Q3 2020 Reata Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to the Reatta Pharmaceuticals third quarter financial results and update on development programs. At this time all participants lines are in listen only mode. After the speakers presentation there'll be a question and answer session.
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An audio recording of todays webcast will be available shortly after the call today on Riyadh is website at Reatta pharma dot com in the Investor section before.
Before the company proceeds with his remarks. Please note that the forward looking statement disclosure in the company's press release, the company will be making forward looking statements on today's call.
There are many factors that could cause results to differ from expectations, including those noted in the Companys SEC filings.
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I'd now like to hand, the conference over to your Speaker day, Videojet Dahl Vice President of strategy. Please go ahead Sir.
Thank you good.
Good morning, and welcome to Reatta management call to discuss our financial results for the third quarter of 2020 and to provide a review of our development programs.
This morning, we issued a press release with the summary of our financial results and the results of the baseline controlled study of them Avelox alone in patients with Friedreichs ataxia.
Definitely we issued a press release announcing data from our Cardinal study a box on DAPL and patients with CKD caused by Alport syndrome, and from Eagle or long term extension study of Murdoch's alone in patients with Alport syndrome.
These press releases can be found on the Investor section of our website at Reatta pharma Dot com.
I'm joined today by our Chief Executive Officer warrant Huh.
Our Chief Research and development Officer, Colin Meyer, and our Chief operating and Chief Financial Officer Manmeet Soni.
Turning to slide three I'll now turn the call over to one.
Thanks, Manny good morning, everyone and thank you for joining us we have a number of important announcements and events to cover today, including the Cardinal phase three year. Two study results that we announced this morning.
Regulatory update on our Alport syndrome program and with respect to our friedrichs a taxi a development program. The results of the Moxie baseline controlled study.
We will also be a financial update.
I apologize in advance for the length of the management presentation, but we have a lot to cover and we're going to start with the Cardinal phase three year two study results.
This morning, we announced positive topline results from the completed pivotal Cardinal Phase three study of our docks alone in patients with chronic kidney disease caused by Alport syndrome.
Cardinal was the largest global interventional study ever conducted in Alport syndrome last year, we announced that we met both the primary and key secondary end points at the end of year one of the Cardinal study, we're very pleased to announce today that we met both the primary and key secondary endpoints at year to where the Cardinal study.
Alport syndrome is a severe form of chronic kidney disease or CKD and many patients with the disease have a 100% lifetime risk of needing dialysis or kidney transplant.
Children and adults with the most severe form of the disease need dialysis or kidney transplant in their twentys, it's a devastating disease that not only affects their kidneys, but also results in depression, and anxiety hearing impairment and vision and I problems.
The patients with Alport syndrome enrolled in the phase three portion of Cardinal we're losing substantial amounts of kidney function when they entered the trial.
After two years in Cardinal patients on placebo lost on average approximately 9 billion liters per minute of estimated glomerular filtration rate or EG fr. The pediatric patients lost on average approximately 15 mills per minute and we're at substantial risk of kidney failure within five to seven years.
[laughter].
Importantly, more than 20% of the placebo patients experienced an event that predicts kidney failure, including a 30% decline in EG fr and EGI fr of less than 15 milliliters per minute or actual kidney failure. We refer to these events is the kidney failure composite events like.
By contrast, after two years of treatment patients treated with paradox, one last on average less than one mill per minute, while on treatment and 4.5 no per minute after withdrawal of treatment. The pediatric patients treated with paradox was lost on average approximately one to two mill per minute on treatment and after withdrawal the treatment importantly paradox loan pay.
She has had a 50% reduced risk of one of the kidney failure composite events.
In addition to the Cardinal year to date.
Also reported data on kidney function for patients with Alport syndrome. After three years of our docks loan treatment during the Eagle long term extension study increases in EG are far from baseline observed after one year of treatment for sustained on average for three years, providing additional insight into the long term.
Effective barge docks lung and kidney function in these patients.
From a safety perspective, the adverse event profile was consistent with prior trials. The majority of adverse event mild to moderate and severe any serious adverse events were reported in approximately 50% fewer bard oxygen patients compared to placebo urinary protein was not increased relative to.
Placebo after two years in part oxygen patients reported fewer non kidney adverse events associated with Alport syndrome.
No imbalances in fluid overload events or increases in blood pressure were observed in summary, paradox loan had a favorable safety profile in patients with Alport syndrome.
Based on these efficacy and safety results, we believe that paradox loan has the potential to become the first therapy to show disease modifying effects in patients with Alport syndrome.
With that background on the efficacy and safety results I'm handing it over to Collin to provide more detail on the study design the results and the regulatory pathway for docs loan in Alport syndrome patients thing.
Thanks, Morgan Alport syndrome, as the second most common inherited cause of kidney failure diseases caused by mutations in genes that encode for type four collagen, which comprises approximately 50% of the filtration barrier in the kidney these mutations cause chronic inflammation, leading to fibrosis and progressive loss of kidney function. These patients not only.
Progressive loss of kidney function, but also have hearing loss and awkward abnormalities. There are no approved therapies for Alport syndrome.
As we mentioned Alport syndrome is among the most severe forms of CKD due to its rapid progression many patients require dialysis or kidney transplant at a much younger age than other forms of CKD mini Alport syndrome patients have a 100% lifetime risk of kidney failure that patients with the most severe forms the disease reached kidney failure.
