated from the single low dose administered in the bridging study.
Does tip lithium not blood levels with too low for both topics B on 48 towers.
While blood levels of the to be commercialized product did fall slightly below the target AUC range within the first 48 hours, we do not consider these differences to be clinically relevant.
We also believe that the use AUC zero to Infinity difference extrapolated by the FDA is likely to be much smaller when multiple using actual blood levels samples from patients receiving <unk> therapeutic dosing regimen.
Rather than the single fractional low dose used in the PK PD study.
It is important to note that <unk> is a fast acting monoclonal antibody with a relatively short half life of 4 days as compared to other monoclonal antibodies that typically have a half life in the order of weeks.
Couple of them have targets. The C. D..3 cell surface receptor converting auto reactive T cells into exhausted T cells to improve immune regulation.
The main mechanism of clearance of debt place them on from the circulation is via internalization of the TERP lithium up on C. D 3 receptor.
The T cell for themselves.
This phenomenon is called target mediated drug disposition.
And he is well understood and characterized in.
In fact this to place them on Cleveland mechanism has been previously invoked in connection with the protege phase III study in newly diagnosed <unk> patients.
Previously published results reported that a lower dose and a shorter course, both demonstrated greater Cleveland than the standard 14 day therapeutic dosing regimen.
Therefore, we believe that when the tech lithium to have therapeutic dosing regimen has followed the exposure achieved by the to be commercialized puppet will be above the threshold associated with T. On the efficacy and the protection of beta cell function as measured by cell C peptide.
Indeed, pharmacodynamic markers in the single low dose PK P. D bridging study in healthy volunteers.
Including lymphocyte drop which is closely associated with clinical response.
All demonstrated compatibility.
As did the safety and Immunogenicity profiles as well as C Max which reflects the strength of product.
And the C O L. The FDA expressed and I quote the need to establish PK comparability appropriately between the intended commercial product and the clinical trial product or provide other data that adequately justify why PK comparability.
<unk> is not necessary.
Earlier this year, we took the precautionary initiative to commence a PK P. D sub study within the ongoing protect trial to enable us to collect blood samples from patients being treated with a 12 day therapeutic dosing regimen of either the Eli Lilly source for clinical.
On material or our to be commercialized product.
We expect relevant samples from this sub study to be processed by this.
By the end of this quarter on the data generated to be analyzed by independent unblinded third parties to maintain the integrity of the phase III protect the placebo controlled trial.
Upon review of these results the company will determine whether to submit our data to the FDA for review along with any other relevant data and analysis to support PK comparability or otherwise justify why PK comparability is not necessary.
We believe these data early on.
And these arguments have the potential to address fda's comparability concerns.
And we look forward to sharing more information with you. Once we have had the chance to conduct our analyses and discuss our results with the FDA.
Before I turn the call over to Andy to provide an update on our financial progress.
I'd like to provide some additional updates from across our company during this period.
We recently announced the tech leasing that has been awarded the innovation passport designation in the United Kingdom. So the delay of onset of clinical type 1 diabetes.
Risk individuals.
We are honored to have been only the fourth drug sponsor to receive such a priority designation since this programs infection earlier this year.
This designation is part of a new UK medicines and healthcare products regulatory agency initiative to accelerate development of innovative medicines following Brexit.
UK has 1 of the highest prevalence of type 1 diabetes globally with approximately 400 times on patients, including roughly 39 times and COVID-19 years or younger.
New diagnoses in the U K on increasing by about 4% every year.
And similar to the United States. He wanted to use manage through insulin therapy and glucose monitoring and there is no approved disease modifying treatment targeting the underlying cause of T..1 day.
We look forward to continuing our engagement with the UK regulatory bodies and participating in the review and approval process for this priority market.
We will provide a better sense of timing for this process and opportunity during future updates.
Also later this year, we expect to initiate the phase 2.8 prevail study with P. I'll be $32.79 in lupus patients.
And in the fourth quarter, we are excited to be having a first look at data from the phase 1 study of <unk> 101, our vaccine candidate against Coxsackie virus, B, which we believe to be a key trigger in the onset of autoimmunity in type 1 diabetes and celiac disease.
These.
With that I'm now going to turn this call over to Andy to provide you with an update on our financial progress.
And then return for some closing remarks.
Andy.
Thanks, Ashley and good morning, everyone.
Before I begin I would encourage you to read our 10-Q that was filed today.
10-Q includes our financial statements risk factors as well as management's discussion and analysis of our financial condition.
I would also like to call your attention to the earnings press release, which was issued prior to this call.
Let me start with the P&L.
