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Edited Transcript of RETA earnings conference call or presentation 12-Nov-19 1:00pm GMT

Q3 2019 Reata Pharmaceuticals Inc Earnings Call

IRVING Dec 5, 2019 (Thomson StreetEvents) -- Edited Transcript of Reata Pharmaceuticals Inc earnings conference call or presentation Tuesday, November 12, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Colin J. Meyer

Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development

* J. Warren Huff

Reata Pharmaceuticals, Inc. - Chairman, CEO & President

* Manmeet Singh Soni

Reata Pharmaceuticals, Inc. - CFO & Executive VP

* Vineet R. Jindal

Reata Pharmaceuticals, Inc. - VP of Strategy

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Conference Call Participants

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* Adam Anderson Walsh

Stifel, Nicolaus & Company, Incorporated, Research Division - MD & Senior Analyst

* Charles Cliff Duncan

Cantor Fitzgerald & Co., Research Division - Senior Analyst

* Jack Kilgannon Allen

Robert W. Baird & Co. Incorporated, Research Division - Research Associate

* Joseph Patrick Schwartz

SVB Leerink LLC, Research Division - MD of Rare Diseases & Senior Research Analyst

* Matthew Lee Kaplan

Ladenburg Thalmann & Co. Inc., Research Division - MD & Head of Healthcare Equity Research

* Maurice Thomas Raycroft

Jefferies LLC, Research Division - Equity Analyst

* Yigal Dov Nochomovitz

Citigroup Inc, Research Division - Director

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Presentation

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Operator [1]

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Ladies and gentlemen, thank you for standing by and welcome to the management call to discuss positive top line pivotal year 1 CARDINAL data. (Operator Instructions) An audio recording of today's webcast will be available shortly after the call today on Reata's website at reatapharma.com in the Investors section.

Before the company proceeds with its remarks, please note 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 company's SEC filings. Today's statements are not guarantees of future outcomes. Please also note that any comments made on today's call speak only as of today, November 12, 2019, and may no longer be accurate at the time of any webcast replay or transcript rereading.

I would now like to hand the conference over to your speaker today, Vinny Jindal, Vice President of Strategy.

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Vineet R. Jindal, Reata Pharmaceuticals, Inc. - VP of Strategy [2]

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Thank you. Good morning, and welcome to Reata Management's call to discuss the positive results from year 1 of the pivotal CARDINAL trial of bardoxolone in patients with CKD caused by Alport syndrome.

Yesterday afternoon, we issued a press release with a summary of these results. The press release as well as an 8-K filing with the slide deck being presented this morning can be found on the Investors section of our website at reatapharma.com.

This morning, we reported financial results for the third quarter of '19. And the press release as well as our Form 10-Q can also be found on the Investors section of our website at reatapharma.com.

We're limiting our remarks today to the CARDINAL trial results, but we would be happy to take questions on any aspects of our business, including our third quarter financial results during the Q&A session of today's call.

I'm joined today by our CEO, Warren Huff; our Chief Medical Officer, Colin Meyer; and Chief Financial Officer, Manmeet Soni.

I'll now turn the call over to Warren.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [3]

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Thanks, Vinny. Good morning, everyone, and thank you for joining us. Yesterday afternoon, we announced positive top line results from the pivotal CARDINAL Phase III study of bardoxolone in patients with chronic kidney disease caused by Alport syndrome. CARDINAL was the largest, global interventional study ever conducted in Alport syndrome patients. Alport syndrome is a severe form of CKD. And the patients enrolled in the Phase III portion of CARDINAL were losing substantial amounts of kidney function when they entered the trial.

After 1 year in CARDINAL, the patients on placebo lost, on average, over 6 milliliters per minute of estimated GFR or glomerular filtration rate. Said another way, these patients were rapidly progressing to kidney failure and the need for dialysis or a kidney transplant.

By contrast, bardoxolone-treated patients experienced a statistically significant improvement in the kidney's estimated glomerular filtration rate or GFR while on active drug, and their estimated GFR was statistically unchanged from baseline after withdrawal drug.

In effect, during the study, bardoxolone treatment substantially slowed or halted the loss of kidney function that leads to the need for dialysis or a kidney transplant in patients with this severe form of CKD and without other treatment options.

On behalf of everyone at Reata, I'd like to extend our sincere gratitude to the patients, families and caregivers who live with this disease and to the Alport Syndrome Foundation. The results we announced yesterday would not have been possible without their efforts and commitment to this program.

For those of you unfamiliar with Alport syndrome, it is a hereditary and severe form of chronic kidney disease caused by mutations in genes that encode for type IV collagen. Type IV collagen comprises approximately 50% of the glomerular basement membrane or GBM of the kidney. The GPM acts as the barrier that separates the blood from the urinary filtrate. Collagen mutations in the GBM lead the leakage of whole blood cells, protein and other material into the proximal tubules of the kidney.

This promotes chronic kidney inflammation and a decrease in cellular energy production that leads to fibrosis and progressive loss of kidney function. Like most other forms of CKD, patients with Alport syndrome commonly take ACE inhibitors and angiotensin-receptor blockers, but there are no approved therapies for Alport syndrome.

We believe that there are approximately 30,000 to 60,000 patients with Alport syndrome in the United States and approximately 32,000 to 64,000 patients in the EU5, which represent the first commercial markets for bardoxolone that we are targeting.

Alport Syndrome is among the most severe forms of CKD. All forms of chronic kidney disease are characterized by a progressive loss in the rate at which kidneys filter blood or GFR. Nephrologists track estimated GFR or eGFR to assess the decline in kidney function and progression of patients' kidney disease.

Normal individuals have an eGFR of approximately 120 milliliters per minute. When eGFR declines to approximately 15 milliliters per minute, patients reach kidney failure and require dialysis or a kidney transplant to survive.

In the most common forms of CKD caused by diabetes or hypertension, patients lose approximately 2 milliliters per minute on average each year. If patients are diagnosed after losing approximately 1/2 of their kidney function, which is typical, these patients are at risk of kidney failure in approximately 20 to 25 years on average.

