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spk04: 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.
spk01: 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.
spk03: 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.
spk06: Thank you, Colin. Good morning. I'll continue on slide 14. RIADA's development of omabaloxalone for the treatment of Friedreich's ataxia and potential FDA approval represents advancement and hope for an underserved patient community. There are no approved therapies and only symptomatic treatment is available today. If approved, omabaloxalone will be the first product to treat Friedreich's ataxia with the potential to slow disease progression. the commercial opportunity is significant. FA is a rare disease with very low prevalence, a devastating and life-shortening disease affecting approximately 4,000 diagnosed patients in the United States. Like many rare diseases, some patients may go undiagnosed until a specific treatment becomes available. We believe that most U.S. Friedreich's Ataxia patients have been diagnosed, and this is our target market at approval. The undiagnosed patient estimate reflects potential future market growth. HCPs treating diagnosed FA patients today have been identified, providing focus for our commercial launch plans. Patients are connected through community, social media, podcasts, and advocacy, all platforms for disease education and information sharing. Actively engaged in research, over 1,000 U.S. FA patients participated in FA comms or FA clinical outcomes measures. This voluntary study evaluates, measures, and monitors the natural progression of the disease, quantifying the change in progression over time. This highly engaged patient community has eagerly awaited a treatment. Turning to slide 15. We've recently accelerated our U.S. launch preparation. Our commercial leadership team is in place, representing all core commercial functions, including marketing, market access, sales, and operations. We've hired the sales leadership team. Brand strategy development is underway, and our launch priorities are clear. For over two years, our disease awareness and educational campaigns have highlighted the severe rare disease and the urgent need for treatment. As we prepare for launch, our focus shifts to creating a brand, educating HCPs, empowering patients to seek treatment, and creating access to therapy. Next slide. Our focus at approval will be to reach and educate HCPs with diagnosed FA patients in their practices. Through claims data analysis, we've identified approximately 2,500 HCPs treating at least one FA patient. We've also included ataxia centers managing FA patients in our list of target accounts and nine U.S. CCRN centers. These collaborative clinical research network accounts are part of an international network of FA research centers where physicians, researchers, and patients work together to advance treatments and best practices for disease management. U.S. sites include the Children's Hospital of Philadelphia, UCLA, St. Jude Children's Research Hospital, and the University of South Florida in Tampa, to name just a few. With FA targets identified, our commercial focus at approval will focus on reaching and educating these most important HCPs. Our commercial team will expand to 55 to 60 employees next year, including our field-based sales and access teams. We plan to hire the sales organization in Q1. They will be trained and deployed following approval in late Q1. Turning to slide 17. A best practice for successful rare disease specialty product launches includes a comprehensive patient access and distribution program. We are pleased to introduce RIATA REACH, or the RIATA Education Access and Care Helpline. REACH will serve as the single point of contact for both patients and physicians and will support access programs, including the management of new patient starts and benefits verification, commercial co-pay assistance, uninsured patient support, and tailored patient adherence and compliance programs. REACH will include an integrated and exclusive specialty pharmacy and be supported by a field-based patient access liaison team. A guiding light for the development of these services includes putting the patient experience at the front and center of what we do and working towards reducing the burden of patient out-of-pocket cost as a barrier to accessing treatment. The REATA REACH program will go live at approval. Thank you. I'll now turn the call over to Manny for our financial update.