We generated a net loss for the second quarter, 2021, $29.1 million or <unk> 46 cents per basic and diluted share.
The increase in net loss compared to the second quarter of 2020 as a result of an overall increase in research and development expenses of $2 million.
Driven primarily by costs for art to pause on that program, including the protect phase III trial regulatory activities and the build out of our medical affairs infrastructure to support the Pleasant Mab, which includes type 1 diabetes disease state awareness and screening education programs.
The increase in research and development cost was offset by lower to put the mab manufacturing costs compared to the prior year period as the company incurred significant costs for production of GMT and P. P. Q batches of drug supply and drug product during the second quarter of 2020.
The increase in net loss also resulted from an increase in general and administrative costs of $5.4 million, which was comprised of an increase of $2.1 million income pre commercial expenses net increase of $3.3 million in other general and administrative expenses.
<unk> from the build out of our infrastructure.
Shifting now to cash.
As of June 32021, our cash position was $176.4 million.
This cash balance reflects the receipt of $1 million from the sale of our 2019, New Jersey net operating losses in April.
Our net cash based operating expenses were $26.8 million for the.
The second quarter ended June 32021.
We expect to use between 31 and $36 million of cash for operations in the third quarter of 2021.
We expect our current cash cash equivalents in marketable securities will be sufficient to fund projected operating requirements for at least for next 12 months.
And that will enable us to actively develop all 4 of our programs.
Pleasant map for type 1 diabetes.
CRB $32.79 for lupus.
<unk> 015 for celiac disease.
<unk> 101, Coxsackie virus B vaccine.
We plan to provide additional cash guidance on each quarterly call as we continue to progress towards potential regulatory approval and commercial launch it's a pleasant map.
With that let me turn the call over to Ashley for closing comments Ashley.
Thank you Andy.
Before we open up the call to address any questions.
I certainly hope we've made it clear today.
We have a tremendous sense of gratitude for all of the hard work dedication and collaboration from everyone who has played a role over the last 3 to 4 years in helping to grow prevention from just a conceptual idea to now being at the forefront in the development of auto immune.
Arun disease, modifying immuno modulator therapy.
We are acutely aware of all the hard work and challenges that lie ahead of us.
And our team has dug in and doing everything reasonably possible to succeed in our mission for patients their families and clinicians on the entire <unk> community as.
As well as our investors, who have stood by us and supported us from the very beginning.
Thank you.
We appreciate your support and encouragement and it continues to keep us motivated and focused on our mission and their responsibilities and expectations. We carry on our shoulders every day.
With that operator, we'd like to take any questions.
Ladies and gentlemen at this time, we'll begin the question and answer session.
To ask a question you May press Star and then 1 using a touchtone telephone if you are using a speaker phone. We do ask that you. Please pick up your handset before pressing the keys to ensure the best sound quality.
To withdraw your question you May press Star 2.
Once again that is star and then 1 to ask a question.
We will pause momentarily to assemble the roster.
And our first question today comes from Alicia Young from Cantor Fitzgerald. Please go ahead with your question.
Hi, This is Emily on for Alethia, Thanks for taking our questions I'm curious what are your expectations for the PK PD comparability data from the protect study and is there anything different about that process from the original study and also maybe you could provide an update on your regulatory submission for Europe, and if there've been any day.
And then there in light of the FDA concerns. Thank you.
Thank you for the questions Emily So taking the last question first.
We will provide an update on the European and U K regulatory process. After we've.
<unk> completed the analysis of our.
PK PD sub study.
Later this quarter.
Along with the discussions that we're having with the FDA.
But I'm going to hand on the first 2 questions over to Francisco too to respond on Francisco.
Good morning Emily.
That process for the PK PD sub study.
It's an odd.
Time points for PK samples.
And to add a few pharmacodynamic PV.
Biomarkers.
In a subset of patients.
This will provide us with robust data that we believe we.
We'll be able to address.
He has concerns.
And our next question comes from Gregory <unk> from RBC capital market.
Please go ahead with your question.
Yeah.
Hey, good morning, Ashley and team. Thank you for other color. It day in and also thank you for taking taking our questions on there just with respect to FCA alignment I'm just curious actually at this point do you have an agreement that the sub study from protect will be sufficient.
For sufficient or is it that you're just your belief that it's sufficient at this point I'm wondering if you do have an agreement perhaps whether in writing on this design of the comparability say that youre doing, especially with historical FDA preference of the single dose file equivalents and comparability being.
The way to go just given the increased precision. Thank you very much.
Thanks, Greg very much for the question. So I think we've quoted.
1 of the graphs from the complete response letter, which really.
