16-week endpoint for atopic derm. Here, we aim to show that with roughly half the number of doses during the induction period and then three months or less frequent dosing in maintenance, we can again transform this market. Beyond atopic derm, we're also planning phase 2B in asthma that will start later this year and a phase 2 in EOE, which would start next year. This will give us kind of phase 2 dose optimization studies going into each of the therapeutic areas where Dupixent currently plays. Beyond that, APG-279 is our co-formulated IL-13 and OX40 ligand combination approach. Here, we are launching this trial later this year head-to-head against Dupixent with data coming next year. Beyond that, in the respiratory space, we feel TSLP is a more exciting and data-backed combination approach. We are combining that with IL-13 there, and we'll share more plans around that later this year.
A little bit more on 777, given that's where the majority of the focus is, and given that it's our next big readout. Psoriasis, a market that you know well, just to set the stage, teaches us how these markets develop over time on the Y-axis as efficacy and on the X-axis dosing frequency. Over time, it's gone from an every two to four-week paradigm to an every three-month paradigm. The market leader, Skyrizi, has come almost last to this market, but very quickly within a few years has become the market leader. Importantly, as each new entrant comes, especially if they extend dosing, they do not just take share, they make share. We see that all of these drugs can happily coexist together, with the biggest grossing drugs today being the ones with the most convenient quarterly dosing, which patients describe as a functional cure.
Atopic derm, by contrast, is the definition of white space, very similar to where psoriasis was 10, 15, 20 years ago. We have talked about Dupixent and Ebglyss in the every two- to four-week paradigm. Nothing else approaches that frontline level of efficacy. We aim to, similar to what we know wins in psoriasis, improve dosing and with time also look to improve efficacy. Our first shot comes this summer with a phase 2 part A coming in the middle of this year. That is aiming to get to every three months or better dosing. We are testing higher exposures of IL-13 inhibition to see if that can lead to better efficacy. That is pure upside. Base case is improved dosing wins the day.
I'll walk through market research with payers, physicians, and patients that speak to why the market is set up for that to be the win. In the part B, which is ongoing, with data coming next year, we're testing additional higher efficacy to make sure that we fully explore that exposure response curve. Finally, second half of next year, that head-to-head trial of our combination versus Dupixent will also read out. Three shots at improving dosing and efficacy in the largest and least penetrated measure of type 2 inflammation compared to Dupixent. We get deep and sustained TARC inhibition out to six months, which is the available data cutoff. On a proximal measure of the pathway, PSAT-6, we actually get very deep and sustained inhibition out to a full year with higher doses.
This sets us up to consider not just three months, but with time, six months, and potentially even annual dosing options. The phase 2 that's currently ongoing is an integrated design. This mid-year, we will have the part A readout. This is a two-to-one randomized trial where we're testing dosing at every week zero, week two, week four, and at week 12. This compares to 0, 2, 4, 6, 8, 10, 12, 14, 16 for current standard of care. Then randomizing to two maintenance arms every three and six months. The week 16 endpoint will be what we read out this mid-year. We are greater than 90% powered for a number of different endpoints, including the primary endpoint, which is change from baseline in EASI, as well as EASI-75 and IGA-01.
The part B, given the integrated design, started enrolling as soon as the part A finished enrolling within a few business days. There, we're testing also a higher dose. An independent safety review committee looked at the unblinded data from the part A and okayed us to go to an even higher exposure level. We're also testing the lower dose. This will give us a full proper phase 2B dose optimization to then inform what we take forward to phase 3. You can see in blue here on the right our projected exposure levels from the phase 2 with our dosing versus in gray what Ebglyss has. Six injections compared to 11. You can see that we get to approximately over the course of these first 16 weeks, 30-40% higher exposures.
There's a number of pieces of evidence that have informed why we are testing higher exposures. One, Ebglyss has never been tested higher, not due to safety or anything else, just due to commercial considerations. They did not want to be disadvantaged on dosing to the market leader, Dupixent. We do not know what could happen at those higher exposures for efficacy, but the phase 2B showed a nice dose response with no dose AE relationship. Additionally, in the Ebglyss phase 3 approval documents, both FDA and EMA noted that there was an exposure response seen. A lower body weight group of not just five, ten patients, but 190 patients that had 30% greater exposures showed consistently greater efficacy across different endpoints. Hence why we are trialing this in the part A. Again, this is upside, base case, and I will walk through the market research shortly, similar efficacy.
I won't kind of walk through each of these, but we've consistently shown what that base case similar efficacy would look like across, of course, safety, but also the primary efficacy endpoint change from baseline and EASI and key secondary endpoints of EASI-75, IGA-01, and EASI-90 tracks. Similarly, we'll look to share a robust data set, so data on each of these endpoints with our readout. Following our monotherapy, our belief is that the best companies look to continue to innovate and continue to provide better solutions in the spaces that they're going after and to beat themselves. The company mantra has refused to stop at good enough. APG-279 represents that view for us. Nice. Here, APG-279 is a co-formulated IL-13 and OX40 ligand.
