Financial information provided by Financial Modeling Prep. Options data provided by Unusual Whales. Live transcripts provided by Quartr. Reported revenue and EPS data from Earnings powered by FinChat.io. All data is provided for informational purposes only, and is not intended for trading purposes or financial, investment, tax, legal, accounting or other advice.
Good morning, everyone. We thank you for joining us today. I'll begin on Slide 4. On February 28, we announced that the FDA approved Skyclaris as the 1st and only FDA approved drug Indicated for the treatment of Friedreich's ataxia or FA in adults and adolescents aged 16 years and older. As Dawn Burrow will share later in the call, our experienced and fully trained teams began engaging customers immediately following approval. We're pleased to share that we have seen strong initial demand for Skyclaris from patients and their health care providers. We've received approximately 500 patient start forms through early May. The patient start forms were submitted by over 250 Prescribing physicians including neurologists, primary care physicians and other healthcare providers providing a broad initial prescriber base. We've been working diligently to ensure we can get drug to the market as quickly as possible. We've completed the final stages of Skyclaris Drug Product Manufacturing and Packaging. As we shared on the approval call in February, we observed a process Related drug substance impurity above the reporting threshold, which required us to update the drug substance specification prior to releasing final product. We're working collaboratively with the FDA to obtain an approval of the revised drug substance specification for the process impurity as quickly as possible.
2m 50s
We now anticipate SkyClara's commercial drug availability to be available no later than mid August. Andrea Loewen, Our SVP of Regulatory Affairs will provide an update on this process. We understand that in some patients Symptoms of FAA manifest early in life and Skyclaris is not currently indicated for patients younger than 16 years of age. Addressing this is a top priority for us and we're evaluating strategies to support label expansion for pediatric patients younger than 16 years of age. We're planning to request a meeting this quarter with the FDA to discuss our possible strategies. We're also planning to initiate a study to evaluate the safety, Colorability in pharmacokinetics of omavloxolone or omav in pediatric patients in the Q4 of this year. Simi will provide additional details on our plans later in the call. Next slide. We submitted a marketing authorization application for omav for patients with FA in Europe in the Q4 of last year And the application is currently under review. We recently received the day 120 list of questions and as Andrea will outline later, We believe that we can adequately respond to the questions that have been raised. We're on track to provide the responses in the Q3 of this year.
4m 13s
Beyond omav, we continue to pursue development of our Nrf2 activator platform And are advancing additional preclinical drug candidates. As Colin will discuss, we anticipate IND filings For 2 additional molecules in 2024. Moving to our HSP90 program, We're developing RTA-nine zero one for patients with diabetic peripheral neuropathic pain or DPMP. We finalized the design for a randomized double blind placebo controlled 2 part 12 week Phase 2 trial of RTA-nine zero one in patients with DPMP and plan to initiate that study during the Q3 of this year. Next slide. Earlier today, Kiowa Kirin reported results from Iyame, Kirin's Phase 3 trial of bardoxolone In patients with diabetic kidney disease. As Colin will discuss, the study met the primary and key secondary endpoints And there were no significant safety issues identified in patients receiving bardoxolone. However, there was no separation in end stage renal These are ESRD events between the active drug and placebo groups after 3 years of treatment. Because there was no improvement in ESRD events And the regulatory implications of that, we and KKC have decided to discontinue our bardoxolone development activities And we decided to refocus our capital and resources on our other programs.
5m 49s
Lastly, we're Pleased to announce this morning a new non dilutive $275,000,000 debt facility with funds managed by Pharmakon Advisors. As Mamir will discuss, this new facility extends our cash runway to the end of 2026 And with the commercial launch of Skyclaris puts us on a path to self sustainability. With that summary, I'd now like to turn the call over to Dawn Birr, who will provide an update on our commercial launch for Skyclaris.
6m 22s
Thank you, Warren. Good morning. I'll continue on Slide 8. Friedreich's ataxia represents a significant commercial opportunity, And we believe that there are approximately 6,000 patients in the United States living with FA today. Through ICD-ten claims data analyses, we see approximately 5,000 unique diagnosed FA patients that can be linked to healthcare providers, Excluding approximately 10% of those diagnosed under the age of 18, the remaining 4,500 or approximately 90% Represent our total on label addressable market. Most patients seek routine care by their local neurologist or primary care physician. Important commercial launch targets include CCRN centers or collaborative clinical research network sites, Ataxia Centers and HCP is currently treating FA patients. Through the evaluation of claims data, we've identified Approximately 2,500 healthcare target providers treating patients with Friedreich's ataxia. These HCPs And the diagnosed FA patients they treat are the primary focus of our commercial launch efforts this year. Next slide please. Patients and healthcare providers have long awaited an approved treatment for Friedreich's ataxia And this is evident through the demand we see for Skyclaris in only 2 months following approval. ReataReach is our single point of contact for our patient services Program and serves as the intake center for all Skyclaris patient start forms.
8m 3s
Start forms received by Reach Are an early indicator of our launch progress. Through early May, we've received approximately 500 Skyclaris patient start forms Submitted by over 250 prescribing physicians, including neurologists, PCPs and other health care providers. 500 FA patients represents over 10% of our current total addressable market. We are pleased with this Quick uptake, which reflects strong demand. Patients are actively seeking treatment and health care providers are willing to prescribe Skyclaris. Next slide. Our 2023 launch objective remains unchanged. Our goal is simple, To establish Skyclaris as the 1st and only effective and safe treatment approved for Friedreich's ataxia. Our commercial launch activities engage our 3 important stakeholders. This includes HCPs currently treating Friedreich's ataxia with patients in their practice Today, on label patients diagnosed with FA and the payer community. With our attention on physicians Currently treating patients with FA, we continue to communicate the value of Skyclaris, the significance of our clinical data and how this data translates to a clinically meaningful impact on the disease. Additionally, we are working to ensure All HCPs understand how to access Skyclaris for their patients and the programs we offer to support utilization. FA patients and their caregivers are also important stakeholders.
