Reata Pharmaceuticals, Inc.

Thank you for standing by and welcome to the Reata Pharmaceuticals third quarter 2022 financial results and update on development programs conference call. An audio recording of today's webcast will be available shortly after the call in the investor section of Reata's website at reatapharma.com. Before the company proceeds with its remarks, please note the forward-looking statements disclosure in the company's press release. There are many factors that could cause results to differ from expectations. including those noted in the company's SEC filings. On today's conference call, non-GAAP financial measures will be used to help investors understand the business performance. These non-GAAP financial measures are reconciled with comparable GAAP to financial measures in Reata's earnings release and presentation from today, which again can be found on Reata's website. Today's statements are not guarantees of future outcomes. Please also note that any comments made in today's call apply only as of today, November 8th, 2022, and may no longer be accurate at the time of any webcast replay or transcript rereading. Following the prepared remarks, we'll open up the call for questions. We ask that you please limit yourself to one question and one follow-up so that we can accommodate as many questions as possible. We are joined today by Warren Huff, Reata's Chief Executive Officer, Mamit Soni, President, Colin Meyer, Chief Innovation Officer, Simi Khan, Chief Medical Officer, and Dawn Burr, Chief Commercial Officer. At this time, I would now like to turn the call over to Warren Huff.

Good morning, everyone. We thank you for joining us today for our quarterly update. I'll start on slide four. Since RIADA's founding in 2002, our scientific mission has been to identify, develop, and commercialize therapeutics with novel mechanisms of action for the treatment of severe, life-threatening diseases that have few or no approved therapies. Toward that goal, we're developing omavaloxelone, or OMAV, a small molecule activator of NRF2 for the treatment of patients with Friedreich's ataxia, or FA. FA is a relentlessly progressive and debilitating neuromuscular disorder which affects approximately 4,000 diagnosed patients in the United States. There are no approved therapies for these patients, and FA patients typically become dependent on walkers and then wheelchairs in their mid-20s, and unfortunately, they pass away from the disease in their mid-30s. We began developing OMAV in FA over eight years ago, initiating the dose-ranging part one portion of the MOXIE trial in September of 2014. Following encouraging results from part one, we initiated MOXIE part two, one of the largest completed international trials in FA. We reported positive data from the MOXIE Part 2 study in October of 2019. We initiated a series of interactions with the FDA, leading to a pre-NDA meeting with the FDA in the third quarter of 2021. During the first quarter of this year, we completed the rolling submission of our NDA, and in May 2022, the FDA accepted our NDA for filing and granted priority review designation. As we reported in our last earnings call, in the third quarter of this year, we completed a mid-cycle communication meeting with the FDA and submitted additional data and analyses to the FDA in response to their comments. The FDA determined that these submissions were a major amendment to our NDA and extended the Prescription Drug User Fee Act, or PDUFA date, by three months to provide time for a full review of the new data and analyses. The PDUFA date is now February 28th, 2023. Next slide. We recently completed a late cycle meeting with the FDA. The purpose of the late cycle meeting is for the FDA to discuss any substantive issues identified in the division's objectives for the remainder of the review. The meeting does not address the final regulatory decision for the NDA. While we have not received formal minutes from the FDA, In the preliminary agenda for and during the late cycle meeting, the FDA stated that they continue to review the analyses and data included in our recent NDA submissions. The FDA did not request any additional data or analyses, but stated that additional data may be requested as reviews are ongoing. The FDA confirmed that no information requests were outstanding and reiterated that they do not currently plan to hold an advisory committee meeting. The FDA stated that no issues related to risk management have been identified. During the meeting, the FDA indicated that post-marketing requirements and label review are ongoing. With respect to post-marketing requirements and commitments, FDA stated that if OMAD is approved, they anticipate requiring a drug-drug interaction trial with CYP3A4 modulators, a thorough QT trial, and an evaluation of pregnancy outcomes. FDA stated that other post-marketing requirements and commitments may be considered, depending on the findings of the review. With respect to label