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Good day, ladies and gentlemen, and welcome to Reata Pharmaceuticals second quarter financial results and update on development programs. [Operator Instructions] As a reminder, this conference is being recorded. An audio recording of today’s webcast would be available shortly after the call today on Reata’s website at reatapharma.com in the Investors section.
Before the company proceeds with its remarks, please note the forward-looking statements disclosure in the company’s press release. The company will be making forward-looking statements on today’s call. There are many factors that could cause results to differ from expectations, including those noted in the company’s SEC filings.
Today’s statements are not guarantees of future outcomes. Please also note that any comments made on today’s call speak only as of today, August 8, 2019, and may no longer be accurate at the time of any webcast replay or transcript rereading.
I would now like to introduce your host, Vinny Jindal, Vice President of Strategy. You may begin.
Thank you. Hello, and welcome to Reata Management’s call to discuss our financial results for the second quarter of 2019 and to provide a review of our development programs. This morning, we issued a press release with a summary of these results, and the press release can be found on the Investors section of our website at reatapharma.com. I’m joined today by our Chief Executive Officer, Warren Huff; Chief Medical Officer, Colin Meyer; and Chief Financial Officer, Jason Wilson. I’ll now turn the call over to Warren.
Thanks, Vinny. Good morning, everyone, and thank you for joining us on our quarterly call. I’d like to begin our call today by reviewing the significant progress the Reata team has made in advancing our development pipeline.
Over the past few years, we’ve reported proof-of-concept data in eight different diseases, and we’ve advanced four programs into registrational studies. We’re poised to report data before the end of this year from two of these pivotal studies, the CARDINAL study in Alport syndrome and the MOXIe study in Friedreich’s ataxia.
Preparations for regulatory submissions and commercial launch for these programs are well underway. And the entire Reata team is working to create a seamless transition from a development stage to a commercial biopharmaceutical company. As many of you know, we’re studying bardoxolone in five rare forms of chronic kidney disease with an aggregate population of over 700,000 patients who have no or few effective therapies currently approved.
Our lead program is the pivotal CARDINAL trial of bard and CKD caused by Alport Syndrome, which is fully enrolled with 157 patients. As we announced in May, enrollment is now underway in FALCON, a pivotal study for bardoxolone in autosomal dominant polycystic kidney disease or ADPKD. In addition to ADPKD, we reported positive data from our PHOENIX study in patients with IgA nephropathy, focal segmental glomerulosclerosis and type 1 diabetic CKD. And as we commented previously, we intend to pursue these indications commercially as well.
The Phase III portion of CARDINAL enrolled 157 patients across a range of ages and baseline kidney function that we believe represents the broad population of patients with progressive Alport syndrome. The FDA has provided us with guidance that an improvement in retained estimated glomerular filtration rate, or eGFR, versus placebo after one year of bard treatment may support accelerated approval in this indication and an improvement in retained eGFR versus placebo after two years of bard treatment may support full approval.
We expect to announce top line one-year efficacy and safety data from CARDINAL before the end of the year. We recently modified the statistical analysis plan, or SAP, for Cardinal to benefit from what we learned from the FDA review of data from the REPRISE study, which served as the basis for approval of Otsuka’s tolvaptan for ADPKD. This was the first drug to gain FDA approval using retained eGFR as an endpoint. The REPRISE staff assessed retained eGFR benefit using an analysis of covariance or the ANCOVA statistical method.
To align with this FDA precedent, we incorporated the use of ANCOVA into the SAP for CARDINAL for the assessment of the retained eGFR benefit. Compared to the mixed effect model repeat measurement or MMRM method selected previously, the ANCOVA method allows for the inclusion of patients who discontinued early, and this minimizes missing data. With 157 patients enrolled, the study can detect the placebo-corrected difference in change from baseline eGFR of approximately 2.5 milliliters per minute.
Last year, we reported long-term results from the Phase II portion of CARDINAL, demonstrating that patients treated daily with bardoxolone experienced an improvement in retained eGFR of approximately 4 mil per minute that was observed in patients that were actively declining by an average of over 4 milliliters per minute annually prior to the study. Using these patients as their own controlled group in our statistical modeling, we estimated the potential treatment effect is approximately 6 to 8 milliliters per minute. As a result, we believe the study remains very conservatively powered for success.
