All right, welcome everyone to the 44th annual J.P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the Senior Biotech Analysts here at JP Morgan. I'm joined by my squad, Priyanka Grover, Joyce Zhou and Rathi Pillai. Kicking off the conference we have BridgeBio. And then presenting on behalf of the company, we have CEO Neil Kumar. Neil.
Well, thanks everyone for taking the time this morning. I'd like to thank Mike, Ben and the entire JP Morgan team for having us here, again this year. This morning I was reminded that BridgeBio turns 10 this year. For a vast majority of those years we've had the absolute privilege of being cajoled, challenged and sometimes supported by the man to the left of me here, Anupam . So thank you for the partnership through the years Anup. Maybe I'll continue in that vein of thinking and thank all of the investors both in the room and on the line for the support over the last decade. Together we have created the second or third most efficient R& D engine for patients suffering with genetic diseases. Three approved products to date, with hopefully three more to come in the next 12 months.
Almost 20 INDs generated and most importantly, nearly 10,000 patient lives affected. With hopefully many tens of thousands of more to come in the coming years and decade. But you didn't come here this morning to hear me talk about the past. You came to hear me talk about where we're going and where we're headed over the coming weeks, months and years. For that we continue to believe that it is day one in this era of genetic medicine. I'll give you updates today, all new information across the three different stages of our business. First, and importantly, our commercial franchise in ATTR cardiomyopathy. Second, updates both on the data front and regulatory front for our late stage franchises in achondroplasia, LGMD2I, ADH1 and Canavan disease.
And then finally, I'll touch on some of that early stage research substrate that's exciting us so much and give you a good example of some of the early stage research we're doing with our EPP, potentially best in class asset that just cleared its phase II-A. But let me start with the most important slide in this document. We are preannouncing today our Q4 revenue number of $146 million. And the reason we get excited about this number is that it suggests we are helping ever higher numbers of patients with ever more numbers of physician partners. $146 million of revenue is a 35% growth over our last quarter and suggests about a 60% CAGR. And just as another reminder, this is actually more revenue generated in the fourth quarter of launch than tafamidis generated as it came out of the gates.
This brings our total in our first four quarters of revenue to $362 million. And even more heartening than this number are the numbers that lie underneath it. Some 6,629 unique U.S. patients that we've been able to serve with Attruby in partnership with over 1,600 physicians. And as you all know, we focus greatly on MBRX share. MBRX share, given the dynamics in this commercial marketplace we believe is suggestive of ultimate TRX. Our goal being 30%-35% peak year share by volume. We're well on our way with greater than 25% MBRX already just one year into our launch. Altogether, with our partner Bayer's efforts in Europe, we believe that the Attruby franchise in 2026 will generate over $1 billion of revenue. Of course, all of this is possible given the unique biochemical and clinical characteristics of the molecule.
As you all know in this room, it is the first and only near complete stabilizer as labeled by the FDA and has provided what we call 3-42-50. At three months, statistically significant separation from placebo. At 30 months, a 42% relative risk reduction against those same characteristics of all-cause mortality and cardiovascular hospitalization, and at 30 months a whopping 50% reduction in hospitalization, suggesting we're able to help patients live longer and healthier lives out of the hospital setting. Over the course of the last 12 months you've seen from us over 50 publications and abstracts delving into various aspects of this overall value proposition as well as trying to better understand where our drug best performs for patient populations like the variant population or patient populations like the AFib population.
Today I want to focus a little bit on one of the aspects that I think has been underappreciated, which is the assets early separation from placebo. Some data that we published at HFSA that I think honestly was missed by most investors and actually a lot of physicians was that we had indeed observed a numeric separation in cumulative morbidity as early as one month with our drug. Now that's a bit of a head scratcher because obviously if you think about the kinetics within the heart, it's probably not the impact of a turning down of the amount of toxic monomer that's depositing in the heart that's actually driving this impact. And so we sort of scratch our heads and ask the question, what might be driving this?
It took us to analyzing some of the very unique hemodynamic and cardiorenal properties of this asset. I won't spoil, nor do I have time to go through the whole story here, but you will see a series of publications over the next 12 months suggesting that Attruby actually has renal protective attributes analogous to the SGLT2 and ARB class and totally unique to this compound. Now, why might that be? Obviously it is because Attruby is delivering the highest known kinetic and overall levels of stabilization in this space. I've said it before and I'll say it again, an Attruby simply sees more of the target TTR, it binds it more effectively with a superior KD2 binding as compared to tafamidis, and ultimately does a better job of gluing the tetramer together over time.
For those of you that have been following the preclinical work in this space, you'll have seen the PNAS or Proceedings of National Academy Sciences paper that came out about a month ago with some really beautiful mass spec work, and I'll read the conclusion from the authors. Just briefly, Our thermodynamic analysis further supports the notion that binding enthalpy, not affinity KD or a change in Gibbs free energy, better predicts the conformational stabilization imparted by these kinetic stabilizers. As many of you know, and as we published in Miller et al, using an ITC approach, we have a vastly superior enthalpic binding mode as compared to tafamidis. Now the good news is we don't even need it because we also have a superior binding approach, and it wouldn't be a talk from me unless I trotted out a new quote from Jeff Kelly.
As many of you know, the inventor of tafamidis and the founder of FoldRx. This is an email that he sent our founders Isabella and Mamoun some time ago and he says given the variability in stoichiometry in the experiments between tafamidis and AG10, which is acoramidis or Attruby and TTR. The data will always tell the same story, that AG10 is better than tafamidis, as would be expected from the determined binding constants. We wholeheartedly agree and will continue to interrogate the advantages of this ever better stabilization for the patients that we serve. Today we're announcing something in tandem to those efforts.
We've long sought the ability to pair upstream turning down of the toxic monomer that deposits in the heart because recall both knockdowns and stabilizers are trying to turn off the faucet of toxic monomeric deposition in the heart with an agent that helps clear the already deposited plaque. Because by and large we are diagnosing patients too late and at a point where there is already pathogenic deposition of amyloid plaque in their hearts. And the right way to do this is to establish a depleter or antibody-associated program that promotes the clearance of that already deposited plaque. We've been greatly privileged to be working with Dr. Richard Scheller, our Chairman of R&D, who as many of you know, ran R&D at Genentech for a very long period of time and was associated with Herceptin amongst many other great antibodies.
He’s been leading this project for the last couple of years alongside our colleague Christine Zhang. What we wanted to do within this space was to build on prior efforts and really optimize an antibody against four key dimensions. First, obviously, we wanted to bind more target. We wanted to find, and in this case, a cryptic previously described but not employed binding site within the fibril to go after. Secondly, we wanted to clear more target by better recruiting macrophages to our antibodies upon binding. Then third and fourth, we wanted to improve antibody half-life by optimizing pH sensitivity within the endosome and then ultimately taking advantage of some of the novel literature on FcRn binding that many of you are familiar with to improve antibody half-life, therefore making it more effective and hopefully more convenient over time.
