Q1 2021 Reata Pharmaceuticals Inc Earnings Call
[music].
Ladies and gentlemen, thank you for standing by and welcome to the Reata Pharmaceuticals first quarter 2021 financial results and update on development programs Conference call and audio recording of today's webcast will be available shortly after the call today on <unk> website at reata.
The search and development officer, calling Meyer.
Chief operating and Chief Financial Officer Man meat, Sony and Chief Commercial Officer Dunbar.
At this time I would like to turn the call over to Warren Huh, Chief Executive Officer of Reata.
Good morning, everyone and thank you for joining US today, we have a number of updates. The we're excited to share with you. This morning will start on slide four.
First off we're pleased with the U S food and drug administration's recent decision to accept our filing of our new drug application for paradox alone for the treatment of patients with chronic kidney disease caused by outport syndrome. The.
The FDA will review the application under standard review timeline and it assigned of Paducah date for the application of February 25th 2022.
The FDA also advised us that it is planning to hold an advisory committee meeting to discuss the application. We've been actively preparing for this meeting the last several months and it will be of key focus for our team during the year.
With clarity on the review timeline for NDA, we're continuing our preparations for the commercial launch of Burdock Salon in the United States subject of course to approval by the FDA.
Our core commercial leadership team is already in place and we're building the organization infrastructure systems and processes necessary for the launch of Murdock's alone in the U S. The.
These include sales marketing market access patient support and distribution. We're pleased to have done per our chief commercial officer join us on this call and look forward to hearing more from her about our commercial launch preparations later in the call.
The next slide.
Beyond the acceptance of our filing of our NDA from Murdoch's alone for output syndrome, we've made significant progress in our Falcon study of our docs alone in patients with autosomal dominant polycystic kidney disease.
Since our last earnings call on March 1st we've been rolled over 70 patients and we continue to anticipate completing enrollment in Falcon by the end of the year.
Regarding our pivotal neurology program with one math and Friedrichs ataxia. We previously reported positive results from the Moxie pivotal trial, the baseline controlled study and the delayed start analyses.
The FDA recently granted our requests for of type C meeting, which is scheduled to occur in this quarter at that meeting we plan to present data from the delayed start analyses that we believe supports oh maps potential as of disease modifying therapy NFA and discuss the next steps for the FAA program.
With that introduction I would like to turn the call over to Colin who will discuss recent updates to our development pipeline Dawn will then provide more detail on our ongoing commercial readiness preparations finally meet will review our financial results and provide an operational update.
The before patients enter the Cardinal which is noted as your zero on the X axis.
The overall trajectory as shown in gray and the pediatric patients are shown in dark blue.
If the same patients followed the same rate of loss and kidney function over subsequent years, you can see that on average the Pietro patients would reach in stage kidney disease, and only five years and all patients and only nine years. This explains by output syndrome patients, which kidney failure at such a young age.
Age unlike diabetic kidney disease patients, who on average reached kidney failure in the sixties pediatric Albert syndrome patients, which kidney failure any of the transplant or dialysis in their twenties.
Turning to slide 10.
The Nephrologist community has spent decades studying the impact of kidney failure on quality of life and survival.
Patients were able to obtain a kidney transplant require lifetime immunosuppression and often develop associated of complications such as cancer.
Patients who cannot obtain a kidney transplant typically spend many hours the week undergoing chemo dialysis.
Beyond the adverse effects on quality of life, we don't replacement therapy greatly increases the risk of of infections cardiovascular disease and premature death.
This slide shows the average decrease in life expectancy by age of kidney failure onset I of highlighted the ages of 15 to 29 years. Since this is the age when the vast majority of patients with the most severe forms of Albert syndrome developed kidney failure.
As you can see once kidney failure occurs in these patients. They have an average loss of life expectancy of approximately 40 years. These day to highlight how important it is to slow the progression of see Katie.
Next slide.
As we discussed of last quarter's call chronic inflammation, it's a primary contributor to the progressive loss of kidney function associated with numerous forms of <unk>, including Albert syndrome, Pro-inflammatory stimuli have two primary effects, including reversible dynamic effects and a.
[noise] reversible structural effects.
Pro-inflammatory mediators can dynamically and reversed simply regulate single nephron GFR by modulating the <unk> surface area for filtration per case of F.
<unk> C. K D inflammation is chronically present, which persistently reduces single nephron GFR and is the key feature of <unk>.