Puts the Fda's perspective.
Into.
In writing as you as you mentioned.
So the first thing that on the agency.
It would be looking for is data.
Support PK comparability and we believe.
We set out in.
Remarks this morning.
But that PK comparability.
Can be accomplished.
Accomplished by.
Looking at patients that get therapeutic dosing over the therapeutic.
Regimen of 12 or 14 days, what we believe okay.
Occurred in the.
Single fractional low dose.
PK PD study in healthy volunteers is that the.
PK PD well the PK.
You see.
Was at a sub receptor saturation threshold and so that exaggerated any difference on.
That difference will close and comparability will fall within an acceptable range.
As the higher doses administered over over several days the agency.
Extrapolated out to Infinity.
On AUC zero to Infinity for a monoclonal antibody debt.
Hum.
Is rapid acting has a.
Relatively short half life, and we believe but it's it's really the first 24 to 48 hours.
That makes a difference in for example, C. Max maybe more clinically relevant and then PK AUC.
AUC to Infinity, and so that is exactly what this sub study will will will accomplish it will collect data too.
Hopefully demonstrate that.
Now the other thing that was in writing in the complete response letter.
With which we.
Showed the agencies open mind is that if PK comparability.
Comparability.
Is not relevant to zero to infinity provide them with data to show that PK comparability is not necessary and.
And there the P D a.
And <unk>.
Who does a team bank might demonstrate that and I'm just wondering I do think about for these 2 concurrent pause you know are there.
For sets of data that are already available.
To suggest that you know.
How do you make that case around you know see Max being more clinically relevant M. P. K U C and you know what the full protect study P. D. The next piece of evidence I'd actually demonstrate that.
[noise], that's just in yet I mean, the the the P. K a U C zero to Infinity is really what we struggled to believe is clinically relevant say relative to P. K.
Uhm, a you see zero 224, and see Max and there is you know published evidence that we believe supports the mechanism of clearance, which is this target mediated drug disposition and I'm gonna ask Francisca.
Go to to explain that because it it is unimportant new ones with <unk>. It's it's fundamentally linked to its mechanism of action.
It's I V administration, and the regimens that have been developed by experts over the years to to arrive at the therapeutic dosage regimen Francisco.
Give them on and Justin.
Just to clarify.
It's not that we say compatibility is not available.
Well, we say is the compatibility has to be assessed.
In its totality the totality of the data.
So first.
We have shown that the products are compatible.
<unk> on the panel of assets.
Hello release <unk> shows comparable.
Hold on he incompatible seafood go chemical carpeting.
Second [noise].
M D O N humans.
We have the single load those study.
And that's where we believe we cannot solely rely on a single load those for an assessment the case for the drug for task privately mediated disposition.
This particular experiment is not representative of the clinical situation in the clinics with those multiple times higher doses.
We have other that sentence published that income.
Interest doses, partially saturate the <unk> bye.
Maybe 8 the disposition by binding to see the street.
On that has been published in the <unk> tasty.
<unk> <unk> <unk>.
With the hold those regimen had less clear than the logos for the partial.
Those for Achiness.
And finally, we have the stomach with on on the state on that shows that the pilot proposed for commercialization huh.
Comparable impact on immune cells.
On the immune system.
Then the nearly product Houston T M K.
So when you look at the totality of the data with family believes the products that are comparable.
We don't have any difference in safety Immunogenicity.
When you put this on the conflicts of the maiden name.
That's where we make the case to the F D a and we believe that products.
Are comparable and that's the blue from actually be approved.
[noise] understood. Thanks, Thanks, so much I if I can just insert maybe 1 more question just with 32.79 can you talk a little bit about what markers might be a touch the ball and in the coffee onto your population and what gives you potentially confidence to move into the affected.
Lucas population.
Francisco.
So with regards to first <unk> to lupus, we have see pieces on the other than that our drug could work on Lucas well first b sales are validated targets and lupus Benlysta was the first struggled Kristen and it's just a yes, a few years back.
So b shows validated second patients with lupus half polymer patients N C D 32 b.
Luckily too on the functioning see these take it to be but she's the amount for the download you later on B cells.
And we have evidence that when you into day.
Visa from lupus patients in vitro.
I would drag we can reduce the activation of nuclear Bishop B cells.
And a visit a production of antibodies.
So that is from other than of April for city search for it to be <unk>.
With regards to the health of alone care day, though.
We have uhm demonstrated that I will drug disabled too for.
<unk> the.
The activation and the production of antibodies by details for about 1 month after a single those.
And 6 months after T doses of drug.