We shared data earlier this year showing that we can co-formulate at greater than 180 mg per mL and that our preclinical inhibition profile gets that deep type 2 inhibition associated with Ebglyss and Dupixent, but also that type 1 and type 3 inhibition, which allows JAKs to get to deeper efficacy without the potential safety profile based off of our preclinical data set, whereas Dupixent lacks that type 1 and type 3 inhibition. This trial schematic is seen here. Fairly simple head-to-head trial versus Dupixent. Safety, PD, and efficacy. We are excited to get this trial going. Just to put kind of the size of this market into context, everyone knows the psoriasis market. You can see in different shades of gray here all the different biologics that have launched well in psoriasis. Eight different blockbusters.
It went from 5% penetration around year five up to 24% in year 2020 and continues to grow with Skyrizi setting new records every quarter. Skyrizi, in particular, despite coming next to last, has gotten to the majority of that share. Atopic derm, by contrast, has almost three times as many patients. To date, there's really only been one player in town, Dupixent. It has launched better than all of psoriasis combined and looks to be on track with conservative growth rates to be at least a $50 billion market. When we profile our drug to patients and physicians and payers, we get overwhelmingly positive feedback. When we ask them about a drug which has similar efficacy and safety to Dupixent, but an every three-month dosing profile and maintenance, 80% + come back saying that they would prefer it for their biological naive.
inadequately controlled patients currently on a biologic, 83% would prefer it, 12% would be neutral, and one-third and two-thirds, respectively, would prefer and be neutral even on controlled patients. Why that's important is when we ask patients, including those who are currently on Dupixent, if they would prefer a profile that gives them an injection once a season versus every two weeks, they come back overwhelmingly at 96% saying that they would prefer our drug. Payers are looking for more competition in this space. Across the board, across multiple surveys, have come back and said that parity coverage with Dupixent and other frontline agents would be expected with this profile as well. Just to wrap up, over the next two years, we have a very robust catalyst map. Of course, we have been very proud to overdeliver on our results to date.
We put out positive data for our IL-4 receptor alpha program just yesterday, showing that we exceeded the bar there in mild to moderate asthmatic patients. We're looking forward to our middle of this year readout for the phase 2. We're also launching that full portfolio of our product initiatives with our lead program in 777 as well. Phase 2B in asthma started this year. Part B and the combo study are coming next year, along with EOE getting initiated. 279, our potential first-in-class combo. Very excited to be leading the way and doing a head-to-head study here, hoping to approach JAK-like efficacy without the safety issues, which our preclinical data has supported. In the respiratory space, some initial proof points in IL-13 TSLP.
However, for agents that are dosed every two to four weeks, we hope to maintain that best-in-category every three-month dosing for a set of very orthogonally validated mechanisms here. Remaining this year in our first-in-human study for our TSLP antibody, we look to report that out by the end of the year. Importantly, especially in this environment, we're very fortunate to have a very robust and strong balance sheet, $680 million +, which gives us runway into Q1 of 2028. Thank you for your time. [inaudible] .
I think we're ready to get started. Hi, everyone. I'm Susan Chor with Tim Anderson, also U.S. Pharma and Biotech team. It's my pleasure to introduce Amylyx, C o-CEOs and Co-founders, Justin Klee and Josh Cohen. Please give us a brief introduction of the company, what you guys are doing, and your assets.
Sure. I see we have the pipeline slide up as well. We're advancing three drugs across four indications. Our lead asset is a compound called Evexetide. It's a GLP-1 receptor antagonist. Different than the agonists that are making quite a lot of headlines, it does the opposite in a sense. It reduces insulin and raises the blood sugar nadir, which is particularly important in diseases of hypoglycemia. It has FDA breakthrough therapy designation in both post-bariatric hypoglycemia and congenital hyperinsulinism. Our focus right now is on post-bariatric hypoglycemia, where there have been five prior trials, all of which showed significant effects on glucose and insulin. We're now conducting the phase 3 trial. We've started recruitment. We expect to have recruitment complete by the end of the year with data in the first half of 2026.
That's our lead program, and we can talk a lot more about that as we go through, including kind of the unmet need that these patients face, which is quite significant. Very briefly on the rest of the pipeline, we have AMX-35, which targets endoplasmic reticulum stress and mitochondrial dysfunction. We just reported data in Wolfram syndrome, phase 2 data that showed benefit across all the measures that we were measuring in Wolfram syndrome, which is an ultra-rare kind of endocrine and neurodegenerative disease. We also have data coming in the third quarter in progressive supranuclear palsy, which we've been excited about based on tau lowering that we've seen with AMX-35. In our view, AMX-35 is the only drug that both crosses the blood-brain barrier and gets intracellular and reduces tau. PSP is a tauopathy. That's where that kind of makes a lot of sense.