9m 38s
Because Skyclaris is the 1st and only drug approved for Friedreich's ataxia, We continue to inform and educate patients and their families on this approval and we encourage them to see their healthcare provider for treatment. To support these educational efforts, we recently launched our branded patient and HCP campaigns, Highlighting the recent approval and communicating that Friedreich's ataxia, previously untreatable, is now a treatable disease. Immediately following approval, Reata created a strong market presence and engaged the FA community with our first branded booth at important neurology conferences, including the Muscular Dystrophy Association, the National Ataxia Foundation and the American Academy of Neurology. Now approved digital, social, paid search and patient webcasts were launched in March April To drive the awareness of Skyclaris and provide clarity on how to access treatment. Lastly, critical to our launch and quarter our patient promise. We continue to facilitate payer coverage, access and affordability through payer education and robust programs Designed to minimize or eliminate patient out of pocket cost burden. Continuing on Slide number 11. Reata's field sales and market access teams are executing on our branded launch strategy, working to drive demand and facilitate payer coverage. Our experienced and fully trained teams began engaging customers immediately following approval on Monday, March 6.
11m 16s
The sales organization is working to reach and educate approximately 2,500 healthcare providers who treat most of the diagnosed FA patients in the United States. They have also engaged FA treatment centers driving early utilization at each of the 9 U. S. Centers of excellence And implementing plans to support the needs of these highly important accounts. Our field access team consists of national account directors focused on SkyClaris coverage by top national and regional payers and a patient access liaison team Hired to educate practices on access requirements. Together, this team's primary responsibility is to Since FDA approval of Skyclaris, The payer team has engaged all of the top U. S. Payers representing 90% of covered lives. We anticipate that most commercial payer policies will be established The second half of twenty twenty three and that plans will place Skyclaris on their specialty tier along with most rare specialty therapeutics. Our patient access liaison team has worked with local practices to educate on access requirements and facilitate rapid payer approvals through medical And prior authorization while awaiting payer policies. We are pleased with early payer coverage of Skyclaris, Tracking as we expected for a rare, progressive and devastating disease with no other approved treatment options.
12m 49s
I will now turn the call over to Andrea Lowen, our Senior VP and Head of Global Regulatory Affairs for the regulatory update on drug availability And omaviloxolone MAA status.
13m 2s
Thank you, Don. I'll continue on slide 13 to provide an update on SEGLARIS availability. We are working collaboratively with the FDA to revise the drug substance impurity specification that is required for Skyclaris distribution to the market. We submitted a supplement to the NDA, which is being reviewed as a prior approval supplement referred to as a PAS or PAS Under expedited priority review. As a pass, FDA approval is needed before we can release finished drug product to the commercial market And not within 30 days after submission as previously guided with respect to the CB30 prior to its conversion by the FDA to a pass. While the FDA's approval target action date is in mid August for standard review timelines, the FDA stated that its review of the past is prioritized An approval should come before the goal date. The approval and its timing are, of course, subject to FDA's review of the supplement, Provided there are no major deficiencies in the content of this mission, which we expect to know by mid June. We believe that the information provided in the NDA is sufficient to support the proposed updated specification limit for the process impurity. We developed the submission content based on FDA and international harmonized regulatory guidance as well as FDA's internal review procedures and engaged with multiple experts to confirm the adequacy of the information to support the change.
14m 26s
Next slide. For more context, the FDA reviews each impurity limit on a case by case basis to determine its impact on product safety and known The characteristics. FDA guidance documents outline key elements required for this determination, which we believe we have provided. For example, safety is of utmost importance. The limit for the proposed process impurity was set at the qualification threshold, Which per guidance should not require toxicology qualification testing based upon the known characteristics of the identified impurity and patient dosages. While not specifically required, we conducted multiple evaluations including gene toxicology studies and in silico structural analysis, Which demonstrate no mutagenic potential. We've also been able to identify the impurity and its structure And it's highly detectable with our validated analytical method. Further, there is no meaningful impact on the total impurities and there are no observed changes to any other properties of the drug substance. We believe we have provided a complete package to the FDA and anticipate I would now like to share an update on our ongoing marketing authorization application in Europe. As you know, we submitted the MAA in the last quarter of 2022. We recently received the European Medicine Agency's Day 120 list of questions, which is the primary mechanism for Questions and responses to be exchanged during the MAA review.
16m 4s
The EMA separates their questions into major and other categories.