By contrast, patients in the placebo group of the Phase III CARDINAL study lost, on average, approximately 6 milliliters per minute over 1 year. This is 3x the rate of loss of more common forms of CKD. And at this rate of loss, a patient with a baseline eGFR of 60 would reach kidney failure within approximately 7 years.

Patients with the most severe forms of Alport syndrome progress to the need for dialysis or a kidney transplant on average in their mid-20s.

We thought it would be helpful to provide some additional background on the design and end points of studies in chronic kidney disease. The only drugs approved for common forms of CKD are blood pressure medications, primarily ACE inhibitors and angiotensin-receptor blockers and SGLT2 inhibitors. These are widely used because they slow the rate of eGFR decline in patients with CKD. Importantly, these drugs do not stop the decline in eGFR, and they certainly do not increase eGFR over time.

In their registrational studies, eGFR over time declined in both the active drug and placebo arms of their trials. You can see 2 examples of these studies on the right.

In the RENAAL trial, an angiotensin-receptor blocker, called Losartan, modestly slowed the rate of eGFR decline. It's difficult to see the difference in the drug versus placebo group on the graph because the treatment effect is so small. In the CREDENCE trial, an SGLT2 inhibitor slowed but did not stop eGFR decline in the treatment group. When compared to baseline, both the active drug and placebo groups are below baseline and had a negative change in eGFR versus baseline.

These drugs are effective and widely used because their therapeutic benefit is slowing eGFR decline in comparison to the placebo group. This translates into a delay in the need for dialysis or a transplant even though they do not stop the decline in eGFR.

Tolvaptan was approved last year in the United States for the treatment of autosomal dominant polycystic kidney disease, and it is the only approved therapy to slow progression of kidney disease for a rare form of CKD.

Like blood pressure medications and SGLT2 inhibitors, tolvaptan only slows and does not stop the decline in eGFR. It was approved because it produced a benefit in estimated GFR versus placebo after treatment for 1 year and then withdrawal of drug. This is called the off-treatment a retained eGFR and has the same registrational end point as our key secondary end point in CARDINAL.

In the tolvaptan registrational study called REPRISE, the change from baseline and retained eGFR for both the tolvaptan and placebo groups was negative, as you can see in the graph on the right. The retained eGFR of the tolvaptan group declined from baseline by 2.34 milliliters per minute over a year. And the retained eGFR of the placebo group declined from baseline by 3.61 milliliters per minute over a year. Tolvaptan was approved based on the 1.27 milliliter per minute improvement in estimated GFR compared to placebo, even though both groups were declining from baseline.

The FDA has provided us with written guidance that in patients with CKD caused by Alport Syndrome, an analysis of off treatment eGFR, demonstrating an improvement versus placebo after 1 year of treatment may support accelerated approval and an improvement versus placebo after 2 years of treatment may support full approval.

This is consistent with their recent approval of tolvaptan on the basis of a placebo-corrected improvement in retained eGFR, they also provided us with similar guidance during our end of Phase II interactions in ADPKD and the retained eGFR versus placebo is the registrational end point of our FALCON study. We are aware that they have provided this guidance to other sponsors, developing drugs for rare forms of CKD.

Following the FDA guidance, the primary end point for the Phase III CARDINAL study is the change in estimated GFR from baseline and compared to placebo after 48 weeks of treatment and the key secondary end point is the change in estimated GFR from baseline and compared to placebo after 48 weeks of treatment and 4 weeks of drug withdrawal.

Obviously, the efficacy analysis compared the bardoxolone-treated patients to the placebo-treated patients because this is the best way to determine efficacy of the intervention versus standard of care.

Measuring estimated GFR after withdrawal of active drug, isolates the effect of the drug on the underlying structure of the kidney.

If the effect of the drug were harmful due to any mechanism, known or unknown, after 1 year of treatment and a 4-week withdrawal, kidney function would be worsened relative to placebo.

However, an improvement in retained eGFR versus placebo is strong evidence that the drug is beneficial, has the potential to modify the course of the disease and may delay or prevent the need for dialysis or a kidney transplant.

With that background, I'll hand the call over to Colin to discuss the CARDINAL trial results.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [4]

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Thanks, Warren. The Phase III portion of CARDINAL is an ongoing, randomized, double-blind placebo-controlled, international study that enrolled 157 patients at approximately 50 sites in the United States, Europe, Japan and Australia. The study enrolled patients across a wide range of age, kidney function and genetic subtypes that we believe represents the broad population of patients with Alport syndrome.

Patients were allowed to be on standard of care ACE inhibitors or angiotensin-receptor blockers unless these were not indicated or medically contraindicated.

Study subjects were randomized one-to-one to either bardoxolone or placebo, and the total treatment duration is 2 years. Patients are initially treated for 48 weeks and then withdrawn from study drug for 4 weeks. After this withdrawal period, patients are restarted on their original treatment assignment and continue on study drug for another 48 weeks. At week 100, patients are withdrawn from study drug a second time, and the last assessment occurs at week 104 after another 4-week withdrawal period.

As Warren explained, the primary end point for the study is the change in eGFR from baseline and compare it to placebo after 48 weeks of treatment, and the key secondary end point is the change in eGFR from baseline and compared to placebo after 48 weeks of treatment and 4 weeks of drug withdrawal.

Both analysis, our intention to treat or ITT and include data from all patients. The week 40-analysis uses all available values, including those from discontinued patients and the method of analysis is MMRM with no imputation for missing data.

The method of analysis for the week 52 end point employees ANCOVA methodology that was used in the reprise trial of tolvaptan in ADPKD. The week-52, off-treatment analysis includes all available data for patients who completed 48 weeks of treatment, followed by the 4-week withdrawal period. If patients discontinue prior to week 48, their 4-week, off-treatment value prior to week 52 was used and the ANCOVA model used a time-based covariant, so these data can be included. In this analysis, multiple imputation is used for missing data.

Since the study is ongoing, we are releasing the 1-year results under a data access plan submitted to the FDA and designed to preserve the integrity of the second year of the study. Therefore, we cannot disclose data today that would unblind individual patients to the treatment assignment. We plan to present more in-depth data at a medical conference following the conclusion of the study.

