Good day, thank you for standing by. Welcome to today's discussion with BridgeBio, which will cover the company's top-line 30-month results from the phase III ATTRibute-CM study in patients with Transthyretin Amyloid Cardiomyopathy. At this time, all participants are in listen-only mode. Please be advised that today's conference is being recorded. I would now like to introduce you to the speakers today. Jonathan Fox, M.D., Ph.D., Chief Medical Officer of BridgeBio Cardio-Renal. Uma Sinha, Ph.D., Chief Scientific Officer of BridgeBio. Matt Outten, M.B.A., A.L.M., C.P.C., Chief Commercial Officer of BridgeBio. I will now hand it over to Neil Kumar, CEO of BridgeBio.
Thank you, operator, and thanks everyone for joining this call. I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive p hase III results of our ATTRibute-CM clinical trial. The strongly positive and consistent data the community worked tirelessly to generate come together today to provide a better future for ATTR cardiomyopathy patients. Before I continue, I'd like to remind everyone that I'll be making forward-looking statements today. Additionally, the slide deck associated with this call is publicly available, and we will refer to specific slide numbers as we progress the discussion. Slide three represents the outline for today's comments. I will begin by providing some context for where we are as a company and remind everyone of the design principles that underpin the acoramidis program and potential best-in-class molecular thesis. I'll then turn it to Dr.
Jonathan Fox, our CMO and President of Cardio-Renal, to walk through the clinical results. Dr. Uma Sinha, our Chief Scientific Officer, will subsequently touch briefly on the path forward, including the expeditious filing of our NDA. Finally, Matt Outten, our Chief Commercial Officer, will also briefly outline ongoing efforts to ensure that we bring this medicine to as many patients as quickly as possible around the world. Before I set the corporate context for this readout, I want to begin with the most important slide in this document, slide four. A thank you to the amazing and inspiring patients and families, advocates, physicians, clinical research staff, and collaborating research partners that made this study possible. Yours were the efforts that lifted this trial to success, and in turn, we recognize our responsibility to you to move expeditiously and to provide this medicine to patients as broadly as possible.
Moving to slide five, I'll take a brief moment to provide some corporate context for today's data. As many of you know, BridgeBio was founded almost eight years ago to target well-described genetic diseases at their source. Our five most advanced programs are shown on this page. Together, these and other ongoing earlier-stage programs should provide, on a risk-adjusted basis, a reasonable tapestry of catalysts for investors and advances for patients in the coming 24 months. I'll turn now to the program of the moment on slide six and begin by reminding everyone of the design principles that underlie our best-in-class thesis. Design objective number one was to create a compound that would continually maximize TTR stabilization for all patients, and therefore minimize the toxic consequence of the destabilized TTR tetramer, which is the toxic monomer population.
Several lines of evidence suggest that maximizing stabilization should lead to ever better benefits for patients. Number one, historical ATTR genotype/phenotype data and the disease protective properties of the transallelic trans repressor variants relative to pathogenic variants in compound heterozygotes. Number two, the performance of 80 mg tafamidis versus 20 mg tafamidis in the previously published ATTRACT trial. Number three, prior results from ATTR polyneuropathy clinical trials. BridgeBio's design strategy was to maximize TTR stabilization by acoramidis by phenocopying the hyper-stabilizing molecular mechanism of the T119M rescue mutation, and I'll lay out further molecular detail in that vein on the next slide.
Design objective two was to pair toxic monomer minimization with the preservation of the TTR tetramer, a protein responsible for vitamin transport to the eye, a protein that no known species lacks or is haploinsufficient for, and a protein that is maintained at high concentrations throughout the course of life. Turning to slide seven, we elaborate on how the 1st objective in the design paradigm was achieved. Briefly, acoramidis was designed to see more target. It is significantly less albumin-bound than other stabilizers in the field, bind the target more effectively, in particularly utilizing a superior KD2, and to then, quote, "Better glue the target together after binding," employing an enthalpic binding mode consistent with the aforementioned T119M rescue mutation. On slide eight, we see just some of the data we have generated over the past years, reinforcing superior stabilization and its characteristic of acoramidis.
