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spk08: Good morning, everyone. We thank you for joining us today for our quarterly update. As you know, our new drug application for bardoxalon for the treatment of patients with chronic kidney disease caused by Alport syndrome is currently under review by the FDA. Alport syndrome is a severe, rare genetic form of chronic kidney disease with no therapies specifically approved for these patients. The FDA scheduled an advisory committee meeting for our NDA on December the 8th and we've been actively preparing for the Advisory Committee meeting. Colin will expand more on this later in the call. The PDUPA date for the NDA is February 25th, 2022. In addition to our regulatory activities, we're actively preparing for commercial launch of Bardoxalon, subject, of course, to FDA approval. Additionally, we recently announced that we submitted a marketing authorization application to the European Medicines Agency for the treatment of patients with CKD caused by Alport syndrome. Finally, we recently reported that we completed our pre-NDA meeting with the FDA for our development program for OMAV for the treatment of patients with Friedreich's ataxia. FA is a severe inherited degenerative neuromuscular disorder with no approved therapies. We're in the process of completing the NDA and plan to submit it during the first quarter of 2022. I'll now turn the call over to Colin, who'll provide an update on our preparation for the FDA's upcoming advisory committee meeting for Bredoxilone, a clinical update for Bredoxilone in rare forms of CKD, and a regulatory update on our program with OMAP for patients with FA. Next, Don will outline preparations for commercial launch, and finally, Manmeet will provide an update on our financials and operations.
spk09: Thanks, Warren. And good morning, everyone. Starting on slide five, as Warren mentioned, we have been actively preparing for the advisory committee meeting for Bardoxalone, which is scheduled for December 8th, and I'll provide more information about our preparations. We are pleased to report that we recently submitted our marketing authorization application to the EMA and look forward to working with the EMA towards securing approval for Bardoxalone for the treatment of patients with CKD caused by Alport syndrome in Europe. We are also happy to report that the MDA submitted in Japan by Keiwa Kirin, our strategic collaborator, is currently under review. We are also working with Keiwa Kirin to assist them in the regulatory process with the PMDA. Turning to slide six, we continue to actively prepare for the upcoming ADCOM, and we have submitted our briefing book for the meeting to the FDA. Over the past few months, we have been working with external key opinion leaders in multiple disciplines to join us for the ATCOM meeting. Additionally, we have already conducted several mock meetings and question and answer sessions with former panelists and regulators to prepare for potential questions and discussion topics. We continue to refine our analyses to ensure we'll be prepared for an active discussion with the committee on the efficacy and safety profile of baroxone for patients with CKD caused by Alport syndrome. Next slide. Moving to our program in autosomal dominant polycystic kidney disease, the most common hereditary form of CKD, we are continuing to conduct our phase three Falcon trial. We are currently enrolling patients across approximately 100 sites globally. Last quarter, we announced that we had received feedback from the FDA regarding our ADPKD program following a type B meeting. The primary endpoint of the study is the off-treatment EGFR change from baseline versus placebo at week 104. We will be analyzing the primary endpoint using only data at week 104, irrespective of time off treatment. Patients who discontinued treatment early will have shortened treatment exposure and a longer off-treatment duration, which is expected to dilute the treatment effect. We are increasing the sample size from 550 to 700 patients to account for the dilution and treatment effect from discontinued patients. More than 450 patients are currently enrolled in the study, and we now expect to complete enrollment by the middle of 2022. Finally, on slide nine, as Ward mentioned, we recently reported that we completed our pre-NDA meeting for development program for omaviloxelone for the treatment of patients with Friedreich's ataxia. The purpose of the pre-NDA meeting was to discuss the content of RIADA's planned NDA submission. Based on the results of the pre-NDA meeting, we are not planning to conduct a second pre-approval clinical study prior to the NDA submission. In response to our questions about the contents of the filing and because of the seriousness of the indication, the FDA exercised its discretion, subject to review, to permit us to submit results of certain clinical pharmacology and nonclinical studies after approval. We will continue to finalize the NDA package for submission during the first quarter of 2022. With that, I would now like to turn the call over to Dawn to provide an update on our commercial preparations.