review, during the meeting, we noted that the original proposed label language did not reflect the data and analyses included in the amendments to the NDA, and that we have updated it in connection with the planned filing of our marketing authorization application, or MAA, in Europe later this year. We committed to submit the updated proposed label language to the NDA. The FDA indicated that post-marketing requirements and label comments will be communicated in early 2023. Next slide. We're also making progress in the preparation of our marketing authorization application for OMAD in Europe. We received a positive opinion from the pediatric committee on our pediatric investigation plan with a commitment to seek scientific advice for additional input on the protocol design. We've received EMA follow-up protocol assistance feedback regarding our non-clinical and CMC programs. The EMA feedback indicated that there were no impediments to our planned MAA submission. We also received agreement that certain non-clinical studies, including two-year carcinogenicity study data, may be submitted after approval. We recently completed our pre-submission meeting and are nearing completion of the MAA. We plan to submit the application before the end of this year. Next slide. Turning to our program with bardoxalone in chronic kidney disease, we continue to enroll patients in our ongoing phase three FALCON trial in patients with autosomal dominant polycystic kidney disease, or ADPKD. ADPKD is a rare and progressive hereditary form of CKD that affects both men and women of all racial and ethnic groups. ADPKD is the leading inheritable cause of kidney failure with an estimated diagnosed population of 140,000 patients in the United States. The FDA has confirmed that the primary endpoint of EGFR change from baseline to week 108 which is eight weeks after the planned drug discontinuation at week 100, is reasonable since the available data suggests that bardoxalon's acute pharmacodynamic effects on EGFR should be largely resolved by that time. We currently enrolled more than 605 patients in the FALCON trial. Finally, our strategic collaborator in Japan, Kaiwa Kirin, is sponsoring the Ayame trial. a large phase three clinical trial in patients with diabetic kidney disease. The primary endpoint is time to onset of greater than or equal to 30% decline in EGFR or end-stage kidney disease. If the results of this trial are positive, it could provide clinical evidence that improvements in EGFR observed in BARD-treated patients do in fact delay progression to kidney failure. The IAME trial enrolled over 1,000 patients with stage three and four diabetic CKD, with over three years of data being collected for all patients in the trial. Kiowa Kieran expects to complete the last study visit in the second half of this year and has provided guidance that top line data will be available in the first half of 2023. With that, I would now like to turn the call over to Colin Meyer, who will provide an overview of the key clinical efficacy data for OMAD and FA. Don Burr will then provide an update on our recent progress in our commercial preparation activities for OMAV. And finally, Mamit Soni will provide an update on our financials and operations.

Thanks, Warren. I'll continue on slide nine. This morning, I would like to review the key lines of evidence we have generated supporting the efficacy of OMAVILOX loan in patients with FA. The primary evidence for OMAP in SA comes from the pivotal Part 2 MOXIE study, a double-blind, placebo-controlled, randomized international study. 103 patients were enrolled across a wide and representative range of age and disease severity. MOXIE Part 2 met its primary endpoint with patients treated with OMAP experiencing a statistically significant placebo-corrected 2.4-point improvement in MFARs compared to placebo after 48 weeks of treatment with a p-value of 0.014. We believe this 2.4 point change is inherently clinically meaningful as patients treated with OMAP on average did not progress and recovered some function during the 48-week period, whereas placebo-treated patients progressed at a rate consistent with the literature. We observed improvements relative to placebo in all subsections of the MPAR scale, all major subgroups, and all analysis populations. Next slide. Beyond the primary evidence from the pivotal MOXIE Part 2 trial, we have provided additional lines of confirmatory evidence to the FDA supporting the efficacy of OMAP in patients with FA. We have provided mechanistic evidence to the division linking frataxin deficiency with NREF2 suppression and impaired mitochondrial function. Deficits in mitochondrial respiration and ATP production are observed in cells and tissues isolated from patients with FA. For example, maximum mitochondrial respiration and spare mitochondrial respiratory capacity, as assessed by oxygen consumption rate, were lower in fibroblasts from patients with FA than than in fibroblasts from