In the second quarter, we announced the enrollment of the first patient in FALCON, a pivotal Phase III study of bardoxolone in ADPKD. Similar to CARDINAL, an improvement in retained eGFR benefit versus placebo after one year of bard treatment may support accelerated approval, and an improvement in retained eGFR benefit versus placebo after two years of bard treatment may support full approval. We’re actively opening new clinical trial sites and enrolling patients, and we expect to provide guidance on timing for the completion of enrollment of the study in the near future.
In summary, our CKD development programs are making excellent progress, and we’re in active preparation for NDA submission and commercial launch in the event that the CARDINAL data are positive. We’ve conducted all pivotal preclinical toxicology studies and clinical pharmacology studies required for NDA submission. We’re making significant investments in supply chain readiness. We’ve put our marketing, commercial operations and sales leadership in place. And we’ve initiated our first disease awareness campaigns for Alport Syndrome.
Following Alport syndrome, we believe that ADPKD represents a significant label expansion opportunity for bardoxolone in CKD, because over 140,000 patients are currently diagnosed with the disease in United States alone. Additionally, the AYAME study in diabetic CKD being conducted by Kyowa Kirin is expected to read out in the first half of 2022, adding meaningful safety and efficacy data for bardoxolone’s clinical profile.
Turning to omav, the Pivotal Part 2 of the MOXIe study in patients with Friedreich’s ataxia enrolled 103 patients across a range of ages and baseline mFARS scores that we believe represents the broad population of patients with Friedreich’s ataxia. The FDA has provided us with guidance that an analysis of the modified Friedreich’s ataxia rating scale or mFARS scores demonstrating an improvement versus placebo after 48 weeks of omav treatment may support an NDA submission for omav for the treatment FA.
We expect to announce top line efficacy and safety data from this trial before the end of this year. Pes cavus is a muscular skeletal foot deformity that interferes with patient’s ability to perform assessments that requires standing, walking or peddling, including components of the mFARS exam like lower limb coordination and upright stability. Because these comprise two of the four components of mFARS, patients with pes cavus may be less likely to have a measurable response on the mFARS exam.
For this reason, we limited the enrollment of patients with pes cavus in Part 2 of MOXIe, and we stratified these patients between active drug and placebo based on pes cavus status. The FDA recently published draft guidance titled Enhancing the Diversity of Clinical Trial Populations that encourages sponsors to study broader participant groups as part of a secondary efficacy and safety analyses, even when the primary efficacy analysis population is narrowed.
Consistent with the guidance, we’ve included a predictive enrichment strategy in Part 2 of MOXIe. The primary analysis population has been narrowed to the 83 patients enrolled in Part 2 of MOXIe without pes cavus. The minimum detectable, placebo-corrected difference in mFARS is approximately 1.3 points, assuming similar variability to that observed in Part 1 of MOXIe. You may recall that in Part 1 of MOXIe, excluding the pes cavus patients, we observed a statistically significant improvement in mFARS scores of 4.4 points relative to placebo.
Several secondary endpoints are also included in MOXIe to provide descriptive data that we hope will support approval of omav if we hit the primary endpoint. Though the study is not powered to achieve statistical significance for any of these secondary endpoints, they may provide additional evidence that omav has important activity in patients with FA, including the patients with pes cavus.
The FDA has reviewed and provided guidance on our revised statistical analysis plan and the predictive enrichment strategy. In summary, the MOXIe study is proceeding as expected. And we are in active preparation for NDA submission and commercial launch in the event that the data are positive. The few clinical pharmacology and non-clinical toxicology studies required for NDA submission are underway and are nearing completion. We’re making significant investments in supply chain readiness. We’ve put our marketing, commercial operations and sales leadership in place.
And we’ve initiated our first disease awareness campaigns for Friedreich’s ataxia. In addition to these three ongoing pivotal trials, we’re currently enrolling a fourth pivotal study, the CATALYST trial of bardoxolone in patients with connective tissue disease-associated pulmonary arterial hypertension. Patients with CTD-PAH generally have a worse prognosis than patients with other forms of PAH. And despite treatment with vasodilator therapies, these patients have a 5-year survival rate of only approximately 44%.
Based on the results observed in our Phase II LARIAT trial and the design of the CATALYST trial, we’re optimistic that bardoxolone has the potential to become the first therapy approved specifically for patients with CTD-PAH. We expect top line data to be available in the first half of 2020. I’ll now turn the call over to Jason to provide a summary of our financials for the quarter.
