Reata Pharmaceuticals, Inc.

Ladies and gentlemen, thank you for standing by and welcome to the Riata Pharmaceuticals first quarter 2021 financial results and update on development programs conference call. An audio recording of today's webcast will be available shortly after the call today on Riata's website at riatapharma.com in the investor section. Before the company proceeds with its remarks, please note the forward-looking statements 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. On today's conference call, non-GAAP financial measures will be used to help investors understand the business performance. These non-GAAP financial measures are reconciled with comparable GAAP financial measures in RIADA's earnings release and presentation from today, which can be found on RIADA's website. Today's statements are not guarantees of future outcomes. Please also note that any comments made on today's call apply only as of today, May 6, 2021, and may no longer be accurate at the time of any webcast replay or transcript rereading. Following the prepared remarks, we will open the call up for questions. We ask that you limit yourself to one question and one follow-up so that we can accommodate as many questions as possible. We are joined today by RIADA's Chief Executive Officer, Warren Huff, Chief Research and Development Officer, Colin Meyer, Chief Operating and Chief Financial Officer, Manmeet Soni, and Chief Commercial Officer, Don Burr. At this time, I would like to turn the call over to Warren Huff, Chief Executive Officer of RIADA.

Good morning, everyone, and thank you for joining us today. We have a number of updates that we're excited to share with you this morning. We'll start on slide four. First off, we're pleased with the US Food and Drug Administration's recent decision to accept our filing of our new drug application for Pardoxelone for the treatment of patients with chronic kidney disease caused by Alport syndrome. The FDA will review the application under standard review timeline, and it assigned a PDUFA date for the application of February 25th, 2022. The FDA also advised us that it is planning to hold an advisory committee meeting to discuss the application. We've been actively preparing for this meeting the last several months, and it will be a key focus for our team during the year. With clarity on the review timeline for our NDA, we're continuing our preparations for the commercial launch of Vardoxelone in the United States, subject of course to approval by the FDA. Our core commercial leadership team is already in place, and we're building the organization, infrastructure, systems, and processes necessary for the launch of Vardoxelone in the U.S., These include sales, marketing, market access, patient support, and distribution. We're pleased to have Dawn Burr, our Chief Commercial Officer, join us on this call and look forward to hearing more from her about our commercial launch preparations later in the call. Next slide. Beyond the acceptance of our filing of our NDA for Bardoxelone for Alport Syndrome, we've made significant progress in our Falcon study of Bardoxelone in patients with autosomal dominant polycystic kidney disease Since our last earnings call on March 1st, we've enrolled over 70 patients, and we continue to anticipate completing enrollment at Falcon by the end of the year. Regarding our pivotal neurology program with OMAV in Friedreich's ataxia, we previously reported positive results from the MOXIE pivotal trial, the baseline controlled study, and the delayed start analyses. The FDA recently granted our request for a type C meeting, which is scheduled to occur in this quarter. At that meeting, we plan to present data from the delayed start analyses that we believe supports OMAP's potential as a disease-modifying therapy in FA and discuss next steps for the FA program. With that introduction, I'd like to turn the call over to Colin, who will discuss recent updates to our development pipeline. Don will then provide more detail on our ongoing commercial readiness preparations. Finally, Mammit will review our financial results and provide an operational update.

Thanks, Warren. I'll provide a high-level overview of our Alport syndrome program, and we'll then review the progress of our other development programs. Starting on slide eight, Alport syndrome is a severe hereditary form of CKD, which is caused by mutations in collagen that promote inflammation, fibrosis, and loss of kidney function. Unlike other forms of CKD, which generally progress more slowly and have low rates of actual progression to kidney failure, patients with the most severe forms of Alport syndrome have a 100% lifetime risk of kidney failure. The high risk of kidney failure is due to the very rapid rate of progression observed in Alport syndrome, as shown on this slide. Adult patients with Alpert syndrome progress two to three times more rapidly than patients with more common forms of CKD, such as diabetic, hypertensive, and ADPKD. The rate of progression of Alpert syndrome is very rapid in pediatric patients. Alpert syndrome in pediatric patients progress approximately four times faster than the most common cause of kidney failure in children, KAKET, which is caused by congenital abnormalities of the kidney and urinary tract. Next slide. The clinical meaningfulness of the rate of loss of kidney function is exemplified on this slide, which shows the time to kidney failure based on historical EGFR data from patients enrolled in the Phase III cardinal trial. The data on the left side of this plot are historical data collected over a five-year period before patients entered cardinal, which is noted as year zero on the x-axis. The overall trajectory is shown in gray and the pediatric patients are shown in dark blue. If these same patients followed the same rate of loss in kidney function over subsequent years, you can see that on average the pediatric patients would reach end-stage kidney disease in only five years and all patients in only nine years. This explains why Alpert syndrome patients reach kidney failure at such a young age. Unlike diabetic kidney disease patients, who on average reach kidney failure in their 60s, pediatric Alpert syndrome patients reach kidney failure and need a transplant or dialysis in their 20s. Turning to slide 10, the