Good afternoon, everyone, and welcome back to Oppenheimer's Healthcare Conference. I'm joined this afternoon by Alumis's CEO and CFO, Martin Babler, and John Schroer. Due to the recent deal the company's done, we aren't going to be doing the Q&A as part of the presentation this afternoon. So with that, guys, I will turn it over to you.
Thank you so much, Jeff, and thank you for the opportunity to you and Oppenheimer to present here. So I will be making some forward-looking statements today, and please just refer to our website for additional information. Before I start with the presentation across our different programs, I just want to give you a quick overview of who we are as a company.
At this point, we are a company with two key assets that are quite advanced. We do have quite a large opportunity across multiple indications with our TYK2 programs. We also believe, based on the work that we've done on the genomic side, on the proteomic side, and the clinical insights that we have, that we have a high PTS for our programs in psoriasis, in lupus, and ultimately MS, and I'll show you some supporting evidence for that.
Given that we're going after a couple of very significant markets, we do believe that there's a very good opportunity here and a large opportunity, but also an opportunity to be a market maker, and I'll walk you a little bit more through this, especially on the psoriasis side, given that that is a market that is perceived to be quite competitive, but we do believe that there are segments that are undertreated at this point. We'll have quite a few near-term readouts. Next year, we'll read out our psoriasis in the first half, our Phase III. We'll read out lupus next year, and also we'll start a trial for MS this year that we hopefully can read out next year, and I do want to briefly talk about our two key assets. The first one, ESK-001, which will have a psoriasis and lupus inflection point next year.
This is a molecule that is quite unique in that it is able to maximally inhibit the target, and we believe, and I'll show you the data why that is absolutely critical. We also, with A-005, now have a first-in-class molecule that is a TYK2 inhibitor that's fully brain penetrant. I'll show you some data today why we believe that is important, but also we will present data at ACTRIMS in a couple of weeks that show that we're getting a blood-to-brain ratio of one to one. And last but not least, we have a strong team here. And as you know, we have announced last week that we have a definitive merger agreement with Acelyrin, a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology.
We're quite excited about this deal because it will really provide us with both a potential additional molecule in our pipeline and the capital required to get into, through all our readouts, into 2027. I'll talk a little bit more about this opportunity and this deal at the end of this presentation. But let me first give you a little bit more information on TYK2 and why we are excited about TYK2 and why we believe that there is significant opportunity in the TYK2 class for us as a company and for patients. Let me first start with the genetic insights here. As you might have heard, there are quite a few mutations on TYK2, and it turns out there's one mutation called the P1104A mutation that is actually doing exactly what we're trying to do pharmacologically with TYK2.
It is basically the opportunity for just having a reduction in the kinase function of TYK2. So we studied this mutation quite extensively, and what you can see here on the right is that if you have that mutation, about 3%-5% of the Caucasian population have it, and a smaller group of other ethnicities have it, but you will have a protective effect from autoimmune diseases, with psoriasis being at the top of that list, with about a 50% protection from when you have this mutation. Lupus just behind that with a little bit less than 50%, and you can see how this goes down. More importantly, one of the interesting findings over the last couple of years is that the more you inhibit this kinase function, the better your protective effect actually is. You see this at the bottom.
The heterozygous carriers of this mutation that have one allele have about a 40% reduction of the kinase function. The homozygous has about an 80% reduction of this kinase function. You can see that for all these indications, it turns out when you actually are a homozygous carrier, you have a way stronger protective effect. And in the case of, for example, IBD, that goes from almost having no effect or up to 20% an effect of an over 80% protective effect. What that really tells you is that TYK2 is a really interesting target because on the left here, you see that these patients actually don't have a phenotype, so there's really no safety risk associated with this reduction in kinase function, but they have a very strong protective effect.
And that ultimately translates into what we want to do with our molecule, which is really strong inhibition of the TYK2 pathway because we believe that ultimately will lead to a better outcome for patients. And to that end, we spend a lot of time in pharmacology and in Phase I and Phase II to really study what does it mean to fully inhibit this kinase function and what does it mean to have full target inhibition. What you see here on the left is that in our study, in our Phase II study and in the Phase I study, patients at the 40 milligram BID dose had a trough ratio of TYK2 inhibition above the IC90. So in other words, the inhibition level we saw was above IC90 24/7, seven days a week, and for all the days that the patients basically had taken our drug.
