Ladies and gentlemen, thank you for standing by, and welcome to the Retrophin Third Quarter Financial Results and Corporate Update Call. All lines are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions] I would now like to turn the conference over to your speaker today, Mr. Chris Cline. Please go ahead, sir.

Thank you, Federica. Good afternoon, and welcome to Retrophin's third quarter 2020 financial results and corporate update call. Thank you all for joining us. I hope you all and your families remain well. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by our Chief Medical Officer, Dr. Noah Rosenberg; Peter Heerma, our Chief Commercial Officer; and our Chief Financial Officer, Laura Clague. Dr. Bill Rote, Senior Vice President of Research and Development will join us for the Q&A session. Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the Risk Factors section in our Form 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, November 5, 2020. And Retrophin specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. With that, let me now turn the call over to Eric. Eric?

Thank you, Chris, and good afternoon. At the outset of this year, our organization came together with a clear focus on the key objectives that we believe would strengthen our position as a leader in the rare disease community and further our mission while delivering innovation and hope to patients. I'm very pleased to report that as a result of our strong execution throughout the year, and in the third quarter, we are currently on pace to meet or exceed our key objectives for 2020. Our highest priority has been ensuring that our continued development efforts will best position sparsentan, if approved, to shape the treatment paradigm for people living with FSGS and IgA nephropathy. Our pivotal DUPLEX and PROTECT studies continue to advance, and we are maintaining high-quality conduct. Specifically, I am pleased to report that the DUPLEX study of sparsentan in FSGS is progressing well and according to plan. Of note, the preplanned sample size reassessment for the confirmatory eGFR analysis has been completed, and we will be continuing with the original plan to enroll approximately 300 patients in DUPLEX. Noah will provide additional detail on this shortly. Based upon recent strength in DUPLEX enrollment trends, we anticipate completing enrollment in the study this year, and we are well positioned to be able to report top line data from the proteinuria analysis in the first quarter of next year. The pivotal PROTECT study in IgA nephropathy is also making sound progress. During the quarter, we achieved enrollment of the 280th patient in the study. This is an important milestone, as it now puts us on track to report top line data from the proteinuria analysis during the third quarter of next year, well ahead of our original schedule. Another key objective for us in 2020 is building upon…

Thank you, Eric. We're entering an exciting period for the pivotal sparsentan programs, both the DUPLEX study in FSGS and the PROTECT study in IgA nephropathy continued to progress despite the challenging environment presented by the ongoing COVID-19 pandemic. Our clinical and operations teams are maintaining contact and actively collaborating with study sites, principal investigators and CRO partners. In doing so, we are reinforcing a focus on the key priorities we've used to navigate the ongoing pandemic. These include patient safety, ensuring continuous drug supply, preserving data integrity, and documentation in alignment with FDA and EMA guidance. We also continue to see a remarkable dedication for patients and their families as well as the investigators and site staff that make up the global clinical network supporting our programs. This has translated into continued progress in both pivotal studies of sparsentan. With regard to our Phase 3 DUPLEX study in FSGS, I am pleased to report that it continues to advance according to plan. As Eric mentioned, the prespecified sample size reassessment for the confirmatory eGFR portion of the trial has been completed. The process was overseen by the independent data monitoring committee, and we remain blinded to the study. Based upon the review of the results, the recommendation was no increase in sample size. The independent data mine committee also concurrently completed the fourth scheduled meeting to assess safety in both DUPLEX and PROTECT. I am pleased to report that the DMC recommended both studies proceed as planned based upon their safety review. We also continued our ongoing dialogue with FDA with the objective of ensuring that we are aligned on a path to generating a strong data package with DUPLEX that can support an accelerated approval filing if our top line results from the 36-week interim analysis are successful.…