nephrology community has spent decades studying the impact of kidney failure on quality of life and survival. Patients who are able to obtain a kidney transplant require lifetime immunosuppression and often develop associated complications such as cancer. Patients who cannot obtain a kidney transplant typically spend many hours a week undergoing hemodialysis. Beyond the adverse effects on quality of life, renal replacement therapy greatly increases the risk of infections, cardiovascular disease, and premature death. This slide shows the average decrease in life expectancy by age at kidney failure onset. I have highlighted the ages of 15 through 29 years, since this is the age when the vast majority of patients with the most severe forms of Alpert syndrome develop kidney failure. As you can see, once kidney failure occurs in these patients, they have an average loss of life expectancy of approximately 40 years. these data highlight how important it is to slow the progression of CKD. Next slide. As we discussed on last quarter's call, chronic inflammation is a primary contributor to the progressive loss of kidney function associated with numerous forms of CKD, including Alport syndrome. Pro-inflammatory stimuli have two primary effects, including reversible dynamic effects and irreversible structural effects. Pro-inflammatory mediators can dynamically and reversibly regulate single nephron GFR by modulating the glomerular surface area for filtration, or K sub F. In CKD, inflammation is chronically present, which persistently reduces single nephron GFR and is a key feature of CKD. When inflammation persists over long periods of time, as it does in almost all forms of CKD, it also drives kidney remodeling by activating pro-fibrotic pathways. Over time, these chronic processes result in irreversible fibrosis and ultimately the complete loss of function of individual nephrons. The target of baroxone is Nrf2, a transcription factor with anti-inflammatory and tissue protective effects. which is suppressed in many forms of CKD, including Alpert syndrome. Next slide. We have spent over a decade conducting a large number of preclinical studies to characterize the mechanism of action of Ardoxalone, These effects are now well-documented in the scientific literature and demonstrate that bardoxalone restores single-nephron GFR by increasing the filtration surface area in the kidney, reversing inflammation-mediated constriction. We have shown that this effect is not associated with any changes in afferent or efferent tone, demonstrating that this effect is not associated with increases in intracranial pressure or hyperfiltration. This is a novel mechanism to dynamically regulate GFR, and as I will discuss in the clinical data, this manifests in patients as sustained increases in GFR with baroxaline treatment while patients are taking the drug. Now on slide 13, During our development program, we have spent much effort and time to determine how Vardoxalin regulates the kidney's handling of albumin, the most common protein found in the blood. Albumin is often present in the urine of patients with kidney disease due to defects in the kidney's filtration barrier caused by patients' underlying kidney disease. Albumin is pathogenic and causes damage to the kidney when it's excessively reabsorbed into the kidneys, which induces inflammation and fibrosis. In preclinical models, we have shown that baroxone affects albumin handling via two mechanisms. First, baroxone increases GFR, which increases filtration of albumin. Importantly, this occurs without any evidence of increased permeability or injury to the filtration barrier. Second, as we published in 2012, baroxaline reduces the expression of megalin, the primary receptor that reabsorbs albumin in the proximal tubules of the kidney. This shunts albumin into the urine, reducing its reabsorption and subsequent activation of inflammation within the interstitium of the kidney. In summary, bardoxelone increases filtration of albumin and reduces its uptake, both of which are a pharmacological effect not associated with injury. Next slide. In regard to irreversible disease modifying effects, we have demonstrated that bardoxelone has anti-fibromic effects and improves kidney structure and function in response to many models of CKD, including pressure overload, hyperfiltration, hypertension, high protein, diabetes, and dyslipidemia. As I will discuss in a few slides, this effect on fibrosis in patients is represented by the off-treatment improvements we have observed in our Alport syndrome and diabetic kidney disease trials. Turning to slide 15, the clinical data from our Alport Syndrome Development Program map to each of these observations from our preclinical studies. we have shown that the reversible increases in EGFR, which are due to restoration and filtration surface area in the kidney, are durable for two years versus placebo in the pivotal phase three cardinal study. As discussed on last quarter's call, for patients receiving baroxalone, which is the MITT analysis shown on the slide, separation occurs in the baroxalone relative placebo treated patients in the second year. The rate of loss of kidney function based on the on-treatment changes in the second year is reduced by approximately one-third. Consistent with the separation in year two of cardinal phase three, in the ongoing EGLE extension study, we have shown that these increases are sustained for a total of three years. This duration of sustained EGFR increase is meaningful since, as I mentioned a few slides ago, on average, these patients would reach kidney failure in five to nine years. We have also demonstrated a persisting increase after withdrawal in EGFR versus placebo after year one and year two in the phase three cardinal trial. And we believe this increase is due to the anti-fibrotic effects of our oxalone and is consistent with the disease modifying profile. These off-treatment improvements also validate that the large durable on-treatment increases in EGFR are beneficial. When we analyzed the off-treatment data using a longitudinal analysis to compute off-treatment slopes, as opposed to calculating changes at discrete time points, we have demonstrated that there is a reduction in progression by approximately 50% in the bardoxelone-treated patients compared to