Importantly, in the middle panel shown here, we have demonstrated near complete stabilization for patients, even at trough levels or trough concentrations of the drug. Turning now to slide nine. Today, excitingly, we connect molecular theory and early results to clinically meaningful outcomes. These data together have exceeded even our upside expectation of what was possible in the context of contemporary clinical management. We find, as Jonathan will elaborate on, a highly significant result on our primary endpoint, a P value less than 0.0001, with a win ratio of 1.8. We find patients surviving more and going to the hospital less on therapy than we have previously ever observed.
Together with improved medical management, we achieve an 81% survival rate on therapy, as opposed to 74% in placebo, bringing us ever closer to the full elimination of ATTR cardiomyopathy-associated survival risk in this population. As a reminder, actuarial modeling suggests an 85%, 30-month survival in our trial population, absent ATTR cardiomyopathy. This absolute risk reduction of 6.4% and relative risk reduction of 25% was achieved despite an imbalance of TAF, famotidine drop-in, favoring placebo. The impact of therapy on frequency of CV hospitalization is also stronger than previously observed, with a 50% relative risk reduction found. As Jonathan will elaborate on, we find continued outperformance and statistically significant impact on other key measures of morbidity and stabilization.
In particular, the observation that 45% of patients on acoramidis have improved NT-proBNP, as compared with 9% on placebo, is striking. In sum, we find clinical support for our molecular hypothesis. Let me now pass it to Jonathan for further detail and comments on our trial results. Jonathan?
Thank you, Neil. Slide 11 reminds everyone of the study design of our trial. The key eligibility criteria are to the left and required patients to have an established diagnosis of ATTR-CM and clinical heart failure. Patients are randomized two to one in a double-blind manner to either acoramidis 800 mg twice daily or matching placebo for a fixed duration of 30 months. At the end of treatment, the primary efficacy endpoint was a hierarchical analysis by the Finkelstein-Schoenfeld, or FS, method, prioritizing all-cause mortality first, then cumulative frequency of CV hospitalization, then change from baseline in N-terminal proBNP, and finally, change from baseline in six-minute walk distance. On slide 12, we see the top-line results for both the primary analysis and important secondary analyses.
The four-component FS analysis was highly statistically significant, with a P value of less than 0.0001, and was associated with a very robust win ratio of 1.8. Of particular clinical impact was the observation that 58% of the ties were broken by the first two hard clinical endpoints of all-cause mortality and cardiovascular hospitalization. Importantly, the FS analysis of just these two components alone was itself highly statistically significant. When analyzed separately, important secondary endpoints, including cardiovascular hospitalization, six-minute walk distance, change from baseline, KCCQ overall score from change from baseline, serum TTR change from baseline, N-terminal proBNP change from baseline, and all-cause mortality, all highly statistically significant, save for all-cause mortality, did not achieve independent statistical significance. Slide 13 summarizes the top-line safety data.
Across the broad categories of any treatment-emergent AE, those with fatal outcome or those leading to hospitalization or study drug discontinuation were fairly well balanced between the treatment arms. With respect to serious adverse events or serious adverse events leading to discontinuation, these favored active treatment with acoramidis. Slide 14 shows the preliminary results of some exploratory post-hoc analyses that were only made possible by the fact that our protocol allowed participants to drop in or initiate open-label treatment with commercially available tafamidis at their and the investigator's discretion after at least 12 months of study. This figure shows the four possible combinations of blinded therapy and open-label tafamidis versus the on-treatment serum TTR level at month 30.
The two middle columns show that adding tafamidis to placebo is only partially effective in boosting serum TTR levels compared to those participants receiving acoramidis, regardless of whether they received concomitant open-label tafamidis or not. In fact, consistent with our preclinical in vitro data, adding tafamidis to acoramidis has little effect on TTR stabilization, as reflected here in the level of serum TTR, measured as the intact tetramer. Slide 15 extends this exploratory post-hoc analysis to the treatment effect on N-terminal proBNP, an established prognostic index of survival across populations with ATTR cardiomyopathy. The two left-hand columns depict the data for those participants randomized to placebo, who either did or did not drop in on tafamidis between months 12 and 30.