16m 9s
We are pleased that we should be able to provide thorough responses and requested information back to the EMA within a standard response period. With respect to major questions on clinical efficacy, the EMA invited us to discuss the robustness of the totality of efficacy results And suggested that the discussion could include the impact of imbalances and baseline characteristics on the pivotal study results and extrapolation of these results to patients with advanced disease And patient groups not included in the pivotal trial. If you recall, in the pivotal omav trial, imbalances in baseline characteristics such as history of cardiomyopathy And longer GAA1 repeat length favored placebo patients who were less sick and had less advanced disease. Since the imbalance favored The statistically significant results of the primary analysis favoring omav treatment despite these imbalances indicate a robust efficacy outcome. The EMA also asked us to justify inclusion of preskevis in the proposed labeled indication. With respect to major questions on clinical safety, the EMA asked us to discuss the similarities between NRS2 activators With respect to chemical structure and safety and to discuss suitable contraindications and warnings in the label for cardiac, renal, diabetic and other conditions Taking into account the population study, we believe that the recent bardoxolone IAME safety data in Japanese patients with diabetic CKD Will be very helpful to address potential bardoxolone and NRF2 carryover safety questions for OMAD.
17m 40s
These data will also be helpful to suitable warnings and precautions, which the EMA asked us to discuss in relation to the summary of product characteristics, which is the EU label. With respect to major questions regarding drug product quality, the EMA requested us to provide additional clarification regarding the potential for nitrophenine formation And to provide further information and justification for our active substance control strategies, a GMP certificate is also required for the questions and are on track to do so in the Q3 of this year. I will now turn the call over to Cecilia.
18m 25s
Thanks, Andrea. Label expansion to pediatric patients with FA is of prime importance to us. As Warren mentioned, We have been evaluating various strategies to support the expansion of the omeberloxolam label for pediatric patients younger than Last year in Europe, we received a positive opinion from pediatric committee On a proposed pediatric investigation plan and as agreed in this plan, we have submitted a request For scientific advice for additional input on the design of a clinical study in pediatric patients between 2 16 years of age. With respect to the U. S, we are completing briefing documents to submit this quarter to the FDA With a request for a meeting to discuss label expansion for younger pediatric patients who are not included in the approved Skyclaris label. We are also finalizing a protocol for a pediatric study of omeveloxolone to evaluate the safety, Tolerability and pharmacokinetics of a single ascending dose of omeveloxolone in pediatric patients between 2 And 16 years of age. We expect to submit this study protocol to the FDA this quarter and plan to initiate this study in the Q4 of Based on feedback from the EMA and FDA, we will determine what additional pediatric studies With that, I will now turn the call over to Colin.
20m 9s
Thank you, Simi. Moving to Slide 19. Mitochondrial dysfunction, neuroinflammation and neurodegeneration are common features across a range of neurological diseases. While mitochondrial dysfunction may not be the initiating event, it appears to be a common downstream pathway that results in subsequent loss of function The specific area of the brain that is affected results in the clinical symptomology, Whether it be movement, balance or memory disturbances, genetic and pharmacologic activation of Nrf2 Have demonstrated activity in multiple preclinical models that demonstrate effects on mitochondrial function, neuroinflammation, neurodegeneration and fibrosis, movement and coordination, memory and survival. Perhaps more importantly, Recent evidence from genetic studies in people have linked Nrf2 to susceptibility and or progression of several diseases, Including movement disorders and Alzheimer's disease. Next slide. We have advanced 2 next generation interrupt 2 activators, RTA-four fifteen and RTA-four seventeen to IND directed studies based on our extensive in house library of over 800 molecules And understanding of the structure activity relationship. The non clinical profiles support advancement to clinical studies. We have shown broad activity in systemic and CNS models of inflammation, autoimmune disease and nerve generation With appropriate AbbVie PK properties, our dose ranging toxicology studies demonstrate an expected profile based on our knowledge of the class And our late stage IND directed studies are underway or planned.
21m 58s
We anticipate IND filings for both molecules in 2024. Next slide. Syndomaspib, also known as ARG901, is a highly potent selective oral Small molecule modulator of Hsp90. It is differentiated from in terminal Hsp90 inhibitors and it binds at the C terminus And promotes mitochondrial function. It affects mitochondrial function by promoting proper protein folding and reducing ROS mediated inflammatory signaling. The drug is active in preclinical models of painful and insensate diabetic neuropathy. It is differentiated from other molecules and that it not only reduces pain, but it also restores sensation and models associated with loss of sensation. Diabetic neuropathy is a serious complication of diabetes associated with substantial morbidity. Approximately 4,000,000 patients in the U. S. Are affected With moderate or severe DPNP. Phase 1 studies in healthy volunteers are complete and demonstrate an acceptable profile. Sindomaspib was well tolerated with no safety signals, drug discontinuations or SAEs. Moving to Slide 22. The Phase 2 trial that we are initiating is a randomized double blind placebo controlled 2 part 12 week Phase 2 trial of sildomaspib in patients with DPMP. The objective is to assess pain using the Numeric Pain Rating Scale or NPRS. We plan to enroll 192 patients randomized evenly across 3 arms in each part For a total of 384 patients, patients are allowed to take up to one standard of care medication.
23m 46s
In order for patients to enroll, They must not have achieved adequate pain control upon entry with a NPRS pain intensity score of at least 4 on a 0 to 10 point scale at screening. We will conduct an exposure response analysis using Part 1 data to select doses for Part 2. The primary endpoint is the change in average pain intensity assessed by MPRS at week 12. We plan to dose patients in the Q3 of this year. Moving to our CKD programs And as shown on Slide 24, the EAME trial was conducted to determine if eGFR improvements observed with baroxolone Could translate to reductions in ESRD. IAME was a Phase 3 randomized double blind placebo controlled trial In diabetic kidney disease patients conducted in Japan, patients who had advanced CKD defined by eGFR values between to 59 mil per minute were allowed to enroll. The minimum treatment duration was 3 years and the maximum was 4 years. Upon completion of treatment, patients then participated in a 16 week observational period. The primary endpoint Was timed to onset of a confirmed 30% decrease in eGFR from baseline for adjudicated ESRD. An important secondary event was timed to ESRD even though the trial was not powered for this endpoint.