spk01: Thank you, Colin. Good morning, everyone. I'll continue on slide 11. This is both an exciting time and a unique time as Riyadh now has two potential product launches in sight. As we look ahead to 2022 and a PDUFA date of February 25th, we are actively preparing for the launch of Vardoxelone for the treatment of CKD caused by Alport syndrome. and inherited and rapidly progressing kidney disease with no approved therapy. Following the positive news of our pre-NDA meeting, we are also reinitiating launch readiness efforts for omaviloxelone. If approved, omaviloxelone will be the only FDA-approved treatment for Friedreich's ataxia, a rare and life-shortening neuromuscular disease impacting children and young adults. Our commercial infrastructure is in place, including our core leadership team. a team of experienced biotech professionals representing marketing, market access, commercial operations, and sales. We've hired, trained, and deployed Riatta's first payer field team with an initial focus on Alport Syndrome. Their primary responsibility is to facilitate coverage of our products to label following approval with the top U.S. commercial payers, Medicare, and state Medicaid programs. Recent pricing and value research confirmed our previous studies reflecting that both payers and physicians see high unmet need in Alport syndrome and placed high value on a specific treatment option when presented the Bardoxilone product profile. We've identified highly influential thought leaders who shape the treatment landscape of CKD, rare kidney diseases, and Alport syndrome. We are now leveraging their insights through final market research and preparing engagement plans that support commercial launch pull-through. Customer targeting and segmentation is complete. This was used to determine our appropriate nephrology sales force size and territory alignment. On November 1st, our team of nephrology region business directors joined RIADA. Their first task is to build our sales organization, identifying experienced kidney and rare disease sales professionals to join our team early next year. Now with Friedrich's ataxia back in focus, we're advancing similar commercial work to prepare us for the launch of omaviloxelone in neurology. For both therapeutic areas, disease awareness efforts will continue through approval and launch, highlighting the significant unmet need, the urgency to treat, and the severity of these life-threatening diseases. I will now turn the call over to Manmeet to provide a summary of our financials and operations for the quarter.
spk00: Thanks, Dawn. Good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results from the third quarter of 2021. Let me start with our cash balance on slide 13. As of September 30th, we maintained a solid balance sheet with approximately $713.2 million in cash and cash equivalents. In keeping with our current guidance, we expect our cash balance to fund our operations through mid 2024. Moving to expenses, our R&D expenses for the quarter were $39.4 million as compared to $37.2 million in the third quarter of 2020. Higher R&D expenses were primarily due to increased personal cost to support the product development activities. G&A expenses for the quarter were $25.7 million compared to $18.3 million for the third quarter of 2020. Higher G&A expenses were primarily due to increased spend related to commercial readiness activities and personal costs to support growth in our development activities. Our gap net loss for the third quarter of 2021 was $71.8 million as compared to a net loss of $65.5 million for the same period of the prior year. Our non-GAAP net loss for the third quarter of 2021 was $46.2 million as compared to a non-GAAP net loss of $44.3 million for the same period of the year prior. The increases in GAAP and non-GAAP net loss are primarily driven by increased personal cost and commercial launch readiness activities. Moving to slide 14, which is our reconciliation of GAAP to non-GAAP financial measures, Non-GAAP research and development, non-GAAP G&A expenses, and non-GAAP operating expenses exclude stock-based compensation expense, while non-GAAP net loss also excludes other income and expense items. To summarize, our non-GAAP operating expenses were $51.8 million during the third quarter of 2021, as compared to $44.2 million for the same period of the year prior. in operating expenses is primarily driven by product development and commercial launch readiness activities. On the operations front, Riyadh's current and planned inventories of investigational product and provincial commercial product are adequate to cover demand for next several years. We continue to invest in our medical affairs team to increase disease awareness and education in the nephrology community for Alport syndrome. We have also initiated building our European infrastructure to prepare to launch in Europe and other countries. With that, I will turn the call back over to Warren.