Thank you, Noah. Our commercial organization is maintaining a clear focus and dedication to understanding the needs of our patients and their ability to deliver important treatment options. For the third quarter of 2020, we reported a 15% organic growth over the same period last year. This growth was driven by new patients initiating therapy across all of our approved products, as well as a moderate increase in patient compliance. Specifically, we are seeing steady demand for THIOLA EC. As we outlined previously, our market research prior to launch suggested that approximately two-thirds of the cystinuria patients would ultimately choose the EC formulation because it provides the potential for freedom of administration and the potential to reduce the number of tablets necessary to manage the cystinuria. Earlier this year, we exceeded this mark. And in the third quarter, we continued to see demand for THIOLA EC from all segments of patients, including those that previously had discontinued the original THIOLA formulation. This serves as a good testament to our ability to be effective in listening to the needs of our patients and providing a new treatment option. It also gives us a high degree of confidence that we can leverage our robust foundation in nephrology to effectively support the launch of sparsentan, if approved. Our bile acid portfolio also had a strong performance in the third quarter. This is driven in large part by the cumulative efforts of our gold bond team to educate pediatric geneticists on the importance of treating the hepatic involvement of cellular spectrum disorder, as well as our commitment to provide genetic screening for cholestatic patients. This commercial team's ability to educate and drive awareness amongst geneticists also provides confidence that we can ultimately be successful in delivering OT-58 to a patient whose HCU is approved. Overall, our teams as well as the patients and families we serve continue to show resilience in navigating the challenges of the COVID-19 pandemic. This is evident in the uninterrupted supply of our therapies, the steady support and access for patients, and the increase we have seen in patient compliance. Looking ahead, we will continue to monitor for any impact from potential shifts in patient insurance governance, as well as patient ability to see their physicians. We have not seen a meaningful change in either to date. Importantly, our commitment remains that all patients will have access to the medications they need. And based on current trajectories, we believe that demand for our products will likely remain stable through the balance of the year. Through excellent execution and performance, our commercial organization has put us on track to exceed our original full year guidance of mid-single-digit growth over last year, and has further strengthened our confidence in the organization's ability to deliver important therapies for people living with rare diseases. I will now turn the call over to Laura for the financial update. Laura?

Thank you, Peter. During the third quarter, net product sales from our commercial portfolio grew to $51.1 million, a 15% increase over the same period in 2019. We reported a GAAP net loss of $22.5 million for the third quarter of 2020. After adjusting for noncash expenses and income tax, we reported a non-GAAP net loss of $5.6 million. On a GAAP basis, R&D expenses were $32.2 million for the third quarter of 2020. The decrease compared to the same period in 2019 is attributable to the discontinuation of the fosmetpantotenate development program in the fourth quarter of 2019. On an adjusted basis, R&D expenses were $29.5 million for the third quarter. Relevant noncash expenses for the third quarter included $2.8 million of stock-based compensation and amortization. On a GAAP basis, selling, general and administrative expenses for the third quarter were $32 million. The increase over the same period in 2019 is largely attributable to higher professional fees. On an adjusted basis, SG&A expenses for the third quarter were $22.9 million. Significant noncash adjustments for the quarter consisted of $9.1 million in stock- based compensation and depreciation and amortization. For the balance of 2020, we anticipate that our operating expenses will increase modestly as we continue to advance our two pivotal studies of sparsentan. Importantly, our financial foundation remains strong. We ended the quarter with $456.3 million in cash and cash equivalents, which includes receipt of approximately $6 million out of the $19 million tax benefit accrued from the CARES Act legislation in the first quarter. This cash balance enables us to fund the recently announced agreement to acquire OT-58, including the $90 million upfront payment that would be due upon closing in the fourth quarter. It will also support our expected operations beyond the DUPLEX and PROTECT readouts, and allow us to invest in pre-commercialization planning activities. I will now hand this call back over to Eric for his closing comments. Eric?

Thank you, Laura. I'm incredibly pleased with our organization's efforts through the first nine months of this year. Each one of our team members continues to approach their work with resilience and a clear dedication to improving the lives of patients in the rare disease community. Collectively, our progress has positioned us to meet or exceed our key objectives for 2020 and finishing the year with strong momentum. We will channel this momentum to deliver high-quality readouts from our sparsentan studies beginning in the first quarter of next year, further build upon the strength of our commercial capabilities, and integrate the OT-58 program to expand our promising pipeline. Let me now turn the call back over to Chris to open it up for Q&A. Chris?