spk05: Thank you, Dawn, and good morning, everyone. We released our financials and filed our 10Q earlier this morning. I would like to highlight a few financial items this quarter, including our strong cash position, operating expenses, and collaboration deferred revenue. I will then provide an outline for our operational readiness for a potential commercial launch in the United States and the European region if OMAP is approved in those territories. Let me start with our cash balance on slide 19. As of September 30th, we maintained a solid balance sheet with approximately $435.9 million in cash, cash equivalents, and marketable debt securities. Based on our current plan, our cash balance will enable us to fund operations through the end of 2024. I wanted to highlight that since we repaid our prior debt from Oxford and Silicon Valley Bank in 2020, we have a clean balance sheet and we have no existing debt or loans. In addition, liabilities related to our potential Blackstone royalty obligation in our balance sheet are only payable on Bardox loan revenues if Bardox loan is approved. Blackstone has no rights on OMAP revenues. Moving to expenses, R&D expense increased by $4.1 million for the three quarter, for the three months ended September 30th, 2022, as compared to the three months ended September 30th, 2021. The increases due to personal and personal related costs to support our product development activities. G&A expenses increased by $1.5 million or 6% for the three months ended September 30th, 2022, as compared to the three months ended September 30th, 2021. The increase was primarily due to rent expenses related to the new headquarters building. Both our GAAP and non-GAAP operating expenses slightly increased as compared to the second quarter of 2022. As mentioned on the last quarter call, we have recognized all of the deferred revenues related to milestones achieved earlier under the QR-KIRIN Agreement in the second quarter of 2022 As a result, we have not recognized any deferred revenues during the third quarter of 2022, and any future revenues will be recognized once future milestone or collaboration revenues are earned. We continue to work on completing the manufacturing of OMAP's commercial drug supply in anticipation of a launch in the United States. We have begun to hire resources, build processes and systems to enable us to record product revenues, tract receivables, report government pricing, and other related compliance requirements. As we are preparing to submit an MAA for OMAP during this quarter, we have initiated build-up of our European infrastructure to support the potential commercial launch of OMAP in the European region by early 2024, if approved. Finally, I would like to highlight that we have strong intellectual property protection for OMAP, including three different patent families. If OMAP receives FDA approval in early 2023, we anticipate that composition of matter, patent production could be extended to early 2037 in the United States. Additionally, composition of matter of patents claiming OMAP have been granted in Europe, Japan, China, and more than 20 other territories. With that, I will turn the call back over to Warren.
spk01: Thank you, Manmeet. In closing, we've made substantial progress in our OMAD program. This includes the submission of additional information and analyses to the FDA, which we believe strengthen the body of evidence demonstrating the effectiveness of OMAD in FA and the completion of the late cycle meeting. If approved, OMAD will be the first drug available for this severe disease, and we're actively working on commercial preparations to be in a position to potentially launch it early next year. Next slide. That concludes our prepared remarks. We'd like to thank everyone who dialed in. I'll now turn the call over to the operator for questions.
spk04: Ladies and gentlemen, at this time we will begin the question and answer session. If you would like to ask a question, please press star followed by one on your telephone keypad now. If you change your mind, please press star followed by two. Please keep your questions to one question and one follow-up. Our first question today comes from Yigal Notramovitz from Citigroup. Your line is now open.
spk12: Hi, Lauren and Dean. Thank you very much for taking the question. So around the labeling commentary and the press release and on the call, can you just please clarify, are you actually in labeling discussions with the agency, meaning has the FDA actually sent the company a proposed label yet, or has it only been Riata sending the FDA's? proposed label language.
spk01: Thank you. Yeah, FDA stated in the agenda for the late cycle meeting that label review was underway. We had a discussion in the meeting where we noted that the original proposed label language by us submitted in the NDA was now stale because of the amendments that we had made to the NDA. And we asked them if they would like us to submit amended language, which we've developed for our MAA submission in Europe to the NDA. And they said, yes, they'd like us to submit that to the NDA. And then they also indicated in the late cycle meeting that they would be providing us with comments on both the label and post-marketing commitments in early 2023. Okay, got it.
spk12: So just to clarify, so when you submit this updated label, will that be a new indication statement or will it simply be an amended label that reflects the updated data submitted earlier in the year for the major amendment? And could you please say, you know, when do we expect this updated proposed label to be submitted to the agency given that they say they're going to be reviewing it in early 2023?