There appears to be little benefit with respect to N-terminal proBNP to adding tafamidis in this context, although, to be fair, the duration of concomitant therapy with tafamidis overall was only 11 months on average. The right-hand two columns conversely show that adding tafamidis to acoramidis actually worsens the increase in N-terminal proBNP. Again, this is a non-randomized post-hoc exploratory analysis that should be taken as hypothesis-generating and not conclusive. Finally, and perhaps most remarkably, treatment with acoramidis, with or without drop-in with tafamidis, is associated with a net decrease in N-terminal proBNP from baseline in nearly half or 45% of participants randomized to acoramidis, compared to only 9% of those allocated to placebo. This observation is very encouraging and suggests that treatment with acoramidis could set a new bar for a variety of clinical and biomarker outcomes for patients with ATTR cardiomyopathy.
In summary, treatment with acoramidis compared to placebo for 30 months resulted in a highly statistically significant outcome for the hierarchical four-component FS primary endpoint, with a P value of less than 0.001 and a win ratio of 1.8. Put into context, we observed an unprecedented 30-month survival of over 80%, which is nearly as high as the actuarial estimate of age-matched individuals without ATTR cardiomyopathy. Importantly, the first and most important component of the primary analysis, all-cause mortality, showed that treatment with acoramidis resulted in a 6.4% absolute risk reduction that corresponds to a 25% relative risk reduction in all-cause mortality. Living with ATTR cardiomyopathy means frequent interactions with healthcare providers, and CV-related hospitalizations can be particularly burdensome for the patient, their family, and related caregivers, as well as healthcare professionals and healthcare systems.
A 50% reduction in the cumulative frequency of cardiovascular hospitalization, coupled with a clinically important reduction in all-cause mortality, suggests that acoramidis could have an important impact on public health. The emerging safety profile of acoramidis remains encouraging, and that chronic administration appears to be generally well tolerated, as no safety signals of potential clinical concern were observed in this study. I would now like to hand it over to our Chief Scientific Officer, Uma Sinha, to summarize the next steps in sharing the acoramidis program data more broadly and in more detail in pursuing regulatory review for marketing authorization in the US and beyond, and some of our plans for additional studies. Uma?
Thank you, Jonathan. As you can tell by now, we are absolutely thrilled about the results and will continue to move the program forward. On slide 18, we lay out our key next steps for this program, building on the absolutely compelling data generated in Attribute. First, we are very grateful to Dr. Julian Gillmore, who will be presenting the results, the primary results of this trial in August at the European Society of Cardiology. Second, building on the comments that Neil has already made about expeditiously moving this program forward for patients, we are planning to submit our NDA by the end of this year and submit additional major market filings, such as to EMA, during the first half of next year. Broad range of activities related to this are already underway in this regard.
Finally, we have IP exclusivity on acoramidis through the year 2039 and plan to continue in our life cycle management efforts. This includes very critical phase 4 work, such as our planned primary prevention study, ACT-EARLY. With that, let me turn it over to Matt.
Thanks, Uma. First, I just want to reemphasize how excited we are to share the results of what a next-generation, near-complete stabilizer can do. While we've been waiting for these results, we have also been preparing. Our global leadership team is in place with strong previous launch experience. We have alumni from Pharmacyclics, Schering-Plough and Vertex, amongst others. The team is also supported by a strong commercial advisory board that includes industry legends Fred Hassan, Jennifer Cook, and Jim Robinson. We've also initiated distribution discussions to bring this drug to patients. Based on the data that you've seen today, we have an opportunity to serve patients globally and improve access. The bottom line is that acoramidis is a commercial launch dream, amazing data with clearly defined areas of unmet need.
We'll have more details on the commercial launch execution moving forward. Now I'll turn the call back over to Anav for Q&A.
Thank you, Matt. With that, operator, we can open the line for questions.
Thank you. If you'd like to ask a question, please press star one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Salim Syed with Mizuho Securities. Your line is open.
Great. good morning, everybody. I'd like to just offer my congrats. It's been a journey for the entire team, Neil. Even on six-minute walk data, the data was really amazing. I guess, a couple of questions from us on the cardiovascular hospitalization data. I know when we were looking at the Pfizer tafamidis study, there wasn't really a consistency, depending on the analytical method. If there's something you can give us, here, Neil, perhaps on the different analytical methods you guys ran on cardiovascular hospitalization, if you can confirm that there was consistency on that P value...
