PTC Therapeutics, Inc. (PTCT) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by and welcome to the PTC Study 045 review call. [Operator Instructions] I'd now like to hand the conference over to your host today, Mr. Stuart Peltz, Chief Executive Officer. Please go ahead.

Thank you, and welcome. I'm now going to take you through the Study 045 dystrophin study results. As a reminder, this is a biomarker study that was recommended by the FDA to support a potential accelerated approval, specifically for the U.S. Shown on Slide 2 are our forward-looking statements. So today, I will be making forward-looking statements. So I ask you to please refer to the SEC filings for our forward-looking statements. Let's go to Slide 3, which is our study design. And as you remember, we enrolled 20 boys, aged 2 to 7 years old, with nonsense mutation Duchenne muscular dystrophy. The boys received baseline biopsies prior to the initiation of treatment, and follow-up biopsy scheduled at 40 weeks following the treatment. However, due to the COVID-related delays, 8 of the 20 boys were unable to undergo biopsies at week 40 and had their second biopsy between 62 and 70 weeks of treatment. The full-length dystrophin levels were measured using both the ECL assay as the primary endpoint and the IHC assay as the secondary endpoint. So let's go to Slide 4. This is the 2 methods that were utilized to assess the full-length dystrophin. These methods were selected to ensure that we can reliably measure full-length dystrophin in a quantifiable way. We have spoken previously about the ECL assay, and the IHC assay is also a quantitative and sensitive assay that not only quantifies the amount of dystrophin but also lets you look at the intracellular localization of the protein. Both assays went through extensive validation and FDA review, and both are sensitive at low levels of dystrophin production. As shown on Slide 5, the ITT population included the 20 subjects enrolled in this study. However, 1 subject was evidently noncompliant and only took half of the study drug, and 1 subject did not have adequate biopsy samples to establish baseline levels. Therefore, we had 18 subjects that were compliant with study drug and had evaluable biopsy samples and are considered to be evaluable population. 10 of the 18 subjects had their second biopsy at week 40, and 8 had their second biopsy between week 62 and 70. Importantly, patient characteristics, including age and steroid use, were consistent across both the 40-week cohort and the longer-term treatment. So let's go to Slide 6. Shown here are the results of the dystrophin expression for the ITT population of 20 subjects and the 18 evaluable subjects. Overall, in the ITT population, there was an increase in dystrophin expression from baseline on both the ECL as the primary endpoint and the IHC as the secondary endpoint, but these did not meet the p-value of less than 0.05. However, when looking at the 18 subjects in their evaluable cohort, we saw a greater increase in dystrophin expression, and this increase did reach a nominal p-value of 0.04 in the analysis of the IHC assay. Also, over 80% of the evaluable subjects demonstrated an increase in dystrophin expression, signifying a consistent effect. On Slide 7, and as I mentioned, 8 patients in the evaluable population had longer treatment exposure, ranging from 62 to 70 weeks. These subjects had markedly greater level of dystrophin increase with an average of approximately 24% on the ECL. These results suggest that longer duration of treatment resulted in greater biological effect, which is consistent with the long-range Translarna treatment benefit we have previously reported from our other clinical studies and our real-world STRIDE registry. Now let me turn to Slide 8, which are measuring creatine kinase or CK levels. So we also collected CK levels and a number of relevant clinical outcomes as the exploratory analyses. First, let me start with CK. Consistent with the increase in the levels of dystrophin, we also saw a marked reduction of approximately 20% in creatine kinase, which is an objective measure of muscle damage. As a reminder, dystrophin acts as a shock absorber during a muscle contraction and would be expected to protect against muscle damage and therefore reduce CK levels. Once again, we observed that longer treatment with Translarna was associated with a greater magnitude of biological effect. On the next slide, there's some clinical endpoints. So let me take you through that. So as you can see, there was a positive trend with an improvement over baseline on every endpoint. Once again, we observed that longer treatment with Translarna was associated with a greater magnitude of clinical effect. So Slide 10 is our summary and that you can see that overall Translarna treatment resulted in increased full-length dystrophin expression on both the ECL and IHC assays. And while the increase did not reach a p-value of less than 0.05 in the ITT population, however, it did reach a p-value of 0.04 in the evaluable population in the IHC assay. In addition, there was a consistent treatment effect across the population with over 80% of patients demonstrating increased dystrophin expression. Importantly, longer treatment with Translarna was associated with a greater increase in dystrophin expression, which is consistent with previous results. Lastly, Translarna treatment resulted in marked reduction in CK levels, again consistent with dystrophin production as well as an improvement in all clinical measures. So on Slide 11, the top line results from Study 045 confirm biological effects of Translarna treatment and add to the existing totality of clinical and real-world evidence, demonstrating Translarna's clinical benefit. This includes data from our placebo-controlled trial, which demonstrate consistent improvement across multiple clinical endpoints and our STRIDE registry, which provides crucial real-world evidence of the long-term treatment benefit of Translarna and key aspects of disease such as preservation of ambulation and pulmonary function. So just to remind you, on Slide 12, the results shown here for the key trial endpoints demonstrate that the totality of the data shows a consistent treatment effect for Translarna across multiple clinical endpoints in a number of studies as well as the meta-analysis. Now let me transition to the STRIDE registry. The other point I'd like to make is related to our real-world evidence, and this is shown on Slide 13. Our STRIDE registry provides real-world evidence of long-term treatment benefits of Translarna, long-term meaningful effects that can't practically be captured in a clinical trial. Specifically, we can study critical disease aspects like loss of ambulation and loss of pulmonary function and long-term functional benefits. The STRIDE registry is the first and largest real-world study of nonsense mutation Duchenne muscular dystrophy patients. This registry includes over 250 patients followed for 5 years in a real-world study. The results on the next slide demonstrate Translarna treatment preserves ambulation by 3.5 years in physical and pulmonary function, all factors that lead to early mortality in these patients. These results have been key to the annual renewal of the marketing authorization in the EU. So Slide 15. In conclusion, the totality of the Translarna results demonstrate biological activity increasing full-length dystrophin production, meaningful clinical benefit across multiple endpoints in several placebo-controlled trials and real-world evidence from STRIDE registry of long-term clinical benefits on key aspects of disease progression. So we plan to discuss the dystrophin results and the totality of the existing clinical and real-world data with the FDA to determine that there's a potential accelerated path to approval. As shown on the next slide, alternatively, we also have a readout on the fully enrolled Study 041 placebo-controlled trial in Q3 of 2022. And based on a positive outcome, we could submit the NDA at that time. Thank you for listening, and I welcome your questions.