At a median age of 25 Psycho social burdens such as anxiety and depression are the most frequently reported symptoms that impact patients daily lives in effect, an estimated 27% of patients.
The phase three Cardinal trial is a randomized double blind placebo controlled international study that enrolled 157 patients at approximately 50 clinical trial sites in the United States, Europe, Japan and Australia.
Study enrolled patients across a wide range of beach kidney function and genetic sub types that we believe represents the broad population of patients with Alport syndrome patients were required to be on standard of care Ace inhibitors are entered Tencent receptor blockers unless these were medically contraindicated study subjects were randomized one to one to either box.
<unk> or placebo and the total treatment duration was two years patients were initially treated for 48 weeks and then withdrawn from studied rod for four weeks. Following this four week off treatment period patients for restarted on their original treatment assignment and continued on study drug for another 48 weeks a week 100 patients with.
Drawn from study drug the second time in the last assessment occurred at week one of four after another four week off treatment period, as we reported last year. The trial met its year, one primary and key secondary endpoints. The year. Two primary endpoint is the change in EG fr from baseline and compared to placebo after 100.
Weeks of treatment. The your two key secondary endpoint is the change in each year far from baseline compared to placebo. After 100 weeks of treatment and four weeks of treatment.
The Cardinal trial was challenging to conduct due to the two year duration in that 18 required in clinic visits.
Total of 13 placebo patients discontinued from the trial twice the number of Bard oxygen patients discontinued. This you can see in the table. Most discontinuations occurred in the first year you balance was due to two factors excess adverse events contributed to part of the imbalance and no more than two patients discontinued due to any one item.
This event.
Protocol specified criteria accounted for the remainder of the imbalance and these were generally due to our conservative approach to managing I mean, you're transferring celebrations. We now have a much better understanding of these changes in a recently published data demonstrating that paradox loan increases production of them you know transfer cases, which we believe explains the increase is observed clinically.
Clinical profile is consistent with a pharmacological effect that is not associated with liver injury. As these changes are reversible and our associated with reductions in bilirubin, suggesting improvement liver function because of this understanding we have adjusted these criteria in newer protocols have been able to manage these elevations by adjusting our titration approach.
Furthermore, the second or the trial was conducted during the COVID-19 pandemic to maintain the integrity of the study and minimize missing data. We proactively worked with sites to obtain in this study visits for almost all patients, including those who discontinued early our efforts were successful in 98% of patients completed follow up this.
Hi percentage is important for data integrity.
Cardinal successfully met its your two primary endpoint of improvement in EG Afar at week 100. After approximately two years of treatment compared to placebo. The ITC analysis demonstrates that patients treated with Murdoch salon experienced a statistically significant placebo corrected 7.7 mill permanent improvement in.
Mean change from baseline in EG, a far compared to placebo with the P value of 0.0005.
Cardinal also successfully met its year two key secondary endpoint of improvement in Egypt far at week, one of four after approximately two years of treatment followed by a four week treatment period. The ITC analysis demonstrates that patients treated with murdoch's loan experienced a statistically significant improvement in each fr 4.3 million.
Minute compared to placebo the P value equal to <unk> 0.02. This difference is over three times as large as the treatment effect observed with 12 apt and the reprise trial in patients with ATP Kt, which is a more slowly progressive disease, we believe the slightly lower placebo crafted differences in year two.
So to your one resulted for two reasons first the placebo rate progression was more pronounced in year, one rather than constant across both years in year, one placebos lost approximately five to six more permanent but in year. Two the loss was less only approximately three to four minutes per minute second because cardinal is a two year try.
While the ITC analysis at your two includes patients who discontinued early including those patients who discontinued in year, one and had not been receiving treatment for more than one year. This analysis made therefore under estimate the treatment effect because it includes data acquired long out withdrawal study drug.
We also analyze the data using the pre specified modified T method that was also used in the reprise trial of toll Baptists in patients with autosomal dominant polycystic kidney disease. This analysis uses all randomized patients, but sensors values received after discontinuation of study drug and shows the effective.
At Oxford treatment for patients, while they continue to receive drug to placebo corrected improvement in EG afar at week 100, using the MIT analysis was 11.3 more per minute with a P value of less than 0.0001 in summary, we believe these on treatment results demonstrate a very clear.
Equally meaningful treatment effect in a population that is rapidly progressing to kidney failure. The maintenance of the off treatment effect you are too from year. One it provides evidence of potential disease modifying activity, which could result in a substantially slower loss of kidney function that leaves the need for dialysis or kidney transplant.
The next slide shows observed mean changes from baseline in EG, a far overtime as you can see the improvements in each year far with box loan treatment were maintained versus placebo over both years of treatment. One important aspect of the trial is that the treatment its not continuous due to the four week off treatment period after.
The initial 48 week treatment period, the second year of treatment begins at week 52 and continues for another 48 week period. The week 52 off treatment value represents a new baseline for evaluating the effect of the drug during your two placebo patients progressed, we lost kidney function over both years and the rate of rock loss was approximately five.
Well for a minute in year, one and approximately three and a half mile per minute and you are too by the end of the second year of placebo patients had lost approximately nine more per minute.
We analyzed the IGI, if our changes over time for the paradox when patients using the ITC and MIT analyses I just discussed in contrast to the placebo patients at the end of year two murdoch's when treated patients were above their baseline values using both the ITC and modified ITC analyses. They are your two base.