When inflammation persists over long periods of time as it does in almost all forms of CJD. It also drives kidney remodeling by activating pro fibrotic pathways overtime. This chronic processes result of an irreversible fibrosis and ultimately the complete loss of function of individual net funds.
The targeted Barack slowness interact to a transcription factor with anti-inflammatory and tissue protective effects, which is suppressed in many forms of CJD, including Albert syndrome net.
The next slide.
We have spent over a decade conducting a large number of preclinical studies to characterize the mechanism of action of Arnox loan. These effects are now well documented in the scientific literature and demonstrate that paradox loan restores single nephron GFR by increasing the filtration.
Surface area in the kidney reversing inflammation mediated constriction.
We have shown that this effect is not associated with any changes in Africa or fr tone, demonstrating the disaffected not associated with increases an integral mail or pressure or hyper filtration.
This is a novel mechanism to dynamically regulate GFR and as I will discuss from the clinical data. This manifest in patients as sustained increases in GFR with pornography on treatment of patients are taking the drug.
Now on slide 13 during our development program, we have spent much effort and time to determine how paradox, one regulates the kidneys handling of albumin. The most common protein found in the blood albumin as often present in the urine of patients with kidney disease the defects in the kidneys for.
Patient barrier caused by patients underlying kidney disease.
Albumin is pathogenic and causes of damage to the kidney when is excessively reabsorbed into the kidneys, which induces inflammation and fibrosis.
In preclinical models, we have shown that barack sewn effects Ottoman handling the at two mechanisms first part oxon increases GFR, which increases filtration of the argument importantly, this occurs without any evidence of increased permeability or injury to the filtration barrier.
And we believe this increase is due to the anti fibrotic effects of our Oxford and is consistent with the disease modifying profile.
These off treatment of improvements also validate that the large durable on treatment increases in egfr beneficial.
When we analyze the off treatment data using a launch of two new analysis to compute off treatment floats as opposed to calculating changes of discrete time points. We have demonstrated that there is the reduction in progression by approximately 50% in the paradox non treated patients compared to placebo treated patients.
The data from the Cardinal trial are also supported by data from the beam and Beacon diabetic CK day trials that also demonstrated significant on and off treatment improvements in egfr relative to placebo.
Overall, the clinical profile of our Oxford is well characterized and the on and off treatment differences in Egfr observe in the pivotal phase III Cardinal trial demonstrate a meaningful benefit in patients with one of the most rapidly progressive forms of <unk> ex.
Next slide.
Our output center on the development program has demonstrated an acceptable safety profile adverse events were mild to moderate generally occur within the first 12 weeks were reversible with treatment discontinuation and were not life threatening.
We identified no safety findings <unk> patients, who discontinued and received on average 33 weeks of treatment.
By the end of the two year study. These patients had kidney function that was similar to placebo treated patients demonstrating that these patients did not experience any adverse kidney findings.
Serious adverse events were observed in <unk> treated patients, we mitigated against the risk of fluid retention.
No new safety signals have been identified and the ongoing extension study.
Overall, our output syndrome data are consistent with the comprehensive safety database of over 3000 patients.
In summary, we believe our data demonstrate that <unk> targets, the underlying pathophysiology of the <unk> syndrome.
The clinical safety and efficacy data to support an acceptable and positive benefit risk profile for <unk> for the treatment of <unk> syndrome.
I will now discuss our other seeking a development program on slide 18.
As you know we are also developing <unk> for the treatment of patients with ADP <unk>. The most common hereditary form of C. J D with approximately 140000 diagnosed patients in the U S.
Despite standard of care, a high percentage of patients ultimately progress to kidney failure.
Similar to the Cardinal trial, the phase III outcome trial is two years in total duration and the key primary and secondary endpoints are at the end of the first and second years of treatment.
We plan to enroll approximately 550 patients from sites in the U S Europe, Australia and Japan.
Currently more than 290 patients have enrolled in Falcon and we expect to complete enrollment by the end of this year.
As shown on slide 19 in the first quarter of 2021, we initiated Merlin a double blind placebo controlled phase II trial evaluating the safety and efficacy of <unk> in patients at risk of rapidly progressing <unk> due to multiple etiologies, including common and rare.
Forms of CK, such as diabetic <unk> hypertensive, <unk>, Iga nephropathy, <unk> and others. The primary endpoint of Merlin is the change in Egfr from baseline to week 12.