[noise] and help people on <unk> and specific T E. D Z I'll give you an introduction to kneel on to James Neoantigens being presented to those.
Those subjects in hepatitis sub studies that we connected.
<unk>.
[noise] great. Thanks, so much.
Our next question comes from Thomas Smith from S. V. B Leerink. Please go ahead with your question.
Hey, guys. Good morning, Thanks for the faith and for taking the questions I guess, just a follow up on some of the earlier questions can you provide any additional details on the the.
The P. K <unk> study within protect specifically looking for you know numbers of patients that are gonna be included on this sub study I guess you know there's some other time points for data collection, how long you're following these patients.
And then any other Francesco I think mentioned some some additional data that could potentially be collected here I guess any additional data for you on the P. K P. D biomarkers that you're gonna look to evaluate here.
Good morning, Tom. Thank you very much we have not disclosed.
The target numbers, we can state.
Kept darkly that we believe the numbers that were collecting would be sufficient for inadequate P. K P. D analysis Uhm, we're on schedule to have completed the analysis by the end of this quarter I'm very pleased with the progress in collecting these.
More frequent samples from patients that are being or have been enrolled in the in the in the protests study.
Uhm Francisco do you want to make any comments regarding particular via markers or will also simple.
Parameters that are being collected.
Give them on on top.
So in the study in addition to the lymphocytes accounts, which is the clinically relevant T V. Marti, we have traditionally collected in this program because they said Thompson dropping emphasize for the fish 5 days up on multiple bills and then could covers quickly.
Bob drop coordinate with efficacy and past studies based on seat that day. So in addition to these interest I'd drop we just have a panel of.
Meal activation parameters that we measure on on the cells of the patients.
To cut off 2 is the impact of the blue some other on on T cells and other cell substance.
Okay, great and just to follow up on I guess, the completion of the analysis by the end of this quarter.
How do you guys intend to communicate the results from that analysis should we expect a a press release with some top line data or maybe you can just walk through how you're intending to communicate.
We have not determined that yet we prefer to complete the analysis on all discussions with the F. D. A and then make a decision regarding the the the the publication of that.
Okay and then just.
1 other follow up in terms of your your level of alignment with the F. D. A on the sub study design, maybe if you could clarify have you participated in a a type of meeting after the C. R. L and I guess, specifically may be following up on.
On Craig's question has any of the feedback then memorialized in right day or is this a parsing. The you know the T V from the F. D. A V C. R L language.
Yeah, we don't comment on our you know interactions with the agency, we well I can tell you is that the agency remains very engaged and we have the option for informal meetings on formal meeting request them as and when we need them.
Okay. Thanks for taking my questions I appreciate it.
And our next question comes from ROM Silverado from it for you Wainwright. Please go ahead with your question.
[noise] hi, Thank you very much for taking my question just very simply.
I need to fully understand a little bit more about the process of how you are going to furnish the compare ability data to the F D. A and what criteria. The F. D. A is likely to need to utilize in order to determine whether comparable it he has been satisfy.
5 or you've demonstrated the comparable if he doesn't need to be demonstrated and just to be specific if we look in particular at the protect study.
Do we currently have a clear understanding or do you have currently have a clear understanding of specifically what the threshold of data is likely to be from that study that would be likely to satisfy the F. D a or that would satisfy the F. D. A and can you give us a sense.
Specifically, the timing with which such data would be furnished <unk>. Thank you.
[noise]. Thanks very much for the question room. So you know as we stated we believe we have sufficient data.
And we're on schedule to be able to analyze that and discuss that with the agency by the by the end of this quarter.
The mechanism by which that day to would be formally furnished to the F. D. A would would be by a BLA resubmission.
And that B L. A resubmission would would then be responded to by the agency with respect to a determination of the class of Resubmission.
We anticipate the the nature of that Resubmission would be a class to submission, but which is which is a 100 and a T. A day review, but I would like to think that that Ah under the circumstances. Since we believe from the complete respond slather that the.
Ah comparability considerations by the agency is is the primary concern.
The agency in light of the unmet need and the you know open public hearing cold for a therapy like this to be made available to patients at risk that the agency would do its best to beat that 180 that day.
You know time requirement, but we obviously can't guarantee you that.
Oh.
In our next question comes from David Home from S. M. B C. Please go ahead with your question.
Hey, good morning, Thanks for taking the questions. So I didn't I didn't want to dig a little bit deeper into you know some of the comments you made about the.
The.
You know lowered and therapeutic dose regimens there were explored in to protect study can you. You know can you talk a little bit about maybe even if it is qualitatively. The you know the 6 day regimen into 14 day logos, it's not actually therapeutic dose regimen.
