Q3 2022 Reata Pharmaceuticals Inc Earnings Call
Yeah.
Thank you for standing by and welcome to the reality of farmed fish codes that caused that 2022 financial results and update on development programs conference call an.
An audio recording of today's webcast will be available shortly after the call in the investors section of reality website at ri ought to pharma dotcom.
Before the company proceeds with its remarks. Please note the forward looking statements disclosure in the company's press release.
There are many factors that could cause results to differ from expectations, including those noted in the company's SEC filings on today's conference call non-GAAP financial measures will be used to help investors understand the business performance. These non-GAAP financial measures are reconciled with comparable GAAP, chief financial measures and Rialto earnings release and presentation from today.
Which again can be found in reality the website.
Today's statements are not guarantees of future outcomes. Please also note that any comments made in today's call apply only as of today now that the H 2022 maybe.
<unk> no longer be accurate at the time of any webcast replay or transcript rereading. Following the prepared remarks, we will open up the call for questions. We ask that you. Please limit yourself to one question and one follow up so that we can accommodate as many questions as possible. We have joined today by Warren Huff Reata as Chief Executive Officer, Mommy Sunny President.
Colin Meyer Chief innovation.
Innovation of Sun Feeney Khan, Chief Medical Officer, and doing bad Chief Commercial officer at this time I would now like to turn the call over to Warren Huff.
Good morning, everyone. We thank you for joining us today for our quarterly update I'll start on slide four.
Since <unk> founding in 2002, our scientific mission has been to identify.
And commercialized therapeutics with novel mechanisms of action for the treatment of severe life threatening diseases that have few or no approved therapies.
Toward that goal, we are developing <unk>, along our own math.
Paul molecule activator of interest to <unk> for the treatment of patients with friedrichs ataxia for FSA.
<unk> is a relentlessly progressive and debilitating neuromuscular disorder, which affects approximately 4000 diagnosed patients in the United States.
There are no approved therapies for these patients and patients typically become dependent on walkers and then wheelchairs in their mid twenties and unfortunately, they pass away from the disease and they're mid Thirty's.
We began developing oh math and FAA over eight years ago, initiating the dose ranging part one portion of the Moxie trial in September of 2014.
Following encouraging results from part one we initiated moxie part too one of the largest completed international trials and FAA.
We've reported positive data from the Moxie part two study in October of 2019.
We initiated a series of interactions with the FDA, leading to a pre NDA meeting with the FDA in the third quarter of 2021.
During the first quarter of this year, we completed the rolling submission of our NDA.
In May 2022, the FDA accepted our NDA for filing and granted priority review designation.
As we reported in our last earnings call in the third quarter of this year, we completed a mid cycle communication meeting with the FDA and submitted additional data and analysis to the FDA in response to their comments.
The FDA determined that these submissions were a major amendment to your NDA and extended the prescription drug user fee Act or <unk> date by three months to provide time for a full review of the new data and analyses that.
The Paducah date is now February 28 2023.
Next slide.
We recently completed our late cycle meeting with the FDA.
Purpose is a late cycle meeting is for the FDA to discuss any subsequent issues identified in the divisions objectives for the remainder of the review the meeting does not address the final regulatory decision for the NDA.
While we have not received formal minutes from the FDA in the preliminary agenda for ensuring the late cycle meeting. The FDA stated that they continue to review the analysis and data included in our recent NDA submissions.
The FDA did not request any additional data or analyses, but stated that additional data may be requested as reviews are ongoing.
The FDA confirmed that no information requests were outstanding and reiterated that they do not currently plan to hold an advisory Committee meeting.
The FDA stated that no issues related to risk management have been identified.
During the meeting the FDA indicated that post marketing requirements and Labor review, our ongoing with respect to post marketing requirements and commitments FDA stated that if <unk> is approved they anticipate requiring a drug drug interaction trial with Sip three or four modulators a thorough qt.
Trial, and an evaluation of pregnancy outcomes FDA.
The FDA stated that other post marketing requirements and commitments may be considered depending on the findings of the review.
With respect to label review during the meeting we noted that the original proposed label language did not reflect the data and analysis included in the amendments to the NDA and that we have updated it in connection with the planned filing of a marketing authorization application or MAA in Europe later.
This year.
We committed to submit the updated proposed label language to the NDA. The FDA indicated that post marketing requirements and label comments will be communicated in early 2023.
Next slide.