You can also see that if you go to a lower dose, that it falls between IC50 and IC90, and that's the range where we believe, based on data available, some of our competitors are. What you see on the right side is that there is a real delta in clinical outcome if you fully inhibit the target versus if you partially inhibit the target. And the delta is actually quite significant in that we see about a 20% difference in PASI 75, 90, and PASI 100. And you can see that you get really nice PASI values for these lower inhibition levels, but the levels that we see when we maximally inhibit this target are really levels that we have not seen with oral drugs today. So therefore, we have a differentiated portfolio because both of our molecules are actually able to have this maximum target inhibition.
They're highly differentiated assets within the TYK2 class because ESK-001 can safely maximally inhibit the target, both measured in the blood, but also in the skin and other tissues. We have a really nice PASI scores, as I just showed you, of 90% for PASI 75 and about 70% for PASI 90 with an oral drug that has not been achieved before. We now have dosed over 800 patients and some of them up to more than two years, and we have seen a very benign and very good safety profile, and we haven't necessarily seen the concerns that we see with some other molecules that have significant skin reactions when given with TYK2.
For A-005, we have shown and will present this data at ACTRIMS that we have a really nice exposure in the CSF and that we get basically a one-to-one ratio between the free plasma and the CSF, and we have ongoing chronic toxicity studies so that we can start a Phase II later this year. And I want to come back for a moment here about TYK2. It's certainly a target that has been of interest to many. Some of the results that we've seen to date have been disappointing, but many of them were not done with a molecule that actually can maximally inhibit the target. But what we already know is that this is a target that works well in plaque psoriasis, works well in psoriatic arthritis, and we even have evidence that it works in lupus.
And we have a lot of genomic and biologic evidence that it works across a broad range of indications, and we're certainly advancing that as well in our situation also by going after MS next. What you see here is our current pipeline that includes the moderate to severe plaque psoriasis, and as I mentioned, we plan on reading this out in the first half of 2026, and then lupus, which we're planning also to read out next year. We will look at additional indications and certainly have plans for studying those once we have the adequate resources. And then for A5, we will start with MS, and that will start later this year and hopefully read out in 2026.
And then, as we always have said, we basically have a strong group of researchers that are building a pipeline behind the TYK2 franchise with other targets and other interesting indications. So this is just a brief overview of where we are in psoriasis. These are the results from our Phase II program, and you can see a couple of things here. One is we had a really well-conducted trial. We had very low placebo responses. In fact, we have zero placebo response across all these endpoints. And you can see that the patients continue to improve even at 12 weeks. The curves still point up, so we should see additional benefit over time. You can also see that this molecule has a really beautiful dose response, which is rare in TYK2 across all the different dose groups.
You can see even that when the daily dose was the same BID or QD, we have exactly the same outcome. You can also see that the safety profile, as expected for TYK2, is really nice. We have really not a lot to report in our Phase II safety data. When you look at our Phase III, sorry, our long-term extension to our Phase II, you can see here that the safety remains very good, and we really don't have a lot of those skin reactions, as you see with other TYK2 inhibitors. Also, most of the serious adverse events really were not related to the drug. Please refer to our filings in terms of those, but it's a very well-tolerated molecule with really no viewable major safety risks at this point in time.
When you look at the efficacy, this is really where we believe this molecule shines. You can see in the long run, when we moved everybody from that in the Phase II study was at different doses and then moved them to the 40 milligram BID, which is our Phase III dose, you can see that we see a really nice increase in PASI 75, 90, and 100, with PASI 75 being in the 90% range if you do it as observed in the 70-plus% range if you do it as observed in the 35% range. And if you look at it as an NRI analysis, you can see there's still very nice values above what we've seen so far with oral drugs. When you look at the secondary endpoints of basically PGA responses, you can also see here that we see very nice values.
Now, we did actually use a six-point scale here, so if you do direct comparisons with other trials, you have to be very thoughtful about that because we used a different basically metric than others have used with five-point scales. But what you see is that even here, we are very competitive with these PGA scores. And again, when you look especially at the PGA zero, we get towards 40% complete remission and therefore clinical cure. This just compares our outcome with what other drugs have been able to do. This is a very busy chart, but ultimately, what we show here is basically every line represents the arm of a clinical trial that was run over the last 10 years with the most relevant psoriasis drugs. All the color-coded arms are active arms. The gray arms at the bottom are basically placebo, and we color-coded them by mechanism.