Yeah.
-or that separate data. Secondly, just on, you know, you've spoken about access to the medication previously, and I think even mentioning perhaps, better net pricing. Just curious how this cardiovascular hospitalization data plays into that pricing framework? Thank you.
Yeah, thanks, Salim. Thanks for the questions. It on CV hospitalization, you're absolutely right. We've spoken about this in the past, where the number of events, if you looked at annual mean frequency, it looked like prior studies went the wrong way. If you looked at the negative binomial analysis, it looked like it went the right way. What was heartening about our data is actually the consistency, not only across different parameters, but also in CVH's analysis. There was no way to cut the data where actually there wasn't a remarkable relative risk reduction, and we'll have more to publish on that going forward.
If you look at it through the negative binomial, if you look at it just in terms of number of events, if you look at it in terms of annual mean frequency, you can see around that 50% relative risk reduction.
Which sort of leads to the next question, which is, actually, having profound hospitalization reductions like that, does that open an opportunity for us, to, you know, obviously, be more aggressive, especially in European markets, and to gain access? I think, you know, we would love to see these products be more broadly accessible than they are now. Certainly, you know, we're reminded of the fact that about a majority of our patients were enrolled in Europe, some in countries that still don't have access to life-saving stabilizers. We're gonna be moving as quickly as possible with these data in hand, to engage with regulators and access authorities to bring these drugs to those markets.
Super helpful. Thanks so much, guys, and congrats again on the data.
Thank you.
Thank you. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open.
Great. Thank you. I, too, would like to offer my congratulations on these incredible results, and hats off to the whole BridgeBio team for keeping your head down and executing to the end despite the Part A surprise.
Thanks.
I have a couple questions that I'd like to ask. The first one is: Can you discuss the time and rate of separation with the mortality curves and the potential for the hazard ratio and statistics to improve as you continue to follow these patients another 6 or 12 months in the OLE? The second question is regarding the hazard ratio in comparison to tafamidis data. I mean, clearly, the 0.75 is impressive, with a lower mortality and tafamidis drop-ins. As we think about the comparative analysis, how tightly correlated is improvements in serum TTR and proBNP to clinical outcomes in this disease?
Great questions, Tyler. First, I would say that the temporal charts and a broader list of tables and figures will be published at ESC Azuma, and Jonathan alluded to at the end of August. You know, I could say at a high level, what's pretty remarkable is despite the left-shifted population and the way lower event rates, as you and I and others have discussed, we see a similar time to separation as did prior trials. That to me suggests a different level of potency.
In terms of the hazard ratio of 0.75 versus, you know, the other trials that have come out, again, you know, as we looked at the placebo survival rate of 74% in this trial, it outperformed the on-drug arm of prior trials. Getting to those survival rates of 80%+, to us is close to top, taking what is possible here. Yes, we expect that the jaws, if you will continue to separate on those KM curves over time, until you should be able to see that through our OLE, where we have almost 89% rollover.
I think, you know, in terms of these cross drug comparisons, et cetera, with all of the appropriate caveats that Jonathan mentioned, post hoc, really hypothesis-generating types of things, the drop-in does allow us the opportunity to have a look at key measures like serum TTR as a measure of TTR stabilization, and then also NTpro, which, as you know, is the best univariate predictor or one of the better univariate predictors of downstream mortality. The outperformance there, you know, ties back to the molecular thesis and gives us hope that this is truly a one-of-a-kind agent in terms of potency.
Great. Thanks very much.
Thank you.
Thank you. Our next question comes from Thomas Shrader with BTIG. Your line is open.
Hey, good morning, guys. This is Solomon for Tom. Congrats on the data, thanks for taking our question. To kind of build off the previously asked question, regarding NT-proBNP, how ready for prime time is this endpoint in the eyes of the regulatory agency and physician? Is there some education that may be involved? Second question is, regarding the European market, are there any hints suggesting that their regulatory agency may have a specific interest in the particular treatment benefit or endpoint? Thank you.
Thanks. I'll pass it to Jonathan for the question on NTpro.