And we're heartened to say that we've been able to create an antibody to date that actually checks off all those boxes very close to development candidate, and we anticipate moving this program into the clinic in the coming 18 months. Okay, so I'd like to turn now from ATTR cardiomyopathy to our development franchise and I'll start with our profound results that we published just a few months ago in the context of limb-girdle muscular dystrophy type 2I. As a reminder, this is a deleterious condition with no available pharmacologic therapy that affects almost 7,000 patients between the United States and the EU. Two and a half months ago, we published the interim phase III results from our trial that sought to look initially at biochemical impact against the causal biochemical damage associated with this condition.
The bad news around this condition is that there are no available therapies. The good news is it's remarkably well described biochemically owing uniformly to conformational loss of function mutations in an enzyme called FKRP, which leads to a lack of glycosylation of what's called the alpha-dystroglycan complex in the muscle. And we sought to turn up that glycosylation level so that we could go forward and help patients. We powered a trial so that we could look at biochemical glycosylation of the ADG complex in tandem with a measure of muscle damage called CK. And sure enough, after one year, as we looked at the trial, we found a 1.8x increase, even more profound than we observed in phase II in ADG glycosylation and an 82% decrease concomitant in a measure of muscle damage called CK.
So those were very heartening, b ut what we saw next we didn't expect. We saw statistically significant improvements against measures of both ambulation and breathing. This is the first data set that looks like this, as far as I know, in the muscular dystrophy space. And what was even more encouraging was for each of those two measures, both ambulation and breathing, we saw a decline in the placebo arm and an incline or improvement in the therapeutic arm, suggesting that we are improving patients, and in some cases on breathing and on EEG, returning a few patients back to normal within a year. That is a profound advance. When we talk about therapeutic cure in the context of what we do, we don't often think about small molecules, but this is truly therapeutic cure for a few of the patients that we have treated here.
I want to elaborate on that data that we announced at Topline with a bit more detail. These are data that we shared with the agency in mid December, and these are the forest plots against all of the primary and key secondary endpoints that I just mentioned, and I don't have time to go through each single one of these plots, but I think you will see that the consistency of the plots and the statistical robustness are encouraging. Furthermore, what you can see from this drug is treatment and effective treatment across a number of different subcategories suggesting either early stage or late stage disease, so for instance, for compound heterozygotes that tend to be more severe in this disease, we see marked efficacy consistent with what we see in the "milder" condition, which is the L276I homozygous population.
Additionally, we see consistent efficacy from young to old people who have had the disease for a long time versus people who have just been diagnosed and at different baselines of FVC. So beautifully consistent data that we were able to share with the agency. Perhaps the most important data pertains to the modified North Star test. As many of you know, this division of the FDA likes to look at North Star or modified North Star, a very difficult endpoint against which to achieve statistical significance. We designed our trial to do so after almost three years. After looking at the interim data one year in, what we showed was a 2.6 delta, again with a decline in placebo and an improvement in what we saw on active with robust statistical significance.
This was certainly our trial was certainly not powered to show this and we were extremely encouraged to see this data coupled with the data I just shared with you. We took all of that data in to a presentation to the agency in mid December and they, quote, were very pleased that we had demonstrated consistent treatment effects on multiple efficacy endpoints and upon seeing the data asked us to file our NDA toward traditional and full approval versus accelerated approval. Knowing that leaving kids on placebo arm for the entirety of the design trial would likely be unethical. W e anticipate filing this NDA sometime mid this year. I'll turn now to our efforts in ADH1. As many of you know, ADH1 is a condition that affects almost 12,000 Americans alone, making it one of the larger markets and certainly one of the more underdiagnosed conditions that we go after.
Again, the good news here is that this condition is remarkably well described owing uniformly to gain of function mutations in the calcium sensing receptor, and we are going after this condition having designed a negative allosteric modulator of the calcium sensing receptor. Again, just about a couple of months ago we were privileged to announce our phase III results in this category where we demonstrated a 76% responder rate following encaleret treatment. Now, response here is actually normalization of urine and serum calcium, which are the two things that drive all of the conditions in this disease. So low serum calcium levels is what drives tetany, brain fog and ultimately seizures. And high urine calcium levels drive downstream nephrolithiasis, CKD, kidney stones and the like. Recall also that standard of care, which only had a 4% response in our clinical trial, is simply calcium supplementation.
So even when patients can get back to normal levels of serum calcium, they're actually downstream harming themselves by loading up their kidneys with calcium. A 76% full normalization of patients once again applies to this concept that I talked about during my comments on LGMD2i. T his is therapeutic cure for these patients. They are back to normal levels of calcium and could undergo and live a relatively normal life on a go-forward basis. Hearteningly, we also showed in 90+% of patients response to the drug. So there's normalization and then there's response. 90+% of patients were normalized as you look at their PTH and they moved in the right directions when we thought about urine and serum calcium levels. So very few segment of this patient population would not be served with encaleret on a go-forward basis.
How do we find these patients? As I mentioned at the outset, this is a relatively underdiagnosed disease. How do we go about starting to find patients that would find this therapy useful? The team has done a really nice job of providing really three angles to this. The first is to improve genetic testing and to partner with Prevention and other local providers so that we might offer a panel to identify pathogenic variants associated with the calcium-sensing receptor. As many of you know, we've also published some literature on what those variants are and really drilled into the constellation of known pathogenic variants as opposed to the VUS's in this gene. Second, our commercial team created an ICD-10 code so that we might better codify and identify patients with frank ADH1 as opposed to chronic hypopara throughout the course of time.
And then finally actually the guidelines were updated to suggest genetic testing for those with nonsurgical hyperparathyroidism so that they might see whether or not they're ADH1 patients actually hiding within the context of that broader HP community. It's not unlike actually ATTR cardiomyopathy or even hypertrophic cardiomyopathy when I got started. These patients are hiding within the context of HFpEF. We needed to find them here. Again we need to establish the algorithm to find the patients that would best benefit from this drug product. And extremely excitingly, what the results of these efforts have been to date is the identification of 1,700 unique patients based on again the efforts of these alone, plus the medical education that we've been doing. This underlies our projection that are about 3,000-5,000 identified patients associated with ADH1 today.
But more importantly in my mind suggests that we have the right approach to continue to find new patients over time, especially after the therapy launches. This is pretty robust growth given the fact that the therapy is not even approved or in the commercial marketplace today. Okay, turning finally to an update on the encaleret program as it applies to an additional indication, chronic hypoparathyroidism. As you all know, for every medicine that we interrogate, our responsibility is to figure out all of the different ways it could be applicable to human health. In this case, the phenotype of restoration of urine and serum calcium suggested to us that this may be a useful and the first oral product in the context of CHP and indeed in a very small but robust in terms of its signal clinical trial in about 10 patients.
What we showed was 80% normalization of urine and serum calcium in the context of chronic hypoparathyroidism. We took that data coupled with the mechanism, coupled with what we learned from our ADH1 trial to the FDA and we aligned on an extremely exciting trial that we intend to prosecute starting mid-year. We call it the RECLAIM-HP trial. What you can see from this trial design are really two salient characteristics. One, this is a six-month trial. We intend to relatively quickly interrogate this compound to better understand whether or not as an oral agent it could provide the types of efficacy we see with PTH replacement therapy or even better. Secondly, the primary endpoint, the proportion of participants achieving albumin-corrected blood and urine calcium within the target range. Now recall our phase II data.