Patients in the Phase III portion of CARDINAL were representative of the broader Alport syndrome population. Patients were on average in their late 30s and 15% were pediatric. The mean baseline EGFR study entry was 63 mL per minute, and there was a good distribution of patients across the eligible range of 30 to 90 mL per minute. Patients have low proteinuria on average measured as a urine albumin to creatinine ratio or ACR, and just under half had ACR above the macro albuminuria range of 300 milligrams per gram.

Blood pressure was under excellent control and approximately 80% of patients were on standard of care ACE inhibitors or angiotensin-receptor blockers.

Importantly, since a high percentage of patients were receiving standard of care ACE inhibitors or ARBs and patients had generally low proteinuria and well-controlled blood pressure, we believe these data demonstrate that patients were receiving exceptional care by their treating physicians and optimize on all available therapies upon study entry.

CARDINAL successfully met its primary end point of improvement in eGFR after 48 weeks of treatment compared to placebo.

Patients treated with bardoxolone demonstrated a statistically significant placebo-corrected 9.5 mL per minute improvement in mean eGFR compared to placebo after 48 weeks of treatment with a p-value of less than 0.0001.

Patients treated with bardoxolone had a statistically significant mean improvement in eGFR of 4.7 mL per minute from baseline, while patients treated with placebo had a statistically significant mean worsening in eGFR of 4.8 mL per minute from baseline. We believe these on treatment results demonstrate a very clinically meaningful treatment effect in a patient population that is rapidly progressing.

For patients on bardoxolone, these data indicate that despite their severe disease, these patients experience a significant improvement in the kidney function while on active drug. In effect, during the study, bardoxolone treatment substantially slowed or halted the loss of kidney function that leads to the need for dialysis or a kidney transplant in patients with this severe form of CKD and without other treatment options.

Bardoxolone also met its key secondary end point of off-treatment change in eGFR compared to placebo. In the off-treatment analysis, patients treated with bardoxolone demonstrated a statistically significant placebo-corrected 5.1 mL per minute improvement in mean, retained eGFR compared to placebo with a p-value of 0.0012.

Patients treated with a placebo experienced a statistically significant worsening in mean retained eGFR of 6.1 mL per minute from baseline with a p-value of less than 0.0001.

Patients treated with bardoxolone were unchanged from baseline with a slight nonsignificant reduction in retained eGFR of 0.96 mL per minute with a p-value of 0.45.

Regarding subgroup analysis of the off-treatment end point, bardoxolone's effect on kidney function was observed across multiple, including among males, females, pediatric patients, baseline ACR categories and genetic subtypes.

These results suggest that disease progression for patients on bardoxolone was essentially halted during the study, even when measured after 4 weeks of drug withdrawal.

Notably, this treatment effect is 4x larger than the treatment effect observed with tolvaptan in the REPRISE trial, which supported approval of tolvaptan in ADPKD, despite the small difference observed in the trial and the tolvaptan group losing 2.3 mL per minute from baseline.

While the absolute change from baseline for the bardoxolone group was lower than observed in the Phase II portion of the trial, this is likely due to rapidly progressive and severe disease in this patient population. This is highlighted by the large loss of 6.1 mL per minute in the placebo group, which puts them at risk of end-stage kidney disease within a few to several years.

Also, the relative difference between the on- and off-treatment eGFR values for bardoxolone-treated patients observed in the study was similar to that observed in other bardoxolone CKD studies. In the Phase III portion of CARDINAL, the relative difference between the week-48, on-treatment values and the week-52 off-treatment values was approximately 6 mL per minute.

In the Phase II portion of the trial, the relative difference was also approximately 6 mL per minute.

In the BEACON trial, the relative difference was approximately 5 mL per minute. In the BEAM trial, the relative difference was approximately 7 mL per minute.

In terms of the meaningfulness to patients, these data demonstrate that after 1 year of treatment, bardoxolone was able to, on average, improve kidney function while patients were receiving drug. And after washout, their kidney function was not significantly different from baseline.

These patients on average did not progress over the course of a year despite the large loss observed in the placebo group. These data indicate that bardoxolone is positively affecting the course of the patient's disease. If they are not progressively losing kidney function, they may never need dialysis.

The mean eGFR values with associated p-values are informative but to better understand the distribution of change, we performed a quartile analysis for the week 48 and 52 time points. When changes in kidney function are assessed by quartile, several key conclusions can be made. In every quartile at week 48 and week 52, bardoxolone-treated patients' kidney function was improved relative to the matching placebo quartile.

Additionally, at week 48, while patients were receiving study drug, approximately 75% of patients receiving bardoxolone did not experience disease progression, while approximately 75 of patients receiving placebo lost kidney function.

At week 52, the second-best-performing placebo quartile had an average rate of progression that is comparable to the average rate of progression in other notable forms of CKD, including diabetic, hypertensive in ADPKD.

The bottom 2 placebo quartiles or half of placebo patients progressed at a rate of approximately 12 mL per minute in 1 year, which is very rapid in result and the need for dialysis or kidney transplant in just a few years.

In patients in the worst-performing quartile, with the most rapidly progressed disease, even though bardoxolone did not increase kidney function, it meaningfully slowed their loss of kidney function. This is evidence that bardoxolone may provide a benefit even in patients who do not have an absolute increase in eGFR. In patients with less rapidly progressive disease that is comparable to other forms of CKD, bardoxolone not only appears to halt progression on average but some patients were able to recover kidney function.

We also conducted a correlation analysis to determine the relationship between the acute changes in eGFR after 6 weeks of treatment and the longer-term changes in on- and off-treatment eGFR after 1 year of treatment. In the bardoxolone group, the acute change in eGFR correlated positively and significantly with the change in eGFR at week 48 on treatment and at week 52 after the 4-week withdrawal. These data demonstrate that the early increase in eGFR is a positive predictor of eGFR change after 1 year of treatment on and off drug.

If the early increases were adverse through hyperfiltration or any other deleterious mechanism, they would negatively correlate with the change at 1 year and will be associated with significant loss of kidney function and eGFR values that were worse than placebo.