We plan to enroll approximately 70 patients aged 18 to 70 with Egfr between 20% to 60 ml per minute and with one of several risk factors for rapid progression.
We anticipate completing enrollment by the end of the second quarter of 2021.
If the results of the study are positive we would potentially proceed to a larger phase III trial with similar eligibility criteria.
Patients at risk for rapid progression experienced a significant risk of progressing to end stage kidney disease.
Population with high unmet need across the multiple forms of <unk>.
Now turning to slide 22, with our neurology programs I will provide an.
Update on our program with <unk> or <unk> and <unk> ataxia.
<unk> is a rare disease characterized by progressive loss of motor function with patients typically requiring a wheelchair by the mid twenties and of median survival of 35 years.
There are no approved therapies for SMA.
On our last call we highlighted the results from the delayed start analysis, where we've compared patients initially randomized to placebo and Omar to each other and the extension.
We believe these analysis demonstrated that <unk> profile is consistent with disease modification.
We requested and the FDA granted a type C meeting to discuss the delayed start analyses as well as the overall data from our <unk> study and the overall development program. The meeting is scheduled for the second quarter of 2021.
Next slide.
Yes.
We believe that the pharmacology of the <unk> activators may be applicable to a wide range of other neurological diseases that have a common pathophysiology of mitochondrial dysfunction and neuro inflammation.
Allomap and analogs have shown activity in numerous non clinical models as well as patient biopsy samples and we believe the pharmacology is applicable to a broad set of neurological diseases, including other movement disorders, such as PSP, Parkinson's disease, and Huntington's disease, as well as diseases that affect neuromuscular function.
The memory.
Finally on slide 25, our earlier stage pipeline includes RTA 901, a highly potent and selective oral small molecule C terminal modulator of Hsp 90, Hsp 90 is a molecular chaperone that facilitates the folder.
<unk> and stability of many proteins RTA 901 increases transcription of Hsp 70, another molecular chaperone that promote cell survival and response distress and effects of mitochondrial function.
901 has demonstrated activity in multiple models of diabetic neuropathy and has been shown to reduce pain acutely the models of painful diabetic neuropathy as well as recovery of lost sensation in models of Insensate diabetic neuropathy.
Of the approximately 4 million U S patients with moderate or severe diabetic peripheral neuropathic pain approximately half of those treated do not achieve an adequate pain reduction with available therapies.
We have completed phase one sad and Mad studies in healthy volunteers and have demonstrated an acceptable safety profile with no safety signals drug discontinuation or CES, while achieving appropriate safety margins.
In the second quarter of 2021, we are planning to initiate clinical pharmacology studies to support the launch the phase III study in the fourth quarter of this year in patients with diabetic peripheral neuropathic pain. This study will be a randomized placebo controlled dose ranging study using a standardized pain scale.
I will now turn the call over to Don Burke, our Chief commercial officer to provide an update on our commercial readiness for <unk>.
Thank you Colin.
Morning, everyone I'll start on slide 27.
It's an exciting time at the reata prepares for our very first potential launch and the commercialization of by docs alone for the treatment of <unk> syndrome.
Layer and deadly kidney disease with no approved therapy with the acceptance of filing of our NDA and produce the date of February 25, 2022 of our timeline of clear we've taken concerted steps to ensure our launch readiness by Q1, 2022 and have hired commercial leadership and their direct reports to support each commercial function.
And we've also been actively preparing the market through disease education efforts designed designed to create a favorable environment to support by docs alone adoption at launch our disease awareness campaign launched over a year ago and reaches Nephrologist through website digital social print and broadcast platforms.
The objective of the campaign is to provide the education, an accurate diagnosis and disease severity and highlight the urgency to recognize and treat <unk> syndrome.
Patient access to therapy at launch it's also a key priority.
The market access team has designed of distribution program to support product availability at approval.
Ongoing payer and pricing research help us understand the reimbursement landscape and identify payer educational needs related to our <unk> syndrome as payer education is critical to facilitating patient access at approval next slide.
Output syndrome represents a significant launch and near term commercial opportunity for reata, knowing where patients are and who is trading them today is important to launch planning.
Currently diagnosed the outboard syndrome patients and the physicians treating them had been located to ICD 10 claims data.
Through this data we believe there are approximately 14000 projected diagnosis of <unk> syndrome patients in the United States with the majority of being treated by Nephrologists claim.