We're also making progress in the preparation of our marketing authorization application for <unk> in Europe , We received a positive opinion from the pediatric committee on our pediatric investigation plan with a commitment to seek scientific advice for additional input on our protocols.
We've received EMA follow up protocol assistance feedback regarding our non clinical and CMC programs. The EMA feedback indicated that there were no impediments to our planned MAA submission.
We also received agreement that certain non clinical studies, including two year Carcinogenicity study data may be submitted after approval. We recently completed our pre submission meeting and are nearing completion of the MAA, we plan to submit the application before the end of this year.
Next slide.
Turning to our program with <unk> in chronic kidney disease, we continue to enroll patients in our ongoing phase III Falcon trial in patients with autosomal dominant polycystic kidney disease or <unk>.
<unk> is a rare and progressive hereditary form of CTD that affects both men and women of all racial and ethnic groups.
<unk> is the leading inheritable cause of kidney failure with an estimated diagnosed population of 140000 patients in the United States.
The FDA has confirmed that the primary endpoint of Egfr change from baseline to week, one way, which is eight weeks. After the planned drug discontinuation at week 100 is reasonable since the available data suggests that paradox loans acute pharmacodynamic effects on egfr should be largely resolved by.
That time.
We currently enrolled more than 605 patients in the Falcon trial.
Finally, our strategic collaborator in Japan, Kiowa Kirin is sponsoring the yummy trial, a large phase III clinical trial in patients with diabetic kidney disease.
The primary endpoint is time to onset of greater than or equal to 30% decline in egfr or end stage kidney disease.
If the results of this trial are positive it could provide clinical evidence that improvements in egfr observed in <unk> treated patients do in fact delay progression to kidney failure.
Gummy trial enrolled over 1000 patients with stage three and four diabetic CK D with over three years of data being collected for all patients in the trial.
Kai with Kirin expects to complete the last study visit in the second half of this year and has provided guidance. The top line data will be available in the first half of 2023.
With that I would now like to turn the call over to Colin Meyer, who will provide an overview of the key clinical efficacy data for <unk> in FA.
Dawn Becker will then provide an update on our recent progress in our commercial preparation activities for <unk> and finally mummies, Sony will provide an update on our financials and operations.
Thanks, Warren I'll continue on slide nine.
This morning, I would like to review the key lines of evidence we have generated supporting the efficacy of <unk> in patients with.
The primary evidence for <unk> and SA comes from the pivotal part two Moxie study a double blind placebo controlled randomized International study 103 patients were enrolled across a wide and representative range of age and disease severity Moxie part two met its primary endpoint.
With patients treated with <unk> experiencing a statistically significant placebo corrected two four point improvement in <unk> compared to placebo. After 48 weeks of treatment with a P value of 0.014.
We believe this two four point change is inherently clinically meaningful as patients treated with <unk> on average did not progress and recovered some function during the 48 week period, whereas placebo treated patients progressed at a rate consistent with the literature.
We observed improvements relative to placebo and all subsections of the Emperor scale, all major subgroups and all analysis populations next slide.
Beyond the primary evidence from the pivotal Moxie part two trial, we have provided additional lines of confirmatory evidence to the FDA supporting the efficacy of <unk> in patients with SMA.
We have provided mechanistic evidence to the division linking for tax and deficiency with interrupt two suppression and impaired mitochondrial function deficits in mitochondrial respiration and ATP production are observed in cells and tissues isolated from patients with SMA.
For example, maximum mitochondrial respiration and spare mitochondrial respiratory capacity as assessed by oxygen consumption rate were lower and fibroblast from patients with OSA and in fiberglass from healthy control subjects. Additionally, a study conducted in 42 patients compared peak <unk>.
Oxygen consumption, which is reflective of mitochondrial function with the <unk> ataxia rating scale score.
<unk> that reduced mitochondrial function correlated with reduced neurological function.
Together these data demonstrate a clear link between reduced mitochondrial function NSA and reduce neurological function in FA patients next slide.
We enter academic collaborators have spent several years to demonstrate the relevance of <unk> to impacting the underlying pathophysiology of S. A.
As shown in the left figure Oh, Matt has been demonstrated to restore and Rev. Two protein levels and FAA patient fibroblasts and the Middle panel you can see that this restoration and rep too is associated with restoration of mitochondrial energy production and FAA disease models in patient samples and the.