Regarding safety, bardoxolone was generally reported to be well tolerated with a safety profile similar to what we observed in the Phase II portion of the trial. Nine patients in the bardoxolone group and 4 in the placebo group discontinued due to an adverse event and no single adverse effect contributed to more than 2 discontinuations in either group. Fewer serious adverse events were reported in the bardoxolone arm, with 13% of patients on placebo reporting serious adverse events versus 5% on bardoxolone. No deaths were reported in either arm.

Importantly, no fluid overload or major adverse cardiac events, including MI, stroke, heart failure or revascularization were reported in patients treated with bardoxolone. Blood pressure was decreased relative to baseline in the bardoxolone group, but was not significantly different between the 2 groups. There was an overall low rate of cardiac and vascular adverse events that was numerically lower in the bardoxolone arm. The most common adverse events were muscle spasms and increases in immuno transferases, which are common findings in studies of our Nrf2 activators and an expected effect of Nrf2 activation. As evidenced that the increases in immuno transferases are a pharmacological effect, acute changes in ALT in bardoxolone-treated patients positively and significantly correlated with acute changes in eGFR.

Lastly, albuminuria in the bardoxolone arm was increased at week 48 compared to baseline but was unchanged when adjusted for eGFR, and ACR was unchanged off treatment at week 52 compared to baseline and relative to placebo.

These data demonstrate that the on-treatment increase in urinary protein excretion is due to the increase in eGFR and the week 52 data demonstrate that this effect is not associated with injury.

Notably, over the course of the trial, the data-monitoring committee met quarterly, reviewing all data on an unblinded basis and did not note any safety concerns.

With that, I will turn the presentation back over to Warren.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [5]

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In summary, CARDINAL met its primary endpoint with a highly significant p-value. It also met its precedented, registrational, key secondary endpoint with a highly significant p-value.

Importantly, during the study, bardoxolone treatment effectively halted the decline in estimated GFR in patients with rapidly progressing disease. Approximately 75% of bardoxolone-treated patients had an improvement in their on-treatment eGFR, while approximately 75% of placebo-treated patients had worsening eGFR. Importantly, bardoxolone treatment showed a potential benefit even in patients who were progressing most rapidly towards kidney failure. Bardoxolone was reported to be well tolerated with numerically fewer reported SAEs on bardoxolone versus placebo. We believe that the results from CARDINAL provide significant evidence that bardoxolone produces a clinically meaningful benefit to patients with Alport syndrome, and we believe it has the potential to become the first FDA-approved therapy for this disease. We plan to work closely with the Alport Syndrome Foundation and the National Kidney Foundation to communicate with the patient community. And we're planning to meet with the FDA and other regulatory agencies soon to discuss the appropriate next regulatory steps.

In parallel, we will accelerate the launch preparations that began over a year ago, and we now plan to extend these activities to include the territories outside of the United States that we recently reacquired.

Operator, I'd now like to open the call to questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions)

And our first question comes from Yigal Nochomovitz from Citigroup.

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Yigal Dov Nochomovitz, Citigroup Inc, Research Division - Director [2]

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Congrats on another positive Phase III readout. My question was related to the eGFR trends seen in the trial. Colin, you mentioned that the acute changes in eGFR correlated positively with the change in eGFR at weeks 48 and 42. However, we haven't seen the time profiles yet for eGFR. So given that, could you provide any additional color on the evolution of the treatment effect for bard from week 0 to week 48 before coming off drug? What was the time to peak effect? And how does this compare to the week-48 benefit of 4.7 units?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [3]

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Yes. Yigal, so the eGFR change over time was not fully disclosed because it could be unblinding. Patients on bardoxolone had an increase in eGFR that manifested early, similar to what we've seen in other trials and it persisted. The increase at week 48 was substantial. The data reported here in the presentation or the ITT analysis that includes patients who discontinued or on low doses of drug, when patients who were on their goal dose were included and patients who were discontinued or excluded, the treatment effect was even higher. The total slope from baseline to week 40 is positive, clearly divergent from the placebo patients, and it's obviously a very meaningful treatment effect, considering the placebo patients lost 6 mL per minute in 1 year.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [4]

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Yes. I'd just add 1 thing. This is in part why we've provided the quartile analysis because you can compare the change on drug to their matching placebos across the complete range of response, and that data clearly shows on and off treatment that the drug treatment improved the effect versus placebos, even in the worst-performing patients.

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Yigal Dov Nochomovitz, Citigroup Inc, Research Division - Director [5]

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Okay. Great. And I think you may have touched on this, Colin, but could you just comment in a little bit more detail with respect to the differences and any differences in treatment effect for bard, dependent on whether the patients were on the 20- versus the 30-milligram dose based on their albuminuria status?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [6]

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Yes. So I think there's 2 separate questions, dose and albuminuria status. And so we haven't disclosed the treatment effect by dose. But in general, patients who are on the higher doses of drug had a larger treatment effect.

In regards to the albuminuria status, we saw similar efficacy. When you compare drug versus placebo in patients with low versus high albuminar at baseline. And as I mentioned, we also see similar efficacy in adults as well as kids, and that's somewhat of a surprising finding because it's well established that pediatric patients are at high risk of progressing at a very young age. Adults progress later, but within our trial, the rate of progression was actually similar. It was also similar between males and females and the treatment effect was similar versus placebo in these subgroups. And so think that's one reason why the placebo patients did so poorly. It's underappreciated in the literature and amongst nephrology community at how horrible and rapidly progressive Alport syndrome is. And our data today are the most robust data ever collected in this patient population.

