On August 8, 2022 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata," the "Company," "our," "us," or "we"), a clinical-stage biopharmaceutical company, reported financial results for the second quarter of 2022 and provided an update on the Company’s business operations and clinical development programs (Press release, Reata Pharmaceuticals, AUG 8, 2022, View Source [SID1234617806]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Recent Company Highlights
Omaveloxolone in Patients with Friedreich’s Ataxia
Following the announcement of the positive data from the MOXIe Part 2 study in October 2019, the U.S. Food and Drug Administration ("FDA") stated that it did not have any concerns with the reliability of the modified Friedreich’s ataxia rating scale ("mFARS") primary endpoint results in the MOXIe Part 2 study and requested additional evidence of persuasiveness to support a New Drug Application ("NDA") filing. We then began a series of interactions with the FDA to provide additional evidence of effectiveness to support a single study approval. This ultimately led to a pre-NDA meeting and subsequent NDA submission in March 2022 after FDA’s review of our Delayed-Start Analysis, which it had requested.
In May 2022, the FDA accepted for filing our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia and granted Priority Review. The FDA has granted Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation to omaveloxolone for the treatment of Friedreich’s ataxia. The FDA advised us that it is planning to hold an advisory committee meeting to discuss the application, and our application has been assigned a Prescription Drug User Fee Act ("PDUFA") target action date of November 30, 2022.
We recently completed a mid-cycle communication meeting with the FDA. The purpose of the mid-cycle communication meeting is for the FDA to provide the sponsor with an update of the status of the NDA review, including any issues identified. While we have not received formal minutes from the FDA, in the preliminary agenda for, and during, the mid-cycle communication meeting, the FDA stated that it has not identified any new significant issues, but it continues to have concerns regarding the strength of the efficacy evidence. The FDA did not identify any significant clinical safety issues. The FDA stated that the safety review is ongoing, and they are continuing to evaluate the cardiac safety of omaveloxolone in patients with Friedreich’s ataxia. They have not identified any other major safety concerns at this stage of their review.
During the mid-cycle meeting, we proposed to address FDA’s concerns in three ways. First, we presented updated results from the Delayed-Start Analysis using a March 2022 data cut-off, which contain new, later time points and increased numbers of patients at later time points than the prior analysis. Second, we proposed to submit a new propensity-matched matched analysis of MOXIe Extension data using the largest, most robust Friedreich’s ataxia natural history study to provide additional clinical data that could be considered confirmatory evidence. Third, we discussed an additional NDA amendment containing compelling mechanistic evidence in the setting of Friedreich’s ataxia’s well-understood disease pathophysiology, which could also serve as confirmatory evidence. The FDA acknowledged these data and agreed that we could submit the updated data to the NDA. We have submitted the following additional data and analyses to the FDA.
Results from March 2022 Data Cut-Off of MOXIe Extension
Results of the updated Delayed-Start Analysis from the March 2022 data cut-off demonstrated that the between-group difference in mFARS observed at the end of the placebo-controlled MOXIe Part 2 treatment period (LS mean difference = -2.17 ± 1.09) was preserved at MOXIe Extension Week 72 in the delayed-start period (LS mean difference = -2.91 ± 1.44). Consistent with a persistent treatment effect on disease, the upper limit of the 90% Confidence Interval ("CI") for the difference estimate was less than zero (-0.09), meeting the threshold for demonstrating significant evidence of non-inferiority. Additionally, the between group difference in mFARS was maintained at Extension Week 96, 120, and 144 (LS mean difference = -2.19 ± 1.38, -2.74 ± 1.26, and -2.58 ± 1.47 respectively), and the threshold for non-inferiority was met at Extension Week 120 with an upper limit of the 90% CI of -0.106.
Post Hoc Propensity-Matched Analysis of MOXIe Extension
We recently completed a post hoc analysis comparing the mFARS progression of omaveloxolone-treated patients in the open-label MOXIe Extension trial to the progression of propensity score-matched untreated patients in the largest natural history study of Friedreich’s ataxia, Clinical Outcome Measures in Friedreich’s ataxia ("FA-COMS"). All patients enrolled in the MOXIe Extension study with at least one post-baseline assessment (n=136) were matched one to one with patients from the FA-COMS study (n=136) using five baseline characteristics, or covariates, including sex, baseline age, age of Friedreich’s ataxia onset, baseline mFARS score, and baseline gait score, which have been demonstrated to be predictive of disease progression. Demographics and baseline characteristics were highly comparable between MOXIe Extension patients and the matched FA-COMS external control group.
In the Primary Pooled Population (n=136 per group), patients in the matched FA-COMS group progressed 6.61 mFARS points at Year 3, whereas patients treated with omaveloxolone in MOXIe Extension progressed 3.00 points for a difference of -3.61 mFARS points (nominal p=0.0001). In this analysis, progression in mFARS was 55% slower in MOXIe Extension patients treated with omaveloxolone compared to matched untreated patients in the FA-COMS study.