spk01: Yeah, so it's obviously going to reflect the additional data and analyses submitted to the NDA, so that can be taken into account in the label. That will be the primary change. We will be submitting it very soon because we've already developed that language for our MAA submission.
spk00: Got it. Thank you.
spk04: Our next question today comes from Madhu Kumar from Goldman Sachs. Please go ahead.
spk09: Yeah, everyone, thanks for taking our questions. So I guess kind of our first one relates to kind of thinking about the timing for the late cycle meeting and the communication through early 23. I guess kind of at a high level, how should we think about the kind of issues that need to be sorted through? Are they really just about assessment of the data you guys submitted a few months ago, or is there anything else beyond kind of the clinical data that needs to be looked at as part of the review process?
spk01: I think that the main focus obviously will be to just continue the review, wrap it up, on the FDA side to reach a conclusion. And then obviously there's a process to go through. If they decide to approve the drug, there's a process to go through to work out the details of the post-marketing requirements, you know, and the label. Those would be the main activities if it's on a track to approval.
spk09: Right. And I guess I'm following from that. I'll just also add,
spk01: You know, they didn't raise any new issues, either efficacy or safety, for approval and just stated that the existing issues were under continuing review. They didn't request us to submit any additional data and they also noted that there were no outstanding information requests that we hadn't satisfied.
spk09: Okay, and then kind of beyond this initial regulatory process, how should we think about kind of the plans for a pediatric trial, and what do we need to see in terms of when we can expect kind of a pediatric trial to start, and how would that trial be different, and what have you learned from MOXIE Part 1 and Part 2 to influence a pediatric trial?
spk03: Yes, so this is Colin. So in our negotiations with the European authorities, we had to reach agreement on our proposed pediatric plan in order to submit our MAA. And so we are actively planning to initiate a pediatric set of studies. Obviously, first we have to make sure we are giving the right dose that is associated with the appropriate exposure to what was achieved in adults. and then we will do a study to assess efficacy. This will be done to not only satisfy the European requirements, but obviously our age range was limited to a minimum of 16 in MOXIE Part 2, and we note that there are younger patients, and so we would like to be able to lower the age range in any future label.
spk01: Yeah, I'd just like to add to that that we're aware you know, we've received a lot of feedback, you know, from the patient community, both in the U.S. and abroad, that they're very anxious to have the drug be available, you know, to patients below that 16 age group. And so we're very aware of that and are very committed to moving forward with the pediatric study.
spk00: Okay, thanks for taking our question.
spk04: Our next question is from Yatin Sineja from Guggenheim. Please go ahead.
spk11: Hey, guys. Thank you for taking my question. Just a question on the efficacy front. I think last time you had said that the FDA continues to have comments on efficacy, and then the MOXIE trial maybe was insufficient to support a single study approval. So during this late cycle of meeting, any color, any discussion around that, how does FDA think about the efficacy efficacy side now, and then the follow-up question I have is with regard to the pest-cavis patient population, will that be part of the label? Are you including it, and then how are you assessing that? Thank you.
spk01: Sure. Yes, I think when they were in the late-cycle meeting agenda and in the comments they made in the meeting, they're directly related to meeting the standard for approval. Of course, we have a single adequate and well-controlled study, and then the issue is the additional evidence that we've provided in terms of the mechanism of action data, the natural history data using, for example, the propensity-matched external control, and the delayed start analysis, you know, do those satisfy the requirement you know, for confirmatory evidence. I believe that is what they are reviewing. Have we met that standard under FEDOMA 115?