As noted earlier, this morning, we reported financial results for the second quarter of 2019. Net loss for the quarter was $34.4 million or $1.14 per share compared to a net loss of $28.2 million or $1. 08 per share for the same period last year. The increased net loss for the 3-month period was driven by an increase in expenses, while revenue remained consistent. Higher expenses were driven primarily by an increase in research and development expenses due to clinical, manufacturing and medical affairs activities and an increase in personnel expenses to support growth of our development activities.
The company incurred total expenses of $41.5 million for the quarter, with research and development accounting for $29.6 million. And this compares to total expenses of $34.2 million for the same period last year when research and development was $23.4 million. Our cash-based operating expenses, a non-GAAP measure we define as total expenses excluding stock-based compensation expense and depreciation expense, were $36.8 million for the quarter. This compares to $31.6 million for the same period last year.
A reconciliation of this non-GAAP measure to total expenses can be found attached to the press release filing this morning. We expect our cash-based operating expenses will continue to increase in the future as we advance bard and omav through ongoing and future clinical trials, continue to scale manufacturing for registration and validation purposes, advance additional product candidates and increase both R&D and administrative personnel as we move forward and plan for commercialization for our product candidates. At June 30, 2019, we had $280.4 million in cash and cash equivalents. And we expect our current cash to fund our operations through data readouts for CARDINAL, MOXIe and CATALYST. With that, I’ll turn the call back over to Warren.
Thanks, Jason. As our presentation today indicates Reata has developed a significant late-stage pipeline, which will yield three pivotal data readouts over the coming year, including potentially registrational data from CARDINAL and MOXIe this year. This concludes our prepared remarks, and I’d like to thank everyone who dialed in for listening. We’ll now open the line up for questions.
[Operator Instructions] And our first question comes from Maury Raycroft with Jefferies.
First question is just on the SAP. I’m just wondering if you can provide any specifics on our early discontinuation rates? Are you seeing any major differences from the control arm? And then any other context on what drove the statistical change?
Sure. And so we haven’t commented on the discontinuation rate in the trial. I will say that the primary analysis at week 48, we’ll continue to use MMRM and all available patients will be included in the analysis, including those who discontinue early. For the ANCOVE analysis at week 52, obviously, as we’ve discussed multiple times, that is the registrational endpoint that FDA will use to determine efficacy with bardoxolone. And that was the endpoint that was used in REPRISE for tolvaptan.
In that analysis – a benefit of that analysis is that allows us to use all patients in the analysis. And so dropouts don’t really affect the numbers. If patients discontinue early before the week-52 time point, if they have the week-4 value after they discontinued treatment, that value is used in the analysis and there is effectively a time adjustment to that particular patient’s value. So there’s a time-based covariate.
And that was the methodology that was used with the REPRISE analysis. And that is the major benefit. It allows those patients to be included in the analysis. If a patient doesn’t happen to have a week-4 value after they terminate study drug early, the values will be imputed using math computation based on an assumption of missing at random. And so therefore, all available patients will be included in the analysis.
Got it. And just a quick one on Friedreich’s ataxia for the trial adjustment there. Just clarifying, is that revised plan finalized? Or is still it an ongoing discussion with FDA?
It’s finalized. We submitted to FDA, and we received minor comments.
Yes, back from the FDA, slightly tuning up the calculation.
Got it. Okay. And a quick question on ADPKD. I’m assuming you can’t comment much on the enrollment that you’re seeing so far. But I’m just wondering if you could talk about the site rollout for the study. You currently have 83 sites listed on ClinicalTrials.gov. Do you anticipate needing more or less sites based on what you’re seeing?
We obviously don’t comment on ongoing enrollment for ongoing studies. But as I’m sure you can appreciate, it’s much quicker to roll out sites in U.S. first. And so when we announced the first enrollment, that occurred in the U.S. And so all those sites are either active or being activated. The next sites typically are from Australia for this trial and then Europe and then Japan after that. And so it’s ongoing.
Got it. Thanks for my question.
Our question comes from Yigal Nochomovitz with Citigroup.
I just had a few clarifying questions on the powering. So I believe that previously, the powering for CARDINAL was 2.2 mL, if I understand correctly. With a switch to ANCOVA, it’s now 2.5. Can you just confirm that or clarify?
Yes, I can clarify that we’re confirmed that it is 2.5. It was 2.2. I can point out that in the Phase II data, we saw a pretty full and pretty meaningful treatment effect. The increase above baseline at withdrawal was about 4.1 mil per minute. Those patients were progressing at a rate of 4.1. And so the estimated treatment effect, based upon the Phase II data, is 8.3. And so we view the change of 2.2 to 2.5 is very small and hopefully meaningless. We have a large margin 3.4-fold margin, we believe, to detect the significant p-value.