25m 17s
Next slide. As Warren mentioned, the primary and key secondary composite endpoints of EAME demonstrated statistical significance favoring bardoxolone. These endpoints were driven by reductions in eGFR decline events. However, no separation in ESRD events was observed. This result appears to be explained by initial eGFR increases that were not maintained in patients who reached ESRD. In regard to the impact of Iyame on our CKD programs, a major challenge for boroxolone The paroxone CKD development program has been the use of eGFR as a surrogate that is intended to predict ESRD. The EAME data show a disconnect in that eGFR improvements were observed, but they were not associated with reduced ESRD events. This poses a significant regulatory challenge. As a consequence, we and KKC are terminating our CKD programs. We will be communicating these plans with regulators and our clinical trial sites immediately. Next slide. Despite the disappointing outcome of our CKD program, the safety data from EAME provide important data for the broader nRF2 activator class. From a safety perspective, there was no evidence of adverse renal safety, including hyperfiltration or other adverse findings. There was also no evidence of adverse cardiovascular safety with no imbalances in deaths, adjudicated cardiovascular events or SAEs, Fluid overload events or blood pressure.
26m 56s
There was also no evidence of drug induced liver injury and the AE profile was consistent with the established safety profile. I'll now turn the presentation over to Manmeet.
27m 8s
Thanks, Colin. Good morning, everyone. Today, I will provide an update on the following key topics. 1st, operational progress on the SkyClaris manufacturing 2nd, European commercial readiness activities. 3rd, amendment on the Blackstone equipment. 4th, brief update on the $275,000,000 non dilutive financing and finally, Q1 2023 financial update, including our Updated cash guidance, which provides funding through the end of 2026 and allows a path to self sustainability. I will continue on Slide 28 to provide update on SkyClaris manufacturing activities. As Andrea mentioned earlier, Subject to regulatory approval, we anticipate SkyClaris models to be available through our specialty pharmacy for shipment to patients During August of 2023 or earlier. From an operation standpoint, we have completed manufacturing and packaging of SkyClaris capsules. To remind everyone, in 2019, we reacquired ex U. S. Rights for OMAP from AbbVie. Accordingly, we currently own The global commercial rise for OMAP. In line with our plans to prepare for the potential label expansion in the U. S. And global expansion opportunity for OMAP, We have ramped up our production for resupply of SkyClip's commercial drug supply. Next slide. Following the submission of our MAA for omav in Europe last year, we accelerated our build out of our European infrastructure outside the U.
28m 41s
S. We have hired an European leadership team overseeing commercial, marketing, market access, medical affairs and supply chain activities In anticipation of omab launch in the European countries. Further, we initiated marketing activities, global value messaging and health technology assessment Work streams for European countries. We have selected a 3rd party logistics or 3PL partner for product distribution in the Europe. If approved in Europe, we will be prepared for our European commercial launch for OMAP during the Q2 of 2024. Next slide. As we announced this morning, based on the results of IAME and our decision to discontinue development of our Bard CKD programs, We have amended our development and commercialization funding agreement with Blackstone. Under the terms of the amended agreement, Blackstone has removed All obligations for bar development and commercialization, removed all restrictions on any new debt and released all prior security interest. Additionally, we have granted a low single digit royalty on worldwide net sales of OMAP for Friedreich ataxia. Our total royalty obligation on OMAP, including academic institutions, Blackstone and AbbVie, will be in the range of 5.5% to 7.5% of net product revenues based on the tiered product revenues. While we are disappointed with the IAME results, our decision to discontinue Badroxellon development and enter into the amended agreement with Blackstone Allows us to refocus our resources and over $100,000,000 in capital towards our future pipeline and programs that were previously planned for CKD development.
30m 26s
Next slide. This morning, we also announced a $275,000,000 Debt facility with funds managed by Pharmakon Advisors LP. The aggregate $275,000,000 in new non dilutive funding will be advanced in 4 tranches. The first tranche of $75,000,000 will be funded this week. This new non dilutive debt facility of $275,000,000 Bolsters our strong balance sheet, which will enable us to extend our cash runway through the end of 2026. Along with the savings from the funds previously planned for BARD development and our anticipated SkyClaris revenues, we believe that we are on a path to self sustainability. I would also like to remind you that with the approval of Skyclaris, The FDA granted us a rare pediatric disease priority review voucher, and we have the option to do non order financing by monetizing this voucher in the future. Next slide. We announced our financials and filed our 10 Q earlier this morning. I would like to highlight a few financial items this quarter, including our strong cash position and our operating expenses. Let me start with our cash balance. As of March 31, 2023, we maintained a solid balance sheet with approximately $321,000,000 in cash, cash equivalents and marketable debt securities.