This suggests a very high probability of technical success associated with this clinical trial, so we are excited not only to launch an ADH1 but also to serve patients with chronic hyperparathyroidism on an ongoing basis. I'd like to turn now to our achondroplasia and hypochondroplasia franchise associated with our small molecule, infigratinib. As a reminder, this affects some 55,000 individuals between the U.S. and EU and represents a significant unmet need. For those of you interested in this program, I would suggest that you listen in to the webinar that was recently published on Friday. Our colleagues Justin To, Daniela Rogoff, and Dr. Legare; we're very privileged to have her on the line. Both talk about the architecture of this condition as well as how meaningful infigratinib could potentially be to the folks we're trying to serve within this population.
On that webinar, Justin mentioned that we have achieved last patient, last visit against our phase III in achondroplasia and anticipate reading out that data to everyone sometime in Q1 of this year. Importantly, we also have first patient enrolled in our pediatric and toddler study. Recall, PROPEL 3 already is interrogating the broadest set of ages within the achondroplastic trial setting from three to 18, but we'd like to go all the way down to as low an age as possible, and therefore PROPEL INT is important, and then really excitingly, we have full enrollment completed for our phase II portion of our hypochondroplasia study. Again, a related condition arising from a different but still activating mutation in FGFR3. As Justin mentioned during the webinar and I think it's important to reinforce, this is the best and most advantaged approach within the context of achondroplasia.
First, it is the only approach mechanistically to target this condition at its source, FGFR3 over activation. Secondly, in the definitive animal model, it provides not only quantitative advantages as compared to the CNP class of medicines, but also qualitatively is able to deliver results against things like foramen magnum surface area and things outside of long bone growth that ultimately are important to the community that we serve. Third, and most importantly, in the New England Journal of Medicine last year we published quantitative outperformance of this agent in the context of achondroplasia, both when looking at change from baseline in AHV as well as absolute AHV, and then coupling that with maybe perhaps the best endpoint given the variance associated with AHV, which is the Z score, where we showed a 0.36+ standard deviation at month 12. The community was incredibly excited about these results.
In addition to the fact that we were able for the first time to provide a statistically significant result against proportionality, a decrease of 0.12, we're the only agent in this space that's received breakthrough designation suggesting that the FDA sees this as a marked leap against standard of care. And finally, and importantly, as we've done our market research, this is a convenient, safe and oral medicine that allows all kiddos that might want to try this agent to be able to try it in a convenient manner. And just so I can elaborate on that a little bit, here you can see a picture of the capsules on your left hand side. Again, 17 mm long, very easy to swallow. And if you have trouble swallowing that, you can break this up into the granules, which are 2 mm long and easily mixable with soft foods.
Okay, so what does this look like in terms of the marketplace? We obviously have to start thinking about our commercial efforts. And for those of you that were here a couple of years ago, you'll remember that as we were getting set to launch in ATTR, we had done quite a bit of market research in using a couple of different tools to better estimate what our share would be and how to size our sales force. And I think actually those projections have been fairly accurate and we marry those now with a third tool that I'll talk about in a moment.
So the first way that we try to understand how this agent might perform is by taking a variety of TPPs and using it in the context of market research, where we're able to go out to 80% of the physicians by volume that are prescribing today's currently available CMPs. The second is that we look at analogs and 3,500 molecules, many of them that are oral versus injections, et cetera. So we were able to look at the appropriate analogs to estimate what peak year market share might look like in this space.
And then finally, in collaboration with MIT, Andrew Lo and his QLS group, we have launched a revenue institute where we will be publishing on in the next few months a brand new algorithm that helps us better predict how our molecules will launch over time and indeed how other molecules hopefully will launch in a future state. So I won't talk about all of the research here. You could expect to hear updates from us in the months to come, especially as we get a glimpse of our phase III data. But here's the TPP that we actually tested in market research most robustly. And you can see again an indication that's the broadest indication in terms of age range being interrogated in our trial in MOA. That's a selective FGFR 1, 2, 3 inhibitors, the dosing and administration, that's a real marked step forward.
A daily oral as opposed to a daily or a weekly injection. We put our delta in HV change from baseline at the tippy top of what CMPs have been able to achieve. 1.5 cm per year. And we put a well tolerated AE profile into the TPP, which is effectively all of the safety that you've seen from this compound to date. Less than 10% hyper phos and importantly, avoidance of injection site reactions, hypotension, because recall, that's really where the CMP category comes from. And the excessive hairiness that has been otherwise observed with some of the CMP products. And what we found based on that TPP was a stubbornly consistent 52% market share. We believe that we will take a vast majority of this market, but we will, at least given the market research, take a majority of the market, given the profile shown on the left.
So again, we anticipate data so we can fill this in for real and go and take somewhere between a majority and vast majority of the market based on data to come. Last, but certainly not least are our efforts in Canavan disease. As many of you know, Canavan is an extraordinarily rare, extremely deleterious neurodevelopmental disease. We've been taking a gene therapy approach to see what we can do to serve children affected with this condition. I don't have time to walk through many slides on this, but what I will show you in this single slide associated with Canavan is the evolution of the data that I presented last year where you can see at our 10 to the 14 high dose robust and profound decreases in the causal biomarker associated with this disease, which is urine NAA and mirrored by CSF.
Very hearteningly you see a dose responsive improvement in the behavior of these children. Improvements such as sitting, head control, reaching and grasping, and in certain cases ambulation where you would certainly not expect to see it. We continue to dose children and assess the safety and efficacy of this product and we anticipate filing its BLA sometime in 2027. Okay, so hopefully three launches upcoming. How are we going to do it? That's a lot for a small biotech and we think we can employ this decentralized model that we have to continue to scale launches. Those three launches, hopefully if we're lucky with the achondroplasia top line and hopefully launches to come with some of these additional indications that I talked about.
And what we've done here is we've preserved the affiliate structure so that we have the teams that are close to the physicians in any given therapeutic area, that are close to the patient and patient advocacy groups and that are close to the data really running the launches. But they're doing so in partnership with the wonderful team that Matt Outten and our commercial colleagues have put together, therefore making it such that we don't have to re spend the money to set up the infrastructure. As many of you know, in rare disease, the preponderance of spend is not against FTE or the field force every time, but rather against the back end of market access, patient services, analytics, etc. So we can use that already established expertise and apply it to launch after launch in tandem with the affiliates.
So that's what we intend to do over these next three launches and hopefully maybe five launches associated with the comments I've made to date. But the question is where else do we want to take this platform in the years to come? That takes me to the final points maybe I'll make on why we believe it is still day one in this era of genetic disease. I won't belabor it because I think many of you in the room know this, but about three years ago I was up here chatting with Anup about this concept of missing heritability. Why is it that so much of what we see in terms of phenotype is not well captured by genetic information?
And it turns out, as many of you know who have been following the literature, that just an increase in whole genome sequences versus exome sequences, coupled with a higher density of data has allowed us to really fill in the gaps around missing heritability and to begin to really tamp that down. But maybe most excitingly, we're able to start to identify these new variants and then connect them with mechanism, and then connect that mechanism with phenotype. What's allowing us to do that? Obviously advances in long read sequencing, allowing us to identify things like structural variants.