Okay. And just so I understand, when you say 2.5 mil per minute, is that the minimum delta that you need for significance? Or is that the way the study is powered such that if you had a lower delta below that, you would still hit a p-value?
Yes, it depends upon the variability. And so based upon the observed variability that we’ve seen in this trial and our large historical database of CKD trials, if we hit that assumed variability at 2.5, the p-value is under 1.5. If the variability happens to be lower, we can detect a smaller difference.
And by the way, if that – with that very small delta, it wouldn’t – it would be, frankly, no ways inside of the variability changes.
Okay. And then are you making the same adjustments on this using ANCOVA for week 32 for FALCON as well or just CARDINAL?
Yes. Yes, for Falcon as well. And so there may be a very small difference with that minimal treatment detectable effect of 1.6. And so we may decide to slightly boost up the sample size, but it should be very small, in part because there are more patients being enrolled in FALCON.
Okay. And then, Warren, you referenced year-end – before year-end 2019 for both CARDINAL and Friedreich’s ataxia, so is it fair to assume that this is more likely now going to be 4Q 2019 event, as previously communicated? It was second half?
No, we’re still just – we’re not going to provide any additional guidance on timing other than what we’ve provided before, which is the second half of this year.
Our next question comes from Adam Walsh with Stifel.
This is Neil on for Adam. Otsuka’s tolvaptan has seen success in the early stages of their launch, despite the difference in the size of the patient population. Can you talk about any read-through that you think this may have here to bard in Alport and the Cardinal ultimately read out positively and bard gain approval? And then in ADPKD specifically, do you have any initial thoughts on positioning bard versus tolvaptan? I know it’s a larger patient population, but do you have any thoughts there? Should the FALCON trial read out positively and bard gain approval in ADPKD as well?
Yes. Yes. Yes, we’re obviously really encouraged by the response to the tolvaptan launch. I mean I think it confirms the research that we had done, which suggests that patients with these diseases, these rare forms of CKD have an extremely high unmet need and are very willing to adopt a new therapy. They just haven’t had anything available to them. We don’t think that in ADPKD that tolvaptan will have an impact, frankly, on bardoxolone.
And there’s a very simple way to distinguish the two. Historically, in the other rare forms of CKD, we’ve produced clinical data showing that patients actually recover on average function in the tolvaptan studies. Both the placebo and active groups were meaningfully declining from baseline. And so I think that obviously will be a significant distinguishing factor. Said another way, because patients are still declining on tolvaptan, there’s need for additional therapy.
Okay, congratulations on the progress guys, thank you.
[Operator Instructions] And our next question comes from Charles Duncan with Cantor Fitzgerald. Your line is open.
Hi, good morning everybody. This is Maria on for Charles Duncan. Thank you for taking my question. As we all know, we’re looking forward to the readouts for both MOXIe and CARDINAL in the second half of this year. Assuming they are both positive, could you please provide a little bit more color regarding next steps? I know you mentioned that commercial preparations are both underway for both MOXIe and CARDINAL, but maybe a little bit more granularity in terms of sales force size, specific positions you’re targeting, early payer interactions and also an update on how the disease awareness campaigns for both are going? Thanks.
Yes, sure. There’s obviously a lot of activity, a lot of activity, because we could be moving forward with two novel products in two completely different disease areas. As you mentioned, both are in rare diseases with no approved therapy, with specialty physicians as the target population. So we have significant work streams taking place in terms of ramping up our manufacturing. As I mentioned, we’ve put our commercial leadership team in place. You only know that’s led by Dawn Bir. Her senior team is all in place and doing the sales force sizing and market development work that’s necessary to position us for a successful launch.
We’ve launched our initial disease awareness campaigns for both Alport Syndrome and Friedreich’s ataxia. We’ve done preliminary sizing work for Alport syndrome. It’s obviously the nephrology, primarily the nephrology community. And I don’t think we’ve given any estimates, but there’s nothing unusual. It’s a specialty – the targeted specialty in the United States, a very reasonable size of sales force to address those physicians.
And we actually have a well worked out plan to have our regional leadership in place and available to scale, frankly, for the demand after launch. This is similar in Friedreich’s ataxia. So there are approximately a dozen key centers treating Friedreich’s ataxia patients, and virtually all of them are actually in the study. And then there’s also a relatively small number, I think, 20 to 30 additional centers that are focused almost exclusively on neuromuscular diseases. So it’s, again, a very addressable target group for our commercial activities that have, again, a very manageable sales force for launch. And so yes, there’s just a lot of activity now to prepare ourselves for a potential success in both studies.