Then finally, we've started recruiting with AMX-114, our antisense oligonucleotide targeting calpain 2 in ALS. We expect to have some early cohort data by the end of the year. With that drug, we've seen effects in the preclinic, including on biomarkers like neurofilament. We will be interested to see if those translate into the clinical data as we get later into the year. Back over to you.
Great introduction, Josh. I actually want to take a step back. Just yesterday, you guys presented the long-term data from the Helios trial in Wolfram syndrome. Can you get the room up to speed on what Wolfram syndrome is and what has the data told you?
Yeah, very happy to. Thank you. Wolfram syndrome is a monogenic disease caused by mutations in WFS1. Those mutations, WFS1 encodes for the Wolframin protein. Wolframin is a transmembrane protein.
When it's dysfunctional, it directly causes stress and mitochondrial dysfunction. That genetic cause causes degeneration and dysfunction first in the beta cells of the pancreas and then in different neuron types. As you might imagine from how I'm describing it, the disease presents as early onset diabetes, kids 6, 7, 8. What sort of cues physicians on that maybe this isn't just early onset diabetes is that kids get progressive vision loss and progressive hearing loss and early mortality. It's really a tough disease. We estimate there are about 3,000 people with Wolfram syndrome in the United States. It's very much a global disease as well. We've been working in Wolfram syndrome now for almost eight years.
As you might imagine, with the mechanism of sodium phenylbutyrate and torsadile targeting stress and mitochondrial dysfunction, it's very much a match of the mechanism of the drug to the mechanism of disease. We've been evaluating AMX-35 in a 12-person open-label clinical study in people, in adults with Wolfram syndrome. When we went into the trial, our hope in a progressive disease, especially in adults who have had the disease for some time, was to slow progression. We've actually seen stabilization or even improvement over time. What we just presented yesterday was the full cohort out to week 48, so about a year of dosing now. What we've seen is actually the sustained improvement over time, particularly in C-peptide. C-peptide is a direct measure of insulin production. It's how much the body is producing, secreting insulin, which means the beta cells are functioning better.
To our knowledge, this is the first time in any diabetic condition that C-peptide is increased because, again, it means that the beta cells are functioning better. We are very excited about the data, what it might mean for people with Wolfram syndrome. We are working on the design of a phase 3 study, and we will update on that this year.
One of the really exciting things about this most recent data update is it is supposed to inform your discussions with the FDA. What can you tell us about what they are looking for, trial design, anything you can share?
Yeah, I would say probably at the highest level, stay tuned. We are still having those discussions. Certainly, when we have the final design of a phase 3, we will share that. I would say, though, we are quite excited about the data as just well.
We showed improvement numerically on the C-peptide. All the other measures move in lockstep with that. You see on the hemoglobin A1C, on the time and target range by CGM, all those are moving in lockstep together with the C-peptide, which is what you hope to see. It kind of gives you added confidence in what you're seeing. Additionally, we saw stabilization or some improvement on visual acuity. These are patients who generally go blind over time. To see the vision pretty flat or even possibly improving was quite exciting. Patients were also asked, and the clinician was asked, is the patient stable, improving, worsening? Every patient was described as at least stable or improving by both the clinician and by the patient.
It was a strong initial result, but it's also the first—we're the first company to be developing an interventional therapy in Wolfram syndrome. I think that's—and it's a multi-system disease. There's a lot of things you could measure. I think those are kind of what drive the discussions with the FDA of what is the best measure, hopefully, to bring this ultimately to patients.
Maybe just in the interest of time, let's turn to Evexetide, which is the company's lead asset. Again, can you just set the stage for the audience? What have you seen in the phase 2 data? How do you expect the data to show up in phase 3?
Yeah, I certainly wish I knew the answer to that now, but I'd say our hope is really if we can even replicate what we saw in phase 2, I think that would be a really meaningful advance for people with post-bariatric hypoglycemia. The phase 2 trials showed very significant reductions in level 2 and level 3 hypoglycemic events. Level 2 is defined by blood glucose. Level 3 means that the person is so incapacitated that they need independent help. That can be severe confusion. It can be loss of consciousness. It can be seizures. These are really dangerous episodes. In both phase 2 trials, Evexetide showed very significant reductions in both of these types of events. Furthermore, it showed dose dependency as well. In the phase 3 trial, we're testing the highest daily dose tested, 90 mg once daily.