Mechanistic Validation of Nrf2 Target Biomarkers in Friedreich’s Ataxia
We have provided additional pharmacodynamic information to the FDA including an integrated and detailed presentation of the disease pathophysiology of Friedreich’s ataxia, a review of the available pharmacodynamic data, justification of the relevance of these data in Friedreich’s ataxia and an explanation of the relationship between the mechanistic data and the observed biomarker and clinical treatment effects in patients treated with omaveloxolone. Substantial evidence demonstrates that Nrf2 levels and activity are suppressed in cells from patients with Friedreich’s ataxia and in preclinical animal models of the disease. Omaveloxolone restores Nrf2 levels and increases the expression of Nrf2 target genes, including those that encode ferritin and gamma-glutamyl transferase ("GGT"), in nonclinical models. Treatment with omaveloxolone in MOXIe Part 1 resulted in dose-dependent increases in Nrf2 activity, as assessed by serum ferritin and GGT levels. Data from MOXIe Part 2 showed an association between omaveloxolone-induced Nrf2 activity and measures of neurological function, with larger increases in Nrf2 target levels associated with larger improvements in mFARS scores.
"We look forward to continuing to work with FDA on its review of our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia, a rare, genetic, debilitating, and degenerative neuromuscular disorder with no approved therapies," said Warren Huff, Reata’s Chief Executive Officer. "We have submitted these additional data and analyses to the FDA and are continuing to prepare for the upcoming Advisory Committee meeting."
Bardoxolone Methyl in Patients with Chronic Kidney Disease Caused by Alport Syndrome
We received a Complete Response Letter ("CRL") from the FDA in February 2022 with respect to its review of our NDA for bardoxolone methyl ("bardoxolone") in the treatment of patients with chronic kidney disease caused by Alport syndrome. The CRL indicated the FDA cannot approve the NDA in its present form. We have recently requested a Type C meeting to discuss the program and continue to work with the FDA to confirm our next steps on our Alport syndrome program.
Second Quarter Financial Highlights
Cash and Cash Equivalents
On June 30, 2022, we had cash and cash equivalents and marketable securities of $481.5 million, as compared to $590.3 million on December 31, 2021.
GAAP and Non-GAAP Research and Development ("R&D") Expenses
R&D expenses according to generally accepted accounting principles in the U.S. ("GAAP") were $39.3 million for the second quarter of 2022, as compared to $40.1 million for the same period of the year prior.
Non-GAAP R&D expenses were $33.0 million for the second quarter of 2022, as compared to $34.8 million, for the same period of the year prior.1
GAAP and Non-GAAP General and Administrative ("G&A") Expenses
GAAP G&A expenses were $25.1 million for the second quarter of 2022, as compared to $22.0 million, for the same period of the year prior.
Non-GAAP G&A expenses were $17.6 million for the second quarter of 2022, as compared to $14.0 million for the same period of the year prior.1
GAAP and Non-GAAP Net Loss
The GAAP net loss for the second quarter of 2022, was $73.6 million, or $2.02 per share, on both a basic and diluted basis, as compared to a GAAP net loss of $72.7 million, or $2.00 per share, on both a basic and diluted basis, for the same period of the year prior.
[1] See "Non-GAAP Financial Measures" below for a description of non-GAAP financial measures and a reconciliation between GAAP and non-GAAP R&D expenses, GAAP and non-GAAP G&A expenses, and GAAP and non-GAAP net loss, respectively, appearing later in the press release.
The non-GAAP net loss for second quarter of 2022, was $49.4 million, or $1.36 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $48.0 million, or $1.32 per share, on both a basic and diluted basis, for the same period of the year prior.1
Cash Guidance
The Company reaffirms its existing cash & cash equivalents and marketable debt securities will be sufficient to enable it to fund operations through the end of 2024.
Non-GAAP Financial Measures
This press release contains non-GAAP financial measures, including non-GAAP R&D expenses, non-GAAP G&A expenses, non-GAAP operating expenses, non-GAAP net loss and non-GAAP net loss per common share – basic and diluted. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.
The Company defines non-GAAP R&D expenses as GAAP R&D expenses, which exclude stock-based compensation expense; non-GAAP G&A expenses as GAAP G&A expenses, which exclude stock-based compensation expense; non-GAAP operating expenses as GAAP operating expenses, which exclude stock-based compensation expense; non-GAAP net loss as GAAP net loss, which excludes stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties; and non-GAAP net loss per common share – basic and diluted as GAAP net loss per common share – basic and diluted, which excludes stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants of stock options and restricted stock units and changes in the Company’s stock price, which impact the fair value of these awards. The Company has excluded the impact of accreted non-cash interest expense from liability related to sale of future royalties as it may be calculated differently from, and therefore may not be comparable to, peer companies who also provide non-GAAP disclosures. The Company has excluded the impact of stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties because the Company believes its impact makes it difficult to compare its results to prior periods and anticipated future periods.
Because management believes certain items, such as stock-based compensation expense and non-cash interest expense from liability related to sales of future royalties, can distort the trends associated with the Company’s ongoing performance, the following measures are often provided, excluding special items, and utilized by the Company’s management, analysts, and investors to enhance consistency and comparability of year-over-year results, as well as to industry trends, and to provide a basis for evaluating operating results in future periods: non-GAAP net loss; non-GAAP net loss per common share – basic and diluted; non-GAAP R&D expenses; non-GAAP G&A expenses; and non-GAAP operating expenses.
The Company believes the presentation of these non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with these non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this press release.
Conference Call Information
Reata’s management will host a conference call on August 8, 2022, at 8:30 am ET. The conference call will be accessible by dialing (844) 200-6205 (toll-free domestic) or (929) 526-1599 (international) using access code 964090. The webcast link is View Source
Second quarter 2022 financial results to be discussed during the call will be included in an earnings press release that will be available on the Company’s website shortly before the call at View Source and will be available for 12 months after the call. The audio recording and webcast of the conference call will be accessible for at least 90 days after the event at View Source.