Great. Thanks, Eric. Federica, can we go ahead and open up the lines for Q&A, please?

Sure. [Operator Instructions] And your first question comes from the line of Scott Puckhaber with Bank of America.

Hey, guys. Thanks for taking my question and congers on the sample size news. So as we get closer to DUPLEX's top line readout, maybe you can give us your view on potential read-throughs on PROTECT? I know we haven't had too much data from that program yet. And what we should be looking for when that reads out? And then I have a follow-up.

Sure, Scott. Thanks for the question. So with regard to the DUPLEX readout in quarter one, that certainly is going to reinforce or support, assuming positive results, the hypothesis and the mechanism of action that sparsentan addresses the common pathway for proteinuria in these glomerular diseases, specifically with DUPLEX in FSGS. And the efficacy profile as well as the safety and tolerability profile will be very important in our understanding of the potential for that disease. Now the read-through to PROTECT, I'd say, certainly, that there is some type of read-through as we think about the role that sparsentan plays in the reduction of proteinuria. But I do want to caution that the studies are two different studies, and they are different patient populations with different disease progressions. And so while there may be some read-through, we want to be cautious that we're going to need to wait until the third quarter of next year to see the proteinuria and safety data in IgA nephropathy.

Got it. That's helpful. And I think I heard you say that you had an interaction with regulators regarding sparsentan. So just wondering, have you had any discussions with them? Or maybe you've thought through on what happens if the data in the DUPLEX study are ultimately mixed and you have significance in proteinuria, but not in eGFR, or vice versa?

Well, certainly, we continue to have conversations with regulators, and I would caution on any kind of interpretation or expectation for what the results may be. We're focused on ensuring clarity of the endpoints, and as we mentioned, the results of our sample size assessment. I'll ask Bill Rote to share any further insights on your question. And Bill, I think you might be on mute.

Yes. Yes, it's an interesting question, Scott. We'll have the full proteinuria data at the interim analysis. But the eGFR component of that data set will not be mature. So the agency is going to be looking at not just what the drug did relative to comparator on reductions in proteinuria, but are the eGFR data at that point in the study trending in the right direction. With any surrogate endpoint evaluation for accelerated approval, it's incumbent upon the agency to look at the surrogate and say, okay, this plus all the data, does that predict the positive results at the complementary endpoint. That's the way we expect the agency will look at that.

Got it. Thanks, guys.

Thank you, Scott.

And your next question comes from the line of Michelle Gilson with Canaccord Genuity.

Thank you guys for taking my question, and congrats on the quarter. Just following up on Scott's question. Do you anticipate – I guess, what is the timing that you anticipate around the eGFR readout, and I guess the timing of your potential regulatory submissions in the entire regulatory process? And then is there a clinically meaningful benefit that you're looking for in terms of eGFR as well as a statistical, I guess, statistically significant benefit?

Thank you, Michelle, for your questions. I'll take the first couple with regard to the timeline of the eGFR readout. I think that would be best informed when we announce the complete enrollment of the about 300 patients, which, as Noah mentioned, we're starting to near that enrollment milestone. And once we have that 300th patient or the final patient enrolled, then it really is going to be two years approximately after where we would have the eGFR data. I'll ask Bill to talk a little bit about timelines for regulatory submissions thereafter. But before I hand it over to Bill, just a little bit on the expected treatment effect. I mean with regard to clinically meaningful changes in eGFR, what we understand is anything beyond a one milliliter per minute change annually would confer benefit in the long-term renal outcomes for patients with glomerular diseases. And so that certainly would be the threshold that we would be looking at. We certainly have powered for a clinically meaningful difference that certainly we would assume to be statistically different as well. So you can assume that they're – we sized and powered the study to ensure that we would show those separations after two years. Bill, do you want to give a little bit further detail on the regulatory timelines?