31m 51s
I would like to remind everyone the above $321,000,000 as of March end excludes the $275,000,000 debt financing announced this morning. And based on our current operational plan with the anticipated commercial launch of Skyclaris and our cash balance Will enable us to fund operations through the end of 2026. We expect that this DART funding may allow us to reach the path of self sustainability barring any new pipeline expansion or in licensing activity. Moving to the Q1 of 2023 financial update. R and D expenses increased by $15,700,000 for the 3 months ended March 31, 2023, as compared to the 3 months ended March 31, 2022. This increase is due to an increase in certain ongoing Clinical study cost and in stock based compensation due to the vesting of certain performance based equity grants Upon FDA approval of Skyclaris. SG and A expenses increased by $30,000,000 for the 3 months ended March 30 31, 2023 compared to 3 months ended March 31, 2022. This increase was primarily due to increased commercial activities And increase in stock based compensation due to vesting of certain performance based equity grants upon FDA approval of Skyclaris. On next slide, we have a reconciliation of GAAP to non GAAP financial measures for the Q1 of 2023 compared to the Q1 of 2022.
33m 25s
Non GAAP R and D expenses increased by $9,000,000 for the 3 months ended March 2023 compared to 3 months ended March 2022. This increase is due to certain ongoing clinical study cost. The ongoing SG and A expenses increased by $14,100,000 As compared to the 3 months ended March 2022, this increase is due to an increase in commercial activities for SkyClaris. With that, I will turn the call back over to Warren.
33m 53s
Thank you, Manmeet. In closing, We're pleased with the approval of Skyclaris, the first and only drug to treat patients with FA. We're encouraged by the significant interest from patients Healthcare Providers to begin SkyClaris treatment and are working to have commercial drug in the channel as expeditiously as possible. Further, we're cooperating with the EMA in their review of our marketing application seeking approval for omav in Europe. Of course, we're disappointed with the results of the EAME study and the need to discontinue development of bardoxolone for the treatment of patients with CKD. We put a lot of effort over the years in an attempt to produce a novel drug with a very meaningful clinical benefit to patients with CKD We've seen little progress in the treatment of their disease. But the EAME data made the decision straightforward And it permits us to focus our resources in future development on our neurology programs. The Pharmakon debt facility of $275,000,000 bolsters our strong balance sheet, which will enable us to extend our cash run rate through the end of 2026. Along with the savings from the funds planned for bardoxolone development and our anticipated SkyClaris revenues, we believe that we're on a path to self sustainability.
35m 15s
These resources will permit us to relentlessly pursue our mission to bring life changing medicine to patients with severe diseases. 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.
35m 33s
Thank you. Ladies and gentlemen, at this time, we will begin the question and answer session. Please keep your questions to one question and one follow-up only. Our first question today comes from Yigal Nochodermic with Citi. Please go ahead. Hi, great. Thank you very much for taking the questions. On the Skyclaris launch, you just give a little bit more granularity perhaps on the pace of the start form accrual since you started accepting the forms on March 6? Just curious if it was More of a bolus effect or if you're seeing a steady ramp over time. And were there any pediatric applications that were off label in that 500 number? Thanks.
36m 28s
Dawn, would you like to take that question?
36m 31s
Yes. Hi, Yigal. Thanks so much for your question. We are really pleased with this early demand And expected that patients and HCPs would be actively engaged upon approval. And so of course, we're only looking at really a 2 month window Here where we've seen these 500 enrollment forms or patient start forms be submitted. So of course that's very quickly over a short amount of time. And it's a bit early to say, is this just a bolus of patients or should it continue? But again, we were really anticipating That we would see this level of support and interest from the HCP and the patient community and that is really very encouraging. As far as your second question around pediatric patients, of course, our label is for adults and adolescents 16 years and older. And so we really do believe that payers are going to really look to this when they look to reinforce, enrollment criteria. And so right now, it's a bit early to really communicate on the number of patients and the demographics within the enrollment. But If you think about the trial enrollment criteria and then also what we expect to see from payers, you can imagine the demographics that we're seeing.
37m 47s
Okay, great. And then just one follow-up on the post approval supplement as you discussed. You mentioned that the FDA may be able to approve this earlier. Can you provide any more granularity on when earlier would be? And then Are you planning to leverage a second source supplier to resolve this impurity for new batches or once you get the PAS cleared That's really not necessary. And has EMA commented at all on this impurity question in their CMC review? Thank you.
38m 19s
Andrea, would you like to comment on those three questions?
38m 23s
Yes, I can take at least one of those questions. So the FDA has not Provided any granularity on the timing of an earlier approval. They have just notified us that the review is prioritized And that it should come sooner provided of course any review issues. But we believe we've provided everything that we need to provide.
38m 48s
And I think the question was on the do we need to change the supplier The supply network. Mami, do you want to take a break?
38m 58s
Yes, sure, Warren. Yigal, as you mentioned already, right, with We have already completed manufacturing of our batches, current batches and capsules and they have been completed and packaged right now. We are just waiting for this path to be approved by the FDA for us to do that. We have enough quantity to supply for the near term and for next several years Already being we are accelerating our effort to produce more resupply capsules. Yes, in the long run, we would be Looking at 2nd supply source and other activities also.
39m 37s
Okay. And then just on the EMA, any comments there from their review of the CMC?
39m 43s
So I can address that. So the Impurity was identified after we had submitted the MAA. So the EMA is not aware at this time of the impurity That we observed. So we plan to actively look to update the MAA either premarket or post marketing, and we're trying to do that as quickly as we can.
40m 9s
Got it.
40m 10s
Thank you very much.
40m 15s
Our next question comes from Madhu Kumar with Goldman Sachs. Please go ahead. Your line is open.