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Operator [7]

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Our next question comes from Maury Raycroft from Jefferies.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [8]

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Congrats on the updated data today. So you see similarities between datasets comparing retained benefit versus baseline in Phase II BEAM and Phase II CARDINAL, and then also in the placebo-corrected data in Phase III BEACON and Phase III CARDINAL. But you see differences in the final eGFR benefit number in the baseline comparison versus the placebo-corrected comparison. And so I'm just wondering how to -- how you guys explain that, if you can add more perspective there?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [9]

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Yes. So that's actually -- your first statement isn't exactly correct. And so we do see a similar relative change between the on-treatment and off-treatment effect across all of our trials that we've conducted. So in the Phase II patients within CARDINAL, recall that the increase at week 48 was approximately 10 mL per minute. And the change post withdrawal was approximately 4 mL per minute, or a 6 mL per minute difference. And so we saw that difference here in the Phase III portion of CARDINAL. The on-treatment was about 5, and the off-treatment was minus 1. And so it's a 6-point delta. And if you look at the quartile analysis, I think it's instructive because the second quartile in the bardoxolone patients mirrors what we observed in Phase II. So you can see that the, on average, bardoxolone-treated patients in the second quartile at week 48 were up 9, which is pretty close to the 10 we saw in Phase II. But those patients were up 2.5 post withdrawal, which is pretty close to the 4. And so we see this relationship across the quartiles here. We saw it, once again, in the Phase II CARDINAL trial, and we also saw it in BEAM and BEACON. The most important aspect is the rate of progression in placebos. That determines the absolute change on and off drug, but the relative change itself is similar.

And once again, what regulators care about in treating physicians is the rate of progression, either in placebos or natural history and these patients in our Phase III cohort in placebo had significant rapidly progressive loss of kidney function. We empowered the trial to show about a 2.5 mL per minute difference, and we saw double that, a 5 mL per minute difference, which, as we stated before, is 4x the magnitude seen in the REPRISE trial with tolvaptan to support approval. So from our perspective, these data are all internally consistent. And when you look in the broader context of our clinical data, it also is consistent. It's just that in this trial, the placebo patients did very poorly. So it drugged down the absolute changes.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [10]

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Got it. Got it. That's very helpful. And the second question is just based on the decline in GFR you're seeing in the placebo group. And the fact that you've got 15% of the population in the study includes pediatric patients. Do you think the FDA might ask you to change the second year of the study to encourage a crossover to drug earlier?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [11]

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It is notable that we had a significant number of kids in this trial and kids on placebo do poorly, adults in placebo do poorly. FDA have had previously requested that this be a 2-year trial. And so we'll, obviously, have to have discussions with regulators to determine if there will be a change to designs.

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Operator [12]

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Our next question comes from Joseph Schwartz from SVB Leerink.

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Joseph Patrick Schwartz, SVB Leerink LLC, Research Division - MD of Rare Diseases & Senior Research Analyst [13]

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We heard from physicians who have experienced using bardoxolone at ASN that patients feel better when they're taking the drug. So could you talk about what quality of life measurements you're performing in the study? And how interested are regulators in that sort of data?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [14]

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We collected one quality-of-life instrument in the trial. And today, we did not disclose the data. And what we previously stated and what you heard is that patients often report that they're feeling better and doing better. In kidney trials, the precedented end point is change in eGFR, specifically for rare forms of kidney disease. It's the retained benefit versus placebo. And so we were given this design by FDA that specifically requested the off-treatment analysis to support approval, and the comparison simply be made to placebo. And so we think that they will consider those data the most important and relevant in the decision as whether or not to approve bardoxolone.

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Joseph Patrick Schwartz, SVB Leerink LLC, Research Division - MD of Rare Diseases & Senior Research Analyst [15]

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Okay. That makes sense. And then can you describe the shape of the albuminuria curve for patients on bardoxolone? And how closely does what you saw in Phase III mirror what you saw in Phase II? And where did the average level of proteinuria end up relative to baseline?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [16]

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Yes. So it's qualitatively similar to what we've seen in the Phase II portion of CARDINAL and in other trials in patients who have pre-existing proteinuria. Once again, the patients already have damage to their filtration barrier. And so if you can just visualize it, so if it has holes that can leak out protein. If you increase filtration through any mechanism, proteinuria will go up. And so we did see that, as I mentioned, and it was stable after the initial increase.

And importantly, when you correct for GFR, there was no increase versus placebo. That's important because it indicates that the increase was due to the change in GFR and that there wasn't some additional increase that could suggest damage and that was further exemplified by the week-52, off-treatment data. And so without even correcting for eGFR, the change from baseline in bardoxolone-treated patients at week 52 was no different than the change from baseline in the placebo patients.

We actually just published a paper in Kidney International. I think it came online a few weeks ago. Kidney International is one of the most prestigious and rigorous kidney journals. The acceptance rate is about 6% these days. And the paper that we published includes many notable global KOLs, and it highlights this methodology and demonstrates a similar effect to what we observed in our BEACON trial.

I think the last thing I'd like to mention is that mechanistically, we've hypothesized for some time. And there's been some confusion in the nephrology community about the mechanism of action for the acute increase in GFR. We believe that we've done the definitive preclinical experiment to demonstrate that the mechanism is associated with an increase in surface area and surface areas often constricted in many forms of chronic kidney disease. We are also able to rule out hyperfiltration. Hyperfiltration within the kidney can only be caused by 2 factors: one is increased blood pressure that's transmitted to the kidney. And in those preclinical experiments, increased blood pressure was not observed. Just like in our CARDINAL Phase III trial, increase in blood pressure was not observed. The only way to increase blood pressure locally within the kidney is to relatively vasodilate the blood vessel going into the filtration apparatus, and that did not occur. The blood vessel going in and out were directly measured, and there was no evidence of hyperfiltration. And so that effectively rules out hyperfiltration as a mechanism and there should no longer be any questions.

In those experiments, the investigator also measured permeability to albumin to determine if bardoxolone could somehow increase permeability, which potentially would suggest injury to the kidney. In normal animals, there was no increase in sieving of albumin in response to the bardoxolone analog. In animals that had diabetes that did have increased permeability at baseline, the analog also did not increase permeability, and so there's no evidence that this increase is deleterious, and it's expected based upon the fact that these patients already had a leaked glomerulus.