Obviously advances in things like having a pan genome, a better reference against which we can understand variants, the prior and aforementioned increase in data density associated with these databases like UK Biobank and the like, and then really importantly, the ability to interrogate the function of these variants in cell and tissue specific experiments so that we can tease out their function and better design therapeutics that target well described conditions at their source. A fingerprint of all of these advances is simply the pipeline that we see at Gondola Bio, a company, as you know, that is a sister company to BridgeBio and a company that you collectively own as investors in BridgeBio. Here you can see 17 different programs in a span of just a year, all pretty early stage, advancing all the way from early stage research to phase II.
But in important areas of high unmet need, investors will be familiar with areas like EPP, ADPKD, Alpha-1 Antitrypsin , CMT1A, neurofibromatosis type 1 and the like. I don't have time to go through all of these programs obviously, but I'd like to touch on one example of again the well described process that we put forward at BridgeBio, which is to take generally small molecules and target these well described conditions at their source. So I want to talk a little bit about our EPP program. Most of you in the room, I think and on the line are familiar with EPP. But for those of you that are not, it is unfortunately a very large unmet need affecting some 20,000-25,000 people between the United States and the EU. So that makes it one of the larger disease states that we work on.
When it does affect people, unfortunately it affects them with deleterious morbidity associated with skin damage and excruciating pain, as well as downstream liver disease. That's the bad news. The good news is that the pathomechanism of this condition has been very well described over the years. What we can see here from the cartoon on the left-hand side of this slide is that this condition uniformly arises from mutations in the heme synthesis pathway, most commonly through mutations in ferrochelatase. And what that does is it promotes the production of a compound called PP9, which then is present in the plasma, the skin and the bile at too high a concentration. And because PP9 is photosensitive, it drives the phototoxicity and pain that I just mentioned. Now there are many different ways to go after this condition.
There are non causal ways to go after it, like using tanning agents. That has been the approach of Clinuvel, Mitsubishi Tanabe. And then there are different ways to target this causal pathway. Certainly Disc Medicine has one where they try to inhibit the intake of glycine. And we looked at that product and we started to ask ourselves, how do we improve upon it? The intake of glycine and its inhibition takes a very long time to provide PP9 reduction. It's not able to provide PP9 reduction to the marked levels that would be required to take people back down to, let's say, quote, a normal range of PP9. And you can't do it safely. As you know, GlyT1 inhibition, which is associated with glycine intake, comes from the schizophrenia field and is associated in EPP trials alone with high levels, almost 50% of dizziness and other AES.
We asked ourselves, how else might we target this well described condition at its source, but do so avoiding some of those handicaps? What we decided on in collaboration with Dr. Ma at University of Pittsburgh was to inhibit the egress of PP9 from the red blood cell by inhibiting potently its solitary transporter, which is ABCG2. We have designed a compound by the name of Port-77, which is an orally bioavailable, highly potent inhibitor of ABCG2 that in cellular models, animal models and the like, has provided best in class efficacy and a beautifully safe profile that allows us to turn down levels of PP9 in the plasma and importantly and uniquely PP9 levels in the bile, staving off both the phototoxicity and pain that patients suffer from, but also the downstream liver disease.
So I'll just go right to the point here, which are the results of our phase II-A trial which we recently just generated about a month ago. And here you can see the design of our gateway trial effectively to interrogate two different doses of Port- 77 and to look at the change in plasma PP9 as compared to baseline and a run- in placebo. We also obviously wanted to interrogate PK safety and tolerability. So what did we find? Firstly and hearteningly we found a profound impact in terms of the diminishment of PP9 in the plasma. This has not been seen before. 75% reduction in PP9 levels.
And even more importantly, because every minute matters for the patients that we serve, we were able to take action in a matter of hours as opposed to weeks from Disc Medicine's drug, and within days we reached steady state at 75% reduction. So the marked efficacy associated with this compound is unique in this space. But perhaps even more encouraging to me was the next slide. I have sat on many clinical trials and I rarely get this level of consistency from a phase II-A. Here you can see all 12 patients and I'll just take your eye to the dark blue lines here. Every single patient dosed with high-dose Port- 77 experienced a reduction in PP9 levels. Maybe the smallest reduction observed was 57% and again the mean was 75%.
So not only do we see profound reductions in PP9 levels, not only do we see relatively quick reductions in PP9 levels, we see very consistent action from this drug across the patient population. And importantly we are doing it safely. You can see a numeric imbalance in actually favor of the treatment as compared to placebo in most of these rows. This is importantly different than the other molecules in this space. Okay, so what I hope I've convinced you of in a few brief slides, and we will certainly be elaborating on this more in talks to come, is that we have a ABCG2 inhibitor that applied in its application to EPP, allows for potential best in class PP9 reduction.
It has a dual mechanism that targets all aspects of the condition, has a clean safety profile, and that we're able to see it and that reduction within hours, not days to weeks. This is just one snapshot of all of the progress that you as investors own across the ecosystem of BridgeBio. We've got BridgeBio and its late-stage franchises. We certainly have early-stage research ongoing as I highlighted with the Depleter program. There are other programs in that same vein at BridgeBio. We have all of what's happening at Gondola Bio, and indeed you are substantial owners of BridgeBio Oncology Therapeutics, where the CEO of that effort, Eli Wallace, will be talking a bit later today about some of the exciting updates against its franchises as well. So lots going on, lots to do for the patients that we serve.
This is just a summary of all of the issues that I've covered today. Commercial momentum, late stage development momentum, early stage research and development momentum, all portending, I hope, in partnership with you all in this room, the ability to serve many more patients in the years to come. It wouldn't be a JPM slide if I didn't end on the comment that we are well financed to undertake all of these activities in the coming years and that all collectively these activities will create a steady drumbeat, hopefully, of advances for both the patients that we serve and investors in and around the stock. With that, I will thank you all for your attention. If we have time, I'll take a question or two.
Neil, your presentation was so robust, I do not have any questions. Thank you.
Thank you, Anup.
I see the strategy. Great job.
[inaudible]
Welcome everyone to the 44th annual J.P. Morgan Healthcare Conference. My name is Tess Romero and I'm one of the senior biotech analysts here at J.P. Morgan. Our next presenting company is Xenon Pharmaceuticals. And presenting on behalf of the company we have President and CEO Ian Mortimer. Ian, over to you.
Thank you, Tess. Good morning everyone. Great to be here. Kick off the year at JP Morgan and a really big update for Xenon. It's been a very important and impressive year over the last 12 months and now we're right on the doorstep of our first phase III clinical data, so we'll go through that today. I'm joined by some of my colleagues here. To my immediate left, Chris Kenney, our Chief Medical Officer. And to his left, Darren Cline, our Chief Commercial Officer. And Tucker Kelly, our CFO is here as well. Tucker and Darren are newer members of the team, have joined over the last 12 months. Both have significant experience in forward integration into a commercial organization, which is our strategic goal, so really nice to have them as part of the Xenon team here at JP Morgan t his year.