Panel on the right, we performed a turtle analysis of <unk> and changes in the interest to target genes ferritin and GTT comparing changes at week 48, and a pivotal moxie part two trial.
This analysis shows that ferritin and GTT increases are associated with <unk> improvements in patients with SMA.
As shown on this plot the patients with the largest clinical improvement or largest decrease in empires at week 48 as shown on the right. We're also the patients with the largest increases in ferritin and GTT to.
To summarize these data provide additional context for the relevance between FAA pathophysiology in rats, two induction and clinical benefit in patients.
Moving to slide 12.
To assess the treatment effect of <unk> more formally in the moxie extension and to provide additional clinical evidence we performed a post hoc propensity matched analysis of the moxie extension data to the largest most robust assay natural history study FAA comms.
E Commerce is a global multicenter longitudinal prospective observational study that has enrolled more than 250 patients clinical outcome measures, including empires are assessed annually and patients are followed for up to 25 years.
Patients from FAA Coms were matched to marks extension patients using propensity score is based on five co periods, including sex baseline age age of onset baseline <unk> score and baseline <unk> score selection of these covariance was made in.
Asian with the principal investigator and statistician for FAA comes based on clinical relevance. The relevance is prognostic indicators for disease progression and availability in both studies.
The change from baseline and empowers at year three for Moxie extension patients compared to the propensity score matched <unk> patients was analyzed as a primary efficacy endpoint using the same mixed model repeated measures or MRM analysis as we used for the primary analysis from oxy part too.
Results of the primary pool population of 136 patients and the Moxie extension compared to 136 patients in that day comes is displayed in the plot on the left in this population patients in the FAA comes match that progressed approximately $6 six <unk> points by year.
III, whereas patients treated with <unk> and the Moxie extension progressed, only three points, representing a significant slowing in the rate of progression by 55% with a nominal P value of 0.0001.
In addition to the primary pool population, we defined two subpopulations, including the placebo to Omar population, which included 95 patients previously randomized to placebo. The moxie part two and patients for Moxie part, one who had been off treatment for a minimum of 21 months. This.
Population is important since none of these patients were randomized to <unk> and part two and therefore this efficacy data is completely independent of moxie part too.
In the plot on the right the treatment effect in this population at year three with similar magnitude to the results from the primary pooled population demonstrating a 56% slowing of the rate of progression with a nominal P value of 0.0001.
In summary, the propensity matched analyses provide a robust assessment of the effect of <unk> and the ongoing extension study. The propensity matched analysis includes 136 patients who've been treated with <unk> for up to three years to match FAA comps patients and all analysis populations demonstrates.
A significant slowing of progression for patients treated with allomap with multiple subgroups and all Empire subsections failing go math.
In conclusion to supplement the efficacy results of Moxie part two we have provided FDA with additional evidence supporting the efficacy of <unk>.
These include mechanistic data showing how old map directly effects the underlying pathophysiology of the post hoc propensity matched analysis of patients in the moxie extension compared to patients from FAA comes demonstrating a significant slowing of disease progression and results from the post hoc delays started analysis, which are.
Consistent with <unk>, having a disease modifying profile and a persistent effect on the course of the disease with that I'll now turn the call over to Don.
Yes.
Okay.
Thank you Colin and good morning, I'll continue on slide 14.
Regarding development of <unk> for the treatment of Friedrichs ataxia and potential FDA approval represents advancement and hope for an underserved patient community. There are no approved therapies and only symptomatic treatment is available today.
If approved <unk> will be the first product to treat friedrichs ataxia with the potential to slow disease progression the commercial opportunity is significant.
<unk> is a rare disease with very low prevalence of devastating and life shortening disease affecting approximately 4000 diagnosed patients in the United States.
Like many rare diseases. Some patients may go under diagnosed until a specific treatment becomes available we believe that most U S. Friedrichs ataxia patients have been diagnosed and this is our target market at approval.
The undiagnosed patient estimate reflects potential future market growth.
<unk> treating diagnosed patients today have been identified providing focus for our commercial launch plan.
Patients are connected through community social media podcast and advocacy all platforms for disease education and information sharing.
Actively engaged in research over 1000 U S patients participated in FAA com or clinical outcomes measures. This voluntary study evaluate measures and monitors the natural progression of the disease quantifying the change in progression over time this highly engaged patient <unk>.
<unk> has eagerly awaited a treatment.
Turning to slide 15.