placebo-treated patients. The data from the cardinal trial are also supported by data from the beam and beacon diabetic CKD trials that also demonstrated significant on and off treatment improvements in EGFR relative to placebo. Overall, the clinical profile of Ardoxelone is well characterized, and the on and off treatment differences in EGFR observed in the pivotal phase three cardinal trial demonstrate a meaningful benefit in patients with one of the most rapidly progressive forms of CKD. Next slide. Our Alpert Syndrome Development Program has demonstrated an acceptable safety profile. Adverse events were mild to moderate, generally occurred within the first 12 weeks, were reversible with treatment discontinuation, and were not life-threatening. We identified no safety findings in Bartoxelan patients who discontinued and received, on average, 33 weeks of treatment. By the end of the two-year study, these patients had kidney function that was similar to placebo-treated patients, demonstrating that these patients did not experience any adverse kidney findings. Fewer serious adverse events were observed in redox-treated patients. We mitigated against the risk of fluid retention. No new safety signals have been identified in the ongoing extension study. Overall, our Alport syndrome data are consistent with a comprehensive safety database of over 3,000 patients. In summary, we believe our data demonstrate that Bredoxone targets the underlying pathophysiology of Alport syndrome, and our clinical safety and efficacy data support an acceptable and positive benefit-risk profile for Bredoxone for the treatment of Alport syndrome. We'll now discuss our other CKD development programs on slide 18. As you know, we are also developing baroxone for the treatment of patients with ADPKD, the most common hereditary form of CKD, with approximately 140,000 diagnosed patients in the U.S. Despite standard of care, a high percentage of patients ultimately progress to kidney failure. Similar to the Cardinal trial, the Phase III Falcon trial is two years in total duration, and the key primary and secondary endpoints are at the end of the first and second years of treatment. We plan to enroll approximately 550 patients from sites in the US, Europe, Australia, and Japan. Currently, more than 290 patients have been enrolled in Falcon, and we expect to complete enrollment by the end of this year. As shown on slide 19, In the first quarter of 2021, we initiated MERLIN, a double-blind, placebo-controlled Phase II trial evaluating the safety and efficacy of ratoxelone in patients at risk of rapidly progressing CKD due to multiple etiologies, including common and rare forms of CKD, such as diabetic CKD, hypertensive CKD, IgA nephropathy, FSGS, and others. The primary endpoint of Merlin is the change in EGFR from baseline to week 12. We plan to enroll approximately 70 patients aged 18 to 70 with EGFR between 20 to 60 ml per minute and with one of several risk factors for rapid progression. We anticipate complete enrollment by the end of the second quarter of 2021. If the results of the study are positive, we would potentially proceed to a larger phase three trial with similar eligibility criteria. Patients at risk for rapid progression experience a significant risk of progressing to end-stage kidney disease in a population with high unmet need across multiple forms of CKD. Now, turning to slide 22 with our neurology programs, I will provide an update on our program with omaviloxelone, or omav, and Friedreich's ataxia. FA is a rare disease characterized by progressive loss of motor function, with patients typically requiring a wheelchair by their mid-20s and a median survival of 35 years. There are no approved therapies for FA. On our last call, we highlighted the results from the delayed start analyses where we compared patients initially randomized to placebo and OMAP to each other in the extension. We believe these analyses demonstrate that OMAP's profile is consistent with disease modification. We requested, and the FDA granted, a Type C meeting to discuss the delayed SART analyses, as well as the overall data from our MOXIE study and the overall development program. The meeting is scheduled for the second quarter of 2021. Next slide. We believe that the pharmacology of our Nrf2 activators may be applicable to a wide range of other neurological diseases that have a common pathophysiology of mitochondrial dysfunction and neuroinflammation. OMAD and analogs have shown activity in numerous non-clinical models, as well as patient biopsy samples, and we believe that pharmacology is applicable to a broad set of neurological diseases, including other movement disorders, such as PSP, Parkinson's disease, and Huntington's disease, as well as diseases that affect neuromuscular function and memory. Finally, on slide 25, our earlier stage pipeline includes RTA901, a highly potent and selective oral small molecule C-terminal modulator of HSP90. HSP90 is a molecular chaperone that facilitates the folding and stability of many proteins. RT-901 increases transcription of HSB-70, another molecular chaperone that promotes cell survival in response to stress and affects mitochondrial function. RT-901 has demonstrated activity in multiple models of diabetic neuropathy. It has been shown to reduce pain acutely in models of painful diabetic neuropathy, as well as recovery of lost sensation in models of insensate diabetic neuropathy. Of the approximately 4 million U.S. patients with moderate or severe diabetic peripheral neuropathic pain, approximately half of those treated do not achieve an adequate pain reduction with available therapies. We have completed Phase I SAD and MAD studies in healthy volunteers and have demonstrated an acceptable safety profile with no safety signals, drug discontinuations, or SAEs while achieving appropriate safety margins. In the second quarter of 2021, we are planning to initiate clinical pharmacology studies to support the launch of a Phase II study in the fourth quarter of this year in patients with diabetic peripheral neuropathic pain. This study will be a randomized, placebo-controlled, dose-ranging study using a standardized pain scale. I will now turn the call over to Dawn Burr, our Chief Commercial Officer, to provide an update on our commercial readiness for doxilone.