40m 23s
Hey, everyone. Thanks for taking our questions. So maybe To think about the impurity situation, so thinking more about the cadence of kind of news flow between now and mid August. So you mentioned in the prepared remarks that The timeline for the FDA suggesting substantial deficiencies would be in the kind of June timeframe. So should we think about Kind of from a no news is good news type perspective, but if it goes through June and there hasn't been any disclosure from you all about a deficiency that that should be kind of considered That things are running along smoothly. And then kind of practically from that, would you announce the kind of resolution of The, PAS and kind of the official formal commercial launch of the drug?
41m 6s
Yes. I think, I'll just take that and Andrea feel free to Chime in. But yes, we wouldn't expect to review it as a routine review. We wouldn't expect we think the filing is adequate. Yes, I would say no news is good news. They're just proceeding with their review. I've assumed that we're going to make an announcement when drug is available in the channel Particularly for the patients and for the healthcare providers. That's correct, Nami?
41m 32s
Yes. That's the plan.
41m 37s
Okay. And then a follow-up question. So you guys have talked about certain expectations towards kind of getting to a breakeven status And that has made certain assumptions around operating expenses that kind of assumes some level of bardoxolone investment. So given today's discontinuation of bardoxolone CKD development. Does that change what those metrics look like? What do you think maybe it's kind of Skyclaris patient number that you think fits into breakeven now versus before the Official discontinuation of Bard and CKD.
42m 7s
Sure. Madhu, this is Manmeet. Great question. As you know, we don't guide on our operating expenses and our revenue yet. But if you do a calculation based on the U. S. Pricing And you look at our current run rate of expenses, right? I'll start with the expenses. Our expenses have been quarterly expenses have been in the run rate of $70,000,000 $75,000,000 A quarter, which equates to a $300,000,000 a year expense rate. And if you think to get to the self sustainable breakeven point, You need approximately 1,000 patients to Skycareous patients, right, to reach that point. And as Don mentioned, We're very excited with the current first start in 1st 2 months to reach 500 patients. We believe that point could come pretty quickly after launch.
43m
Great. Thanks very much everybody.
43m 6s
The next question comes from Yatin Suneja with Guggenheim. Yatin, please go ahead.
43m 15s
Thank you for taking question. Sorry, asking more question again on this impurity issue. So it seems like, I mean, if you read the press release, you're trying to ask the FDA to increase a certain acceptable threshold of the impurity. Is that the right way to read it? Have you actually resolved it? Can you just tell us what the impurity was? So that's just on the impurity side. I do have a question on our Bardo. I was curious If you can comment on what did you see did you see any worsening of albuminuria In that study, just trying to understand what the read through would be to the broader pipeline for CKD, At least each pipeline. Thanks.
44m 9s
Okay. Andrea, do you want to address the Yes. So yes, you are correct. We are proposing to increase The impurity this specific impurity specification to the basically to the reporting threshold above the Reporting thresholds, but not beyond the qualification threshold, which would require qualification, additional toxicology qualification. The impurity itself is an acetone adduct that is part of our normal process chemistry that basically forms The presence of acetone. And so again, we saw that in our direct process validation and this is the appropriate control strategy to manage What is what we believe to be inherent variability to our process.
44m 57s
And then Colin, would you like to address the question about the safety read through for Marion?
45m 4s
Yes. And so Kieran and their KOLs will be presenting the data at a future medical meeting when we're publishing the results. But at a high level, I can say that we were pleased with the safety. Number 1, there were no adverse Cardiovascular findings, so no one balances in deaths adjudicated cardiovascular events, including CHF events, no differences in blood pressure. From a renal safety perspective, I think it's important to note that there is no evidence of hyper filtration. There was no worsening kidney function relative to placebo. What was observed was that there was a modest increase in kidney function That was not sustained in the patients who reached ESRD. And so the drug just there wasn't enough drug or it wasn't able To meaningfully maintain that separation. And the albuminuria profile is consistent with what we've seen before. And lastly, there is no evidence of any liver injury. And so this is a large trial that resolves some overhang from the BEACON trial. It shows that we can administer our drug safely to patients. And so we think it's favorable as far as the read through to the class.
46m 28s
Our next question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead, Charles. Your line is open.
46m 36s
Yes. Good morning. Thanks for all the color on the initial interest in Skyclaris in taking our question. I had a couple of questions. One is relative to the European process. I'm wondering, Andrea provided a fair amount of information. But I'm wondering if your overall perspective would be that the questions were Fundamentally different from those by the FDA and require any new analysis Or do you believe that your, I guess, preparation for the NDA really fully address All the questions from the EMEA, but for the impurity.
47m 25s
Hi, Charles. Yes, I'll take this. Actually, we think that they're very consistent with the questions that were addressed raised By the FDA during the review process, I think they basically want a summary of the totality of the data. Some of the things that we provided in the FDA review process were things like that Andrea mentioned like we looked at the imbalances and the baseline characteristics And showed that those favorite placebo and that when you adjusted for those actually strengthened the p value of the primary analysis. I think that the FDA did a thorough review of where the drug should be used based on like the subgroup analysis and Read through the various groups including the PES cabas patients. So yes, I think we're in very good shape to answer those questions.
48m 24s
Okay. And then my follow-up is relative to pediatric expansion. I guess it seems to me like that's a really important thing for the patient community. When could you anticipate that PKPD study to be complete and file for an sNDA. And then I guess And associated thing is PRV. I know it's not directly related, but any current updates In terms of how to monetize that? Thanks.