Claims data also indicates that there are approximately 4500 nephrologists with diagnosed patients in their practice. This lift can further be refined by volume of patients, allowing us to target our launch planning efforts on the right audience treating patients today.
We've also identified key market Influencers. These adult and pediatric nephrologist have of broad reaching presence and are recognized by their peers for their expertise and the diagnosis and the management of <unk> syndrome.
Continued disease education efforts genetic testing programs and the introduction of a specific therapeutic option for output syndrome may help to increase the awareness and recognition of the disease.
Turning to slide 29.
With the fundamentals in place we are now prepared to grow and advance our commercial launch strategy. We've hired a seasoned commercial leadership team with a combined 150 years of biotech and product launch experience at successful companies, including Pharmacyclics Genentech, Alexia on Shire and Biomarin.
<unk> has assembled a strong teams to support all key commercial functions functions, including marketing sales of commercial operations and market access in Q1, we finalized the planning for our product distribution platform that will leverage of tightly controlled specialty pharmacy network and front end patient hub.
Commercial <unk> packaging has been designed customer targeting is complete.
As launch preparation accelerate several key events will take place in the coming months, including the deployment of our market access directors. This team will be charged with educating top regional and national payers about output syndrome burden of disease. They will share pivotal cardinal data with pharmacy directors and see coverage and reimbursement of BARDA.
The loan upon approval.
Additionally, we will finalize our patient access programs.
And design services to support reimbursement of out of pocket patient costs in both bolster patient adherence to therapy.
Branded launch development will gain momentum and we will prepare to onboard train and deploy our first sales force of small force focused team of nephrology specialists.
We are moving forward quickly from the very strong foundation I will now turn the call over to <unk> to provide a summary of our financials for the quarter.
Thanks.
Volume Collyn and dawn and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the fourth quarter of 2021.
I will be covering three topics, our cash position, our Q1 financial results and our operational readiness.
Let me start with our cash balance on slide 31.
As of March and we maintained a solid balance sheet with approximately $777 6 million in cash and cash equivalents.
In keeping with our current guidance, we expect our cash balance to fund our operations through mid 2024.
Moving to expenses, our R&D expenses for the quarter were $44 9 million compared to $47 $7 million for the fourth quarter of 2020.
Lower R&D expenses were primarily due to a net decrease in spend related to completed preclinical and clinical studies and manufacturing activities.
Offset by increase of regulatory expenses for our NDA submission.
G&A expenses for the quarter were $20 7 million compared to $20 8 million for the fourth quarter of 2020.
G&A expenses were consistent with the prior year spend.
Our GAAP net loss for the fourth quarter of 2021 was $67 5 million or $1 86 per share on both basic and diluted basis.
As compared to a net loss of $48 9 million or $1 47 per share on both basic and diluted basis for the same period of the prior year.
Our non-GAAP net loss for the fourth quarter of 2021 was $41 $9 million or of $1 16.
For sure on both the basic and diluted basis.
As compared to a non-GAAP net loss of $29 6 million or <unk> 89 per share on both of basic and diluted basis for the same period of the year prior.
The increase in GAAP and non-GAAP net loss was primarily driven by the recognition of tax benefits related to cares act totaling $22 $2 million stock the recognized in the fourth quarter of 2020.
<unk> offset by a decrease in R&D expenses discussed earlier.
Moving to non-GAAP measures on slide 32, our non-GAAP R&D expenses were $28 $1 million for the fourth quarter of 2021.
As compared to $46 7 million for the same period of the year prior.
Our non-GAAP G&A expenses were $12 8 million for the fourth quarter of 2021 as compared to <unk> million for the same period of the year prior.
To summarize our non-GAAP operating expenses were $41 $2 million during the fourth quarter of 2021 with multiple programs, reflecting the potential of our pipeline.
The key regulatory and commercial launch readiness activities.
The next slide.
We are making the necessary investments to ensure the strong and successful commercial launch of biopsy zone early next year.
<unk> FDA review and approval.
From an operations and manufacturing standpoint, reata us current and planned inventories of investigational product and product and potential commercial product is adequate to meet our 2021 and planned 2022 demands.
Are actively engaged in key CMC development registration and validation activities across the blood oxygen program to ensure commercial availability post approval and beyond.
We continue to invest in and expand our medical affairs team to increase disease awareness and education in the nephrology community for output syndrome.