[Operator Instructions] Our first question comes from the line of Eric Joseph from JPMorgan.

Okay. Great. So Stu, a couple questions on the data here. I just want to get a sense of some of the variability in expression particularly in what seems to be like a lot of the mean dystrophin increase being driven by the 8 subjects that were treated beyond the protocol period. Can you sort of segment -- well, I guess you do segment what the mean expression is in those 8 subjects? Can you talk about mean expression in the 10 patients that were treated per protocol? And maybe sort of characterize what median expression is above baseline across all study subjects. You note that 80% of subjects saw some increase. Can you just sort of characterize what that minimum level of induction that you saw?

Sure. Okay. Yes. Thanks for the question. So the -- obviously, what we're seeing is that we have 18 evaluable patients and some were from 60 to 72 weeks where we saw a greater response. And that's probably not untypical of what we've seen in general when you look at our longer-term data as well as the real-world evidence data that -- well, we see read-through. It takes time to see the expression of it. It takes time to see it from the clinical results as well as seen in the real-world data over 5 years, you see such really strong data in there. And so what's really true is that the -- while it's true that the 80% we saw that there are obviously within the 18 patients, 8 of those showed stronger effect. Yet, obviously, 10 showed smaller magnitude of an effect. So yes, you're right that a lot of it was driven by, as you see, those 8 patients. But again, we saw 80% of all the patients demonstrating some increase of that. And there's just some variability that occurred, I think, as a consequence of getting near but not getting the 0.05 level.