We have recently accelerated our U S launch preparation our commercial leadership team is in place representing all core commercial functions, including marketing market access sales and operations, we've hired the sales leadership team.
Brand strategy development is underway at our launch priorities are clear.
Over two years, our disease awareness and educational campaigns have highlighted the severe rare disease and the urgent need for treatment as.
As we prepare for launch our focus shifts to creating a brand educating hcp's empowering patients to seek treatment and creating access to therapy.
Next slide.
Our focus at approval will be to reach and educate hcp's with diagnosed <unk> patients in their practices.
Through claims data analysis, we've identified approximately 2500 hcp's treating at least one patient. We've also included a taxi or centers managing patients in our list of target accounts and nine U S. CCR and centers. These collaborative clinical research network.
Accounts are part of an international network of FAA research centers, where physicians researchers and patients work together to advance treatments and best practices for disease management.
S sites include the children's hospital of Philadelphia, UCLA, St. Jude Children's Research Hospital, and the University of South, Florida, and Tampa to name just a few.
With FAA targets identified our commercial focus at approval, we will focus on reaching in educating these most important HCP.
Our commercial team will expand to 55% to 60 employees next year, including our field based sales and access team we plan to hire the sales organization in Q1, they will be trained and deployed following approval in late Q1.
Turning to slide 17.
Best practice for successful rare disease specialty product launches includes a comprehensive patient access and distribution program.
We are pleased to introduce three out of reach or the reata education access and care helpline, which will serve as the single point of contact for both patients and physicians and will support access programs, including the management of new patient starts and benefits verification commercial co pay assistance uninsured.
<unk> support and tailored patient adherence and compliance program reached.
<unk> included an integrated and exclusive specialty pharmacy and be supported by our field based patient access liaison team.
A guiding light for the development of New services includes putting the patient experience at the front and center of what we do and working towards reducing the burden of patient out of pocket cost as a barrier to accessing treatment. The reorder reach program will go live at approval.
I'll now turn the call over to Manny for our financial update.
Thank you Dawn and good morning, everyone. We released our financials and filed our 10-Q earlier this morning I.
I would like to highlight a few financial items this quarter, including a strong cash position operating expenses and collaboration deferred revenue.
I will then provide an outline for our operational readiness for a potential commercial launch in the United States and the European region. If all of that is approved in those territories.
Let me start with our cash balance on slide 19.
As of September 30th we maintained a solid balance sheet with approximately $445 $9 million in cash cash equivalents and marketable debt securities.
Based on our current plan, our cash balance will enable us to fund operations through the end of 2024.
I wanted to highlight that since we repaid our prior debt from Oxford and Silicon Valley Bank in 2020, we have a clean balance sheet, and we have no existing debt or loans.
In addition liabilities related to a potential Blackstone royalty obligation and our balance sheet are only payable on botox loan revenues if blood oxygen is approved.
Blackstone has more rights on <unk> revenues.
Yes.
Moving to expenses R&D expense increased by $4 1 million for the three quarter for the three months ended September 30th.
2022, as compared to the three months ended September 32021.
The increase was due to personnel and personnel related costs to support our product development activities.
G&A expenses increased by $1 5 million or.
Our 6% for the three months ended September 30 of 2022 as compared to the three months ended September 32021.
The increase was primarily due to rent expenses related to the new headquarters building.
Both our GAAP and non-GAAP operating expenses slightly increased as compared to the second quarter of 2022.
As mentioned on the last quarter call. We have recognized all of the deferred revenues related to milestones achieved earlier under the QR code and agreement in the second quarter of 2022.
The result, we have not recognized any deferred revenues during the third quarter of 2022.
And any future revenues will be recognized once future milestone or collaboration revenues are owned.
We continue to work on completing the manufacturing of <unk> commercial drug supply in anticipation of a launch in the United States.
We have begun to hire resources built processes and systems to enable us to record product revenues practice, we were bold support government pricing and other related compliance requirements.
As we are preparing to submit an MAA for <unk> during this quarter we have.
Buildup of our European infrastructure to support a potential commercial launch of <unk> in the European region by early 2024 if approved.
Finally, I would like to highlight that we have strong intellectual property protection for <unk>, including three different patent families.
<unk> received FDA approval in early 2023, we anticipate the composition of matter.
Bantered upbeat in production could be extended to <unk> 37 in the United States. Additionally.