Find value at week 52 was approximately five will permit higher than placebo because the off treatment EG. If our increase observed after one year of treatment. When we started on box loan in both analyses.
Patients had an increase in Egypt part three weeks 64, the IBT population gradually lost a portion of this increase over time. This group includes patients who discontinued treatment in year, one and the observe means therefore to include patients who had been off treatment for one year or more and behaved like the placebo population. This is the reason for the apparently.
Loss of EG, a far at the end of year. Two by contrast, using the modified T analysis part oxygen patients on study drug maintained at most to each of our increase observed at week six before and continue to experience a slower rate disease progression than placebos. Thus.
Thus the separation that was observed in the first year was maintained in the second year with no evidence of loss or convergence of the treatment effect, especially for patients remained on treatment. These results are consistent with an inconsistent with an adverse effect on kidney function and support a beneficial effect with paradox when treatment that may result in delays.
Need for dialysis or kidney transplant.
The next slide shows the data for Alport syndrome patients that have had the longest duration of box on treatment as you can see on the slide 14 patients have reached three total years of treatment with Barack slow.
The data shown are for the same 14 patients overtime showing their data for years, one and two in the Cardinal study and your three from the Eagle extension trial the pattern of IGI apart changed for these patients is similar to the Cardinal data discussed above after year, one and two the patients are withdrawn from drug and establish new baseline at the beginning of both years.
Two one year three these off treatment values were above their baseline value from the beginning of the study when we started on paradox loan subjects had an increase in each year far from their new baseline that was for the most part maintained through the end of the year Importantly, Alport syndrome patients are high risk for progression to end stage kidney disease, but.
For three years about ox on treatment that IGI, if our values that are meaningfully above their baseline values at the beginning of the study.
Even though the trial was not powered were designed to show a difference in adverse kidney outcomes. We pre specified analysis of an established can you tell your composite. This composite is defined as EPS Katie confirmed 30% each of our decline were confirmed EG a far less than 15 milk a minute. This composite is important.
Because it includes heart events, such as dialysis or kidney transplant and events that have been validated to predict risk of yes, Katie 17 placebo patients experienced an event in only nine burnt oxygen patients experienced an event the risk of an event was reduced by 50% in the box one group with a hazard ratio of <unk> 0.49, an appeal.
Hi of 0.086 that trended towards significance or these data do not provide definitive evidence that Oxford reduces events. They do demonstrate that within the cardinal trial, but oxylate patients experienced fewer clinically meaningful adverse Kevin events.
The change in easier far at week 100 in the pre specified subgroups as shown on the next slide as you can see all subgroups favorite box loan efficacy was observed in pediatric patients and adults males and females in patients with high and low albumin area and easier far those on standard of care and those with X linked.
Autosomal genetic sub types of Alport syndrome.
One of the most notable efficacy findings of the trial is the effect in pediatric patients as discussed earlier. These patients have the most rapidly to progression, resulting in the need for a kidney transplant or dialysis. When most patients are in their twenties, the historical rate of decline for pediatric patients and cardinal prior to their entry into the trial.
<unk> was approximately 10 million per minute per year, the pediatric placebo patients lost approximately 15 they'll per minute by weeks 101 to four given the baseline SFR at the start of Cardinal you observed decline rate would be in the need for dialysis or transplantation and approximately five to seven years the pediatric.
In summary, with the box loan had a very large improvement in Egypt far at weeks 101, or four relative to the pediatric placebo patients, which produced a statistically significant improvement versus placebo in this subpopulation of approximately 15 mile per minute the treatment effect observed with our docks in the pediatric population represents an.
Important milestone for patients with Albert syndrome, the greatest risk of progression to kidney failure.
As shown on the next slide a similar proportion of patients reported adverse events in each group there were no desks and Cardinal and the number of patients who experienced a serious adverse event or say easy in the box on group was approximately half the placebo rate importantly, there were no fluid overload or cardiac SCS impart oxygen patients.
And no essay ease were recorded in pediatric patients treated with box loan discontinuations due to adverse events were higher in the current Oxylate group and no individual he contributed to more than two discontinuations as seen in the bottom table. There were no imbalances and other AG categories of interest overall the rate of infections was the same.
Across both groups there were numerically fewer nervous system vascular cardiac and malignant cancer adverse events reported in the Broxton group compared to placebo group.
The adverse events reported in greater than 10% of patients as shown on the next slide overall the AG profile was consistent with prior trials. The majority of adverse events were mild or moderate intensity and most of balances have been well characterized and believed to be pharmacological effects of the drugs that are not associated with injury muscle spasms are not assume.
Issue with evidence of muscle injury as we recently published a multi an assay elevations are thought to be pharmacological effect of the drug as Bart OXXO increases production of these enzymes clinically there was no evidence of liver injury, including no cases of Hys law and these changes were associated with a reduction in total daily revenue mile BMP increase.
Says are not associated with PPL blood pressure elevations or fluid overload adverse events and weight loss was more pronounced in patients with higher BMI mean decreases in way were not observed in pediatric patients hyperkalemia events have not been previously reported were mild in almost all occurred in patients receiving an ace inhibitor for air.
Which can cause hyperkalemia. These events were not associated with any discontinuations or Esa use.
As shown on the next slide blood pressure, which is a sensitive measure of fluid status was unchanged relative to placebo no imbalances and adverse events associated with fluid status, such as hypertension or peripheral edema were observed as mentioned previously no essay ease of fluid overload occurred in patients treated with murdoch's loan we.