Thank you, Neil, and thanks for the question. I think we should look at N-terminal proBNP as an index of morbidity or an index of severity of chronic heart failure in this particular form of heart failure. Again, ATTR-CM is an infiltrative restrictive cardiomyopathy. It is fundamentally different, pathophysiologically, from more common forms of heart failure, where N-terminal proBNP may not be as robust an index, to predict morbidity and mortality in the affected population, compared to ATTR-CM, where the data, in our view at least, strongly support its use as a prognostic factor in this particular form of heart failure.
That being said, to answer your question more directly, as a standalone endpoint for registration, it does not appear to be widely accepted either in the U.S. or elsewhere, but as supportive data and as part of a sequential hierarchical analysis, certainly it is a consistent index of how effective the treatment may or may not be, and in our case, it was highly statistically significant. Having said that, as I said in my prepared remarks, the 58% of the ties in the analysis were broken by the first two hard endpoints. You know, to look at N-terminal proBNP as a standalone may not be ready for prime time, but certainly our data lends credence to its utility as an index of prognostication and as an index of disease severity in the affected population.
Thanks a lot. Thank you.
Thank you.
Oh, what was the second part of your question? Oh. Oh, was there a second part?
European.
Oh, the second part was, any hints from European Regulatory Agency about a specific interest in a particular treatment benefit or endpoint from today's results?
No, I.
Yeah, no. It's Jonathan Fox again. Our preliminary interactions with the EMA have been pretty general in nature. You know, we'll be interacting with the regulators in Europe, more specifically, now that we have the data in hand to have a more focused discussion.
Thank you very much.
Thank you. Our next question comes from Greg Harrison with Bank of America. Your line is open.
Hey, good morning, and huge congrats on the data. How are you thinking now about EU commercialization strategy? Are partnerships on the table, or is this opportunity large enough combined with the achondroplasia and others, that you'd build your own commercial organization, especially just given the strength of the data?
Yeah, thanks, Greg. Appreciate the question. You know, I think at the baseline, we're prepared to launch this medicine worldwide. We're obviously always open to partnerships that help improve access to the medicine, or to partners who have differential capabilities to us. But as you know, with, you know, four potential launches over the course of the next 28 months here with our late-stage pipeline, and the work that we have done already in Europe, vis-à-vis the phase three clinical trial, we'd be excited to launch the product there as well. And we've been doing a lot of work on the health economic side so that we can bring that medicine, as quickly as possible to some of the markets that have just started to open up, to modern therapy.
That's how we're thinking about it, the high level, if that helps.
Okay, that's helpful. Then if I could sneak in one more. You know, what does today's update mean for your financing options going forward? Any thoughts you can share on your overall strategy?
I think at a high level, you know, we'll continue to interrogate, what the best cost of capital is across a variety of different avenues. You just alluded to one, which is potential partnerships. Another set with a late-stage pipeline, such as this, is, royalty financing. There's obviously equity financing as well. You know, the focus is effectively low cost of capital, coupled with great partnership, and we've been very privileged to work with wonderful investors to date. Our hope is that we can add a few more going forward as, continue to build this company.
Great, thanks. Thanks for taking the questions, and congrats again.
Thanks, Greg.
Thank you. Our next question comes from Mani Foroohar with Leerink Partners. Your line is open.
Thanks, and my congratulations as well. Obviously, a long road to get here for you guys and a great result. A couple of quick questions.
Thanks.
On the commercial side, ever since the early days of the tafamidis launch, there's been a lot of talk about the impact of patient out-of-pocket costs, role of the donut hole in the U.S. in particular. Can you talk about how you see that evolving, since launch and now, given legislation in the interim? I have a quick follow-up question.
Yeah, sure. I think what you're referring to, Mani, is, as we've discussed, the Medicare population, for whom, unfortunately, the copay associated with current therapeutics is out of reach for many, and that's leading to a lot of scripts that are being written, but unfortunately, can't be filled. One of the heartening parts of the Inflation Reduction Act is that it'll dramatically reduce that copay. You know, our estimates are coming down from something like $14,000+ to something around a little bit above $2,000 in a future state.
That should help dramatically in terms of access to medicines here, and then I think, you know, as sponsors like us get on the playing field, our hope is that there are other ways that we can improve access through tried and true mechanisms that are associated with Medicare coverage.