Certainly. And Michelle, I don't – I think you're the first to ask about our timing for filing. We expect to have data from the interim analysis to announce to the world in Q1 of this year, looking forward to – sorry, Q1 of 2021, and looking forward to that. With the work that needs to be done to analyze that, we're anticipating a filing in the second half of the year. So that will be the filing for – under Subpart H with the FDA. Subsequent filing with the EMA will follow closely thereafter. Won't be simultaneous, but it's going to be as close as we can get it.

Got it. And just one follow-up as well. Obviously, there are quite a few IgA nephropathy studies currently ongoing. And I'm just curious if you have any plans to evaluate sparsentan in combination with any of those agents at some point if others are approved, and how you kind of think of sparsentan in – within the IgA nephropathy landscape. I guess these patients are primarily managed with blood pressure control. And so maybe how you imagine kind of that switching process? Or are you mostly targeting newly diagnosed patients? I guess could you just give us kind of an overview of how you're thinking about the market as it evolves?

Sure. So I'll ask Noah to share a little bit about our thinking on evidence generation and combination, and then Peter can certainly add anything further with regard to how we see the IgA nephropathy market evolving. Noah?

Yes. Sure. Great question, Michelle. In terms of the agents that are currently out there being studied in IgAN, majority have some immunosuppressive component. And so – and then there is also the SGLT2s, right, as well that have been looked at. And so regardless of the mechanism, there really is no particular reason to believe that we wouldn't be additive or be able to add sparsentan into those, based on the mechanism of action and the data that we've seen. So we think that whatever is out there being developed currently has the potential for complementarity. So I think that's the first key point. I think clearly, as I mentioned, we've got an advantage in terms of being a non-immunosuppressive therapy, once-a-day oral. So there are some advantages to sparsentan. I think it's partly how we've really had such positive results in COVID in recruitment because of that. But I think that's the main thrust of my thought there. I don't know, Peter, if you want to speak to the market?

Yes. Certainly, Noah. And thanks, Michelle. Thanks for that question. Yes. I think it's good to take one step back and look at the unmet need. And the unmet need is really high, both in FSGS, but also in IgA nephropathy, to your question. Listening to our thought leaders, we are very pleased that they often mention that they see sparsentan as a new potential standard of care. Other development programs could also be promising, but are more in the immunosuppressive therapy component or in complement, which is more downstream and information cascade. And we believe that those molecules could be complementary to sparsentan, but I think the sparsentan profile of the product and the mechanism of action, I think we have the opportunity to position this as a new standard of care.

Okay. Thank you guys so much for taking my questions, and congrats on next quarter.

Thank you, Michelle.

Thanks, Michelle.

And your next question comes from the line of Laura Chico with Wedbush Securities.

Good afternoon. Thanks for taking the question. I’ve got one on sparsentan tolerability. So congrats on having the fourth DMC review. Just wondering if you could delve a little more into expectations surrounding – around the adverse event profile. So one question we've gotten is around the impact of edema, specifically in subjects, as we're looking ahead to the DUPLEX readout. So maybe help us understand how we should be thinking about what would be considered manageable versus clinically meaningful. And then I have one quick follow-up.

Great. Thank you, Laura. Noah, would you like to take that one?

Certainly. So let me just take a step back on that question. One of the keys in understanding this disease state, whether it's FSGS or IgAN, is that especially in FSGS, you've got highly venomous patients in the hands of nephrologists that are very well versed at treating patients with edema. So I think when you look at some of the baseline levels of edema, for instance in DUET, you can see that. And so I think it's important to recognize that within the realm of the drug-related edema, it's a small percentage overall. The nice thing that we have is we've now got a dataset in the open-label extension out to six years. We've got patients followed for a median of 42.5 months. So we've got a pretty strong dataset, a long-term dataset, and we don't see dose-related effects on edema per se. But again, we're duplexes of a larger study. We're going to explore that there. We're not seeing – all we're seeing really is the mild to moderate category. So it isn't really significantly impacting tolerability. And again, so that doesn't seem to be a major concern. It's certainly something we're monitoring and we're following. But again, we've got this large, long-term data set within this disease state.