healthy control subjects. Additionally, a study conducted in 42 patients compared peak oxygen consumption, which is reflective of mitochondrial function, with a Friedreich's ataxia rating scale score and found that reduced mitochondrial function correlated with reduced neurological function. Taken together, these data demonstrate a clear link between reduced mitochondrial function in FA and reduced neurological function in FA patients. Next slide. We and our academic collaborators have spent several years to demonstrate the relevance of OMav to impacting the underlying pathophysiology of FA. As shown in the left figure, OMav has been demonstrated to restore Nrf2 protein levels in FA patient fibroblasts. In the middle panel, you can see that this restoration of Nrf2 is associated with restoration of mitochondrial energy production in FA disease models and patient samples. In the panel on the right, we performed a tertile analysis of MFARS and changes in the Nrf2 target genes ferritin and GGT, comparing changes at week 48 in the pivotal MOXIE Part 2 trial. This analysis shows that ferritin and GGT increases are associated with MFARS improvements in patients with FA. As shown on this plot, the patients with the largest clinical improvement, or largest decrease in MFARS at week 48, as shown on the right, were also the patients with the largest increases in ferritin and GGT. To summarize, these data provide additional context for the relevance between FA pathophysiology, NREF2 induction, in clinical benefit in FA patients. Moving to slide 12. To assess the treatment effect of OMAP more formally in the MOXIE extension and to provide additional clinical evidence, we performed a post hoc propensity match analysis of the MOXIE extension data to the largest, most robust FA natural history study, FACOMS. FACOMS is a global, multicenter, longitudinal, prospective observational study that has enrolled more than 1,250 patients. Clinical outcome measures, including MFARS, are assessed annually, and patients are followed for up to 25 years. Patients from FACOMs were matched to MOX extension patients using propensity scores based on five covariates, including sex, baseline age, age of FA onset, baseline MFARS score, and baseline GATE score. Selection of these covariates was made in collaboration with a principal investigator and statistician for FACOMS based on clinical relevance, the relevance as prognostic indicators for disease progression, and availability in both studies. The change from baseline and MFARS at year three for MOXIE extension patients compared to the propensity score matched FACOMS patients was analyzed as the primary efficacy endpoint using the same mixed model repeated measures, or MMRM analysis, as we used for the primary analysis for MOXIE Part 2. Results of the primary pool population of 136 patients in the MOXIE extension compared to 136 patients in FACOMS is displayed in the plot on the left. In this population, patients in the FACOMS match set progressed approximately 6.6 MFARS points by year three, whereas patients treated with OMAP in the MOXIE extension progressed only three points, representing a significant slowing in the rate of progression by 55%, with a nominal p-value of 0.0001. In addition to the primary pool population, we defined two subpopulations, including the placebo to OMAP population, which included 95 patients previously randomized to placebo and MOXIE Part 2, and patients from MOXIE Part 1 who had been off treatment for a minimum of 21 months. This population is important since none of these patients were randomized to OMAP in Part 2, and therefore, this efficacy data is completely independent of MOXIE Part 2. In the plot on the right, the treatment effect in this population at Year 3 with similar magnitude to the results from the primary pool population, demonstrating a 56% slowing of the rate of progression with a nominal p-value of 0.0001. In summary, the propensity match analyses provide a robust assessment of the effect of OMAV in the ongoing extension study. The propensity match analysis includes 136 patients who have been treated with OMAV for up to three years to matched FACOMS patients, and all analysis populations demonstrated a significant slowing of progression for patients treated with OMAD with multiple subgroups in all MPAR subsections favoring OMAD. In conclusion, to supplement the efficacy results of MOXIE Part 2, we have provided FDA with additional evidence supporting the efficacy of OMAD. These include mechanistic data showing how OMAP directly affects the underlying pathophysiology of FA, the post hoc propensity match analysis of patients in the MOXIE extension compared to patients from FACOMS demonstrating a significant slowing in disease progression, and results from the post hoc delayed start analysis, which are consistent with OMAP having a disease modifying profile and a persistent effect on the course of disease. With that, I'll now turn the call over to Don.