Great. As a quick, commercial follow-up, Japanese rights live inside Alexion, AstraZeneca company right now. Can you give us a little sense of what the ongoing state of that collaboration or partnership, and what this data suggests potentially for how they might pursue that market?
I don't know. Jonathan, do you want to announce?
That's a great question. Our collaboration with our partners at AstraZeneca, Alexion, remains healthy and productive. There's an ongoing open-label evaluation of acoramidis in patients, in Japanese patients with ATTR cardiomyopathy. Those results, paired with the outcome shared here from the ATTRibute-CM, are planned for submission to the PMDA. If successful, will lay the path for commercialization in that geography.
Great, that's helpful. Congrats again, guys.
Thanks, Mani.
Thank you. Our next question comes from Ellie Merle with UBS. Your line is open.
Hey, guys. Thanks so much for taking the question, and congrats on the data. Just in all the commercial work that you-
How are you thinking about, like, potential for switches, relative to new starts and how this could play out, in the real world? I guess secondly, how are you thinking about the use of acoramidis relative to potential silencers? If I'm thinking about what to look for from a commercial competitive perspective into that data. Thanks.
Yeah, great questions. I think one of the interesting charts that's consistent with the biochemistry we've observed to date is that we weren't getting a lot more effect in some of those post-hoc exploratory analyses that Jonathan presented when we put one medicine on top of the other. That portends potentially use for certain types of patients if, in the switching context, someone wanted to put acoramidis on top and then wean them off of existing stabilizers. Certainly, the way we've modeled it is the new starts will tend to come from the newer patient population, and there's gonna be a very robust new patient population, given the fact that diagnosis is really beginning to take off worldwide.
In the context of the overall market research that we've presented over the course of the last two and a half, three months, you can see that our continued belief is that small molecule stabilizers will be the mainstay of therapy. That's not to say that knockdowns aren't going to play a vitally important role in this large market, but I think we've already published what our market research suggests relative share will be between all four of what I think will be the medicines on the playing field going forward. You know, I think the last piece of commercial intrigue is likely the potential for combination and exciting potential for combination between something like a potent small molecule and an antibody.
Some of the early antibody research that's been published over the course of the last 6 months, which obviously would be immune-mediated clearance of already deposited pathogenic amyloidotic plaque, coupled with stabilization upstream, I think that could be very, very exciting. We'll be looking at that and trying to interrogate that as things evolve.
Great. Thanks so much.
Thank you.
Thank you. Our next question comes from Paul Choi with Goldman Sachs. Your line is open.
Hi, good morning. Let me add my congratulations as well. This is a great result, not only obviously for BridgeBio, but for the field. 2 questions from us, please. First, can you maybe comment on the differences you saw between acoramidis and the placebo patients who didn't get TAF therapy, in terms of post-hoc analysis, was that stat sig? Our second question is, can you maybe also comment on whether the benefit was broad-based? Did you see separation in all New York Heart Association class patients, or was the benefit mostly seen in Class I and Class II patients, similar to what was seen with tafamidis?
Thanks, Paul. I think for a lot of those subclass analyses, wild type versus variant, and temporal analyses, we want to save some steam for ESC. You'll see all of those published there. What I can say, consistent with what Jonathan has shown, is this is one of the more consistent data sets, certainly that I've had the privilege to be a part of. You know, the details of that will be forthcoming. The first question on subpopulation analyses, we didn't really break out the post-hocs in that regard. I mean, I think what you can see, and as I mentioned, is that tafamidis has an effect. Obviously, you can see it does have an effect on TAF plus placebo.
Our expectation was that we were actually hindered a little bit because TAF was imbalanced on the placebo. Yeah, we didn't do all those subcuts. Those could be forthcoming if those would be interesting.
Got it. Okay. Thank you very much. Congrats again.
Thanks, Paul.
Thank you. Our next question comes from Eun Yang with Jefferies. Your line is open.
Thank you. Congrats on the study's success. I have a few questions. On the primary endpoint, and obviously study is highly successful, but all-cause mortality p value didn't really hit the stat sig. How do you think that's going to play into approval? Was there any discussion with the FDA or other regulators about all-cause mortality statistical significance?