spk03: And in regards to your question about pescavis, I'd like to first clarify that the definition that we use for pescavis in MOXIE Part 2 was severe pescavis. And so patients had to have complete loss of lateral support of their feet. So they basically had to stand on their feet and toes. Importantly, we took x-rays of all patients in the study. And even those who did not meet that definition of severe pes cavus did have pes cavus in that they were different than the literature references for patients who do not have pes cavus. Recall that amoxy part two, the primary analysis population did not include pes cavus, severe pes cavus, yet we saw a treatment effect in patients with severe pes cavus. Importantly, in our propensity match analysis and reference the preprint, that is available online with a pre-submission manuscript. Out of the 136 patients, a meaningful proportion of patients did meet the definition for severe pes cavus, and we do see a treatment effect in those patients. That is statistically not different than patients who did not meet the definition of severe pes cavus. And so for all those reasons, we believe that patients who did not meet the definition or patients who did meet the definition of severe pescavis would be included in the label. Thank you.
spk04: Our next question comes from Charles Duncan from Cancer Fitzgerald. Please go ahead.
spk08: Hey, good morning, Warren and team. Thanks for taking our question. Lots going on this morning, so I apologize if I missed it. I'm just kind of wondering if, I think you've referred to some post-marketing requirements. Would you see that as typical for Friedreich's ataxia patient population or specific and driven by any observations on OMav? And then my second question is related to manufacturing of OMav. Have those manufacturing facilities been inspected and are you relying on a single site or multiple sites? Thanks.
spk01: Sure. I'll take the first question. I'll ask Mammeet to respond on the CMC. With respect to the post-marketing commitments, those are going to come from several sources. First, they gave us quite a bit of dispensation when we submitted the NDA in that They allowed us to, for example, as a post-marketing requirement, do certain work on metabolites of OMAP, you know, post-approval. Carcinogenicity studies, they gave us dispensation on that, that those could be submitted, you know, post-approval. And then specifically, They requested in this late cycle meeting, they anticipated that they would be requiring, as I mentioned, a drug-drug interaction trial with CYP3A4 modulators. That's because of the impact of the drug in connection with those, a thorough QT trial, as well as an evaluation of the pregnancy outcomes. They've also mentioned that although they haven't identified, you know, any major safety concerns, and they clearly stated that they had no issues related, you know, to the risk management identified to date, and also they did not see the need for a REMS, they're still considering whether they need to have some characterization of the long-term effects of OMAV on the liver and the heart because of the observed clinical chemistry changes in transaminases and BNP, we would plan to address that. We had already proposed a registry study. We would propose to address that in tracking outcomes in a post-marketing registry study. So I think these are fairly straightforward based on the standard requirements for approval as well as observations that have been made during the review.
spk08: Thanks. And then regarding manufacturing.
spk05: Sure. Sure, Shaz. This is Vanmeet. And as I said earlier, we continue to work on completing the manufacturing of OMAP commercial drug supply in anticipation of the launch. To answer your question, we have a couple of CDMOs, right, a couple of contract manufacturers whom we are working with to do that. And we have been working very closely with all of them, and we believe they are very well prepared for the FDAPI inspection, of the drug product and the API manufacturing sites. And the companies or the CDMs which we are working with are very well-known who regularly receive FDAPI inspection, and we work with them on a continual basis. So that's all I could add. Does that answer your question?
spk08: Yes, it does. Can I ask a question about European commercialization? I guess my quick question is, What are you thinking about in terms of strategy there? Would you seek a partner or do you think that you can execute well going along?
spk05: Yeah, as you recall, in end of 2019, we acquired these European rights from AbbVie and our intention and strategy has been since then to go and launch in Europe directly over there. Obviously, we'll assess all, you know, everything will be on the table, but right now we are planning to launch directly. We have hired our leadership team, including marketing, payers, medical affairs, all have been established very recently, and we continue to enhance the infrastructure over there in the next coming quarters, as we plan to file it later this year. Got it. Thank you.
spk04: Our next question comes from Carter Gold from Barclays. Please go ahead.
spk10: Good morning. Thank you for taking the questions. And maybe change it up a little bit. As you think about, I don't know if there are any lessons you guys have incorporated as you think about other recent neuro launches and go-to-market strategies and some of the pushback they've received. Maybe just kind of best practices as well as you think about potential commercialization early next year. And then separately, just as we think about bardoxolone, obviously you're going to have the Japanese study is going to read out early next year. Is there a chance to engage with FDA simply based on that data versus also having to wait for Falcon, just given sort of the paced timeline to enrollment there? Thank you.