Okay. That’s helpful. Thank you. And maybe one last one. Just you mentioned doing market research. I'm curious, how do you think about the benefits of an agent kind of having a fixed-dose dual mechanism compared to administering single agents and having the ability to titrate? I guess any reactions thus far, either positive, negative? Yes. Thank you.

Sure. I'll share a little bit about my perspective on that, and I'll ask Peter to share any insights that he has in speaking with nephrologists and their market research. So Laura, I worked in a number of therapeutic areas with specialists who have standards of care where fixed-dose combinations are essential for patients, areas like diabetes, COPD, asthma and HIV, all of which have, again, fixed those combinations as the standards of care. There oftentimes are these questions about whether, and I think it's more academic, whether physicians like to up and down titrate different combinations that are not part of a fixed-dose combination. Now of course you know this, but I'll remind that sparsentan is not a fixed-dose combination, it's one molecule with dual mechanisms. But regardless, we know that there are questions about whether some finished physicians would want to use a different ACE or an ARB. We see that – and I've seen that not really play out in the commercial success of products, and in fact, once you have an effective and safe therapy, oftentimes, convenience is a critical part of how that disease is managed. Peter, I'll ask you to share a little bit more insights and perhaps some thinking on specifically the role that ACEs or ARBs play in this disease.

Yes, very good. And thank you, Laura, for that question. I mean speaking to physicians as well as listening to the market research, physicians seem to be quite comfortable with that – the dual mode of action that the sparsentan provides. As Eric mentioned, RAS inhibition has been, for a long time, the standard of care. But we also know that a large amount of those patients are currently not being managed. In fact, out of market research, we see that over 90% of FSGS patients are not optimally being managed. And I think this is where sparsentan comes into the game. I think that additional mechanism of endothelin receptor antagonism, I think that really provides the additional power to page down to a level that physician would like to see. So it's building on the RAS component, but adding that endothelin part, that's a logistic effect that we expect to see there as well. That makes physicians feel quite comfortable with the dual mode of action. And like I said, endothelin receptor antagonists are currently not available. So I think this is a combination that is – that makes sense. I think they're majestic. We haven’t heard any concern that it's a fixed tool mechanism. I think, in contrary, physicians view it actually as a possible.

Great. That’s really helpful. Congrats on the progress, guys.

Thank you, Laura.

And your next question comes from the line of Maury Raycroft with Jefferies.

Hi, everyone. Congrats on the progress and not having to resize as well. I guess I'll ask a question on the commercial side. If you can just provide any more specifics into the commercial growth you're seeing with THIOLA EC? And maybe comment on how compliance, new starts or other variables are contributing?

Thanks, Maury. Peter, I'll turn that one over to you.

Thanks for that. We have been very pleased with the uptake of THIOLA, and THIOLA EC in particular. As you could expect that the EC formulation allows for better compliance because it's more flexibility for the patients. They can take it with and without food intake. And more importantly, I think the reduced pill burden really makes a difference for patients. So I think from that element, you could have expected an improvement of compliance, and that's, in fact, what we see. Additionally, I think within the current environment of COVID, it's never good to have a kidney stone. But now in particular, in these circumstances, patients want to stay away from the hospitals. I think there's also a component there that could feed into the additional compliance. And then a little bit ironic maybe is more patients are being at home right now due to working from home. With THIOLA, it's advised to have a 24-hour urine test every three months. I think there's more patients at home. I think you see an increase there, and that also allows for early dose adjustment if needed.

Got it. That's very helpful. And then I had a question on the ASN, the sparsentan post hoc analysis that you reported on where you showed that patients who received a complete response at any visit had UPC of 1.7 versus 3.6 for patients who did not achieve a complete response. Then you also had some data there on background immunosuppressives as well. And so I'm just wondering if you can contextualize the data in respect to the ongoing Phase 3 DUPLEX study and how the post hoc data factor into your expectations based on the type of patients that you've enrolled?