How much the day clearly differ.
From the full dose and his dad, you over what time period.
Yeah is that that.
He would you expect it to convert you know that you know a couple of days or do you really need to get close to 14 days to to see her for sex.
Thanks for the <unk>. The question, so I'll ask from Cisco to respond to that in detail, but I mean overall, we believe that that uhm published evidence is is very strong support for our belief that the mechanism of payments for.
Kept lizzy ma'am is target mediated drunk disposition and that if you evaluate in different studies or you know different patches. If you evaluate uhm completely mad comparability at 2 low 8.8.
A threshold in dos or in Uhm accumulation of dose, but then you will exaggerate differences uhm that will not necessarily disappear, but substantially clothes as you saturate those receptors and reach a plateau.
Above the the the the target receptor saturation pretzel. So that's the general concept, but Francisco can you recall some of the details from the actual protege publications regarding the 6 day those verses the the the 14th day dose as <unk>.
L as the the the lower dose this is the full dose.
[noise] cause I'm on invaded Uhm.
Uhm the publication list at the T arms.
6 days of for course versus 14 days, which is.
For for the physics building.
And then the fifth Uhm is.
The 14th day at 1 of.
For those.
Basically they were comparing full strength for the totality of the 14 day versus.
Oh for 10 days, but just wanted a for those or the food they need those that's only for 6 days.
And both the a V a day.
Course, and they want to both of those course.
<unk> very substantial.
Increased.
Yeah.
With respect to the full day they'll get the course.
The exact percentage okay for the exact number has nothing.
For this yet and we haven't disclosed it is it is very substantial and is fully support our hypothesis.
That the reason.
We still less or or a substantial difference in that.
Yes.
In the single logos study.
Is that okay.
Mediated this decision is not saturated up on single logos.
And will be partially set to day did our in our P. T. P. D Substudy, that's our expectation.
I see okay. That's really helpful. Thanks for walking through that and just maybe 1 follow up.
It seems like you've really zero game on just T. M. D. D. S. As they're really did you know the driver of the UK differences you see here, but I need to have you considered any other you know possibilities and I know, it's hard to I, you know hypothesize, but for example could there be anything with S. C. R N or any other mechanisms that you may have thought about that.
Could be contributing to the difference you know clear its differences aside from T. M D D.
So you know we we we've obviously put a lot of thought into this the you know the the the the.
Issue is that we can't detect comparability differences outside of this low dose.
Single low dose P. K P. D. A study that was done as a bridging study for the pro tactile.
The manufactured product is comparable you know it falls within all of the Physicochemical comparability range is that were agreed in advance of moving forward without G. M. P production on a P. P 2 batches validation and and and so.
On.
You you you have parameters within the P. K P. DS study that was conducted including C Max and and the lymphocyte drops the show compatibility.
Well, what we really have been evaluating with that laser focus is why is there. This single P. K a U C anonymous uhm you know outlier.
And we are very pleased to to to to be quite honest that we feel we have a legitimate you know well.
For through and evidently supported hypothesis that is this target you know target mediated drug disposition it makes sense.
And it explains the observations that we've seen and it it. It also means that the the sub study we're doing in protest you know has a very good possibility of meeting the requirements of supporting our arguments and providing day.
To the agency that that that that the app therapeutic dosing there is sufficient comparability there and then he differences.
Is not clinically relevant as as shown by the the the P. D. The P D Biomarkers, but Francisco do you want to add anything else to the specific question.
Oh.
I would just add that.
In the case for the C. N N. They tell this day was an initial hypothesis potential explanation.
It is a laser mechanism of prevention of clear by recycling.
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It it's not actually rapid ask the defense that day, so and that single logos study so the timing.
And it suggests that.
There's a difference between the 2 activities for choosing these is is very small and still will be within a reasonable margin is something that happens rapidly.
And it is well known that the main mechanism appearances by noon to see it says it maybe a day like this decision. So when you put those 2 factors together.
It is available on stewards are gonna hit the disposition and the the second come into the bed F. C. R and binding it's Parker the standard package shows up release for.
Any therapeutic monoclonal antibody so.
While we have not disclosed any specific information as you can imagine that that has been done.
Got it thanks, so much for providing the contact stem. So both of you. Thank you.
Hello, Ladies and gentlemen, with that will conclude today's question and answer session.
To turn on the floor back over to Ashley Palmer for any closing remarks.
Well. Thank you again for your time and attention. This morning, we hope you will have a great day, and we look forward to speaking with you again soon.
And ladies and gentlemen, with that will conclude today's conference call I do thank you for attending May now disconnect your lines.
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