spk06: Hi, Carter. This is Dawn Burr. I'll take your first question. So as we think about commercialization early next year, we've been preparing internally for quite some time and putting a lot of effort in to understand the market, the patient community. And so as I consider other rare disease launches, this is really critically important to gain support of the community well beforehand. And so Riyadh has been quite engaged on this front for quite some time. We've also scaled the organization very appropriately and carefully. And we believe that we've got the right headcount in place and we continue to grow with the regulatory progress that we make. And so we've done a bit of work now to understand the target market audience who are the treaters of SA and we know who they are and where patients are in the United States and we'll be focusing our initial commercial efforts in that particular area. So with rare diseases it's quite complex because sometimes patients go undiagnosed until there's a therapy available. So we're very fortunate that with SA, we believe that most of that patient population has been diagnosed, and it really helps guide our efforts. And so in terms of commercialization and contrasting to other launches, I can really look at the preparation that we've taken and really highlight the fact that we've been very aligned with the communities that are necessary. So I hope that answers your question.
spk05: Yeah. Carter, I would add one more thing, which I know we are working very actively is, as you see, the peers, right? We have been very actively engaged with the peer community and, you know, increasing awareness of both RIARA and Omavalex Loan and Friedrich Ataxia, right? So all that has been initiated, and we believe that will help us in a smooth launch as we proceed in the next coming quarters.
spk01: So I'll take the question on Vardoxilone. Of course, we were, you know, very disappointed, you know, to receive the CRL for Bardoxelone, you know, in Alport syndrome. My personal belief is that the principal issue that we have had with the approval of Bardoxelone is that it's so novel. The acute improvements, you know, in EGFR, you know, which are driven by improving mitochondrial function in the kidney It's a very different approach that's been taken, and the improvements have been unexpected. And obviously, it raises the question of whether those are driven by, you know, pressure being pressure mediated or some other effect that might be harmful in long-term dosing. The Ayame study should definitively answer that question. It's a very large study, over 1,000 patients. The PMDA in Japan asked our partner, Kaiwa Kirin, to run the study so that every patient would have at least three years of exposure. So that means that most patients will have at least three and a half years of exposure to the drug. It's large enough to collect, to give a read on outcomes, both positive or negative. And so, if that study is positive, I would say, you know, if it's unequivocally positive so that there's a meaningful reduction in the events that have been validated to predict the risk of end-stage renal disease, I think that will change the landscape for bardoxelone. And I think that data could be important in re-engaging both with the FDA as well as with the regulatory agencies around the world and the nephrology community. I think the data will be important in answering this fundamental question about bardoxalone. Did that answer your question?
spk11: Thank you.
spk04: Our next question comes from Annabel Simimi from Stifel. Please go ahead.
spk07: Hi, thanks for taking my question. Just a couple here. So first on OMav, I know that when you submitted the additional three-year data, one of the reasons was to answer a question for FDA that it wasn't patients who discontinued but patients who just hadn't been followed up in a timely fashion due to COVID. Will you be required to submit any further patients who have completed through your data just to complete the set, the data set. And then secondly, just as you talk, think about the launch and you mentioned the payer, that you've been having payer discussions. Can you describe what you expect the onboarding process to be? I mean, I know that the patients are pretty well just identified and It's a tight population, so that shouldn't be, you know, really a problem to raise awareness among them, but maybe among payers. How difficult a process do you expect that to be and the timing of an onboarding from the time that you launch to getting first patient in?
spk01: Yeah, I think I'll have Colin address the delayed start analysis question and Dawn address the onboarding question.
spk02: Yeah, Annabel.