Beyond our Albert's under program, the infrastructure and capabilities that we of buildings support our long term goal of becoming a commercial global entity, providing a platform to support multiple additional indications and new product launches over the next several years and beyond.
With that I will turn the call back over the water.
Thank you ma'am.
As our presentation today indicates we're making significant progress across a broadening set of programs.
Yeah sure you call thanks for that.
Yes, I think that the.
You've been in as I mentioned in active preparation.
With the first class outside help.
And review.
And of course have gotten.
Good review of the data and program by many outside key opinion leaders as well as the advisers that I mentioned.
I think the issues that we anticipate are basically just the known issues around our program paradox alone is the.
New molecular entity with a novel mechanism of action.
It has.
Very different mechanism.
Then the agents that have the previously been approved in the Ctd's day space like blood pressure medications and the <unk> inhibitors.
At the directly treats the inflammatory processes.
We see a nice improvements in GFR that are you know have not been observed frequently obviously.
The effect of those it was the key feature of the design of the clinical program.
The the off treatment of key secondary analysis.
Think that.
That those issues will be kind of of the key.
Issues that will be explored.
In the in the.
In the review process.
And at the outcome.
Okay got it and just one quick follow up do you have any thoughts on one of the FDA opted for the standard.
Already review given the severity of all of our syndrome and the lack of any of from therapies to treat alcor.
Well I think it's the same answer it's the the proximate of new molecular entity again. It has a novel mechanism. It's unlike other agents that have been approved and so it per of it presents novel review issues.
We're in the process of seeking guidance from the EMA and we will incorporate that into the development program and so at this point, we have no additional comments on.
What day may require of us.
Got it Okay and then.
For the Kirin phase III study in diabetic <unk>, Japan.
Data of unexpected until first half of 'twenty two just checking if there is any possibility for FDA to request blinded data from that study or potentially from the Falcon and ADP <unk> study to augment their output of review or could.
Are we out of potentially submit some blinded data from either of those studies to help with the review.
Yes, so the mowry.
Those studies are ongoing.
And we view it is highly unlikely that they will request any data from those two ongoing trials that by the way are overseen by an independent data safety monitoring board.
And so our NDA filing for output syndrome. It doesn't just include the approximately 200 patients that we've treated with <unk>, who have upward of syndrome.
The data set of 2005 hundred people, who have been exposed to <unk> with hundreds of other placebo treated patients. So.
In our view, it's a very large dataset for FDA, especially for such a rare disease. We believe the safety profile is very well characterized and as I've discussed.
This call in the past couple of calls in the output syndrome program of the adverse event profiles very similar to what we've seen in prior trials.
The frequency of serious adverse events was actually cut in half in the paradox Fund group relative to placebo. There were no signals for fluid retention that we observed in a trial in 2012 and Albertson and trial of any trial. Since then that of enrolled over 600 and.
600 people to <unk>.
And so from our perspective, the safety data is very well described and just one last point is that we've been able to characterize the.
The specific adverse events of interest that we've seen and for most of them and we have no peer reviewed publications that we believe describe the underlying mechanism of action pharmacology.
Clearly all of this is very well detailed in the NDA that we submitted and so it's our view of the safety profile.
Is very well characterized.
Great. That's all helpful perspective, thanks for taking my questions.
Yeah.
The next question is from Annabel <unk> of Stifel. Please go ahead.
Good morning, everyone. This is Nick <unk> on for Annabel <unk>.
Congratulations as well and thanks for taking our questions.
I think we along with.
Most of them.
The one offs as well expect the topic of hyper filtration to be front and center at the AD com.
What can you provide the the FDA to get them comfortable with the Egfr increases.
Can you demonstrate that the egfr increases are due to increases in glomerular surface area, rather than the force filtration and are there other factors that youre using to demonstrate.
The damage.
Yes, so we obviously as I talked about on many calls over the past few years, we've spent literally over a decade to characterize the novel profile of <unk> and <unk>.
So from a preclinical perspective, we've conducted a few studies, including working with one of the top labs in the world Professor cash of horror.
In Japan as the.
The president of the Japanese society of Nephrology and using sophisticated imaging techniques.
The living animals. He has shown that <unk> increases single net find GFR without increasing pressure.
In the kidney and it's due to an increase of the increase in GFR is due to an increase of infiltration surface area, which is constricted in many forms of <unk>.