Yes, it's Jonathan again. Yeah, that's an important question, but we really don't have the answer in the sense that while we've had very close collaboration with the FDA and other agencies, all of those previous discussions have occurred in what I refer to as a data-free environment. Now that we actually have the data, we will be engaging with the FDA and other health authorities with respect to the data. Of course, the study and the entire program will be evaluated in its totality, so that the signal, the encouraging signal, and treatment effect on all-cause mortality is only one element that will be considered in their review of our data. It's too early to say, but we're optimistic that it will be a productive discussion.
Thank you.
Yeah, Eun, just as a reminder, the study wasn't designed for stat sig on ACM. The study was designed for stat sig against the FS primary endpoint.
Okay.
There was never an expectation that it would be stat sig across everything.
Yeah. I guess it's worth adding that the large treatment effect on not just all-cause mortality as a point estimate, but the 50% reduction in cardiovascular hospitalization, those two endpoints taken together.
... have a huge impact for patients and health systems. We're optimistic that those data will be relatively well received by health authorities.
Yes, thank you. A couple more questions. Do you expect a priority review at the FDA similar to tafamidis? Another question is on the commercial side. Tafamidis, with the pattern term extension, exclusivity could expire around 2028. I'd like to ask you how that plays into your pricing for acoramidis. On the commercial side, in order to compete competitively, how many sales reps do you think you would need in the US? Thank you.
Yeah, I'll take those quickly. That's a lot of questions. On priority review, yes, we actually do think that the totality of this evidence could potentially open things up for priority review. The meaningful separation on mortality coupled with what Jonathan just mentioned, the huge impact on CVH, will be the baseline for that. We'll know more as we go forward. We'll be prepared for an accelerated launch based on priority review. Secondly, in terms of commercial patent, 2028 is not the correct date, it's 2029. I know that that comes from a Pfizer slide, they miscalculated their own patent term extension.
As we've now said, I think multiple times, our belief is that this market is durable in the US out to 2035, because of the lowest energy polymorph that's protected by the formulation patents that go out to 2035. I think we've been on record and discussed that a few times. Then, the final question on number of sales reps. I don't have the exact number for you. One thing we will be doing over the course of the next couple of months is Matt's gonna be holding some sessions just talking a little bit about our commercial strategy.
I think it is interesting to note, despite the 30,000 cardiovascular practices that exist in the U.S., that the call point today is quite constrained, the majority of scripts coming from 200 prescribers or so. You know, to the best of our understanding, it's not going to be a massive sales force that's required, at least initially. But certainly, we're focused on medical education for now, and we are trying to get the word out on this exciting data.
Thank you.
Question. Thanks.
Thank you. Our next question comes from Dane Leone with Raymond James. Your line is open.
Hey, thanks for taking the questions, and congratulations.
Thank you.
with the data today and the detail today, right? You have a regulatory package that should, you know, get approved, right? You have an approvable drug. You know, you now have to go through the commercial fight, and I think a lot of people on this call are expecting some sort of partnership, whether that's US, ex US, whatever. The question I have is, when you get into more of the details of the study, how do you position the data, to one, you know, beyond just proving you can win with a frame shift in the clinical landscape, which you clearly did very successfully, really solve the argument of, is this a differentiated drug versus tafamidis, right?
You put some data out in terms of the NT-proBNP biomarkers, you know, with the data set today, which looks really encouraging. Do you think there's going to be a post hoc analysis that really gets into for these patients that had a median exposure, I think you said, of 11 months on tafamidis in the control arm? If we start the clock when they started on tafamidis and then do a comparison to the acoramidis arm, what actually happened on some of the more critical endpoints, like cardiovascular hospitalization rate? I would imagine that that analysis wouldn't be robust, but is that something that we could expect or your team would be exploring to maybe solve that question for the clinical community?
Is this just kind of irrelevant and, you know, what you have in totality today is really what you need to go forward with? An easy question on the back of that loaded question. Would you be able to give us the CV-?
Let me take that question first, Dane. I'm gonna forget your second one because that. Oh, yeah, that was a good question.
Yeah.
That's a good question. And it had multiple parts. Let me start at the very end, which is, I don't actually think it's fair to tafamidis for us to look at those endpoints because tafamidis, as you just said, didn't have the totality of 30 months on our trial. I can tell you right now, if we looked at any of those, what you call ACM, CVH frequency, any of that, our drug would be a whopper winner versus them, and, you know, so we can look at that. Well, the only comparisons we thought were fair were the short duration type of outputs like NT-pro and serum TTR, which you know, I think as you and I have discussed, change very rapidly.