I will be making some forward-looking statements. So I do refer you to all of our risk factors that are filed with the SEC. So let's get started. Today we're going to spend time talking about our lead molecule, azetukalner, both in epilepsy and in psychiatry. This is the most advanced potassium channel modulator in late-stage clinical development today. And really the only Kv program that is unblinded clinical data and over 800 patient years of both efficacy and safety data. So I'll go through a number of those points throughout the presentation. We also have a really nice emerging earlier-stage pipeline that I'm going to spend some time on. We've got two phase I molecules right now that eventually will be developed in the pain space.
I'm going to actually show a little bit of data and updates on one of those programs this morning. If we look at our pipeline, there's really three key areas of today's presentation. I'm going to talk most of the presentation on our lead molecule, which is azetukalner. We have six ongoing double-blind phase III clinical trials for azk. That's what we call the shortened version of azetukalner, three in epilepsy and three in neuropsychiatry. Today we'll spend time on the epilepsy program, we'll spend time on the psychiatry program. Then as I mentioned, the third thing is to give an update on some of our earlier-stage molecules that have transitioned now into human clinical development.
If we start with the azetukalner, just more broadly, before I get into the epilepsy program, the feedback we're getting from physicians, both in the psychiatry space as well as in the epilepsy space, is there's high anticipation for a drug with a novel mechanism. There are no potassium channel modulators available either in epilepsy or in psychiatry. The other feedback we get are really the attributes of the drug. This drug is easy to administer, it's a QD drug. Once a day, daily dose and no titration. A lot of neurology drugs and drugs in the CNS, you have to start low and go slow. You're on a therapeutic dose on day one for azetukalner. We also have no meaningful DDIs, so we don't have to make adjustments to other background medications. The drug is backed by a significant amount of clinical data a lready.
As I mentioned, we have over 800 patient years just in patients with focal onset seizures. We have some patients that have been dosed for more than five years now. So I'll go through both the clinical data as well as the safety profile of the drug. Both in efficacy or both in epilepsy as well as in neuropsychiatry. So let's start on the epilepsy side. So if we just take a quick look at the epilepsy market. So epilepsy is actually more common than I think many people recognize. It's the fourth most common neurological condition. You have a one in 26 lifetime risk of developing epilepsy. Epilepsy, if you look at the right, it's a breakdown of the different epilepsy subtypes. There's about three million Americans that have epilepsy. The most common form is focal onset seizures, or about 60% of the market.
In terms of the generalized epilepsy market, the most common form of generalized epilepsy are these patients with primary generalized tonic-clonic seizures. And for azetukalner, as you'll see throughout the presentation, we're developing the drug both in FOS as well as in PGTCS, s o the most common forms of epilepsy. W hat we find when we do all of our primary and secondary market research is about half of the patients are not getting good treatment today. So there are many drugs available to treat epilepsy. We recognize that this is a novel mechanism. And about half of the patients are still requiring better therapy, either because of efficacy or because of side effects. So the total addressable market that we think for a branded ASM in the conditions that we're developing is about a million patients in the U.S.
Our excitement and our confidence in epilepsy really is off of our phase II-B trial that we unblinded in 2021, really underpinning our key leadership position in the epilepsy space. This was our X-TOLE study. This was a study where we randomized 325 subjects. It was a four-arm study, three active doses and placebo. Now we're following those patients in open-label extension. I'll go through both the double-blind data as well as the OLE data in today's presentation. If we first look at the efficacy data that we unblinded, there's two different graphs on this slide. On the left is what we call the MPC. This is looking at the percent reduction in seizures. This is the key primary endpoint for FDA. On the right is a responder analysis.
So this is the percent of patients that have at least a 50% reduction in their seizure burden when we compare the double-blind period to the baseline period, and that's the key primary endpoint for European health regulators. I'm just going to focus on the left for a second, but you can see it on both graphs. There's a clear dose-response. So as we move from 10 mg to 20 mg to 25 mg, you get a deepening of the seizure reduction and the response. You'll also notice that we had p- values of less than 0.05 at all seizure reduction endpoints all doses and obviously even more significant p- values as you move up in dose. If we just look at the 25 mg dose on the left, that was the 52.8% reduction in seizures. And we placebo can adjust that.
The high dose minus placebo, that placebo-adjusted MPC. This is the greatest reduction in seizures ever seen in an FOS study that's been unblinded. I n a patient population that has been the most severe or most refractory that's ever been tested b ased on our review of the literature. W e look at that severity of patients based on three different measures. We look at the number of drugs that these patients have failed, the number of background medications they are coming on to study, as well as their baseline seizure burden. The median patient in our phase II program had failed six drugs. They were on three background medications and they had 13 and a half seizures per 28 days. Quite a severe population.
Another thing that we looked at in the phase II program and we're going to look at in phase III is also the rapidity of onset, so this is a similar analysis to the last slide. The last slide was on a monthly basis. This is looking at the data on a weekly basis, so what you'll see on the left graph, it's again, we're looking at both the reduction in seizures as well as the responder analysis, but just focusing on the left graph for a minute, you'll see quite a deep response at week one, so all doses were statistically significant or less than 0.05 at week one, so not only do we see a deepening of response over time, but you see a rapidity of onset.
For these patients that are having breakthrough seizure, for them to have an immediate seizure reduction within days or within the first week of being on drug is really important for these patients. As I mentioned, we continue to follow these patients in open label extension. What started as a one-year OLE has been extended to a three-, five-, and now a seven-year open- label extension. We have a huge amount of both efficacy and safety data in the long term. At the American Epilepsy Society meeting every December, we mature these data and we show these data to the epilepsy community and get feedback. This is the 48-month data that we presented last month at the AES meeting. A couple of key messages from this slide. One, overall, we're getting over a 90% reduction in seizure burden for the population.
As I mentioned, this was a very severe and refractory population. We actually, if we look at those patients that were on fewer background medications, either one or two background ASMs, you have 100% reduction in seizure burden for these patients. They're not having any seizures at all. It's quite remarkable when we look at the overall. What's otherwise interesting to notice is not only do we get a reduction immediately, as we talked about at week one, but it looks like that response is deepening over time. Looks like there's a deepening of the response a few months into the open label, and then again as we look out about 12 months or so. We've also been looking at seizure freedom.
I wouldn't say there's a consensus definition for seizure freedom, but overall, when we talk to epileptologists and neurologists, patients being seizure free for 12 months is incredibly important. This provides patients independence because in most jurisdictions, if you have no seizures over a 12-month period, you can drive again. We're looking at all of the patients in our open label that have been dosed for 48 months and what you'll see, about two in five patients, or just under 40% have had 12 months of seizure freedom. So if you remember, these patients were having a seizure every other day. And now we're getting these long periods of seizure freedom with the medicine. And what we're hearing back from physicians, their patients are gaining more independence, they're working more, they're having more social interactions.
Not shown on this graph, b ut if you look at our AES data from last month, we also looked at those patients that had a breakthrough seizure. And this was an analysis that we don't believe ever has been done before. So people can have a breakthrough seizure for a number of different reasons. It could be a missed medication, it could be a change, something in their lives. And what we found is that if you have a breakthrough seizure on azetukalner, you can regain seizure freedom for long periods of time and the majority of patients can regain seizure freedom for six or more months. So I think that's really important as we start to think about this drug in the real world.