Okay. Got it. Is there any reason to think there will be sort of -- well, any thoughts around the sort of latence -- is there any reason to think there will be sort of a mechanism behind the latent increase or induction of expression, higher-level expression you're seeing in those patients that were treated over the longer period? And I guess, is there any opportunity for further follow up at this point across the study? Is there any opportunity to go back and sort of conduct secondary biopsies in patients on the trial?

Yes. I think that's a good question. Obviously what we're doing is thinking about this and exploring our options in terms of the notion of what -- and of course, we'd like to sort of talk about with the FDA with the totality of the data that we have right now that with the combination of the biological results from 04 and this, we were certainly making dystrophin. And then the clinical results, real-world evidence, really, we think has set it up for a potential for accelerated approval [indiscernible] Study 041 for the full approval. So we're certainly going to be talking to the FDA about that. But one of the considerations, obviously, could be, is that an alternative to then just take a longer-term biopsy. So we are trying, obviously, to thread the needle between the notion of getting Study 041 completed in the third quarter of 2022 versus getting the accelerated approval now. But those, I think, are going to be the focus of our discussions with the FDA on the potential approval pathways or what pathways we need to go forward on. So I think, obviously, that's something that we're considering. Obviously, what we're talking to our advisers now, I think, our best path's to go talk to them, showing them -- they have not yet seen in a formal way the real-world evidence that goes along with all the other data that we have. So we believe that the combination of the biological, the clinical and the power of the real-world evidence is pretty potent data demonstrating that these patients are being benefited as a consequence of Translarna. And that's the argument that we're going to be making. And then I mean, if you think about it, this is really, I think, the strongest clinical package of results that we have. So along with that, we have the biological results that could lead to -- but we have the backdrop of due to a longer dystrophin a third one. And then we always have the backdrop of clinical study for Study 041.

Our next question comes from the line of Gena Wang from Barclays.

I also have a few questions. First, Stu, just wondering if you can give a little bit more color -- and I do ask -- I wanted to ask again regarding the baseline characteristics for these patients. Firstly, what is the age median or mean age of these patients? And then also the ECL, what is the percentage? If we look at -- what is the percentage of the wild type if we wanted to have some kind of a benchmark to compare? And then in terms of the IHC, immunohistochemistry, what is the roughly percentage of the positive fiber, if you can give a little bit more color on the baseline and as well as the CK level? So this is the first question. I have a follow-up question.

Sure. I'll do that. I'll start with the CK level, and then I'll ask Matt to delve in on the other questions that you've had. We -- as you probably know, from -- since dystrophin is a protein that acts as a shock absorber for -- during contraction, the notion that it protects it during that period is -- so the fact that we see the production of dystrophin and then see the reduction of the CK, I think, is consistent with the notion that dystrophin is being made and protecting the muscle over that time. So we thought that was strong and, again, was greater in the longer-term treated patients, again, consistent with what we see with the Duchenne with both the clinical data as well as what we saw with dystrophin. So I think that's all pretty well consistent, and I think really quite positive from the point of view of putting all the pieces together from when you think of the story that they should be like that. So we feel pretty good about that. In terms of the baseline characteristics, Matt, do you want to go through that a little bit?

Yes, absolutely, Stu. So you look across the population, we enrolled subjects on the full range of 2 to 7 years of age. And the overall mean age in evaluable population was about 4.5, Gena. The median was in a similar area, between 4 and 5. And actually if you look at the COVID-impacted subjects and the not impacted subjects, you end up looking at very similar age groups, age at first symptom, age at diagnosis and also, as we mentioned, importantly, that the steroid use was similar across the 2 different cohorts. So overall, when we look at the evaluable population -- actually, the entire population, we had 13 to 20 subjects who were using steroids at baseline. And one of the key requirements of the protocol was to ensure that they were on a stable regimen of steroids for 3 months prior to initiation of therapy. And then, again, we saw an equal proportion in terms of steroid use both within the cohort as well as the longer treatment cohort.