I believe these data together with data collected in multiple clinical trials that have enrolled over 2000 patients in the past several years without any signal for fluid overload demonstrate that our risk mitigation strategy for fluid overload has been effective.
Albumin urea measure does that urinary albumin creatinine ratio or are you. A CR is typically increased in patients with alport syndrome due to defects in the filtration barrier the kidney since part oxon increases the kidneys filtration rate in acute increasing you HCR is observed in this effect is accounted for by the increase in each fr. After.
This early increase you will see our did not further increase in remained stable through two years of treatment by week 100, the U.S share value in the paradox. One group was lower than that observed at week 12, and 48, while the placebo you a CR increased in year two relative to year one.
Both week 101 or for you STR was not significantly different between the paradox, one and placebo groups. This pattern is consistent with an initial pharmacological increasing new SCR due to increased filtration and not consistent with entry, which will cause a progressive increase overtime that separates from placebo.
Non kidney symptoms associated with Alport syndrome include depression anxiety hearing in particular disturbances. In addition in AI problems as can be seen in the chart adverse events for all of these categories were meaningfully reduced import oxygen patients fewer knocks on patients reported psychiatric adverse events, including depression anxiety.
As well as hearing of a steeper adverse events.
As shown on the next slide the Cardinal data address other questions that happened radius regarding the profile of our docks loan there are likely to be review issues. During the NDA process. The Cardinal data are helpful to clearly demonstrate that the profile of our docks loan is inconsistent with a known profile hybrid filtration hybrid filtration, which is exemplified.
I am moda pain associated with a deleterious pressure mediated and modest initial increase in fr that peaks. After six months and thereafter is associated with the steep easier far decline since hyper filtration causes injury to the filtration Barry the kidney albumin nuria progressively worsens over time.
Bart oxen has a novel anti inflammatory and HP pipe Roddick mechanism of action that is not associated with changes in glabellar pressure in preclinical models in Cardinal the initial increase in EG a far is much larger than what has been observed with ammo to pain in a sustained for three years. It is associated I'm sorry.
Not associated with evidence of accelerated loss of kidney function or progressive worsening of albumin area. Furthermore, badakhshan reduced the risk for adverse can the outcomes that would conversely be increased if its mechanism or hyper filtration. We therefore believe the cardinal data provide very strong evidence demonstrating that paradox lens pro.
File is inconsistent with hyper filtration.
Regarding discontinuations patients, who discontinued Blackstone performed no different than placebo patients at the end of the trial. These smart oxygen patients had an average treatment duration of 33 weeks and the EG a far was not significantly different than placebos at weeks 100, and mean and median changes were similar.
These data demonstrate that these patients behave like placebos once the discontinued and did not demonstrate any worsening beyond what was observed in the placebo group.
Separately, we performed a sensitivity analysis to compute the off treatment, Egypt part change at week, one or four using the same methodology that was used in the reprise trial of pullback than an 80 PKD as shown on the slide the estimated off treatment FGF our change in P value using the reprise from methodology are very soon.
Once the results from the pre specified and primary methodology for Cardinal. Additionally, the treatment effect with our Doksone. We won a foreign Cardinal is over three times as large as the treatment effect observed with pullback often in the reprise trial in patients with 80, PKD, which is a more slowly progressive disease.
Lastly, we have evaluated the time to resolution of the acute increases in EG, a far using our integrated summary of safety dataset, which contains data from over 3000 patients and has off treatment values that ranged from one day to many weeks post discontinuation it demonstrates gradual loss it easier far within the first two.
Weeks post discontinuation that plateaus beyond a 14 in our protocol the target date to collect the off treatment. Each CFR value was 28 days after the last dose due to operational considerations. Some of these visits happened before and others occurred after day 28, almost all early values occurred within a few days of day 28.
And only one box land values collected before day 21 overall, the mean and median days off drug were 35, and 28 days, respectively. Therefore, the off treatment data collected during cardinal are appropriate to assess the persisting effector Murdoch Sloan after resolution of the acute increase in EG a far.
The overall conclusions of the trial are shown on the next slide as mentioned earlier Alport syndrome is a rare severe disease with no approved therapies the rate of loss of kidney function is rapid and drives the need for dialysis or kidney transplant at a very young age for many patients Cardinal was the largest interventional trial conducted in patients with Alport syndrome.
All year, one and year, two primary and key secondary efficacy endpoints were met and demonstrated clinically meaningful improvements in each CFR. The largest treatment response was observed in pediatric patients who have the highest risk for kidney failure. The composite of kidney failure events was reduced by 50% and the safety profile was consistent with prior.
Trials without any major safety signals in summary box on has the potential to become the first therapy to show disease modifying effects in patients with Alport syndrome.
Ill now provide a brief update on the regulatory status. We recently completed a pre NDA meeting with the FDA to discuss the India submission and content plans as part of the pre NDA meeting the ft confirmed our India content and data plan, including the presentation and content of our safety data and the adequacy of our non clinical and clinical pharmacology.
RG programs. In addition, the ft confirmed their agreement with our manufacturing scale stability program and testing plans and provide a comments regarding their expectations and recommendations for testing and analytical method development. The ft indicated to date do not foresee an impediment to a filing based on what was provided to after you did indicate.