You know, that I think is a fair comparison, and that's why we, in a hypothesis-generating manner, tested and delivered those outcomes. I think everything we've seen in the trial is consistent with that acoramidis outperformance. I mean, how do you really make it, like, certain for the clinical community that's a double-blind head-to-head? We've said in the past, I think this data support a future double-blind head-to-head against, you know, you can hypothesize a couple different endpoints that one might want to do that will continue to build the differentiated profile of this drug versus the other.
Look, I mean, I think overall, with the frame shift, you know, if you look at the impact on survival, if you look at the impact on hospitalization, which I think is fairly unique, et cetera, we feel like we've got a very strong data package right now, to differentiate. I think the last thing I would say is if you look at our preference share surveys that we posted up online when we did the market research, you'll see a lot of different folks looking for different things in terms of what is going to differentiate.
Some people actually accept the path or mechanism of the disease and say, "Well, more stabilization, the better." I think we have done a incredible job over the last four years of publishing that data, suggesting that we have an ever more potent stabilizer. That's enough for some folks. Some people will be looking at a variety of different endpoints and trying to do cross trial comparisons. Others may look at things like univariate predictors, NT-pro, et cetera. There's no one size fits all here, and I think that's why you have error bars around the market share. We think we have a pretty good package to compete. Does that answer your first question?
Thank you.
I'll give you the second one, though.
Yeah. No, that was great.
All right.
All right. The easy question now. As you'd highlighted earlier, I think on a different question, there's various ways of really looking at cardiovascular hospitalization rates. In the TRACK study, I think the actual total number of subjects with the CV hospitalization was kinda 8.2% delta between the active and the control arm. What was maybe more interesting was the average CV hospitalization rates during the period for those alive at the end of the period. Has your team had a chance to look at that at this point? Is that also concordant in effect size with, you know, the cumulative frequency of CVH events?
Yeah, I mean, we've looked across four different analytic techniques, and all of them, as I'd mentioned at the outset, have demonstrated this pretty impressive reduction. I mean, you know, as a layman in the field, I would say I just look at number of events, and if you look at number of events, on and off, we are doing very consistently better than what's been published in the past. If you Poisson correct it, if you negative binomial correct it, if you look at annual mean frequency, if you look at overall frequency, against all of those measures, it looks like we're having a pretty striking effect.
Great. That, will that be at the upcoming medical congress or a later date to get those details?
Probably won't be in the SC, you know, top line, but, yeah, definitely at AHA, probably we can dig into that. It'll be in the NDA submission for sure.
Okay.
Yep.
Excellent. Congrats, guys. Thank you.
Thanks.
Thank you. Our next question comes from Anupam Rama with JP Morgan. Your line is open.
Hey, guys. congrats on the data.
Hey.
Really awesome outcome.
Thanks.
I had a, maybe a broader question, following up on one of your points, Neil. Just about your overall KOL, physician education now that you have the data in hand. Obviously, you have ESC coming up. Any new analyses you'd focus us on there? There's likely a journal publication and additional cuts of the data following up, just your overall education about the market somewhat. Thanks so much.
Yeah, thanks for the question. I would say, firstly, really, we got here on the shoulders of the very talented KOLs in this community. They immediately understood and grasped the concept that ever more stabilization could be interesting for patients and have helped us through an obviously trying period. Our commitment back to them is that, number one, we preserve a little bit of gunpowder for ESC. Number two, and more importantly, that we interrogate these data and start to generate new data as quickly as possible.
A big part of, you know, what you might call KOL engagement, but what we call around here, partnership, is starting that at ACT-EARLY trial and starting other phase 4 studies that can help us to better learn about the disease and better learn about this medicine, too. We're gonna be firing on all fronts there.
Congrats again on the data, guys.
Thanks.
Thank you. There are no further questions. Please to turn the call over to Neil Kumar for any closing remarks.
I'd like to thank everyone for their time this morning. Bye.
Goodbye.
This concludes the program. You may now disconnect. Everyone, have a great day.