And you can see the IL-17s are always the fastest. Those respond very fast, but ultimately, many of them lose efficacy over time. You can see the yellow ones, that's IL-23 inhibitors, and then you have Stelara as the red one as an IL-12-23 inhibitor. And you can see when you look at the orals here, whether it's Otezla, so TYK2, or the J&J Phase II data, you can see that we basically have a very competitive molecule that is about in this 80%-90% range so far, whether you do this as an NRI or whether you do this as observed. So we do believe we have a competitive molecule that is one of the only molecules that comes close to where the high-efficacy injectables are today.
We have basically set out to study whether this molecule can get there, and at least our Phase II data to date points to the fact that we have a molecule that could not just be a great oral drug, but actually reaches now the kind of level of efficacy, as you see with injectable molecules. One of the most important things about the psoriasis market is that it is a very fragmented market, and yes, there is a busy corner of that market, if you so want. Here is a claims analysis that we did as a company. This claims analysis really looked at what is the treatment paradigm for psoriasis patients. What you can see here is that there is, of all the patients that are diagnosed with psoriasis, actually only about 8% of that total population is on a high-efficacy oral today.
92% of patients that are diagnosed with psoriasis today actually are treated either with a topical, with light therapy, or with an oral drug, and you can also see that even in this context, methotrexate, which is not a very efficacious oral drug, still actually has the highest patient share of any molecule, so as you think about the psoriasis market, we believe, especially when you have an oral option, there's quite a few segments that are quite attractive, and you can see here, we believe that most of the segments that we should focus on is really the hit early and hit hard segment where patients today are maybe on a topical, and they could eventually move to an oral drug. It is the oral segment where we believe that there's an opportunity to improve over Otezla and methotrexate.
And then there are the patients that have needle phobia that might consider an oral instead of an injectable. But overall, there's a huge opportunity for a market maker approach in psoriasis rather than a market taker approach trying to compete with Skyrizi, Tremfya, and other of these high-efficacy oral injectables. And we will certainly spend a lot of time over the next couple of years looking at our target product profile and thinking very carefully where we are and what approach we should take. But I do want to leave you with the fact that while the market looks competitive, it is really one segment of the market that is highly competitive versus other segments that are a lot less competitive. So to do that, we're now running a Phase III , and we are fortunate that our Phase II open label extension is as sizable as it is.
Because of that, we actually have agreement with the FDA that we only need to run a six-month Phase III study followed by an open label extension that would be sufficient to file. And so we do believe we have an opportunity to catch up with our competition a little bit here because we can run a shorter Phase III study. And this study will read out in the first half of next year as we've guided. I want to spend a quick moment in SLE because we do believe that SLE is actually a key value driver for our program. And the interesting part about SLE, while these are complicated trials to run, we have a lot of in-house expertise, and I'll share with you in a moment a little bit more about this.
We do believe that there's a lot of evidence and really validation for SLE. First and foremost, though, we all know that there's a really significant unmet need in SLE for effective therapies, and if this could be an oral effective therapy, that would be even better. More importantly, also, we do believe that there's significant validation for TYK2 in SLE. The first one is that the loss of function variant that I just showed you earlier really shows a very strong protective effect for patients to get SLE. The second one is when you look at the Safnelo or anifrolumab data that shows that inhibiting the interferon pathway strongly should lead to an improvement for patients with SLE.
That really, we believe, is at least mechanistic evidence that what we're doing here by maximally inhibiting the interferon pathway with a TYK2 inhibitor should also lead to a beneficial outcome for the patient. And then last but not least, there is data out there from another TYK2 inhibitor in SLE that showed that a molecule actually showed a nice benefit for SLE patients as well. So with that in mind, we started our own SLE study, which is designed as a pivotal trial. So if this has a good outcome, we might have the opportunity to only have to run a second trial as a Phase III. And then we basically have the primary endpoint as BICLA 48 weeks, and we plan to enroll almost 400 patients to have a really good data set to understand how well this drug works in SLE.
It also includes an OLE to build a safety database, and we have enrolled the first patients in that open label extension. So one of the aspects of SLE always has been that these trials are hard to run. And so we spend a lot of time to de-risk as much as we can one key factor. And the key factor really is that in a lot of these lupus trials, the placebo rate is too high, and it makes it really hard to distinguish it from the active arm. And so we do believe that these placebo rates are driven by insufficient disease activity, excessive concomitant medications, but they're also driven by inconsistent and/or not good use of the endpoint measures and then the trial design.