48m 59s
Yes. So I'll start with the first one. And Simeon feel free To chime in, with respect to the U. S. Adjusting the label for pediatric patients in the United States, The forthcoming interaction with the FDA will be critical to understanding what that path is. We have a number of approaches To that, so I want to make clear, we don't anticipate that the PK study alone would support. It may be great if it did. But we haven't yet had that interaction with the FDA. We're actively in preparation for that to get their feedback on a number of approaches To expanding that label. Having said that, when would we anticipate having the PKPD data, Samee?
49m 45s
So the level of interest is very high at the moment as we have discussed earlier on. So the PKPD study will initiate The last quarter, Q4 this year. And as we mentioned, it's a short term single dose study. We anticipate that within a few months we will be having the data. We are anticipating at the moment 3 to 4 months.
50m 10s
Yes. There's been a high level of interest. We think it will enroll relatively rapidly. Mameet, do you want to Comment on the pediatric review voucher?
50m 20s
Sure. So Charles, this is Manmeet. And yes, with the grant of this Yes, we voucher. We always have the option to monetize that and we actively look into those options. But Right now, I think with this new funding, there is no current need to do an instant monetization of anything. I think we are both Self funded and sufficiently funded for now.
50m 49s
Okay. Thanks for taking the questions. Sure.
50m 56s
Our next question comes from Carter Gould with Barclays. Carter, please go ahead.
51m 3s
Great. Thank you for taking the question. Maybe first just Just a clarification, Andrea, I think in your comments you made some I think I heard earlier some clients have heard some commentary around nitrosamine impurity. Can I want to make sure I get that clarified? And secondly, maybe just on the change in the Blackstone structure, can you talk a little bit about the decision process to start offering The switch to a royalty on OMav sales, my understanding was you kind of were under no obligation to do that. So would love to kind of just hear some background on how you guys sort of arrived at that. Thank you. So yes, hi, this is Andrea. So regarding the nitrosamine impurity, so that is specifically related to a question that the EMA Has asked to us specifically wanting clarification on our necroscene risk assessment Such as clarifying the manufacturing steps that we basically have identified in that report As they match that up to the manufacturing steps in the MA itself. So I think this is Pretty much an expected question based upon the report that we put in and I think we can answer it with no issues.
52m 32s
Ricardo, this is Manmeet. And I'll take your second question regarding the Blackstone Good morning. I think you're right. We had no obligation on OPAP towards Blackstone. Blackstone had full rights on buttocks loan development and commercialization. And as you know, we made this decision To discontinue Parox loan program and it was in conjunction with Kyowa Kirin, our partner in Japan and Our collaboration partner, Blackstone. So it was all decided together. And in order to discontinue our Falcon program And also to make sure we get release from all future obligations for bar development and commercialization and free from liens and security interest On our whole pipeline, we decided to do this OMAP royalty. But it's a slow low single digit number And it's also capped.
53m 39s
Okay. Our next question comes from Annabel Samimy with Stifel. Annabel, please go ahead.
53m 47s
Hi. Thanks for taking my questions. Just a quick one on with regards to the PFs. Were there any patients who were on compassionate use that just transitioned to the And contribute to the big bolus of that you saw. And have you gotten any sense Of the timing and transition to approval, are payers approving these PES in A 6 to 8 week time frame and an expected time frame or have they not even considered until the product is released and available to deliver to the patients? Thanks.
54m 31s
Hi, Annabel. I'll take the first question. Not aware of any number of patients that we had in compassionate use. We do have a group of patients that are participating in Still participating in the open label extension study. For now, we're continuing that study unchanged. And so, I mean, there may be a patient who have dropped out or something come up, but we wouldn't really be aware of that. So I don't believe that's having any impact On the start form initiations that we've been seeing. Dawn, do you want to comment on the payer experience so far?
55m 8s
Yes. Happy to, Annabel, thanks for the question. So we've engaged with payers really for the last year. And since approval, our payer team has reached All of the top U. S. Payers responsible for 90% of covered lives. And so what we do know about payer policy development is that generally takes 3 to 6 months, sometimes a little bit longer with payers with a rare specialty therapeutic. And so we are expecting policies to be published In the second half of this year, right now what we're seeing are payer authorizations through medical exception and prior auths. And that's really tracking as we had expected. So we're very pleased with that as well.
55m 54s
Okay, great. Thank you. Our next question comes from Maury Raycroft with Jefferies. Maury, please go ahead.
56m 6s
Hi. Thanks for taking my questions. Just clarifying for Skyeclaris, it sounds like there's no need or plan in place to change the manufacturing process. Is that correct? And then for the DPMP study starting in Q3, How long do you think it will take to enroll that study and get to data?
56m 24s
I'll take the first one. We're really not changing the process. Again, just to reiterate, the impurity that was identified was a known impurity. We'd observed it in the process. So it wasn't from a change in the process Steps, Ora new impurity, it had just been below the reporting threshold of basically 0.1. It ticked up just above 0.1. And so we needed to amend the specification now for it to bring it up to below 0.15 which is the qualification limit, But essentially no change in the manufacturing process. And then the second question was? The DMP.
57m 8s
The DMP study.
57m 10s
Simeon, do you want to comment on that? The enrollment what we think about enrollment for the DPMP study for RTA-nine zero one?
57m 18s
Yes, I can take that Warren. We have guided that we will initiate the study in Q3. We have not guided yet on the timing. As we complete enrollment, I think we'll give some more I think we're hopeful that we'll see good enrollment there. There's obviously a huge bolus of these patients and it's a very underserved.
57m 40s
It's only a 12 week study. Yes. Got it. Thank you. And so we plan completion enrollment. Yes.