Additionally, composition of matter of patents, claiming Omar had been granted in Europe , Japan, China and more than 20 other territories.
With that I will turn the call back over to Warren.
Thank you ma'am and.
In closing we've made substantial progress in our <unk> program.
This includes the submission of additional information and analysis to the FDA, which we believe strengthens the body of evidence demonstrating the effectiveness of <unk> and FAA and the completion of the Leach cycle meeting if approved <unk> will be the first drug available for this severe disease and we're actively working on commercial.
Preparations to be in a position to potentially launch it early next year.
Next slide that concludes our prepared remarks, we'd like to thank everyone, who dialed in I will now turn the call over to the operator for questions.
Yes.
Ladies and gentlemen at this time, we will begin the question answer session. If you would like to ask a question. Please press star followed by one on your telephone keypad now AC change your mind. Please press star followed.
Please keep your questions to one question and one follow up.
Our first question today comes from Eke out not some of it from Citigroup. Your line is now open.
Hi, R&D team. Thank you very much for taking the question so around the labeling commentary in the press release and on the call can you. Please clarify are you actually in labeling discussions with the agency, meaning has the FDA actually sent the company proposed label yet or is it only been reached.
Spending in the SBA proposed label language. Thank you.
Yes, FDA stated in the agenda for the late cycle meeting that label review was underway.
We had a discussion in the meeting where we noted that the original proposed label language by US submitted in the NDA was now scale because of the amendments.
That we had made to the NDA.
And we asked them if they would like us to submit amended language, which we've developed for our MAA submission in Europe to the NDA and they said, yes, they'd like us to submit that to the NDA and then they have also indicated in the late cycle meeting that they would be providing us with comments.
On both the label and post marketing commitments in early 2023.
Okay got it so just to clarify so when you signet updated label will that be.
A new indication statement or will it simply be an amended label, which reflects the updated data submitted earlier in the year.
The major amendment and could you. Please say when do we expect the updated proposed label to be submitted to the agency given that they say theyre going to be reviewing it in early 2023.
Yes, so it will it's obviously going to reflect the additional data and analysis submitted to the NDA. So that can be taken account taken into account in the label that will be the primary change we will be submitting it very soon.
Because we've already developed that language for our MAA submission.
Got it thank you.
Our next question today comes from Madhu Kumar from Goldman Sachs. Please go ahead.
Yeah, everyone. Thanks for taking our questions. So I guess kind of a first of all unrelated to kind of thinking about.
Sure.
The timing for the late cycle meeting and they connect communications early 'twenty three.
It's kind of at a high level, how should we think about the kind of issues you need to be sorted through or are they really just about assessment of the data you guys submitted a few months ago or is there anything else beyond kind of the clinical data that needs to be looked at as part of the review process.
I think that the.
The main focus obviously will be.
Youtube just continue the review wrap it up on the FDA side to reach a conclusion.
And then obviously there is a process to go through if they decide to approve the drug there is a process to go through to work out the details of the post marketing requirements and the label those would be the main activities. If it's on a track to approval.
Alright, and then I guess.
Following project.
Okay.
I would just also add they didn't raise any new issues.
Either efficacy or safety.
For approval.
And.
<unk> stated that the existing issues were.
We're continuing to review they didnt request us to submit any additional data and they also noted that there were no outstanding information request that we hadn't satisfied.
Yes.
Okay and then.
Beyond this initial regulatory process, how should we think about kind of the plans for a pediatric trial and what do we need to see.
In terms of billing and when we can expect kind of a pediatric trial to start and how would that trial be.
Different and what have you learned from Moxie part, one and part two to influence the pediatric trial.
Yes. So this is colin so in our negotiations with the European authorities, we had to reach agreement on our proposed pediatric plan in order to submit our MAA.
And so we are actively planning to initiate.
Pediatric set of studies.
Obviously first we have to make sure we are giving the right dose.
<unk> is associated with the appropriate exposure to what was achieved in adults.
And then we will do a study to assess efficacy.
This will be done to not only satisfy the European requirements, but obviously.
Our age range was limited to a minimum of 16.
And moxie part too.
And we note that there are younger patients and so we would like to be able to lower the age range and any future.
Label, Yes, I'd, just like to add to that that we're aware we've received a lot of feedback from the patient community.
Both but in the U S and abroad.
They're very anxious to have the drug be available to patients below that 16 age group and so we're very aware of that and are very committed to moving forward with the pediatric study.