And so we spend a lot of time thinking about all of these very carefully and have really made sure that all these elements are in place in our trial to minimize the placebo effect and hopefully show a decent benefit for patients. I just want to briefly touch on A-005. We do believe that's another key value driver that we have data now available and will present at ACTRIMS, but we will also have additional data for that in the next 18 months or before the end of 2026. And we do believe that's another key value driver for the organization as we think about key milestones over the next two years. We've already communicated that we achieve plasma ratios that are basically one-to-one compared to the free drug in the brain and the plasma.
We also have achieved maximum target inhibition, not just in the CNS, but also peripherally, and we'll show that data. We have really not seen any major safety signals that would be of concern in the Phase I. And as I mentioned, we have strong genetic validation here for MS with also really interesting emerging data in Alzheimer's, Parkinson's, and ALS. More importantly, we do believe the fact that this affects microglia and astrocytes, really key drivers of neuroinflammation and neurodegeneration, gives us also the belief that this could be a very interesting mechanism, not just in MS, but across multiple indications. And we are currently doing a chronic tox and believe that that enables us to start a very solid program towards the end of this year. Here's some preclinical data that we believe is actually extremely interesting for this molecule.
You can see here that we ran both a prophylactic and a therapeutic EAE model. And in the prophylactic model, interestingly, you can see that by giving our drug at the highest dose in this model, we can literally flatline the model, and we can actually avoid the induction of any inflammation in these animals. And you can see in the therapeutic model, we also are seeing a very nice benefit that exceeds the benefit of fingolimod, which is currently used as the gold standard in this model. And so the data that we'll present in a couple of weeks is really about CSF exposure. It is the safety profile. It is basically PK and PD. And as I mentioned, we're ready for Phase II , and we believe and have completed the tox study by the end of this year. And the first indication we're going after is MS.
And the reason for that is because we believe that is the best indication where we can, in a relatively short amount of time with a three-month study, really establish what the likely clinical dose for the future will be. So it's the best way to find the best dose used for maximal target inhibition in the brain. So I want to close briefly with a little bit of information about the deal that we did with Acelyrin. And I just want to share with you a little bit more about this deal. So basically, through this combination with Acelyrin, Alumis will have the financial flexibility and runway to advance a late-stage pipeline.
With a pro forma cash position of approximately $337 million as of December 31st, 2024, Alumis expects that this cash position provides us a runway to advance a combined companies pipeline through multiple planned key data readouts across several clinical trials to find and to fund operating expenses and capital expenditure requirements into 2027. Additionally, though, through the Acelyrin merger, our pipeline will expand to include lonigutamab, a subcutaneously delivered anti-IGF-1R molecule for the treatment of thyroid eye disease that has demonstrated robust efficacy in TED patients comparable to the IV-administered standard of care with a favorable safety profile.
We've done some preliminary work on the lonigutamab program, and in lieu of pursuing Acelyrin's previously planned Phase III , we plan to undertake a comprehensive analysis, including reviewing all of the available data to identify the most capital-efficient plan to confirm differentiation for this program, and we look forward to sharing that plan in the future. Let me review a few transaction details. Upon the close of the transaction, Alumis stockholders will own approximately 55% of the combined company, and Acelyrin stockholders will own approximately 45% of the combined company on a fully diluted basis. Following the close, the combined company will be led by the current Alumis executive team and operate under the Alumis name, with its corporate headquarters remaining in South San Francisco.
And the transaction is expected to close in the second quarter of 2025, subject to approval by the stockholders of both companies and satisfaction of any customary closing conditions. Importantly, our Alumis programs remain on track. We remain focused on execution against the key milestones that we have in front of us at Alumis, which will now be fortified with a strong balance sheet and an additional pipeline program that we will evaluate to determine the most capital-efficient paths going forward. And we have a strong portfolio that brings broad opportunities to make a significant impact for patients with immune-mediated diseases, and we look forward to sharing our progress with you in the near future. And with that, thank you very much for your attention, and we really appreciate your interest in our company. And I'm going to hand it back to you, Jeff. All right. Thank you, guys.
As we said, we're not doing questions today just due to the recent transaction announcement, and the company is doing one-on-one meetings, so with that, I will turn you guys loose to go back to your one-on-one meetings. Great to hear from you and get the update post-transaction announcement again, and look forward to being in touch as things move forward. Good luck with the rest of your meetings.
Thank you so much.
Thanks, guys.