spk08: Thanks, Mameet. As our presentation today indicates, we're making significant progress across our broadening set of programs. We remain focused on working with the FDA during their review of our NDA for Pardoxelone and on completing our preparations for the December 8th Advisory Committee meeting. In addition, we continue to make steady progress in our other programs in CKD. We've now submitted an MAA with the EMA for Predoxalone for the treatment of patients with CKD caused by Alport syndrome. Finally, we remain dedicated to advancing OMav in Friedreich's ataxia and look forward to updating you on the next steps for this program as we prepare to submit the NDA during the first quarter of 2022. That concludes our prepared remarks. We'd like to thank everyone who dialed in, and I'll now turn the call over to the operator for questions.
spk05: Thank you. We will now open the line for questions. Please keep your questions to one question and one follow-up. If you'd like to register a question, please press star followed by one on your telephone keypad. If you'd like to withdraw a question, please press star followed by two. Our first question comes from Egal Notramovic from Citigroup. Please go ahead, your line is open.
spk06: Hi, thank you very much for taking the questions. I had three interrelated ones. First of all, have there been any additional questions posed by the FDA on the OutCourt NDA since the four issues in the mid-cycle review? And if so, can you discuss them? Second, regarding the steps to prepare for the panel column, what issues were you identified in the mock panels where you feel you need to clarify or revise your presentation? And thirdly, Can you identify the two or three biggest questions around Vardoxone's efficacy and safety profile that you believe you need to successfully address at the adcom to provide a framework for a positive panel vote? Thank you.
spk08: Thanks, Ugal. I'll start and then hand it over to Colin. We're not going to comment any further on our day-to-day interactions with the FDA, so we won't be discussing, like, So I think the issues that we think are the key issues were the ones that the FDA set forth in the mid-cycle meeting and that we disclosed last quarter.
spk09: Yeah, and just one additional point, Yigal, the purpose of the mid-cycle review meeting was for FDA to disclose us the issues that they had raised. And so the plan had been to be able to provide them with additional information to address any remaining concerns. And getting to your second and third questions about adcom preparation and biggest questions, I think, as you know, the FDA will provide a briefing document in addition to us, and they will frame their questions around the main topics that we've been addressing with them. And so recall in the soccer review meeting, there were four significant issues that they raised, and there were no significant safety concerns. And they said they do not expect a REMS. And so we'll be prepared to address all topics, including safety topics. And we're focusing our preparation on basically clinical meaningfulness of GFR change over time. That's the central issue with any kidney program that does not have outcomes data. And so being able to clearly articulate that our endpoints are a derivative of the NKF working group. where they show that even a change as small as 0.7 mL per minute per year over two years is associated with reduced clinical outcomes. And as we discussed before, after two years, our on-treatment change is 7.65 mL per minute in the primary endpoint, and in the key secondary off-treatment endpoint, it's 4.26 mL per minute, and so much, much larger changes. And so I think there will be a lot of probing about that and how do you interpret data, and we believe we'll be adequately prepared to address any of those questions.
spk06: Thank you.
spk05: Thank you for your question. Our next question comes from Salveen from Goldman Sachs. Salveen, please go ahead. Your line is open.
spk04: Thank you for taking the question. This is Tommy on for Salveen. And about your adcom preparations, what in particular is driving your confidence heading into the event? Thank you.
spk09: We've, I think, known the issues for boraxone for some time because of our extensive development history. We've had several years to address questions that have been raised about the mechanism, since it is novel, the clinical profile, including both efficacy and safety. And so, in FDA, we believe it's been transparent with us to raise, you know, any remaining key issues. And so, as I just mentioned in response to Yagal's question, you know, we are prepared to address, you know, those and other questions. The data set from our Alport syndrome trial is somewhat small because it's a rare disease. We enrolled 157 patients in the trial. But there's two years' worth of data. data that's accumulating in the extension study that we believe helps to clarify the profile over time. But it's not just data from those 157 patients. It's data from the broader data set. And so we've exposed approximately 2,500 people to bardoxelone. And so that gives us a large amount of data to interrogate the clinical profile, both safety and efficacy, and address any real or perceived concerns.