Hey, great. Thanks for taking my question.
Our next question is from <unk> <unk> from Guggenheim. Please go ahead.
Hey, guys. Thank you for taking my question.
Just a question on the efficacy front I think last time, you had said that the FDA continues to have comments on efficacy and then the moxie trial, maybe were insufficient to support a single study approval. During this late cycle meeting any color any discussion around.
Around that how is the FDA think about the efficacy side now and then the follow up question I have is with regard to the <unk> patient population will that'd be part of the label are you, including they've done and how youre seeing that thank you.
Sure Yes.
Yes, I think when they are in the late cycle meeting agenda and in the comments they made in the meeting.
Because they are directly related to the meeting the standards.
Standard for approval.
Course, we have a single adequate and well controlled study and then the issue is the additional evidence that we've provided in terms of the mechanism of action data.
The natural history data using for example, the propensity matched.
External control and the delayed start analysis or do those satisfy the requirement for confirmatory evidence I believe I believe that is what they are reviewing have we met that standard under phenomenal $1 15.
And in regards to your question about <unk> I would like to first clarify.
That the definition that we use for <unk> and Moxie part two was severe pest scabious and so patients had to have complete loss of lateral support their feet. So they basically had to stand on their feet and toes importantly, we took X rays of all patients in this study and even those who do not meet that definition of severe pest scabious did have pest.
<unk> in that they were different than the literature references for patients who do not have test gave us recall that amongst your part two.
The primary analysis population did not include <unk>.
Yet we saw a treatment effect in patients with severe <unk> importantly in our propensity matched analysis referenced.
Preprint.
That is available online with the pre submission menu.
A manuscript.
Out of the 136 patients a meaningful proportion of patients did meet the definition for severe pest gave us and we do see a treatment effect in those patients that is statistically not different than patients who did not meet the definition of <unk>.
So for all those reasons, we believe that patients who do not meet the definition.
Patients who didn't meet the definition of Ctrip escaped us would be included in the label.
Thank you.
Our next question comes from Charles Duncan from Cantor Fitzgerald. Please go ahead.
Yeah.
Hey, good morning, Warren and team. Thanks for taking our question lots going on this morning, So I apologize if I missed it.
Just kind of wondering if.
You've referred to some post marketing requirements would you see that is typical for friedrichs ataxia patient population or specific end driven by any observations on <unk> and then my second question is related to manufacturing of <unk>.
Have those manufacturing facilities and inspected and are you relying on a single site or multiple sites.
Yes.
Sure I'll take the.
I'll take the first question and I'll ask <unk> to respond on.
On the CMC.
With respect to the post marketing commitments.
Commitments those are going to come from for several sources.
First they gave us quite a bit of dispensation when.
When we submitted the NDA.
In that.
They allowed us to for example, as a post marketing requirement.
Do certain work on metabolites of <unk> post approval.
Carcinogenicity studies, they gave us dispensation on that that does could be submitted post approval.
And then specifically.
They they requested in this late cycle meeting they anticipated that they would.
Would be requiring as I mentioned, a drug drug interaction trial with <unk> hundred 80, <unk> modulators, that's because of the impact of the drug.
In connection with those <unk>.
Thorough Qt trial as.
As well as an evaluation of the pregnancy outcomes. They've also mentioned that although they haven't identified any major safety concerns.
And they clearly stated that they had no issues related.
Two the risk management identified to date and also they did not see the need for a rems.
Considering whether they need to have some characterization of the long term effects of <unk>.
On the liver in the heart because the observed <unk>.
Clinical chemistry changes in transaminase and BNP.
Wed plan to address that we had already proposed a registry study, we would propose to address that and.
And tracking outcomes in a post marketing registry study.
So I think these are fairly straightforward based on the standard requirements for approval as well as observations that have been made during the review.
That's helpful. Thank you and then regarding manufacturing.
Sure sure sure. So this is I mean and.
As I said earlier, we will continue to work on completing the manufacturing of <unk> commercial drug supply and.
In anticipation of the launch.
To answer your question, we have couple of <unk> by a couple of contract manufacturers.
We are working with to do that and we have been working very closely with all of them and we believe they are very well prepared for the FDA inspection of the drug product and the API manufacturing sites and.
The companies are the CDM hauls, which we are working with a very well known who regularly receive FDA API inspection and we've worked with them on a continental basis. So.