And once again, the off-treatment data showing that proteinuria returns towards baseline, and it's no different than placebo, is evidence that it is not harmful. But truthfully, regulators care much more about the off-treatment retained eGFR because that is the ultimate evidence if any drug is harmful or hurtful. If this -- if bardoxolone was harmful after 1 year of treatment, eGFR in the bardoxolone-treated patients will be worse than placebo or be worse than the 6 mL per minute of loss seen in the placebo group. But as we've mentioned, it was no different statistically than baseline and was separated by 5 mL per minute. And so that's the best evidence that the drug is beneficial to the kidney.

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Operator [17]

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Our next question comes from Adam Walsh from Stifel.

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Adam Anderson Walsh, Stifel, Nicolaus & Company, Incorporated, Research Division - MD & Senior Analyst [18]

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Let me add my congratulations. Just a couple of questions here. On the albuminuria, adjusting for eGFR, I'm curious, have you discussed that with FDA? Or they -- do they have a similar understanding of the way you look at albuminuria in your discussions with them? That's number one.

And then number two, on the safety side, Colin, I know you said that we might not get individual patient-level data today. But is it possible you can talk about the SAEs that were seen in the bard? And also, there's -- these are really small numbers, but there's slightly more bard patients with an AE that might permanent treatment discontinuation, if you could comment there as well, that would be great.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [19]

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Sure. And so I think the first thing is with regulators, and specifically, FDA, albuminuria has not come up. They actually do not care about changes in albuminuria. They care about changes in estimated GFR. In our interactions with them face-to-face and in written comments to us, they wanted to see change in eGFR. Because once again, proteinuria can be pharmacodynamically changed, independent of effects on the kidney. And there are a few extremely large cardiovascular trials that show that proteinuria goes in the opposite direction of kidney function, and these trials were much larger than the nephrology trials that were mentioned. And so in the on-target trial that was conducted several years ago, dual RAS blockade reduced proteinuria versus the single intervention. But eGFR in clinical outcomes were actually worsened.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [20]

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In ESKD events.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [21]

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Yes. ESKD events. And that was a 25,000-patient trial. In the ACCOMPLISH trial, an ACE inhibitor plus amlodipine actually worsened proteinuria than the other group but kidney function and renal events were actually improved. And so there's actually plenty of conflicting evidence in the literature that proteinuria does not necessarily translate directly to improvements in kidney function.

And that's why in setting of agents that may reduce proteinuria within nephrology, FDA requires for full approval that they show an eGFR benefit because ACR may or may not reflect actual improvements in kidney function. And once again, that's why FDA and we did not have discussions about albuminuria, and the focus was on actual kidney function.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [22]

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The -- again, the retained eGFR point is definitive in terms of whether the intervention will either harm or protect the kidney.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [23]

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In regards to the safety -- go ahead.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [24]

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And that's why they take it for approval.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [25]

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In regards to the serious adverse events, once again, 10 on placebo, 4 on bardoxolone. So meaningfully lower in the bardoxolone group. And they were sporadic in ins of 1, so we cannot disclose it. There was nothing concerning to the data-monitoring committee, as I stated. And importantly, no deaths, no fluid overload events, no CHF events, no MIs, no stroke. So no evidence of any adverse cardiovascular effect in the bardoxolone group and even less severe adverse events. So non-SAE, both cardiac and vascular were reduced in the bardoxolone group. And once again, no change in blood pressure.

As far as adverse events, we commented on the most common. We can't disclose the specific distribution because it may unblind, but it's similar to what we saw in Phase II CARDINAL and those that contribute to discontinuation were few. The difference was only 5.

And as I mentioned, individual adverse events accounted for no more than 2 discontinuations. And so for instance, despite the muscle spasms that I mentioned, a maximum of 2 patients discontinued from that. The tolerability that we've reported, we believe, is quite good. The titration design that we have is able to effectively deal with any individual patient who may have a tolerability issue.

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Operator [26]

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Our next question comes from Brian Skorney from Baird.

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Jack Kilgannon Allen, Robert W. Baird & Co. Incorporated, Research Division - Research Associate [27]

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This is Jack Allen dialing in for Brian. Just 2 quick questions from us. First, I was hoping you could dive a little bit more deeply into the 2 different statistical plans that were used for the 48- and 52-week analysis and provide some additional color as to how many patients specifically were evaluated at each time point?

And then my second question just real quickly. With respect to presenting the results, will you wait to read out the full results of the 2-year trial? Or would you present the 1-year results in medical conference prior to completing the study?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [28]

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Sure. So I'll start with your second question, and we will wait to present the full results until the trial is completed. Much of the data that we would like to present at a medical conference would unblind. For instance, the serious adverse events would be necessary to disclose, but they're ins of 1 generally, and that would unblind individual patients and investigators. We had to submit a data access plan to FDA to detail how we would maintain the integrity of the second year of the trial while it's ongoing. And because of that, we'll have to wait to disclose the detailed data until a future medical meeting.

As far as your first question. And -- so yes, we had 2 different methods of analysis. The method of analysis for the week-48, on-treatment is MMRM. That uses all patients. And so it's an in of 157, which is all patients randomized. When patients have missing values, the model is able to appropriately handle it and model the population. There's no imputation for missing data. So what that means is that no individual value is basically added into the model, such as last observation carry forward or any other methodology.

And for the week-52, off-treatment analysis, it also included 157 patients. Obviously, that's the most important analysis. That's the analysis that FDA will use to determine if they believe the drug is efficacious. We used the same methodology that was used in the Otsuka trial with tolvaptan, so the REPRISE trial. Their statistical analysis plan is publicly available, and we used almost identical methodology. One of the reasons why we decided to use that methodology and change from when we started is because that is the methodology that FDA did accept, and we were unaware of that methodology. And when we initially met with FDA back in 2016, a benefit to that methodology is it allows every single patient to be included. And so for patients who completed the 48-week treatment period and had an off-treatment value, those patients were included. For patients who were discontinued and had an off-treatment value before the week-52 period, those values were also included in the analysis. And as I mentioned, there was a time-based covariant to appropriately adjust.

And then for patients who discontinued early and had no off-treatment value. Those patients had multiple imputation to effectively add a value. And so it's a full 157 patients. So there's no missing data or no incomplete data, I should say.