Okay. What about the ECL and IHC regarding percentage of cut and percentage of positive fiber?

Yes. So we -- right now, we're just reporting the overall percentage change from baseline. We haven't completed all the staining work on percent positive fibers. So -- again, at this point, we're disclosing the change from baseline in, obviously, both the IHC and ECL populations. One of the key things, obviously, there were patients, of course, who had lower levels of dystrophin expression, which was fully expected, which is one of the key aspects of the study design, ensuring that we had 2 assays that were validated to detect those low levels of dystrophin so that we would be able to have a basis of comparison on the follow-up biopsy. We did also have subjects who had over 1% dystrophin expression at baseline, but I can say that one thing we did look very carefully on is was there a relationship between baseline dystrophin levels and response to treatment and if it was not. We actually found that there was no correlation between baseline dystrophin expression. Also -- as a matter of fact, we also looked at genotype-specific mutation location, and we didn't see any correlations in any of those baseline characteristics or genetic characteristics and Translarna response. The one response we did see overall as we talked about, which was really longer duration of treatment was associated with an overall greater response rate and also overall greater increase in dystrophin expression.

Okay. In positive fiber, so there is no major differences, right? If we understand like based on the other studies, usually positive fiber as a baseline is a low single digit and that you see the protein level usually certainly below 1%. So those are what we understand the baseline and so that will be very consistent with your data overall. Is that a fair statement?

Okay. Yes. I didn't actually understand, Gena, the question. Just to clarify, you're asking is if [indiscernible]

Yes. Like -- just wanted to know if your baselines are pretty consistent with what we've seen so far from the other studies. We've seen usually the protein level is certainly less than 1%, could be 0.1% to 0.5%.

Yes. Like that.

Okay. And then the positive fiber in the low single-digit range, and that's also consistent with your observation, right, like undetectable to low single digit?

So we haven't reported -- we're not reporting any positive fibers. We don't have those data at this time.

Okay. So regarding the assay part, they -- did you pre agree on the ECL measurement? Or would the IHC assay -- which assay did you agree on before the analysis?

Yes. So we -- both were included in the protocol and both were -- we received inputs from the agency on both assays, both the ECL and the IHC. The primary endpoint was the change in dystrophin expression in the ITT population using the ECL assay. And the secondary endpoint, we're using the IHC assay. But again, both were discussed with the agency, and the key factor was ensuring that we had validity in the assay. And then both assays were able to have detection, linear detection, precision and accuracy down at lower levels of expression, which as you mentioned, we talked about that we fully expected and saw lower levels of baseline dystrophin expression.

Okay. And my last question is regarding Slide 14, STRIDE and CINRG. Just wondering, did you -- for the CINRG, was that also matching genotype of the patient population, basically, the nonsense mutation, the inpatient population here?

Yes. So that's a good question. So the CINRG database includes not just nonsense mutations but all different mutations. However, the one important thing we did was the baseline matching for the propensity scores. And what we wanted to do is use the several factors that are predictors of disease progression such as age at onset of first symptoms which is known disease surrogate in terms of loss of ambulation, steroid use and other key baseline characteristics that would, in spite of potential differences in specific mutation type, allow us to have apples-to-apples comparison in terms of likely progression, likely age of loss of ambulation, likely similarities in terms of overall disease severity.

And then we also removed like the exons that we know have less -- there's a couple of known skips that are -- give a different phenotype and those were also removed.

Yes, such as exon 41.

Our next question comes from the line of Alethia Young from Cantor.