Patients are not going to necessarily be seizure free forever, but if they have a breakthrough seizure they should remain on therapy and they can do well over longer periods of time. So what I've really shown over the last number of slides is a huge amount of efficacy data overall for azetukalner in epilepsy. When we look at safety and tolerability, this drug is very active in the CNS and it has an adverse event profile that you would expect for a drug that's consistent with other ASMs and consistent with a drug that's active in the central nervous system. So we do see treatment-emergent adverse events, things like dizziness and somnolence, many of these in a dose-dependent manner. But overall the safety profile is something that we're very comfortable with and the feedback we've had from treating physicians as well.
Also nice to know is that we're not seeing new adverse events in open label extension. As we mentioned, we now have patients that have been on the drug for more than five years and we have the safety profile in open label extension is consistent with the safety profile that we see in the double blind period. All of these data have given us a huge amount of confidence to go into a large phase III program. This phase III program was started a few years ago after an end of phase II meeting with FDA in focal onset seizures. We're running two phase III clinical trials in parallel. They're exactly the same. X-TOLE 2 and X-TOLE 3, two active doses of the drug versus placebo. Each study was targeted to randomize 360 subjects. For X-TOLE 2 we have completed randomization.
We've randomized 380 subjects. Randomizations were complete last fall. The last few patients are just going through their final follow-up visits. We'll be analyzing the data and as we guided this morning we'll have our first phase III clinical readout in March of this year. X-TOLE3 is a little bit behind but we did have an important announcement this morning as well. We've completed an ethnobridging study, a phase I study in Japanese subjects, and we had last fall a meeting with the PMDA, the Japanese health regulator, and we're now including Japanese subjects into X-TOLE3, so of the 360 subjects, 60 of them will be Japanese subjects, and what's really important here is we're not going to have to run separate phase III clinical trials in Japan. We can incorporate that into the global phase III program into X-TOLE3.
The non-Japanese subject enrollment will be completed this year. That was another update and milestone we announced this morning. And then we'll incorporate Japanese sites and Japanese subjects into X-TOLE3 as well. As I mentioned, we're continuing to do work outside of FOS and we have an ongoing phase III clinical trial in primary generalized tonic-clonic seizures. What's a little bit different on this approach versus what other companies have done in epilepsy is we're running this study in parallel with our FOS study. Very common. You choose your high dose to randomize versus placebo. This says 25 mg versus placebo. Sample size of about 160. These studies do take a little bit longer than the FOS study. So the study continues to recruit and randomize patients.
So that's the update on epilepsy. Really exciting, exciting time to be on the doorstep of unblinding our first phase III clinical trial with top line data a s I mentioned in March of this year. So if we now expand the azetukalner opportunity outside of epilepsy and give an update in neuropsychiatry, we ran a smaller phase II study. This was really more signal finding, what we would call a proof of concept study in MDD. So a smaller study that unblinded in the fall of 2023, we were looking at two active doses of the drug, 10 mg and 20 mg versus placebo. Key primary endpoint was a clinical scale of depression called the MADRS scale. This drug works in the reward circuitry in the brain.
One of the, based on the preclinical data and some other clinical data that was generated, we've also been looking at a scale of anhedonia and this scale is called the SHAPS scale. I'll walk through the data from the phase II study, which supports us moving into the large phase III program in major depressive disorder that we have ongoing. If we look at the MADRS, this was the primary endpoint. A couple of key points from this slide, one, you see a clear dose response. The 10 mg arm outperformed placebo and the 20 mg arm outperformed the 10 mg arm at every time point. What you'll actually see, again, very consistent with epilepsy, you see that rapid response immediately. This is really important in depression.
Many of the drugs that are used to treat depression right now take weeks if not months to show an effect. So to be able to have early onset of efficacy is important. We were able to show that in this study as well. We had about a three-point separation on MADRS between the top dose of 20 mg versus placebo. So a little bit of a high placebo rate in this study and a p- value based on sample size of 0.135. Interesting. We looked at a different scale of depression, which is called the HAMD-17 scale. And we also had a three-point separation, but a p- value less than 0.05. And the reason that was based on variability. So what we saw when we looked at HAMD-17 is we saw less variability in that endpoint compared to the MADRS scale.
And so now in phase III, we're looking at HAMD- 17 as the primary endpoint. As I mentioned, we looked at a clinical scale of anhedonia called the SHAPS scale, a gain very similar. We saw a clear dose response and separation between the two active doses in placebo. About a 2.5 point difference between active and placebo at the high dose and also a p- value of less than 0.05. When we looked at the safety and tolerability data in depression, this was actually quite surprising to us. It looks like the tolerability profile is a little bit softer in the depression patients versus the epilepsy patients. Obviously this is a cross trial comparison, but overall it was quite a benign adverse event profile in depression. And importantly, when we think about depression , we didn't see any notable weight gain and no notable sexual dysfunction and w e do see that with some of the current standard of care.
When we think about our approach in psychiatry, a novel mechanism, rapidity of onset and having a different adverse event profile is the feedback that we're receiving from the psychiatry community is really important in the advancement of this new medicine. We now are in a large phase III program in major depressive disorder. Two ongoing phase III clinical trials, currently X-NOVA 2 and X-NOVA 3. A significant number of differences that we made between the phase II program and phase III, obviously a huge increase in sample size, one to one randomization using HAMD-17 as the primary endpoint, as well as we're looking at patients that are a little bit more severe coming into study. That cutoff of patients to get into study as a more severe depressed population.
We also announced this morning, execution on these studies have been going really well and we'll have X-NOVA 2 data in the first half of next year. We've expanded in neuropsychiatry beyond major depressive disorder, also into bipolar depression. Really significant unmet medical need in bipolar depression. Fewer mechanisms and fewer drugs available for these patients. So we started a study mid year last year called the X-CEED study where we're looking at patients with both bipolar I and bipolar II. We're looking at scales of clinical depression as measured by MADRS single dose of 20 milligrams versus placebo. So as I mentioned, we also wanted to give an update. Obviously a huge amount of the focus for investors is on azetukalner, both in epilepsy as well in psychiatry. But we've made some great progress on the early stage portfolio and I wanted to provide an update this morning.
I'm going to focus on our Nav1.7 program. We do have a second program that's targeting a potassium channel called Kv7 that's also in a phase I clinical trial. Today, in the interest of time, we're going to focus on our Nav1.7 program. The genetics of Nav1.7 are absolutely remarkable. Xenon led some of this work. About 20, 25 years ago, the history of the company started as a genetics company. These patients in a gene called SCN9A which encodes for a protein called Nav1.7. If you're complete loss of function for Nav1.7 or even a partial loss of function of about 75%-85% loss of function, these patients feel no pain. They feel no pain regardless of noxious stimuli. There's also gain of function in the channel. If you have too much activity in Nav1.7 you feel non precipitated severe pain.
There's a genetic condition called inherited erythromelalgia where these people have extreme pain in their extremities. It was an absolutely remarkable genetic target when it was identified about 25 years ago. For years pharma, almost every of the large pharma companies were trying to drug this target. It's proven to be very challenging to target from a chemistry point of view. I think we've really made a breakthrough over the last couple of years. Some of the challenges with the first, what we would call kind of the first and second generation molecules against Nav1.7, we didn't have the potency and selectivity, so they didn't have isoform subselectivity on the sodium channels. We need to selectively hit Nav1.7 w hile not hitting the other isoforms.