That's what I could.
Does that answer your question.
Yes. It does can I ask a question about European.
Commercialization I guess my quick question is what are you thinking about in terms of strength strategy, there, which you would you seek a partner or do you think that you can execute well going on.
Yeah have you recall.
End of 2019, we.
Acquired European rights from Abbvie, and our intention and strategy has been since then to go and launch in Europe data can you over there.
Obviously, we will assess all.
Everything will be on the table, but right now we are planning to launch directly we have hired our leadership team, including marketing Bears Medical affairs, all up and established very recently and we continue to enhance the infrastructure over there the next coming quarters.
As we plan to file it.
Yes.
Got it thank you.
Yeah.
Our next question comes from Carter Gould from Barclays. Please go ahead.
Good morning, Thank you for taking my thinking.
Other questions.
Maybe we've changed it up a little bit.
Do you think about I don't know if there any lessons you guys has incorporated that you'd think about other recent neuro launches and go to market strategy and some of the pushback agencies.
Maybe just kind of best practices as well as you think about potential commercialization early next year and then separately just as we think about our docs alone.
Obviously youre going to have.
The Japanese study is going to read out early next year is it the chance to engage with FDA.
Based on that data versus also having to wait for Falcon, just given sort of the paced timeline to enrollment there. Thank you.
Hi, Carter this is Don I'll take your first question. So as we think about commercialization early next year, we've been preparing internally for quite some time and putting a lot of effort into understand the market the patient community and so as I consider other rare.
These launches this is really critically important to gain support of the community well beforehand, and so <unk> been quite engaged on this front for quite some time.
We have also scaled the organization very appropriately and carefully.
And we believe that we've got the right head count in place and we continue to grow with the regulatory progress that we make.
And so we've done a bit of work now to understand the target market audience, who are the treaters that essay and we know who they are and where patients are in the United States and we will be focusing our initial commercial efforts in that particular area. So with rare diseases, it's quite complex because some patients go undiagnosed.
Note until Theres a therapy available. So we're very fortunate that with assay. We believe that most of that patient population has been diagnosed and it really helps guide our effort and so in terms of commercialization and contracting to other launches I can really look at the preparation that we've taken.
And really highlight the fact that we've been very aligned with the communities that are necessary. So I hope that answers your question.
Yes, Carter I would add one more thing, which I know we are working very actively as is.
See the peers, while we have been very actively engaged with the payer community and increasing awareness of <unk> and <unk> and predict ataxia rights all of that has been initiated and we believe that will help us.
<unk> launch as we proceed in the next coming quarters, yes, So I'll take the.
The question on <unk> alone of course, we were very disappointed.
To receive the CRM for <unk> in output syndrome.
Personal belief is that the.
The principal issue that we have had with the approval of our docs alone.
Is that it's it's so novel.
Acute improvements in Egfr.
Which are driven by improving mitochondrial function in the kidney.
It's a very different approach, it's been taken and the improvements have been unexpected.
And obviously it raises the question of whether those are driven by.
Pressure being pressure mediated or some other effect that might be harmful in long term dosing.
The <unk> study should definitively answer that question.
It's a very large study over 1000 patients.
The <unk> in Japan.
<unk>, our partner Kiowa Kirin to.
To run the study so that every patient would have at least three years of exposure. So that means that most patients will have at least three and a half years of exposure to the drug.
It's large enough to collect to give a read on outcomes, both the positive or negative.
So if that study is positive I would say if it's unequivocally positive. So that there is a meaningful reduction in the events that have been validated to predict the risk of end stage renal disease, I think that will change the landscape for <unk> and I think that data could be.
Gordon and re engaging.
Both with the FDA.
As well as.
With the regulatory agencies around the world and the Nephrology community I think the data will be important in answering this fundamental question about paradox alone.
Did that answer your question.
Thank you.
Okay.
Our next question comes from Annabel <unk> from Stifel. Please go ahead.
Hi, Thanks for taking my question just a couple here.
First on <unk> I know that when you submitted the.
The additional three year data one of the reasons wants to answer a question for FDA that it wasn't.
Patients who discontinued patients you just hadn't been.
Followed up.
It's highly fashion due to Covid will you be required to submit any further patients who have completed.
Three year data just to complete the set.
Dataset.
And then secondly, just as you think about the <unk>.
<unk>.
And you mentioned that hair.
But having payer discussions.