I just wanted to explore a little bit more kind of the regulatory story line, how to unpack that. One, just in light of what's kind of gone on with Sarepta and where we're at with the FDA and the commissioner, I mean what kind of pushback or what do you expect are going to be the key points of argument? I know, obviously, Sarepta was sort of a consensus approval and you have more real-world data. But just if you can help us think about that. And then second was, [indiscernible] data that you feel so very confident with your regulatory position in Europe as well.

Yes. So there is -- so I think the next steps for us, I think, again, the argument is that obviously we're talking about the totality of the evidence to support the Translarna benefit. That includes obviously the full-length dystrophin expression that we've seen in 2 studies, the clinical benefit across several placebo-controlled trials and the real-world evidence from the STRIDE registry. And so our argument is going to be that those are the 2 -- those are the strongest evidence, I think, that we have that demonstrates the benefit -- the clinical benefit that the DMD patients have. Not only do you see many different endpoints from the clinical results, but the real sort of preservation of being able to walk as well as the preservation of the pulmonary function in real-world evidence over 5 years and the protection that you see in Slide 14, I think, is quite remarkable and also demonstrates very nicely just how the drug is actually helping patients in both of those situations. So that's, I think, going to be our regulatory path is the combination of all of those. And then obviously when you think about it from the argument that we want to make is that you have this and then you also have from an accelerated approval pathway, the ongoing clinical study that's fully enrolled and will be completed in -- at the end of 2022, second half of 2022, so it's not that long. And that the risk benefit, we think, is strong. We got a strong safety profile, strong data set already. It's been approved in multiple countries around the world -- or distributed to over 50. So I think there's a strong reason why one should be able to also bring it to patients in the United States. We already have probably well over 100 of those. So I think that's going to be our regulatory arguments that we're going to go to. We'll be working on that pretty hard over the next few weeks to get ready for our meeting to discuss that with the FDA. From a commercial point of view, we don't think that really when we think about the EU, Latin America that the key here has always been the totality of evidence for Translarna from the commercial market. And I think the approvals of the reimbursement has been based on clinical data, not biomarker data. And you could see that that's true when you look at other companies trying to get approval based only on that in other countries, but they really want to see clinical data. And maybe, Eric, you're close to this as well, so you may want to comment a little bit on [ what you see ], whatever impact we have here. We think it's positive. But Eric, what -- you want to comment a little bit?

Yes, Stu. Alethia, thanks for the question. I mean, clearly, we had very strong year-over-year growth over the last 5, 6 years since we've launched Translarna outside of the U.S., and we continue to see that growth even in the first -- for the part of 2021. And the Translarna was approved outside the U.S. based on clinical data, as Stu mentioned. But the payers really look at HTA assessments and more importantly, since I have been directly engaged with many payers outside of the U.S., the real-world data in STRIDE really supports the value proposition. So I have never been asked by any payer or actually a regulator at this point in time about the dystrophin data because they really value the clinical data and what we prepared in terms of our Health Technology Assessment. All of that is really based primarily on the extension of the clinical results and the real-world evidence that Stu described right now, which we have over 1,000 patient-years of. And we've been able to break that data, not only with regards to the totality of the data, but we've been able to break that out on a country-by-country basis and share the value proposition of delays and loss of ambulation and pulmonary function. So we don't see at all that the dystrophin data interpretation by FDA or anyone else is going to have any impact outside of the United States. They're really formulating their opinions on regulatory approvals and reimbursement on clinical and the overall data.

And I think you could see the year-over-year growth as well from the existing and geographic markets have been continuing. And so there's been -- we're seeing increased penetration and high compliance with the existing patients. So that's -- and we continue to secure new patients as well.

Our next question comes from the line of Joel Beatty from Citi.

The first one is on the EU regulatory outlook. And can you discuss whether you anticipate the EU regulators will be reviewing this new data as part of their annual review?