spk05: Thank you for your question. We will now move on to Morrie Raycroft from Jefferies. Please go ahead.
spk02: Hi, good morning, and thanks for taking my question. Just as a follow-up to your earlier response, I think part of the plan was to submit your four statistical rebuttals to FDA soon after your 2Q call. Can you say if the four rebuttals were adjusted at all since your 2Q update, or were they as you presented them in 2Q?
spk09: I would say that, once again, we're not going to comment on our day-to-day interactions with FDA, but the plan had always been to respond, and we're always continuing to refine any potential questions, and that's part of this process. Occasionally, FDA will ask additional questions, or they may not, and we've had extensive preparations for ADCOM. Literally, almost every single day, we do mock sessions. Some of them are very formal with prior panelists who actually sat on the CARDAC committee and We've been working with ex-regulators from this and other divisions, and so occasionally we will realize that there could be a new analysis that will further support our position, and so I think we're continually iterating, and we may or may not provide that to FDA in advance, or we may just have that as backup information for the actual outcome.
spk02: Got it. That makes sense. And for the briefing documents, I think the public will get those closer to the adcom. But I'm just checking to see if you've received a draft set of discussion topics and questions from FDA yet. And do you know who's going to be on the panel at this point and who's going to be joining you for the adcom?
spk08: Yeah. We wouldn't expect to receive the FDA briefing document or that additional information until a couple of weeks before the ad come, based on their guidance as to timing.
spk09: Yeah, you can find that in their formal guidance on FDA's webpage. The public will see our briefing document and FDA's briefing document approximately 48 hours before the meeting. There's standing members on the panel, and so once again, it's on FDA's webpage. The ad hoc members won't be disclosed to us or the public until about two days prior. And then as I mentioned, during our prepared remarks. We do have several external KOLs that cover many disciplines, and we will not disclose those specific individuals until about two days prior.
spk02: Got it. Okay. Thanks for taking my question.
spk05: You're welcome. Perfect. Thank you. Our next question comes from Annabel Samimi from Stifel. Please go ahead. Your line is open.
spk03: Hi, thanks for taking my question. I just wanted to ask about the recent ASN updates, specifically on ABLE. There were some more patients that were released this week. And, you know, obviously, Vardoxilin continues to show EGFR benefit, although declining a bit. Can you just go into a little bit more detail or give us some other color of things that we should be thinking about and some of the critical points that you drew from the EGLE data that was presented this week. And then separately on the Falcon trial, if you could just give us a sense, you know, the statistical hit that you're taking for the discontinuations, can you give us a little bit more sense of what discontinuation rate you assume there and how you're going to be treating this patient? Thanks.
spk09: Yes, and so the EGLE data, it has been very helpful for us to be able to characterize the longer-term efficacy and safety profile. We released an N of 19 for a number of patients who've completed three total years of treatment. There's obviously more patients, some who have not reached year three, and there's a good amount of patients who were initially randomized to placebo during the pivotal cardinal trial who have since rolled over to EGLE. And so those data demonstrate a profile that shows clinically meaningful and durable improvements through three years of treatment. And so if you have access to the poster, I believe it's on our website, we see a similar profile in year one and two as compared to the randomized population for Barnoxelone in Cardinal. And we see that the curve over time on treatment flatten out in the second year, and that continues in the third year. And patients are still above baseline by about six mil per minute after three years. And so that's a very large increase in the context of the historical rate of decline, which is approximately five mil per minute per year, which we collected for most patients prior to enrollment in Cardinal. And furthermore, the placebo rate of decline was approximately four to five mil per minute And so these data to us are reassuring and we will be releasing additional data in the future with larger ends at appropriate venues. From the Falcon perspective, and so, yes, the statistical hit is that we will be including patients who discontinued from the trial in the week 104 analysis, which is different from the analysis at week 104 in the cardinal trial. Here, we can power the trial so that we can effectively run a week 104 analysis without including early values. And we know based upon the adverse event profile that most patients who discontinue the trial do so earlier. And so based upon the cardinal trial, we know that patients who discontinued early behave like placebos. And so we're simply modeling in a conservative rate of discontinuations so that we can still maintain hopefully a very significant p-value in the FALCON trial upon its completion. And so I won't provide the specific discontinuation rate, but it's a conservative rate. Okay.