That while decision can only be made after submission. They do anticipate an advisory committee meeting based on the meeting results. We plan to proceed with an India filing for for marketing approval. In Q1 2021. We're also continuing our preparations to file for marketing approval in Europe with that I'll now turn the presentation back over to Warren.
Thanks Collyn.
I'd like to briefly comment on the effective COVID-19 pandemic on the Cardinal trial, the second year, a cardinal was challenging to conduct since it occurred during the height of the COVID-19 pandemic in Europe and the us.
The 19 has serious implications for patients with CKD. Since these patients are at increased risk of severe illness.
Beyond the inherent risk of COVID-19 to CKD patients it pose significant operational challenges to the study conduct which were not unique to cardinal as all of you are aware many countries in local jurisdictions were locked down many sites closed or restricted access to study patients for many month period and even when these restrict.
Ones were lifted many patients were unwilling to travel or attend in clinic visits.
To accommodate the COVID-19 logistical challenges, we work with our study sites and suppliers and partners to Institute several measures since scheduling was difficult for study sites and patients we relaxed visit windows to increase scheduling flexibility for patients to conduct visits as we previously discussed we allowed direct shipping of.
Study drug to patients and arrange for home health nurses to travel to patients homes to conduct study visits to understand the impact of Carbonite team, we documented all covenant related disruptions.
The clinical trial sites investigators, our suppliers and partners and the patients and their families. In the study took extraordinary steps to complete Cardinal successfully.
On behalf of everyone at Reata I'd like to extend our sincere gratitude to all of them for their cooperation in the conduct of the study in the face of truly unprecedented challenges. The results. We announced this morning would not have been possible without their efforts and commitment to this program.
We'd now like to provide an update on our development program in Styrenics attacks here.
As we announced during our second quarter earnings call. The FDA provided us guidance that we will need to conduct a second pivotal trial that confirms the m. far as a result of the Moxie part two study with a similar magnitude of effect.
As an alternative we proposed a second study the baseline controlled study previously called the crossover study in which patients service their own controls and changes in EMD forest during the pretreatment period in either part one or part two of the moxie study or compared to changes in M. Fars during the treatment.
Period in the open label Moxy extension study the.
The FDA has stated that they would consider this study and determine if the results increased the persuasiveness of the part two results sufficient to support submission of an anda for Omar.
We're pleased to announce today that the baseline controlled studies successfully met its primary endpoint and that all pre specified and sensitivity analyses demonstrated a significant treatment effect. We believe that these results provide support for the positive and far as result of the Moxie part to study and strong additional evidence.
The effectiveness of Oman and patients with ebay.
With that I'll have call and provide more detail on the study design and results.
Thanks, Warren the objective of the baseline controlled study was to help assess the strength uncertainty of the positive primary endpoint findings in the Moxie part two study evaluated the efficacy of Allomap treatment in the Moxie extension and patients who were considered treatment naive prior to initiation of OMAP treatment. This included patients Remoxy part one.
Who had been off drug for approximately two to three years prior to entering to the extension as well as the placebo patients from oxy part two.
Patient serve as their own controls to assess changes in empires with a comparison of their pre treatment to treatment periods. The pretreatment period for Moxi part one patients was from their entry into Moxy part one to the day of entry into the Moxie extension. These patients were followed off treatment for a minimum of 21 months before entering them.
Oxy extension the pretreatment period for the Moxie part to placebo patients was the 48 week placebo period during part to the treated period for both sets of patients was defined as the mox extension.
The primary efficacy endpoint the baseline controlled study was the paired difference in annualized in far slope in the treatment period during the mox extension relative the pretreatment period during part one or part two the primary analysis population included part one and part two placebo patients without pesky this quite an EPS.
Pars assessment at week 48 of Mox extension importantly, the baseline Conns controlled study maintain operational and analytical rigor. The imparts assessments were conducted in a similar manner and rigorous throughout moxy part one part two and extension even though the mox extension is open label all invested.
Theaters in patients remain blinded to prior treatment assignments. Additionally, all analyses will perform using the mox extension database lock that occurred just before we Odyssey public announcement of the crossover study and the data we are therefore, not biased by the knowledge of the importance of this study.
As shown on the next slide that baseline controlled study demonstrated statistically significant evidence of efficacy for the primary endpoint of the pair difference in annualized in far slopes between the treatment and pretreatment periods in the primary analysis population with a 3.76 point improvement and P value of 0.00.
To to evaluation of the data for patients Remoxy part to impart one separately also demonstrated a statistically significant treatment effect consistent with the primary analysis based on controlled study and part two of the Moxie study all three analysis populations, including the primary analysis population the party.
[music] placebo population and the part one population on average demonstrated worsening during the pretreatment period and an improvement in reversal of disease course during the treatment period.
We also conducted a pre specified analysis of the pair differences between the part one and part two populations to determine if they were different the mean and median pair differences were similar across both populations and there was no significant difference between the pair differences of patients from part one and part two with a P value of zero.
<unk> 0.53, these data confirm suitability for pooling of these populations for the primary analysis population and demonstrate that the primary results were not skewed by either of the populations.
Sensitivity analyses will perform to assess multiple alternate methods for calculating slope and comparing treatment and pre treatment periods. Additionally, the all enrolled population was assessed which included patients with and without pesky bus.