And so those data had been presented publicly we have other peer reviewed manuscripts that support. These findings we've demonstrated in other models of hyper filtration specifically.
Part of Oxford and analogs are protective.
So from our perspective, we've thoroughly characterize the specific.
Mechanism of action in relevant animal models.
And Theres actually no controversy about what the drug is doing I think clinically it's important to note that you can never proof of mechanism in people.
Since the FDA acknowledges that they've required of trial design that in their view would allow them to determine if the mechanism of action of <unk> is beneficial or harmful independent of mechanism and that's why they gave us the two year of trial design for both output syndrome as well as for.
Sure.
ADP <unk> recall this is the same endpoint the off treatment endpoint. The served as the basis for approval for <unk> for ADP, KD and so and at the ACO in the view of the National kidney foundations working group with FDA and EMA in settings, where there is an acute effect of a drug that either increases or decreases GFR.
In terms of how much of the three year data from Eagle are you going to be able to discuss with the FDA by the time of the AD zone.
Yeah.
So we have.
<unk> disclosed.
Data, obviously from the Eagle trial through three years.
In that phase II patients.
We have many patients from.
<unk> phase II, but also the phase III trial, who are still being followed in the Eagle trial all of the data that we had but the data cut use of the NDA were included in the NDA itself.
So publicly we will disclose data as it matures and the FDA has access to all of those data and we think that it provides some additional support beyond the primary cardinal data.
Great. Thank you very much.
The next question is from Brian <unk> of Baird. Please go ahead.
Hey, good morning, guys. Thanks for taking the question.
Just one on BARDA ox alone as part of your partnership with care and I'm. Just wondering if you will be able to submit any of the safety data to the FDA. During the course of the review of <unk> for Ion and obviously there is there is a lot of information on that back from just not sure of what the partnership sharing privileges or in the up.
Yeah without access to them.
No I mean, the end of the arrangements will have access to the data when the trial is completed but it's an ongoing blinded study. So we wouldn't anticipate being able to use that data during the the current review of the output syndrome NDA.
Got it and then on the.
The type C meeting for <unk> do you know currently who is going to be intent in attendance there and.
I know that para has the the petition to the FDA.
I was just wondering if you know if Sarah Hasnt meeting with <unk>.
Now other examples of our senior leadership held meetings with advocacy groups around.
Drug applications outside of the sponsor.
No we actually we actually don't know of actually who will be in attendance at the type C meeting, we make requests, but you really never know until you.
Until you actually attend the meeting and we're not.
Privy to or aware of what the ferrous activities are with respect to their interactions with FDA.
Great. Thank you.
Okay.
The next question is from Charles Duncan of Cantor Fitzgerald. Please go ahead.
Good morning, everyone Warren and team.
Congrats on the progress NDA acceptance also clearly certainly calling seems ready for an AD com present presentation.
Had a quick question.
On the AUM of program I guess I'm wondering.
If there is a possibility for another pivotal study I think you kind of outline that in our point to that on slide 35, but would the next steps be another pivot.
Pivotal study in Friedrich <unk> ataxia.
Or could you see moving to another.
Potential indication or moving on to a different candidate look what do you anticipate for the neurology program going forward.
I think we are committed to pursuing.
The approval.
Of the math for <unk> ataxia.
Despite the fact that we have not yet been able to submit the NDA and we may have to do another study we have a very well done pivotal study the largest one thats been done in FA patients with the clearly a positive result.
It will be a disappointment, if we have to repeat or add to that but we're prepared to do it and we feel like there will be high enthusiasm for the study and that we could execute.
Executed in a very efficient way of it with relatively low risk since we've already have one positive pivotal study in hand, so we.
We very much believe that the pharmacology is applicable to a broad set of.
Of neuro degenerative diseases as Colin outlined earlier, but.
We have a business to finish in FY <unk>.
Yeah that suggests and other question to me the I'll take offline regarding strategy, but I did have one question forward, perhaps don or Colin regarding the total addressable market.
When you think about ADP KD in patients that have high percent of.
<unk> ability of progression and then those patients included in the Merlin study.
Can you give us a sense of the total percentage or total total amount of patients that you could see being able to treat with <unk>. If it demonstrates the clinical activity that it's shown in <unk> syndrome.
So chances are you specifically, referring to the Merlin patient population of ADP J D.
Well, it's kind of.