Sure, Maury. Noah, would you like to take that one?

Sure, Maury. Great question. So just to remind everyone, the ASN post hoc analysis essentially is looking at the DUET open-label extension and the percentage of patients on sparsentan who were able to achieve complete remission, or less than 0.3 UPCR. We previously, as you are aware, published the FPRE data. And this was at the request of the academic nephrology community. And I think the key message there is a substantial proportion of patients were able to achieve complete remission. And I think that's extremely supportive of the potential first sparsentan nephro protective ability. We – when you also mentioned the baseline imbalance in steroid use, and I just want to highlight a point there, which is that was the percentage of patients at baseline on steroids. So the question was, would – did steroids affect the results. That was kind of my read-through of your question. And we did actually do that analysis. We looked – or if you recall, two years ago at the 84 week data, and we were able to show that regardless of steroid use, whether they were on steroids or not, there's still – there wasn't an impact on the results in terms of sparsentan’s effect. I'll add one more quick point there, is many of these patients, because they had to be stable on their steroid dose, were on low dose steroids. And so there may have been a few, but not likely a significant impact on our overall result there. So I think in summary, Maury, I would say – you asked about read-through to DUPLEX. You asked a lot of questions, sorry I'm going on, I just want to make sure I nail all of them. The read-through to DUPLEX, I think it's directly supportive of the expectation of the beneficial impact thus far, but just be cautious not to directly compare. Remember, DUET was 200, 400 or 800. DUPLEX, the goal is to get to the 800-milligram dose. There's no control. But I would just say that we saw a dose-related effect on the proteinuria reduction. And I think that, that's – it's plausible to expect the same from the eGFR as well. And I think that, that bodes well. Again, post hoc analysis, we don't make too much hay out of it, but it's a really great data set and directionally supportive of our DUPLEX thesis. Hopefully, that answered your multiple questions there, Maury. It was well thought out.

Great, that’s very helpful. Thanks for taking my questions.

And your last question comes from the line of Tim Lugo with William Blair.

Thanks for squeezing me in. I was interested by the preclinical data on Alport syndrome. Can you just maybe discuss about what you think the dual-acting mechanism will show as an improvement over ACE inhibition? And clinically, how you can expect, especially, I guess, the auditory benefits that you saw in these preclinically, how that could translate into the clinic?

Sure, Tim. Thanks for the question. So Noah, I'll ask you to cover some of the thinking with regard to preclinical, but also some of the thinking that your team had in ultimately making the decision not to pursue a Phase 3.

Yes. While the preclinical data was quite impressive, Tim, to your point, and we did see a benefit on the structure and function of the Alport model with regard to both kid renal as well as a hearing impact. I think, again, that's preclinical data. Exciting fits into the big picture of the common pathway, but I think the read-through – to get from there to a clinical study, and this is really where we came up with our analysis for, our Alport team spent a great deal of time trying to figure out a way or path to a regulatory – a late clinical study, and I think the challenge was that in proteinuria, the progression of proteinuria in Alport is much slower than FSGS and IgAN. As a result, the link between proteinuria that we have, the strong link in FSGS and IgAN to outcomes is simply not there with Alport. And so that's really why we decided not to pursue a late-stage study. Again, an incredibly important community. There's a common pathway across these diseases. We'll continue to maintain engagement with that community and look for other paths, but we'll maintain our focus going forward on our Q1 readout for FSGS and our Q3 readout for IgAN, respectively, next year.

Understood, thank you for that. I definitely miss that, I had seven calls after the close here. So thank you for saving me back on that. Thanks for the opportunity.

We know it’s a busy day. Thanks for the question.

No problem at all. Thanks everyone.

And this concludes our Q&A session. Do you have any further closing remarks?

Thank you, Federica, and thank you all for joining us this afternoon. As Federica mentioned, this concludes our call for today, and we look forward to sharing additional progress with you as we move through the balance of this year and into an exciting 2021. Thank you all and have a great night.

Ladies and gentlemen, this concludes today's conference call. You may now disconnect.