Can you describe what you expect the onboarding process to be I mean, I know that the patients are pretty well.
<unk> identified and its a type population so they shouldn't that can be really it probably looks it raises awareness among them, but maybe among payers.
Difficult to process do you expect that to be and the timing of the onboarding from the time that you launch to getting first patient in.
Yes, I think I'll have Collin address the delayed start.
Analysis question and on address the on boarding question.
Yes, Annabel so to answer your question. The FDA has not made any additional requests.
For any new data since we submitted.
Dated data.
After the mid cycle meeting and I believe your question is in reference to the delayed start analysis.
Where FDA question, whether or not the.
Low in at certain time points was due to patients who discontinued or simply missing data due to COVID-19 and so recall in the mid cycle meeting.
We clarified that the discontinuation rate had been low, but only approximately 16% and that the vast majority of patients still continue in the study.
And since Covid has been impacting.
The country less patients have been able to come back and.
And because of that we have additional data at the later time points as well as that new time points that further demonstrates separation and the delayed start analysis. So for all those reasons FTA. Thus far has not requested any additional data.
Don.
Yes, Thanks, Colin and so to address your question related to to Payors and essentially adopting I'll never locked alone.
Our product on their formulary and available to patients for reimbursement. So we began discussions with payers back in March and we focused on.
<unk> disease severity educating and informing about this deadly disease, which most payers quite honestly did not have any understanding of and so generally we believe that payers will create re embark reimbursement policies that will follow the approved label and so our goal is to make sure that payers.
Are covering.
<unk> to label and so that will take a little bit of time for payers to update their policies. So we're anticipating anywhere between four and eight weeks some payers may move a little bit more quickly, but initially we think it will take a few weeks and then.
Following several months of launch we think that will take much much less time.
Thank you.
Our next question comes from Maury Raycroft from Jefferies. Your line is open.
Hi, Thanks for taking my questions.
I just wanted to clarify at this point has FDA commented on or provided reasons why they canceled your AD com and did it have anything to do with the <unk> experience.
They they have not commented that not provided any specific reason for canceling the ad com.
But obviously the context of this is that in the mid cycle meeting.
<unk> com.
Commented about whether we had met the standard.
For confirmatory evidence.
We went into the mid cycle meeting prepared to address that issue.
With all of the data that.
And analyses that Colin mentioned.
The elucidating the mechanism of action.
Of <unk> in the context of the pathophysiology of MFA.
We did the propensity matched we proposed the propensity matched analysis external control study and.
And we updated the delayed start analysis all of these were submitted.
As amendments to the NDA. In addition to that we did additional work on the secondary endpoints and provided them data on a global statistical test and how that would support.
Good support from secondary endpoints all of this went into them after the mid cycle meeting.
As you point out the analytics Advisory Committee meeting then did occur and obviously a lot of that meeting was about what the regulatory standard was for confirmatory evidence.
And all we know is that after that they let us know that they were not planning to have an advisory committee meeting, but they never explain their rationale in this context just their decision.
Got it that makes sense and one other question just for the K K see phase III data in first half 'twenty three based on the baseline Egfr requirements for that study, which I think are lower than some of your other part excellent studies what are your expectations for the REIT.
And can you provide more specifics on what next steps would be to leverage the data in the United States.
Hey, Maury, it's Colin and so obviously, there's a lot of data that's being generated within the trial and so from an efficacy perspective.
We would hope to see that barack slowing it reduces the rate.
Events in the primary analysis, which include actual dialysis events as well as confirmed 30% reduction in Egfr, which has been shown to be predictive of.
Kidney failure events as well as confirmed egfr of less than six and so.
Best case scenario, there is a significant reduction in.
And the primary endpoint that the secondaries are significant and that there is no new safety findings and so there is there is actual dialysis events being accumulated obviously in the primary endpoint.
So.
Best case scenario would be that those directionally favor blocks alone.
And if we see data that supports that the drug over the long term.
It reduces the risk of kidney failure and has.
An appropriate safety profile, we would then want to leverage that as Warren said with global regulatory agencies. Since it does address some of the fundamental questions about <unk>.
Got it okay. Thanks for taking my questions.
Thank you and again, thank you for your participation on today's conference call. As a reminder, I know again recording of the call will be available shortly often call on <unk> website at react to pharma dot com in the investor.
Section. Thank you very much for your participation today you may now disconnect.
Okay.
Okay.