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Jack Kilgannon Allen, Robert W. Baird & Co. Incorporated, Research Division - Research Associate [29]

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Awesome. And then, sorry, I just have 1 more quick follow-up. With regard to the baseline eGFR, are you seeing that patients with higher baseline eGFR are progressing more rapidly or less rapidly as compared to patients with lower baseline eGFR?

We've seen some interesting literature that might suggest higher eGFR patients with Alport syndrome might actually progress more rapidly. But I was wondering if you guys could provide any comments on that.

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [30]

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Yes. So patients with higher GFRs can't progress more rapidly. And I think that's highlighted by the pediatric patients. And so their normal is typically a little bit higher than adults. And even though the -- their baseline eGFR was slightly higher than the adults', they probably lost more kidney function from a percentage basis than the adults, and those patients progressed, as kids do earlier in life. And so that may also contribute to the larger loss in the placebos than we initially expected.

But overall, we believe the loss is due to the fact that patients across the spectrum, kids, adults, males, females lost kidney function at a rapid rate.

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Operator [31]

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And our next question comes from Charles Duncan from Cantor Fitzgerald.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [32]

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Warren and team, congrats to really interesting data and rigorous program. I had just a couple of questions more operational because lots of good clinical questions have been asked. But with regard to regulatory strategy. Could we assume that you'd be meeting with the agency, perhaps to enable an NDA by roughly mid '20. And then with regard to international or MAA filing, what kind of time frame would you anticipate for that? And is there any additional clinical work you need to enable that?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [33]

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So our plan with all of our lead programs, including our Friedreich's ataxia program, where we also have positive data, is to meet with regulators as soon as possible. And so we do not comment on ongoing regulatory interactions but we will provide commentary after our initial meetings, and it would be our plan to expeditiously meet with them and if positive proceed with filing the NDA as quickly as we can.

From an international perspective, obviously, we just reacquired the rights from AbbVie for both of our drugs, and so we're currently developing the strategy. It was their responsibility to interact with regulators externally or globally. We were allowed by AbbVie to conduct the trial in their territories, and so we'll also be planning to meet with those regulators. And then KKC or Kyowa Kirin Company are Japanese and Asian partner with bardoxolone, has already obviously had ongoing interactions with the PMDA, and those will continue.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [34]

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Okay. And then, Colin, with regard to other uses of bardoxolone in terms of rare kidney diseases, say, ADPKD, do you have any thoughts regarding, obviously, and fact size is pretty impressive here. Predictive value for, say, FALCON or anything along those lines. Can you help us understand how to think through that?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [35]

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Yes. And so we were extremely pleased by the CARDINAL data, in part because the patients were so rapidly progressive, yet there was such a meaningful treatment effect. And so this increases our confidence in FALCON, not only because of that but because the sample size for FALCON was approximately 2x the size of CARDINAL, where we had an extremely low p-value in the on-treatment as well as the key secondary off-treatment regulatory end point.

Our view is that in the FALCON trial, those patients likely won't have disease that's as rapidly progressive as we saw in CARDINAL. And so once again, I would refer to our quartile analysis. Based upon the approval of tolvaptan, and based upon the REPRISE trial for patients not on tolvaptan, they progressed at a rate of about 3.4 mL per minute, it's about -- or 3.6, it's about 2.4 in patients on tolvaptan. And so our best estimate is that the rate of loss will be somewhere around 3 mL per minute off treatment in our FALCON trial.

And you can see in the quartile that had approximately that loss in the placebos, there was 5 mL per minute treatment differences, quartile 2. And so we would expect that these data would translate broadly. And once again, the main determinant of the absolute treatment effect is the rate of progression, but we would expect a similar relative change across all of our trials.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [36]

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And if I could ask just 1 operational follow-up, and that is regarding commercial strategy, maybe bring Manmeet in or Warren. Could you anticipate increased visibility on commercial strategy over the course of 2020? And can you provide any color on how we might measure that over the course of the next year or so?

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Manmeet Singh Soni, Reata Pharmaceuticals, Inc. - CFO & Executive VP [37]

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Sure. So we believe like bard presents an extremely exciting commercial opportunity. And based on the data which we have shown you, we believe that if bard is approved by regulators that will be the first approved treatment options for patients with Alport syndrome in the United States and then followed by Europe and around the world. And as we have said earlier, right, this is a great opportunity, right, in the U.S., we have approximately, we estimate around prevalence of 30,000 to 60,000 patients in the U.S. and approximately 32,000 to 64,000 in the EU5, which will be the first countries where we plan to commercially launch. So -- and also, we have claims data on AS, which we believe are approximately 11,000 diagnosed patients in the United States, which we believe is a decent opportunity. And we have been very committed to succeeding commercially and understand the unique aspects of these rare diseases. They have been engaging with the KOLs for the last couple of years to understand this disease. And the insights which we have gained are very helpful for engagement and advocacy for education and clearly aid the speed and accuracy of diagnosis. As you have seen, very often in the rare diseases. And I've labeled treatment options, speeds formation of multidisciplinary teams and centers of excellence, and that's what we expect will happen over here.

We have an exceptional medical sales team, including field-based MSL liaisons that are focused on medical education and disease awareness in North America and in Europe. We are already working to expand our MSL team in the coming weeks to increase the focus and penetration to Tier 1 and Tier 2 beyond the KOLs, which we have a decent coverage. And disease awareness campaigns have already been launched to design to educate physicians about Alport syndrome. A genetic testing program has been initiated to improve the accuracy and timely diagnosis in the United States. We also have our core commercial organization in place with the leadership team, which includes marketing, commercial operations, market access and sales capabilities. Obviously, sales reps and the other staff would be hired based on your PDUFA date at the time lines, but we are already working on the patient hub centered model, which is under development to support the label utilization and ease of access to make sure we can manage the compliance and adherence over there. We have preliminarily completed our field force sizing and structure is complete for sales and access team. So we feel very comfortable with our commercial readiness based on the state we are right now.

Warren, anything to add?

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [38]

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Yes. I was just going to say, I think we're very comfortable with where we are. But based on the results, we'll obviously be accelerating our activities like really across the board.