These are what supported FDA breakthrough therapy designation. The fact that PBH is a really significant unmet need. We estimate about 160,000 people in the United States currently have PBH. Unfortunately, it does not go away. The population will only grow. There are no treatments currently approved for PBH. As Josh was saying, we go into this trial with a lot of excitement at the potential of what this could mean for people with PBH. We will look forward to having those results in the first half of next year.
Maybe just to highlight as well, probably one of the key results from the past trials, five past trials, so maybe to distill one of the key results.
In the phase 2B, the 90 mg dose, which is the dose we're taking forward in phase 3, showed a 53% reduction in level 2 hypoglycemic events with a p-value of 0.004 and a 66% reduction in level 3 events with a p-value of 0.0003. In the phase 3 trial, we're measuring level 2 and level 3 hypoglycemic events. Our primary outcome is the composite of level 2 and level 3 hypoglycemic events. We'll share the data on the composite as well at Endo upcoming in July. As Justin said, strong evidence coming from the past trials and the hope to again see that benefit on the level 2 and level 3, which is the agreed-upon primary outcome with FDA. This program is breakthrough therapy status. There has been a lot of FDA interaction. That is the agreed-upon endpoint we believe to support a potential approval.
Just to make it really clear, in your discussions with the FDA and physicians, what's considered a clinically meaningful number of PBH event reductions?
Yeah, it's a really important point and question. I'd start with currently, as I said, there's no approved treatments for PBH. Unfortunately, the bar is low, especially given what a severe condition this is. In terms of FDA, as Josh was saying, I think the composite endpoint that we're looking at as a primary outcome is particularly meaningful. The level 2 and level 3 hypoglycemic events have been defined now for several decades by the American Diabetes Association and other endocrinology fields, as well as in FDA guidance. When we talk with physicians, what we really hear from them is that they want to keep their patients safe.
If you think any one of these level 3 events can be life-altering, we've heard many stories about someone driving a car, their blood glucose crashes, they pass out, they crash their car, they end up in the hospital. As we've started to do market research, the number of times people end up in the hospital because of post-bariatric hypoglycemia is just astonishing. You understand from the physician's perspective, really being able to reduce any number of these events is really meaningful. For people with PBH, what we hear consistently is, gosh, I just wish I had something. I mean, I think it's so frustrating for them that they finally get the diagnosis and then only to find out that, try to stick to this very draconian diet, avoid all carbs, eat small meals very, very frequently. Besides that, there are no approved therapies for PBH.
I think it just highlights what an unmet need there is. Again, our hope that we can change that.
One thing to touch on very, very quick too. In the past studies, patients were also interviewed in kind of a structured interview that was conducted with the patients. They were asked, now that you have completed this trial, been on this therapy, how would you rate it on a scale of 1 to 10? Every patient but one that was interviewed rated it a 10. The one other patient rated it a 9. Their reasoning was, yes, the reduction in hypoglycemic events, but they also described just being able to feel a difference in terms of energy, fatigue, things like that.
Because if you imagine constantly having hypoglycemia, sometimes severe enough to cause loss of consciousness or otherwise, but even when you have hypoglycemia that's just severe enough to make you lethargic, low energy, et cetera, to suddenly be out of that fog is a dramatic thing for patients. We are certainly, as it relates to the events, as Justin said, even one level 3 event, which could be losing consciousness or otherwise, is a big deal. Preventing even one of those. What we hope is kind of a more holistic ability for patients to kind of return to their normal life and their normal activities.
Okay, maybe just to wrap up on Evexetide, we know that you guys will have top-line pivotal data in the first half of 2026. Just coming back to something you'd mentioned, you'll be presenting some data at Endo very soon.
Can you just highlight what the main takeaways investors should have from this data?
Sure. Two abstracts that we'll be presenting. One on pharmacokinetics, basically showing that Evexetide's pharmacokinetics last through 24 hours. We stay above the level where we believe there's therapeutic benefit through 24 hours. We have one abstract kind of on PKPD modeling. An additional one is running kind of the phase 3 model on the phase 2 data so that you can kind of see how that performs. I'll say neither of these do we expect to be particularly surprising, but nice kind of confirmatory and further evidence as we continue going along. I’d say we also noticed at the conference, there is an abstract on the prevalence of PBH.
It's a question we get frequently about, since it's a new market, exactly how many patients have this, how severe are they, et cetera. It was quite an interesting abstract, arrived at pretty similar numbers to our 160,000, but arrived from a very different angle and different methods. It is an interesting abstract to look at as well.
With that, I think we're coming to the end of our presentation time. We have another company presenting. I just wanted to add that, as you mentioned earlier, you will have data in PSP in 3Q 2025. Look for Josh and Justin to maybe follow up on that. With that, let's stop there.
Excellent. Thank you.
Thank you so much.