Yes, sure. So I think as we've said here before that the results that the EU has worked on has been based on clinical data. They've made it very clear that they understand that from a regulatory point of view that dystrophin as a biomarker doesn't really predict clinical benefit. And we've even asked them in terms of previous times what they used for potential approval and they said they don't believe in dystrophin as a clinical biomarker. They focused on really the study -- the studies that we had previously, the STRIDE registry data and the Study 041 confirmatory trial. So the combination, as I talked about, is really the combination of the clinical data that we had from 007 and 020, and then the powerful STRIDE registry has really helped it as well quite a bit, and then they know that there's a confirmatory trial in 2022. There's no -- and as you probably know, there are no DMD therapies that are approved in Europe or in Latin America or elsewhere solely based on dystrophin as a biomarker.

Got it. Yes. That's helpful. And another question on dystrophin expression. In the slide deck today, I see there's a lot of the presentation of relative increases of dystrophin. Would you be able to quantify the absolute increase in dystrophin? I think one of the reasons I ask is with the EXONDYS 51 label from Sarepta, it seems to have been approved in large part because of a median increase in dystrophin of 0.1% of normal absolute increase. So just curious how your data compares to that and any implications of that?

Yes. I guess the way I would think about this is -- and I think we -- you've probably heard me talk for years in terms of the amount of dystrophin that's being made. There is really no correlation that people have been able to assess between dystrophin levels versus clinical benefit. So nobody really knows to say how much is enough. I mean if you look at the exon 41 and 44, there are really -- these patients do better at very, very low levels. So that's why, you might remember when Vyondys was first approved, it was a consequence of, you remember Dr. Woodcock said any dystrophin is important and the fact is that if you make it, that's an indication that it could be better. And so no one really knows that number. So really the answer, I think, is anything above background is something that they will consider. And so that's why I think that's where we're at. So we all knew the key issues in measuring that is it's not always a -- and that -- and the reason this is true is that the key -- the issues when you think about it is that not only the assay but the variability of the muscle within itself, and that in a sense the potential probably problem is that within the muscle you're going to have low and high levels of muscle within it, within variability, within Duchenne patients and then have high levels of either fibrosis or fatty infiltrates, and this inflammation leads to low levels of muscle and function. I mean that's part of the problem. So we can't really define what is the amount that leads to approval, I think what you could -- or leads to changes in function. But I think the data here really sort of demonstrates that even with low level of dystrophin that's being produced, when you look at it over time, you could see the tremendous effects that it can have in terms of both its ability to preserve ambulation as well as the its ability to preserve pulmonary function. And at the end of the day, when you think about what do people really care about, it's those 2 items are pretty important, in particular pulmonary function, where that's [ mainly ] where mortality comes from, is a consequence of poor cardiac and pulmonary function. So by preserving that, you're preserving the patient's ability, obviously, to breathe and to survive.

Our next question comes from the line of Robyn Karnauskas from Truist Securities.

Great. All right. Stu, I guess, 2 direct questions for you. Maybe entertain us in thinking about what do you think the FDA will view -- how do you think the FDA will view this data? We hear more and more from FDA consultants that they're very transparent with people they work with and the applicants they work with. And do you have to change anything regarding the trial that we'll be reading out later in the year? Would you add anything to that trial? And then I have another question just now. So what's the mean change from baseline in the 10 patients treated for only 40 weeks? So if you back-calculate into that mean number using the ECL results, it's just, by my math, which could be wrong, it's very late, so it could be negative. And then what's the difference between ECL and IHC data. So 1 big picture and 1 math question for you.