Many of the drugs also had significant protein binding, so they didn't have enough free fraction to interact with the target. And many of them were restricted to the peripheral nervous system, so they didn't act centrally. And if we want to mimic the human genetics, which is what we're trying to do as a novel analgesic, we believe we have to mimic where the target is, which is both in the peripheral nervous system as well in the central nervous system. So what we've been saying is that our lead molecule, XEN1701, which is now in a phase I clinical trial, has a profile that addresses all of these limitations and has a profile that's never been tested in a human clinical trial previously.
Here's just a little bit of the early preclinical data. What you'll see on the left part of the slide on the graph is that we have molecules, and specifically 1701, but other molecules in other chemistries that are order of magnitude is more potent than the previous drugs that were targeting Nav1.7, shown here as both a Pfizer molecule as well as a Genentech molecule, which was actually our drug in collaboration with Genentech. We had a large collaboration with Genentech, Roche for many years. So we have significant increases in potency and significant increases in selectivity as well. What the right graph shows is that we need to get into the brain. So if you can get into the brain and you can have free drug in the brain, that can drive efficacy. So that's important for the profile overall.
What we announced this morning, which I think is incredibly exciting, we're partway through the phase I clinical trial, but we've already reached exposures in the SAD portion of the study that are above concentrations predicted to mimic the human genetics. We don't believe that something like this has ever been seen in a healthy volunteer study. We will wrap up these phase I studies later this year and we're excited to get into a proof of concept study, probably something like bunionectomy before the end of 2026. In addition to the work on azetukalner, really nice progress on the early stage pipeline as well. Just to wrap up in milestones before we hit Q&A, as I said, it's been a really important year of execution for Xenon across a number of our clinical trials.
We have six ongoing phase III clinical trials for azetukalner in both epilepsy and in psychiatry. The first of those is going to read out in March of this year, which is our X-TOLE2 study in focal onset seizures. That'll be followed by a number of clinical readouts in the coming quarters and coming years, both in epilepsy and in psychiatry. And we have a really nice maturing early stage portfolio and pipeline as well and some really nice progress on our Nav1.7 program. So thanks very much. An exciting year for Xenon coming up. And Tess, I'll pass it back to you for Q&A.
Okay, thank you, Ian. So I thought I'd actually start our conversation with a little bit of a bigger picture strategic question for you. Just around how you think about investment and balancing it across azetukalner and epilepsy, but also neuropsychiatry and maximizing the value there, but also expanding some of your pipeline?
Yeah, I think it's a great question. A couple of comments. One, we've been really clear on what our strategic objective is. We want to be a fully integrated biopharma company. We want to discover, develop and commercialize our own molecules. We have deep expertise, I didn't mention this at the beginning. In drugging ion channels in the CNS. We've been doing this for many, many years. I think that expertise is world class. So obviously a huge amount of focus is on azetukalner. That's where the vast majority of our effort is, the vast majority of our spend is.
And not only are we going to have our phase III X-TOLE 2 readout in March of this year, that'll be followed by a new drug application in the second half of this year and put us in a position to get our very first drug approved. But as you mentioned, we really want to build a world-class company, which means we have to think about the portfolio. That's both the expansion of azetukalner into psychiatry, but also the early stage portfolio. And as I mentioned, two molecules transition in the phase I clinical trial last year and you'll see more molecules transition from our labs into human clinical development over the coming years.
So we know now that top-line results from the phase III X-TOLE2 trial are expected in March. And you know, quite frankly I feel like we've been talking about this trial and expectations for a long time, but I'll just ask it to be complete here. What would you consider a win in terms of efficacy and safety here and how could the longer treatment duration, 12 weeks versus eight weeks in X-TOLE impact the results?
Sure, I'm happy to start and make a few comments, but I think Chris should provide his perspective, and then I want Darren to weigh in as well as we think about just the overall profile and the importance of that from a commercial perspective. So you've asked a couple of questions in there. One of the principles that we had at Xenon, given the great success we had in our phase II-B X-TOLE study, is that X-TOLE 2 and X-TOLE 3 should be very similar studies, and so if you look at the inclusion and exclusion criteria, the phase III program is exactly the same as the phase II program. You did mention one difference, and one difference is that the double blind period is 12 weeks i n phase III, it was eight weeks i n phase II.
W hen we look at the open label data, it actually looks like those patients continue to have a deeper response over time. So I think moving from eight weeks to 12 weeks, we're very comfortable with the 12-week double blind period overall. I n terms of just kind of managing expectations going into data, o bviously that's a question we get a lot. I think you did really nice work, Tess, in your preview for Xenon coming into the conference and coming into our X-TOLE 2 data, s o I would encourage people to look at the analysis that you've provided. You know, I think at the highest level, obviously this study needs to be positive, it needs to be statistically significant, which will put us in a position to file a new drug application later this year.
Obviously, every study is a little bit different. We have already commented that the patient population in phase III looks very similar to phase II and the open-label extension rollover rate in phase III is very similar to phase II. So that gives us a lot of confidence going into it, and I think I also always want to remind people that the X-TOLE study will be on-label. Right. That study's already been complete with the best placebo adjusted efficacy ever seen in a focal onset seizure study, and so this is really a study that'll add to that and be part of the new drug application. Chris?
I think you covered it.
Darren, do you want to provide just your perspective on the overall profile?
Yeah, I think, you know, when you think of the X-TOLE data, it really has set the precedent. And when you think about the prescribing epileptologist, general neurologist, the novel mechanism of AZK is really going to be transformative in there. It's just not another sodium channel blocker. And so commercially we already know, based on our market research, our discussions most recently at AES, there's a tremendous amount of excitement for, as Ian outlined, the attributes of azetukalner and particularly with the general neurologist, they view this as a really easy therapy to incorporate into their practice. And so I think with the backdrop of the clinical data, the safety and tolerability, we're pretty excited to get this to physicians and their patients.
Okay. And I did get this question this morning. I thought it was kind of a good one. Have there been any protocol amendments to X-TOLE 2 or X-TOLE3 ?
Chris?
Yeah, there have been some amendments, but nothing that has. I mean, to Ian's point, basically the spirit of X-TOLE2 was to maintain consistent with X-TOLE. And so if you look at the major sort of inclusion and exclusion criteria, you look at the baseline characteristics, you look at the geographical spread, specifically percentage of patients from the U.S., we're seeing a great deal of consistency. So there isn't anything within any of the differences between those protocols that we think are substantive and would drive a difference in efficacy.
With all that in mind, what keeps you up at night on this study?
I can start and then Chris can add, you know, look, every clinical trial, you know, we're enrolling a large number of patients dispersed throughout a number of clinical sites. But I think, you know, what gives us great confidence is we have the most experience of running epilepsy studies over the last decade. And so I think both internally in our team, we have epileptologists and psychiatrists that work at Xenon that have a huge amount of experience. We've run the largest, you know, the largest study ever run in FOS that's been unblinded. So I think we have tremendous confidence. So I wouldn't say that there's anything that we're really concerned about as we think about the epilepsy work.