The multiple imputation analysis imputed value for patients with at least one value in the Moxie extension, what I'm missing week 48 value. The linear regression analysis used all available imparts assessments to calculate slopes the mix model analysis estimated MPAR slope for each period and did not require paired values as fee in the table all.
Analyses consistently demonstrated a significant treatment effect and upheld the conclusion the primary analysis.
In conclusion, the baseline controlled study met its primary endpoint of pair difference in annualized in far slow with a statistically significant difference between the treatment and pretreatment periods in the primary analysis population with a P value of 0.00 to two and all sensitivity analyses of the primary analysis sort of signet.
Second treatment effect additional categorical analyses, which were not discussed in the prior slides demonstrate that these results are robust and unlikely due to chance. Thus we believe that the results of this baseline controlled study, which utilize patients as their own control support the positive in par's results of Moxy part two and provide additional evidence of the effective.
Miss of Oman and FX.
In our type C meeting with FDA Division of Neurology products, one doctor done with the director of the office of neuroscience that the FDA acknowledged they would consider opportunities to increase the persuasiveness of the moxie partly results we discuss our proposal to utilize in parse data from patients who crossed over to Omar treatment in the Marxist.
Study as a means to provide additional evidence of effectiveness to increase persuasiveness of the positive results from oxy part II. Dr done in that Division agreed to consider this proposal and requested that the study design concept be provided for their review, let's say you design concept was provided immediately after the meeting followed by submission of the final.
Allies Statistical analysis plan for this baseline controlled study prior to conducting the analyses described the proposed plan. The division has not provided comments the proposed plan and requested that we provide results. The analyses. We recently submitted the results of the study analyses to the division the FDA confirmed that they will review the study results.
It's after which they may request, a meeting with us to discuss the conclusions of the review.
Well, we view the results of the base on controlled study as positive and sufficient to increase the persuasiveness of the Moxie Party results. There can be no assurance that the division will accept the design based on controlled study will review the results of sufficient to increase the persuasiveness of the Moxie part two study to support approval of OMAP as a single study if the FDA does not accept these results.
We will determine next steps, including weather is feasible to conduct a second pivotal study to confirm the part two results as previously suggested by the FDA with that I will turn the presentation over to meet for the financial and operational update.
Thanks, Paula and good morning, everyone. Thanks for joining us today the results for all patients for the third quarter of 2020 are included in our press release and our form 10-Q, which was filed earlier today.
Due to all of the news on our operations, we wanted to share I won't go into details on the financials here, but.
But I will briefly highlight a couple of key north for the core.
We ended the third quarter of 2020 with a strong cash position of $578.3 million.
We have focused on being prudent without photo sources to consult about expected cash on me by maintaining efficient effective capital allocation and controlling expenses.
As a quick note regarding our income statement I would like to point out that our income other income and expenses for the current quarter was $11.2 million as compared to $1.1 million for the same period in the prior year. This increase was primarily due to the non cash interest expense related to sale of future royalties to Blackstone.
In the second quarter of this year, we will continue to record non cash interest expense as we adjust the current value of that unlimited liability. As a reminder, these amounts are able to Blackstone and the formal for warranty payments based on the net sales of box loan subsequent to regulatory approval.
Moving to non-GAAP financials, excluding the impact from stock based compensation loss on extinguishment of debt and non cash interest expense. Our total cash operating expenses increased by approximately $5.3 million in the current quarter as compared to the prior quarter.
This increase was due to the increased regulatory and manufacturing activities as we appropriating for NDS filings.
Moving to operational update update in preparation for the launch of box loan animal backed loan we have built a strong foundation to support our efforts to reach and educate customers develop a tightly controlled product distribution network and scale the organization to the right people processes and infrastructure our core commercial leadership team is in place at present.
Adding marketing market access sales operations and ex us commercial planning and we have been engaging with key wells and patient advocacy for several years to understand the current treatment of Alport syndrome, and Frederic Akcea as well as the gaps in our current therapeutic options pending regulatory approval. We are confident that we have the pieces in place to six.
Yes, let me launch both products.
Turning to our operational activities that support the potential launch of our products, we got us current and mentally and planned manufacturing capacity off our investigational product as adequate to meet up product demands for both the programs. We are actively engaged in CMC registration validation activities for both board and OMAP to ensure commercial of Liberty post approval.
I will now turn the call over to water and for concluding remarks.
On me.
To conclude regattas development pipeline is very robust and we expect it to yield several commercialization opportunities in the coming years.
Alan Cardinal and Falcon or pivotal study in patients with 80, PKD, we intend to develop our docks loan for the other rare forms of CKD, where we generated strong proof of concept data in our phase two Phoenix study in which include a large number of patients with the need for more effective therapies.
Beyond Friedrichs attacks, we also intend to study Omar and neurological diseases, where we believe there is a clear pharmacologic rationale we have compelling preclinical proof of concept and where patients are underserved on current standards of care. Additionally, we retain worldwide development and commercialization rights to two additional phase two.
[music] ready assets in our team and I have one and our th 17 at one both are small molecule therapies with novel mechanisms with favorable safety profiles and the potential to address both orphan and large market diseases.
With our nephrology and neurology programs, making good progress and the potential to expand our late stage pipeline significantly we're excited about the near and long term future of Reatta. So that concludes our prepared remarks, operator, you can open up the line to questions. Please.
Thank you.
As a reminder to ask a question you'll need to press star one on your telephone to draw your question press the pound key.