57m 50s
Our next question comes from Brian Skorney with Baird. Brian, please go ahead.
57m 57s
Hi. This is Luke on for Brian. On the preclinical NRS, can you talk about how your understanding of the science has Changed maybe since bringing omaV and BAR to the clinic and how you're deciding what neuro indications on the list you provided you might want to go after first? Thanks.
58m 12s
Colin, you want to comment on that?
58m 14s
Sure. So we've been working with the top Nrf2 experts for over a decade now to collaborate and understand The role of Nrf2 and similar to CKD, Nrf2 is broadly applicable in neurological diseases. And as I mentioned in my prepared remarks, there's now a large amount of data in the literature that links polymorphisms in the Nrf2 pathway to susceptibility to diseases. Not surprisingly based upon our FA data, there's relevance to many other movement disorders. There's also relevance to Alzheimer's disease and other forms of dementia. And so we're deploying these assets In neurological diseases as well as potentially other therapeutic areas and it's really the wealth of data we have non clinically and from the Human studies that's giving us a path. We're having to wait through the Inflation Reduction Act obviously to figure out how we triage the opportunities and that process is ongoing. But there are opportunities not only in rare forms of neurological disease, but common forms. And so we have multiple assets to address Those sets, indications.
59m 26s
I'd just add one thing too. I think over the past probably 5 years or so as the Biology around Nrf2 has become better understood. I think the role of Nrf2 on mitochondrial function It has been very well delineated. And you may recall that prior to initiating our FA clinical trials, we did studies of FA patient fibroblast ex vivo and showed that they had as you would expect severely impaired mitochondrial function And omav was able to restore that. We think that is a really important potential biomarker For selecting future indication and we'll be looking at that data like that for each of the selected indications.
1h 23s
Thank you.
1h 27s
Our next question comes from Matt Kaplan with Ladenburg. Please go ahead, Matt.
1h 35s
Hi, good morning. Thanks for taking the question. Just going back to the impurity for a minute. I guess, is the supply that you've manufactured Could it risk at all by the discovery of this impurity?
1h 50s
We don't believe so. Again, the Impurity is well characterized. It's easily measured. We're requesting a very slight increase in the specification Above the reporting limit, but below the qualification threshold. So don't expect also based on the you should comment on this Andrea, the safety Profile of the impurity?
1h 1m 14s
Yes, exactly. This is part of our normal process chemistry as I had stated earlier. So again, I think we're confident that The control strategy of adding and increasing the specification limit for this specific impurity is the right thing. The safety testing that we have done, which includes Testing as well as in silico structural analysis all indicate that the impurity is non mutagenic. And so at this time, I think we're very confident in our manufacturing process and the lots produced. We just need to get through this PAS and we'll be fine.
1h 1m 51s
Okay. And did you seriously, did you change your analytical methods when you discovered this level of impurity? Or was it Were they consistent and you just discovered a higher level?
1h 2m 4s
Yes. So they we're very fortunate that Our validated analytical method is able to detect this. So we do not have to change per se that. We obviously had to add in the specific Just specific impurity to look at that now and have that as part of the validated process and testing.
1h 2m 28s
Okay. Thanks. And then last question in terms of understanding that you made the Strategic decision to discontinue bardoxolone, but I guess maybe a question for Colin.
1h 2m 41s
In the AMI study, I guess, why do you think The improvement in eGFR that you observed did not translate into an impact on the end stage renal disease events?
1h 2m 54s
So what we noted in the data is that in the patients who reached ESRD, both drug and placebo, there was separation In eGFR for the 1st approximately 2 years. And then there was conversions and they overlap each other For the following 2 years and we don't have any clear answers for why, but we noted is that when patients had a 30% or 40% Client eGFR, the vast majority of patients were still receiving placebo or bardoxolone. But after that, we noted in the data That both bardoxolone and placebo treated patients were discontinued from drug and the average duration was 5 to 7 months Until they reached ESRD. And so we don't know if investigators had a difficult time managing patients as their kidney function approached ESRD, If there were concerns about the large loss that was observed, but once again, we just the EGFR Increase was not maintained, which explains why initially there was an increase, why there's separation of 30% 40% declines, but ultimately not In the ESRD events.
1h 4m 11s
All right. That's helpful. Thank you. And thanks for taking questions.
1h 4m 19s
Thank you. Those are all the questions we have time for today. Again, thanks 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 atriasapharma.com in the Investors section. Thank you very much for your participation. You may now disconnect.
Key Insights
FDA approved Skyclaris as the first and only treatment for Friedreich's ataxia (FA) in patients 16 years and older; strong initial demand with ~500 patient start forms from over 250 prescribers within two months of approval.
Commercial drug availability for Skyclaris is anticipated by mid-August 2023, pending FDA approval of a revised drug substance impurity specification; manufacturing and packaging are complete with sufficient supply for near-term demand.
Company is prioritizing label expansion to pediatric patients under 16, with a PK study planned to initiate in Q4 2023 and regulatory discussions ongoing in both the US and Europe.
European marketing authorization application for omav is under review, with responses to EMA’s Day 120 questions expected in Q3 2023; company is building out European commercial infrastructure in anticipation of a potential 2024 launch.
Discontinued bardoxolone CKD development due to lack of ESRD event separation in Phase 3 data; amended Blackstone agreement and secured a new $275M non-dilutive debt facility, extending cash runway through end of 2026 and targeting breakeven at ~1,000 Skyclaris patients.