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Operator [39]

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(Operator Instructions) And our next question comes from Matt Kaplan from Ladenburg Thalmann.

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Matthew Lee Kaplan, Ladenburg Thalmann & Co. Inc., Research Division - MD & Head of Healthcare Equity Research [40]

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Congrats on the results. Just wondered, if you can give us a sense in terms of what's related to safety, the dose titration and the, I guess, the average dose patients were able to achieve in the study? And I guess reasons why they weren't able to -- perhaps why patients weren't able to dose titrate higher?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [41]

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Sure. So we haven't commented specifically on the numbers at a given dose but most patients were able to reach their goal dose. What we've typically seen in our prior trials is approximately 2/3 of patients can reach their goal dose. Occasionally, a patient can't because of real or perceived tolerability issues. Muscle spasms is a good example. That was one of the most commonly reported adverse events in the Phase III cohort. But as I mentioned earlier, no more than 2 patients discontinued for any single adverse event. So clearly, those do not preclude continuation on bardoxolone.

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Matthew Lee Kaplan, Ladenburg Thalmann & Co. Inc., Research Division - MD & Head of Healthcare Equity Research [42]

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And I guess, once patients achieved the goal dose, do you typically see any dose-down titration or is that allowed in the study?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [43]

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Typically, what we see is that if there are any tolerability issues, they occur within the first 6 to 12 weeks. And so in our MOXIe call about a month ago, we highlighted the adverse events that were more frequent in the omav treated patients, were typically more common in the first 12 weeks, but those imbalances typically went away or were much smaller after that. And so it's similar for bardoxolone, we haven't done that analysis yet. But in our prior trials, we see a similar pattern. And so any adjustment that's needed occurs when the patients are coming in the clinic frequently. And typically, once they get to approximately week 12, they're at a good steady state at whatever dose they're on.

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Operator [44]

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Our next question comes from Brian Skorney from Baird.

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Jack Kilgannon Allen, Robert W. Baird & Co. Incorporated, Research Division - Research Associate [45]

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This is Jack again on for Brian. Just one more quick follow-up. I know you are not going to disclose the specific eGFR benefits earlier in the trial. But you mentioned they might be similar to magnitude to what we've seen in the Phase II. Can you provide any color as to whether double-digit benefits? Or if it was kind of a smaller or closer to BEACON type benefits in that 12 weeks, anything in that regard?

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Colin J. Meyer, Reata Pharmaceuticals, Inc. - Chief Medical Officer & Executive VP of Product Development [46]

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Yes. We're not going to comment specifically on what the change was over time, except to say that there was a very meaningful increase that, once again, on treatment that was meaningfully above baseline with a positive slope versus baseline on treatment.

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Operator [47]

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And that does conclude the question-and-answer session for today's conference. I'd now like to turn the conference back over to Warren Huff for any closing remarks.

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J. Warren Huff, Reata Pharmaceuticals, Inc. - Chairman, CEO & President [48]

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Thank you. In closing, I'd like to briefly review the developments at Reata over the last few weeks.

On October 10, we announced that we reacquired certain development and commercialization rights to develop bardoxolone, omaveloxolone and our other Nrf2 activator programs. This provides us with the opportunity to control the development and the launch of our products in Europe and around the world with our partner, Kyowa Kirin.

On October 11, we announced the presentation of several important studies at ASN, including the work from the lab of Dr. Kashihara, which we mentioned earlier, which demonstrated the precise mechanism of GFR improvements elicited by activation of Nrf2.

Of course, on October 14, we announced positive data from the MOXIe study of omav in patients with Friedreich's ataxia. MOXIe was the largest global interventional study ever conducted in FA and was the first to demonstrate a statistically significant improvement in neurologic function in patients with FA. We believe that omav has the potential to become the first FDA-approved therapy for Friedreich's ataxia.

And of course, yesterday, we announced a positive data from the CARDINAL study of bard patients with Alport syndrome.

These develops position us to achieve our long-standing goal of becoming a fully integrated global pharmaceutical company, marketing drugs with novel biology and the potential for high clinical impact on severe diseases with no approved therapies.

We're working to build a franchise in treating severe forms of chronic kidney disease. In addition to Alport syndrome, we've generated positive proof-of-concept data for bardoxolone in 4 other rare forms of CKD. The improvement in kidney function observed at 12 weeks, in patients with autosomal dominant polycystic kidney disease in our PHOENIX trial was similar to the improvement observed at 12 weeks in our Phase II study of patients with Alport syndrome. This similarity and the significant unmet need in ADPKD prompted us to initiate the FALCON study in May of this year. It had a design that's similar to CARDINAL with identical treatment schedules and end points for accelerated and full approval and is conservatively powered.

We've observed similar, significant improvements in eGFR in our PHOENIX study in patients with IgA nephropathy, CKD caused by Type 1 diabetes and FSGS. The consistent improvements we observed across types of CKD that originate from very different causes, reinforces our view that bardoxolone addresses a common final pathway of progression in CKD and strengthens our view that significant growth opportunities exist for it in rare forms of CKD.

We're planning to pursue the development of bardoxolone for the treatment of each of these additional rare forms of CKD. Collectively, the programs in rare CKD address many of the most severe forms of CKD in a total population that we estimate to be approximately 700,000 patients in the United States.

We're also planning to expand our work in neurologic disease based on the MOXIe results. We believe that the MOXle results provide proof of concept and improvements in myocardial function from omaveloxolone treatment may provide a therapeutic benefit in a number of other neurodegenerative diseases.

2019 has been a remarkable has been a remarkable year for Reata. It goes without saying that we remain grateful to the patients, their families, the caregivers, the investigators and the study staff who participated in CARDINAL, MOXIe and our other clinical studies. And of course, we're grateful for the efforts of our dedicated employees at Reata. We want to thank all of you for your commitment to our company over the years, and we look forward to updating you on our continued progress in the coming weeks and months.

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Operator [49]

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Thank you. An audio recording will be available shortly after this conference call on Reata's website at reatapharma.com in the Investors section.

Ladies and gentlemen, this now concludes today's conference call. Thank you for participating. You may now disconnect, and have a wonderful day.