spk03: Great. Thank you. I gathered that. Thanks.
spk05: Perfect. Thank you, Annabelle. We will now move on to Brian's corny from bed. Please go ahead.
spk10: Hey, good morning, everyone. Thanks for taking my question. Also on Falcon, I was wondering if you can comment at all on the rate of progression to ESRD that you would expect in these patients, either just the expectations in this patient population or the actual rate that you're seeing would obviously be more helpful. Just trying to understand if you saw it, given the size here, if there's an equivalent reduction in progression to ESRD in the study that you saw in Cardinal and Deacon, if this sample size is big enough to approach statistical significance?
spk09: we would expect very few patients to actually reach kidney failure, so dialysis or transplant. The rate of progression that we're expecting should be similar to what was observed in the placebo group in the reprise trial, because we have very similar eligibility criteria. And so even if the rate of progression is three to four mil per minute per year based upon a minimum GFR of 30 in the trial and a treatment duration of two years, we would expect that only outliers would hit that. But we do have an endpoint that's included. That is a kidney failure composite that includes time to first of actual kidney failure or confirmed reduction of EGFR of 30% or confirmed EGFR less than 15. And so the trial is not powered for that. We don't want to set any expectations. If you look at the reprise trial, they did not, you know, post significant fractal kidney failure outcomes. But with a large number, we should have high confidence with the EGFR trajectories over time.
spk10: Great. And then, sorry if I missed it, but I didn't hear if there's an update on Merlin. Are we still going to get to see those results this quarter?
spk09: We are going to have those results in the first quarter. And so, slide adjustment, we're obviously very busy in our primary. On the developed R&D side, our primary tasks are to get through ADCOM successfully and then submit our OMAP NDA in the first quarter. And so, MERLIN will be helpful, but it's primarily a setup for a future phase three trial. And so, we'll have those results in the first quarter. Great, thank you.
spk05: Thank you very much for your question. Just as a reminder, if you'd like to ask a question, please press star followed by one on your telephone keypads. That's star followed by one on your telephone keypads. And we have a question from Joseph Swartz from SEB Lyric. Please go ahead.
spk07: Hi, thanks very much. I understand you don't want to give us a play-by-play of all of your interactions with the FDA on Bardoxalone, but I was just wondering if you can help us understand in general overall, whether the list of issues which remain to be resolved with the FDA seems to be narrowing or broadening since the mid-cycle meeting you had. And then I have a follow-up.
spk09: Joe, so once again, we're not going to give you day-to-day discussions, but I will say that the list had been much larger prior to the NDA submission. We cited many potential review topics in our annual report at the beginning of the year, and we were pleasantly surprised that there were only four significant issues during the mid-cycle review meeting. And by that point in FDA's review, they will have had to review most NDA and consolidate their thinking cross-functionally and start formulating the key issues for the advisory committee. And so that number to us was already small. Once again, we believe we have answers to adequately address those questions as well as any other potential questions that have been raised in the past or may be raised at the meeting.
spk08: I would just add one thing, and that is that while it's called mid-cycle, it's actually very late in the review process normally.
spk07: Thanks, Warren. Very helpful also. I appreciate it. And then could you give us some metrics around the marketing and sales organization you're planning for Bardox alone and whether you expect or where you expect it to be size-wise and reach-wise relative to the PDUFA date? How many reps and MSLs do you expect to hire before then versus later?
spk01: Thanks for your question. Yeah, we're certainly excited about the time that we're in right now, and we're really on track for a successful commercial launch in Q1 of next year. And so while we're not providing guidance on the exact number of headcount, we have hired our region sales directors who are busy recruiting and actively interviewing for our future sales organization. We also have deployed a payer field team that's engaging with customers at this time And so, as you know, through a claims data analysis, we can assess the market, the number of patients, the physicians treating that population. And so we've designed our sales organization to support the need of reaching those customers.
spk04: Thanks again.
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