Obviously, with psychiatry, we're always these studies in terms of execution is critically important as we spend a lot of time working with the sites and making sure that we're getting the right patients into a psychiatry study. So that's something that we spend a lot of time thinking about as well, and then as we think about the early stage portfolio, it's really the excitement of where we could take this. I think if we have a novel analgesic and non-opioid mechanism with the profile of our Nav1.7 program, I mean, the opportunity to have an oral non-opioid chronic pain drug is incredible, and so there's a lot of excitement and thinking internally about how do we develop that in the most efficient way? Chris?
Yeah, I mean, I think we're in as good a shape as we possibly could be for all the reasons that Ian and I have mentioned so far, so I'm sleeping well.
Okay. And you know, as maybe this is a zoom ahead question here. So beg your pardon, but how should we think about the marketing message here? And is there any kind of key differences that you expect there could be between epileptologists and general neurologists?
Yeah, you know, traditionally with anti-seizure medications, typically the epileptologist or the early adoption, which is not surprising. Right. Everybody, every patient they see in their practice every day are patients with seizures and typically refractory seizures. Right. So they're getting referred to the epileptologist because of the severity of their disease. And then the general neurology community, they are typically a more late adopter. And remember, when we are approved and launched, it'll be an eight-year gap between the last time a branded ASM was approved. And so there's been this kind of period of really nothing new for the general neurologist. And so from the last branded medication that was approved, you know, the general neurologists are really finding that medication difficult because of the ability to have to titrate both up with the medication and down on other ASMs and other issues.
Again, back to my earlier comment. I think with azetukalner , it's very clear that the ease of use, and then you're talking about kind of what will make a difference here. And I think because of the daily dosing, the novel mechanism, no drug-drug interactions, titrated dose right out of the gate. Tremendously excited to bring this to the general neurologist. So they're able to incorporate this into the patients that they're currently managing, keep getting them to get seizure control, potentially seizure freedom and not have to refer and be able to manage that. And again, all our market research suggests that this is the perfect medication for them to do that. And so I think the messaging for us is going to be around the attributes that we're able to to really see in X-TOLE and what we anticipate, an X-TOLE 2.
Any other learnings of like what the keys to success are for a branded epilepsy launch and what Xenon may be doing differently or similarly to others?
Yeah, there's several. I think as I think about commercial success, there are a few different areas. One is it's all centers on the data. Right. So we feel confident there and then it's about how. How do you think about patient identification, the treating physicians and really think about those epileptologists, the general neurologists and also the advanced practice APPs that are in the community that are more and more getting involved in patient management. So we look at where do we think about taking the AZK message depending on where the patients are. So that's the key and then those key messages and what have you. But then there's other key stakeholders involved. Obviously the payer, that landscape is, you know, can underestimate how important that is.
And again, I think the ability for us, which we'll start executing on post data late this year, is that engagement with payers. Right. Again, that kind of gap between the last launch to be able to bring them up to speed on the current practice of treating epilepsy patients, seizure patients, and really understanding and letting them understand still what is a tremendous unmet medical need. And so making sure that upon launch that we could have as quick an update as possible. The other component is, you know, that patient experience I think is critical to a successful launch. How do you set up your distribution, your patient support, all those services that really make what I say, you want that patient to have that outstanding experience early on. All those things hinge around.
The last thing that I think is absolutely critical is the team that you build. And I think that when I think of a commercial team that we're starting to build, really a lot of deep, deep epilepsy experience both across all facets. Sales, marketing on the payer side. And then I believe one thing about epilepsy and it's a lot of people, if you think about sales representatives, people in the field, MSLs, they commit their careers to epilepsy. And so I think we'll be able to attract the top talent that will want to come with this new medication with the impressive efficacy, the opportunity to bring something new and novel to their customers. And so I think those are the things that I think about that make this a successful launch.
Maybe I could just add, on the talent side, azetukalner based on the profile so far has the opportunity to be a generational asset. Right. The profile is different than we have seen in so long in the epilepsy space. And the team to execute is critically important. You know, Darren joining as chief commercial officer involved in the launch of Epidiolex, the most successful epilepsy launch ever. Darren has already added to his team in terms of head of market access, head of sales and marketing who has probably some of the deepest epilepsy experience over the last two decades. And Chris, on the medical side, we've had MSLs in the field for the last 18 months. So we have already invested in building relationships in the epilepsy community for Xenon as a trusted partner, a nd is azetukalner a trusted brand.
I think our data disclosure and our relationships and information and scientific sharing with the community has been incredibly well received. We had over 50 employees at the American Epilepsy Society meeting and there's a real buzz around Xenon in the epilepsy community.
Well said.
Tess, will you indulge me with one thing? So just real quick. You know, Ian talked a lot about how well patients are doing in our open label extension study in epilepsy. It's really quite impressive. If you take a look at how they're doing compared to the double blind period, over 90% of them had a 50% reduction in seizures. A lot of the data we show starts at the baseline of the open label. So if one were to compare the phase III open label studies, and one comparison you were looking at the beginning of the double blind and the other you were looking at the beginning of the open label, it would be a comparison that would be tough to make. So I just want to point that out. Thanks.
Thinking through the expansion potential of azetukalner here, you know, how does the next three to five years look for Xenon if you are successful in both epilepsy and neuropsych versus just epilepsy?
Sure. Darren, do you want to talk about kind of the launch first in epilepsy and then as we'd expand? A nd actually maybe even before that, Chris, one of the things that we haven't talked about today that I think is important is maybe talking about the comorbidities in epilepsy as well, and that we're looking at endpoints of depression and anxiety in our epilepsy studies. That's probably a nice segue to psychiatry.
Sure. We haven't shared the baseline characteristics of X-TOLE 2 just yet, but we're expecting them to be quite similar to X-TOLE. Depression, anxiety, migraine, headaches are all very common comorbidities. We're expecting to be able to gather that data in the ongoing phase III program.
Yeah, I think, you know, obviously epilepsy is the focal seizure launch is the initial focus. But if we were being so fortunate to have great data in MDD, that's a tremendous opportunity and we would pivot to, you know, building out that psychiatry business. And again, Ian pointed it out today, tremendous unmet need. A lot of patients that suffer with MDD that could be helped by the novel mechanism, the rapid onset and really, really favorable safety profile. So, yeah, tremendous. That would be. That'd be a nice outcome.
Just last question for me here is just on formulation. Are you exploring any other formulations of azetukalner?
Are you specifically thinking about intravenous? Yeah. Yeah. So often in epilepsy, we think about kind of two parts of life cycle management. One is on the pediatric side and one is on the IV side. So, yes, all of that work is ongoing. We have agreed upon pediatric development plans with FDA as well with EMA. So over time, we will get into younger and younger patients. Obviously, adolescents can take a pill, but as you get into younger patients, you need a specific pediatric formulation. So a lot of that work has already taken place, and we'll get into younger patients over time. The other thing, often that the epilepsy community is asking for is whether you have an IV formulation. So as patients come into the hospital that they may start on an IV formulation and then they leave the hospital with an oral formulation.
So that works ongoing as well.
Great. Thank you.
Thank you.
Thanks, Tess.
Thanks.