We ask that you please limit yourself to one question and one follow up so that we can accommodate as many questions as possible.
And our first question comes from Google.
Yes.
With Citigroup your line is open.
Thank you very much and congrats foreign Collin monument mandate.
On the positive data on multiple fronts.
Had a question with respect to the filing strategy or Doxil on could you just provide a little bit more perspective.
On why you decided to file for full approval.
On the one year end the tier data as opposed to an accelerated approval just on the one year data.
Thanks.
Yeah.
Sure your goal.
It was obviously a very difficult ask of the division to seek accelerated approval on the one year data when it was clear that we'd have the two year data either during the review process or even before the initial NT a submission.
We previously said that the FDA had questions about the one year data that we believed would be answered by the two year data.
Also it was likely that we'd have a three month PDUFA extension, if we submitted the year one data.
Because we would have to submit the year to data as a major amendment during the NDRC review.
And so we propose to submit the India with the full two year data and that led to a very productive discussion with the division on the planned content of the India.
They stated during the meeting that there was no impediment to submitting with the year to data.
And based on the timing of the year to data moving to that submission plan for full approval.
Basically left us with minimal delays to the potential approval timeframe.
Okay got it that makes a lot of sense.
And then just one data question did.
Did you measure retain benefit or modified intent to treat population or was that was that not done Im just curious if you have that that havent endpoint.
It's been a it's since the modified intent to treat is the patients that they're on drugs by definition.
They are not included in the off treatment.
Okay understood. Thank you.
Mhm.
Thank you and our next question comes from Maury Raycroft with Jefferies. Your line is open.
Hi, everyone. Good morning, and congrats on the update today.
First question is just on.
Pediatric patients can you comment on if those patients were on ace is or our EPS.
And then for any of your subgroup analyses on slide 15, where those were there any Scott big differences observed there.
So yes patients were required to be on the maximum labeled dose of an ace inhibitor or an Arab.
At stable doses party entry and so as we disclosed last year most patients one in that that applies to the pediatric patients as well.
Many of the the subgroup analyses did show significant differences obviously.
The slides, we pointed out the difference in the pediatric patients that was statistically significant.
And the trial wasn't powered to show a separate significant efficacy in all the subgroups, but as you can see on the slide 100.
Many of the subgroups you had.
Arab they do not overlap.
So there is significant across many subgroups.
Got it and for the liver enzyme elevation. So you mentioned that was related to some of the discontinuation can you talk more about what was done to.
Determined to manage the liver enzymes I guess.
What solution has been determined to manage that kilograms, EPS and can that be applied.
Steady order commercial setting.
Yes, it already has been applied to the PKD setting.
And we anticipate that it will apply to the commercial setting too and we actually very recently published a manuscript that describes the underlying pharmacology, we've demonstrated that Barack Sloane.
Increases production of these enzymes and multiple cell types actually not just the liver.
And clinically there reversible when patients come off drug they come down and so some patients respond.
Differently and so to manage them we simply.
Give them a drug holiday and then start them on a lower dose.
If they have initial elevations that are beyond a certain threshold. So like I said weve relaxes criteria in our Falcon phase three trial.
And are much better able to manage these patients and so we don't think it will be an impediment to.
That protocol or commercially.
Got it okay. Congrats again, thanks for taking my questions.
Thank you.
Thank you. Our next question comes from Brian Skorney with Baird. Your line is open.
Hey, good morning, guys. Thank you so much for that question and congrats on the data on two quick ones from me just on slide generates more more more general.
On the risk of kidney failure.
Good.
What did that when we see the hazard ratio can you talk a little bit about the dialysis initiation of the study and whether there are differences here.
I see that the breakdown of the endpoints, but are all these patients going on dialysis is not only the espeed the patients and and can you talk at all about changes on dialysis and then on slide 15, just to confirm the urban parts. Here. These are these are the 95% competence levels.
So for your first question. So this composite include.
Includes dialysis transplant confirmed 30% loss Sochi as far as well as confirmed Jia far of less than 15 and so.
Yes, so it's validated by the Theres a joint working group at the National Kidney Foundation Ft, and he May that's now published.
Multiple papers validating this composite predicts actual events.
So once again as I said in my prepared remarks, the trial wasn't designed or powered to show an actual difference.
But we saw a much larger hit rate of progression.
In the placebo patients. So many more of them had large losses, and so are at or near basically dialysis versus.
At Oxford treated patients.
And your second question. So what's five are you referring to about the 95% comments interval.
The subgroups that.
Those error bars are 90.
50 on slide 15.
I believe they are.
Thank you and congrats again.
Thank you.
Thank you. Our next question comes from Annabel Samimy with Stifel. Your line is open.
Hi, Thank you for taking my question congratulations on the data.
Yes, I just want to.
Go back to the off treatment.
Just want to understand how the ft.
Might read the more rapid rate of decline during the off trade and the Barnes group's relative to placebo.
In in that 40 to 50 to decline about five points.
In the 100 to one of four it declines that Threep Cline well.
See that doesn't really change much are they going to read much into that or.
You know.
Hey that ahead of the general idea.
Damaged and then alleviate at this pilot this with this data and then.
Secondly on math.
With the statistical significance is going to be looking at 4.01 again or is that standard statistical significance. The question. Thank you.
Yes, if your first question for the off treatment chains recalled that the mechanism of action of our docks loan is two acutely increase jia far by improving the surface area in the filtration apparatus of the kidney.