Okay. Okay. So I'll start with the FDA and what we think, and then Matt, you'll go into some of the details of Robyn's question in terms of the ECL and IHC. So yes, I think that in reading the tea leaves and hearing, I think there has been a little bit of changes within the FDA, both in thinking about rare disorders as well as thinking about what evidence there is. So in our view, I think when we look at this, and they haven't actually seen -- they haven't seen either the real-world average yet or the staging yet, or at least we didn't have a discussion on it yet, that we think -- if you think about clinical benefit, right, in a disease that has obviously been proven difficult to treat in the study in terms of clinical benefit, these packages in my view are the best packages that we have in terms of a precision-based medicine to treat Duchenne muscular dystrophy where you see -- and the argument that we'll make is the biological effects, the clinical effects, the real-world evidence, the fact that we have an additional ongoing study and that they've written up a number of new guidelines about real-world evidence and to utilize those for the real-world evidence in order to show the effects in a rare disease community. So that's the package. And my view of this is that it should be approved. I mean, from my point of view, I think this is the best clinical data set in order -- that shows that. And we're working obviously with some internal as well as external advisers appropriately to put the package and find the best pathway for this engagement. And so we're putting this all together so that we can then have a discussion with the agency on what's the best approval pathway to move forward on. And so we have obviously, like I said, the results that I talked about with looking at the dystrophin, the 2 clinical trials and real-world evidence. And then we have the backstop, which I've already talked about, of Study 041 that we'll have. So we're shooting to win now, but then we always have the backstop in terms of the clinical study. I think in terms of your question of the clinical study for 041, we believe that's a well derived study which we're doing longer-term efficacy, right? We're at 18 months treatment in a broad population, but with the right -- with the primary endpoint being the really specific population of patients that we've learned from all the natural history work we've done that are likely to decrease but not go rapidly nonambulatory. So that was the -- so that study, I think has been based on a large amount of natural history data that includes our own natural history data as well as history data from virtually all of the other studies that have been done. So we thought we had a pretty good handle on this. And so -- and we have the right, I think, patient population to look at in terms of what's most likely to see changes like what we've talked about in the past with that subgroup that will be declining but won't rapidly go nonambulatory. So that's -- we feel pretty comfortable with the study that we've done. There's clearly no study with dystrophin within that study. It's really more -- and so what we did is we took the learnings of what we've had in the past, elongated the study so that there's more time on it, have the right population that we have. So we have -- and we have a long term not only at the treated date of the patient placebo control side but also have the part where everyone's followed on drug but they still remain blinded. So we get a look at the changes that occur within that patient population as well. So we sort of have multiple shots to be able to find -- to increase the amount of evidence demonstrating Translarna's clinical benefit on these patients. Does that help?

And -- yes, it does. Given the transparency, and we've heard this repeatedly from different divisions that they're so transparent, you have to know what they're thinking. I mean given this data, don't you think they probably want to see that other data set just to make sure they're making the right decision? Or what's your gut? That's -- I know, that's just a gut, right. You have no idea what they're going to do. No one does. I think I mentioned -- then there's the math question. That's really -- do you think that they'll -- it's usually ahead of that because you've got a big data set coming up. Why don't you just wait and see it?

Well, it's a bit of time away. There's a lot of patients already on this drug. In a way, this is the sort of system that they've set up that they can approve it now knowing that they have another ongoing clinical trial that they can see. That's sort of what they've set up in the past to be able to approve things knowing that they have something earlier. But my view is that, do we believe that the drug is both efficacious and should patients have it? My answer to that is, yes. I believe that very strongly. Therefore, we have this data set. Can we get it to them sooner for not only the patients who [indiscernible], to remove the patients that we currently have on commercial and other patients, then make it available to them? I think that would be an advantage to those patients to get on now and then we'll have the data set in the second half of 2022. So I think we've built in a strong plan to get the results to be able to attempt to bring the drug to patients now, and then have the backstop of the ongoing clinical trial that's currently ongoing. So our job is to try and bring it to patients, and I think it's worthy of a discussion. That's how we're thinking about it. And Matt, talk a little about the...

Yes. Sorry. Robyn, thanks for the question.

Is my math horrible? It's so late. I was just curious. Like it seems like those calculations actually declined. Back-calculating it looks like they actually declined? So did that actually happen?