Sure. Thank you. And I have a quick question about MOXIe. Given the prior failures in FA, it seems that you guys are taking a much more conservative approach with longer duration size and limiting the enrollment of [indiscernible], the lessons the placebo corrected difference in mFARS. I guess my question would be, what type of results do you think will be clinically meaningful to drive patient interest? And also, are you guys measuring biomarkers in the secondary and what type? Thank you.
Sure. So we think that any significant difference is likely to be very clinically meaningful. As you may know, there’s a natural history registry that is led by Dave Lynch, the PI of our trial, having sponsored by the main patient efficacy group FARA. And they’ve demonstrated in this registry that’s enrolled over 2,000 people and followed them for up to 10 years that the annual rate of progression is one to two points.
And so that may seem like a small number, but that’s just the scale that’s used. And so if we see a significant difference at the minimum detectable difference of 1.3%, that would be a one year’s difference in the rate of progression. And so we think that would be very clinically meaningful. And as you know, there are no approved therapies for these patients. They’re unfortunately on a predefined course to significant disability and premature death. And so we think there would be a high demand for the drug if FDA deems it to be efficacious and safe.
We’re conducting a battery of secondary endpoints. The key secondary endpoint is the Patient Global Impression of Change, and it’s simply a question to the patient, if they’re doing better than they think they were when they started the trial. There are seven gradations. And so in the middle, no change. And three for improvement and three for worsening. And so it’s important endpoint in the trial to generally understand if the patients think they’re doing better.
There’s also a Clinical Global Impression of Change and then a series of other endpoints, including 9-hole peg test, falls diary, activities of daily living, timed 25-foot walk test and a few others. Importantly, the trial is powered to show a difference in the modified FARS test. The trial is not powered to show a significant difference in the secondary endpoints. We hope that we see a lean in several of these to support the change in the mFARS. But we think that the overall the data should obviously tell us if the drug is working. And we believe that the mFARS is significant and we would proceed to discussions with FDA and hopeful NDA submission.
Thank you for taking the questions.
Thank you. And we have a follow-up from Yigal Nochomovitz with Citigroup. Your line is open.
Thanks. I was just wondering on FALCON, the old powering was 1.6 retained benefit. Given the change on the stats plan, what is the new number? Or is there any number?
There isn’t a new number yet. It might be modestly higher if we keep the sample size to 300, though we may increase the sample size slightly to make up for that small difference. But obviously, with the CARDINAL trial, with that enrolled to 157 patients, the difference goes from 2.2 to 2.5., so 0.3. We’ve – we’re planning to enroll double the patients approximately with FALCON. And so we think that, that delta would likely be smaller and much less. And probably, if we wanted to, I’m sure we could easily bridge it with a small increase in the sample size.
Got it. Okay. And then, Colin, just going back to the basic science, I know that there were some experimental work that you were working – one of your collaborators was working on with the multi multiphoton imaging to explore vascular flow with bardoxolone at the single methylone level. Where does that work stand? And do you have any updates there?
So yes, as you may recall, that physician investigator, Professor Kashihara is the President of the Japanese Society of Nephrology procuring colleagues, the most important nephrologist in Japan. He published data in circulation of Prominent Journal a few months ago, demonstrating that the mechanism of acute reduction in GFR with empagliflozin, an SGLT2 inhibitor, a reduction in diameter of the blood vessel going into the glomerulus.
And so just to remind you, all the work that he’s doing with bardoxolone is similar to that work he’s able to in living animals. So [indiscernible] artificial system image the glomeruli. And he’s able to determine if there’s any change to the diameter of blood vessel going in and out to be able to measure blood pressure to determine if there is any change in pressure or to potentially roll out hyperfiltration, is able to measure the size of the glomerulus as well as the permeability of the glomerulus to a protein as well as dextrans. And so this work has been ongoing and will be presented at a future medical meeting. And we think it will be, hopefully, very enlightening and put to rest any question about the mechanism of acute increase in GFR with bardoxolone.
Okay, got it. Thank you.
Thank you. That concludes our Q&A session for today. An audio recording will be available shortly after this conference call on Reata’s website, reatapharma.com, in the Investors section. Thank you for participating in today’s conference. You may all disconnect. Everyone, have a great day.