That effect is reversible.
And the purpose of the off treatment effect is to understand if the drug has a beneficial or harmful effect on the underlying structure and so forth that analysis, we require that the acute reversible effect is washed out and so the change from 100 to 104 or 48 to 52 simply.
Due to the reversal of these acute improvements in surface area that are not permanent.
And so in both.
The week 52, and one of four analyses, we demonstrated twice in the trial significant placebo corrected separation.
In the off treatment analysis both.
Both were statistically significant both were similar magnitude they were not significantly different from each other and importantly that magnitude is three times larger.
Then what supported approval of toll vap done in 80, PKD, which is a more slowly progressive disease. You. Obviously don't see a similar change from week 42 to 52 and 101 important placebo patients because they were receiving placebo there was no acute effect.
Placebo and so we believe the persistence of the off treatment effect.
Shows twice and confirms that the draw is having.
A disease modifying effect and therefore would be beneficial over the long term and thats consistent with the durability.
The on treatment effect this placebo in Cardinal and the continued.
Increase above baseline in the extension trial.
And so for the Omars question. So FDA has not given us guidance about what P value would be appropriate.
And so we hit statistical significance with a P value of <unk> 0.01 in the pre specified primary analysis of Moxy part two.
Then as obviously, we just disclosed we had a P value of <unk> 0.00 to two and so in the baseline controlled study and so that was obviously less than point of five and less than 0.1.
So as I said, we are awaiting feedback from from FDA about the results that we recently submitted to them, but overall, we demonstrated significant effect in the baseline controlled study and consistency across part one and part two.
Across all the pre specified and post hoc sensitivity analyses of the primary analysis.
Great. Thank you.
You want.
Thank you and as a reminder, if you'd like to ask a question Press Star then the one key on you touched on telephone.
We have a question from Joseph Schwartz with SVB Leerink. Your line is open.
Great. Thanks, very much and congratulations as well I was wondering if you could expand on the feedback you received from the FDA in your pre indeed meeting when you ask them questions regarding your submission plan for Q.
Clinical data and based on this feedback do you sense of how much new reviewed you share.
As the prior one which provided you with the written guidance.
After four weeks of withdrawal of greater than two and a half milk for men could serve as the basis for approval.
Okay ill address the first part the.
As we said in the prepared remarks, we submitted a comprehensive set of questions addressing base.
Basically the data submission plans for clinical Clin pharm non Clint CMC.
And got very thorough responses back.
That we think provide us with the information necessary to make the filing.
In the first quarter.
They agreed with our submission plan to submit the two year data as well as the data structures.
For all of that and it was really a very very straightforward conversation.
I didn't I don't think I understood second part of the question about the review teams could you repeat that joke.
Sure.
Again.
Hi, or an update on that second quarter call. I think you alluded to new review team or change in your team and I know that in the past.
You had received written guidance from the FDA.
Retain benefit construct.
Essentially agreed to you know so I was wondering as you know.
That seems to be.
The case now that.
They view that construct is suffering.
For.
For approval essentially.
Yes, that's our impression we had a new review team and that of course meant that the the initial review team really didnt have familiarity with the the development background the pharmacology of the drug.
Items of that type, but theres been no indication that.
That they're changing their approach to the endpoints.
Okay, Great. That's very helpful. Thanks, and then based on the magnitude of the juice bar benefit pension drug treatment combined with a lower rate of foreign loss after treatment as well.
Now I see it.
Data it would seem that there is no evidence supporting.
The concept of hyper filtration.
But turning this around or are there any biomarkers, which could support the contention that the primary mechanism is by reducing inflammation and improving structural and functional viability that kidney.
Anything like did you look at CRP or any other anti inflammatory benefits translational biomarkers that.
Bring bring to an advisory panel and continue to support a favorable dialogue.
So we obviously published a wealth of information about the preclinical effect in kidney diseases and so there is over 454 and 50 peer reviewed publications about paradox loan me those are preclinical models demonstrating that the drug has anti inflammatory effects, an anti fibrotic effects Clint.
Finally in one of our very first studies that we published its I think its nine or 10 years ago now in American Eagle Nephrology, and our very first trial in patients with CKD.
We showed that there was a reduced number of circulating endothelial cells.
Which are damnation slough off in the context of injury, including pressure mediated injury.
We also showed that in that assayed, though was a reduction.
Nf Kappa B positivity so.
Supporting the drug as an anti inflammatory mechanism of action.
In the upfront so no patients.
We've shown we collect biomarkers demonstrating the interwrap to the target up our docks loan is induced and so we see very.
Induction of the target in the Alport syndrome patients, yes, I just add to some of the reviewers.
And we were struck by the impact on the non kidney effects in the Alport syndrome patients.
And so their effects on you know hearing loss you know dizziness.
Ocular effects were meaningfully reduced if you look at the age profile. It's included in the data presentation, and so thats, obviously consistent with.
Proven in mitochondrial function and anti inflammatory effects.
Totally unrelated to their kidding.
Very interesting and actually some of those neural function answer similar to obviously, what we see with own math outside of.
Outside of.
CKD patients.
Right right.
Very interesting thanks for all the color.
Sure. Thank you.
Ladies and gentlemen, this concludes today's conference call an audio recording will be available. Shortly on Riyadh is website every out of pharma dot com in the investors section. Thank you for participating you may now disconnect everyone have a great day.
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