It's kind of both the ADP KD per those patients who have high probability of progression, but also <unk>. If you could group those are you going to split them out.
So.
We don't have estimates right now, but we think the number is obviously much larger than than just the effort syndrome in the PKU population.
What's different about our approach.
Then other approaches recently is that.
There's been several trials conducted.
With agents that affect pressure within the kidney and other <unk> inhibitors, the complement ace inhibitors and <unk> day.
Treat the underlying cardiovascular disease, it's typically systemic.
That affects the kidney and promote the progression.
We're targeting intrinsic kidney disease, using the Merlin trial, and so trying to exclude out of the patients that have cardiovascular disease.
And identify those that still have rapidly progressive disease. Despite all available therapies and so were not willing right now to comment.
On that opportunity, but I think it's broader.
But you see this being able to provide of target product profile that may ultimately be if not disease modifying certainly of delayed too.
Risks and this ties into.
Our thesis for output syndrome, and as I discussed here and I think it's been lost a little bit.
That output syndrome is extremely rapidly progressive and so the first few slides cypress entered.
I think people have the other okay. Its output syndrome progressive a few more from an it faster, but it's still the kidney failures.
Often the future, but for Albert syndrome patients of five to nine years on average and when you see the the fee.
<unk> the <unk>.
Plot and so we're targeting patients like that who of likely have some inherited or acquired disorder in a risk for progression to kidney failure.
Not just in their lifetime, but in the near term and not just in the near term, but in the near term for relatively young patients.
Excellent. Thanks for taken the and that's the whole concept I think thats the whole concept from Maryland, right, where we are concentrating on the risk of rapid progression in those multiple etiologies right of <unk>.
Appreciate the color.
Okay.
Thank you.
Other reminder, if you have a question. Please press Star then one the next question is from Joseph Schwartz of <unk>.
<unk> Leerink. Please go ahead.
Hi, Thanks, and best wishes heading into a couple of very important FDA meetings.
Soon I was actually hoping to ask on.
Both of them for Bard and AUM of first time barred.
The FDA seems to be making life difficult for many sponsors lately by taking issue with things that seem to be taken for granted in the past.
So how confident are you that you are on the same page with the division reviewing bar Docs alone that you followed the guidance to a T. Because of this increasingly it seems like it would be required to bring any new markets trumps the market nowadays.
Joe So I think that we've been.
Transparent with our.
Discussions with the agency dating back to our pre IND meeting with Albert syndrome, which we had in 2016, they gave us the design for the output syndrome trial, which.
Which we've executed they gave us the same design for the Falcon trial and as I mentioned previously at the same endpoint that services the basis for approval first of all the <unk>.
And so from our perspective, the design is what they told us to do.
We've executed it we do.
Don't believe Theres any.
The discrepancies between what they've told us to do what we've executed from the analysis perspective, we defined the statistical analysis plan and of course, we have filed with us with the FDA being transparent and of the way that we analyze the data.
So I think thats.
We've done all of that we can do to.
Transparently.
Conducted analyze the trial and provide the data to FDA and I think it is distinct from other so I don't think that any of the recent issues that you may be alluding to are.
Relevant to to us.
Okay. Yeah. That's helpful. Thanks, I mean, I recall that you refined the stat plan that seem to be good proactive work. So.
Hopefully that will help.
Now just on <unk>.
I was curious how much of your upcoming type C meeting will focus on the delayed start analysis that you have now versus establish what's required for the pivotal trial for <unk> and.
And what is the purpose of discussing the former of the ladder is already expected to be required.
We're going to discuss the overall set of data that we've generated and so what's new or the delayed the start analyses.
And it's important because we believe the data demonstrate disease modifying activity.
And if FDA agrees that interpretation.
That would put them in a position where they will view of the development program differently and so.
So we're hopeful that once again upon review of all the data that we'll have the successful meeting and what's the game will provide guidance about the outcome. Once it occurs but it's not just about the delayed start analysis. Its about the overall development program and data generated to date.
Great. That's helpful. Thanks for taking my questions.
Youre welcome.
Thank you and I'm showing no further questions in the queue at this time, ladies and gentlemen, Thank you for your participation on today's conference as a reminder, an audio recording of the call will be available. Shortly after the conference call on <unk> website at Reata pharma Dot com in the investors section. Thank you very much for your participation you may.
Now disconnect.
Yeah.