spk03: So to answer your question, the FDA has not made any additional requests for any new data since we submitted updated data after the mid-cycle meeting. And I believe your question is in reference to the delayed start analysis where FDA questioned whether or not the low in at certain time points was due to patients who discontinued or simply missing data due to COVID. And so recall in the mid-cycle meeting, we clarified that the discontinuation rate had been low, but only approximately 16%, and that the vast majority of patients still continue in the study. And since COVID has been impacting the country, less patients have been able to come back. And because of that, we have additional data at the later time points as well as at new time points that further demonstrates separation analysis. So for all those reasons, FDA thus far has not requested any additional data. Don?
spk06: Yeah, thanks, Colin. And so to address your question related to payers and essentially them adopting Omavaloxalone as a product on their formulary and available to patients for reimbursement. So we began discussions with payers back in March. And we focused on SA disease severity, educating and informing about this deadly disease, which most payers, quite honestly, did not have any understanding of. Generally, we believe that payers will create reimbursement policies that will follow the approved label. And so our goal is to make sure that payers are covering OMAVA LOX loan to label. And so that will take a little bit of time for payers to update their policies. So we're anticipating anywhere between four and eight weeks. Some payers may move a little bit more quickly, but initially we think it'll take a few weeks. And then, you know, following several months of launch, we think that will take much less time.
spk07: Thank you.
spk04: Our next question comes from Maury Raycroft from Jefferies. Your line is now open.
spk02: Hi. Thanks for taking my questions. I just wanted to clarify, at this point, has FDA commented on or provided reasons why they canceled your adcom? And did it have anything to do with the AMLEX ALS experience?
spk01: They have not commented, they've not provided any specific reason for canceling the adcom. But obviously the context of this is that in the mid-cycle meeting they commented about whether we had met the standard for confirmatory evidence. We went into the mid-cycle meeting prepared to address that issue. with all of the data and analyses that Colin mentioned, elucidating the mechanism of action of OMAP in the context of the pathophysiology of FA. We did the propensity matched, we proposed the propensity matched analysis, external control study, and we updated the delayed start analyses. All these were submitted you know, as amendments to the NDA. In addition to that, we did additional work on the secondary endpoints and provided them data on a global statistical test and how that would support, provide support from secondary endpoints. All of this went into them after that mid-cycle meeting. As you point out, the AMLEX Advisory Committee meeting then did occur. And obviously, a lot of that meeting was about what the regulatory standard was for confirmatory evidence. And all we know is that after that, they let us know that they were not planning to have an advisory committee meeting. But they never explained their rationale in this context, just their decision.
spk02: Got it. That makes sense. One other question, just for the KKC Phase III IAMI data in first half 23. Based on the baseline EGFR requirements for that study, which I think are lower than some of your other bardoxelone studies, what are your expectations for the readout? And can you provide more specifics on what next steps would be to leverage the data in the United States?
spk03: Hey, Maurice. Colin. And so, obviously, there's a lot of data that's that's being generated within the trial. And so from an efficacy perspective, you know, we would hope to see that baroxalone reduces, you know, the rate of events in the primary analysis, which include actual dialysis events, as well as, you know, confirmed 30% reduction in EGFR, which has been shown to be predictive of kidney failure events, as well as confirmed EGFR of less than six. And so, best-case scenario, there's a significant reduction in the primary endpoint, that the secondaries are significant, and that there's no new safety findings. And so, there's actual dialysis events being accumulated, obviously, in the primary endpoint. And so, a best-case scenario would be that those directionally favor bardoxaline. And if we see data that supports that the drug over the long term reduces the risk of kidney failure and has an appropriate safety profile, we would then want to leverage that, as Warren said, with global regulatory agencies since it does address some of the fundamental questions about paroxysmal.
spk02: Got it. Okay. Thanks for taking my questions.
spk04: Thank you. And again, thank you for your participation on today's conference call. As a reminder, an audio recording of the call will be available shortly after the call on Reata's website at reatafarmer.com in the investors section. Thank you very much for your participation today. You may now disconnect.
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