Good evening, everyone, and welcome to the Global Jefferies Healthcare Conference. My name is Camden with the Jefferies Healthcare team, and it is my pleasure to introduce Martin Babler, CEO of Alumis.
Thank you very much, and welcome to our presentation this afternoon. I want to thank Jefferies for actually offering us to present our company here and participate in some one-on-one meetings. I'm going to give you a brief overview of who we are as a company. I'll be making forward-looking statements this afternoon, and I ask you to look up our forward-looking statement on the website. As you all know, we recently completed a merger with Acelyrin a couple of weeks ago, and we really did that to, as a combined company, be a very strong immunology company going forward. There's really two key elements here. One is the combination of our pipeline.
The other one is our combination of our financial resources that we believe builds a very strong company, well-capitalized to look into the future and build a position in an immunology company, like we set out to do earlier, and now in the combined company with a stronger foundation. Some of the key hallmarks of that merger are that we now have several key readouts over the next 12-18 months, the first one of that being our psoriasis readout, which will happen early in 2026. We guide it now to basically early in the first quarter of 2026. We recently announced that we have completed enrollment in this trial. There is a six-month readout for that trial, so you can do the math that we should be somewhere in the early part of the first quarter to get that done.
The next readout that is also planned is our lupus readout. We have an ongoing phase II in lupus that we plan on reading out next year. We hope to complete enrollment for that trial sometime this summer, and it's a 48-week endpoint. We plan on announcing later this summer what we're doing with our lanigutamab program and what we're doing with our A5 program, both of which are planned to have start also some development activities in phase II. For lanigutamab, depending still what the plan is, phase II or phase III later this year. Those could also read out in 2026. Overall, a really rich portfolio. We are very judicious on how we're spending the capital we have. We want to make sure that we are indeed getting into 2027.
No matter what we do, we will have a cash runway into 2027. As a company, that's a really important aspect for us because we do want to make sure we have sufficient capital beyond the readout of both psoriasis and lupus before we make any key strategic decisions. As you can see right now, the cash that we have will guide once we have finalized the merger and submit the queues. Basically, at the end of the first quarter, it was about $600 million in cash in the company, and we have about 100 million shares outstanding now. When you look at the pipeline, where are we with our respective programs in psoriasis? We are in phase III. That has completed enrollment of more than 1,700 patients. We were able to do this really at a fast pace, faster than we anticipated.
We're about four or five months ahead of our own schedule. Very pleased with that outcome and really excited how many people wanted to try our drug and get enrolled into this trial. That really leads to what I said earlier, that readout early 2026. We also have an ongoing lupus trial. That trial is important to understand. That's a phase 2B trial, but it is designed as a pivotal trial. If that trial is successful, we will have discussions with the FDA whether we could actually just do one phase III confirmatory trial. We had agreement with the FDA at the time of the start of this trial what it is that we would need to do to make sure that we have a successful outcome if we have a positive trial, that we could use this as a pivotal trial.
That trial is on track, as I mentioned, to complete enrollment later this summer. We look at the 48-week endpoint with BICLA being the primary endpoint for that trial. We are working on identifying the best path forward for lanigutamab. I'll come back to that in a moment. This is a molecule that came in with the merger with Acelyrin, and we do believe that there are some differentiating aspects about that molecule that could make it really interesting for value creation. As a third molecule in the clinic at this point, we do have our A5 program. That program is a brain-penetrant TYK2 inhibitor, very different from most other molecules in the class. It has a one-to-one ratio between the blood and the brain and is able to really fully inhibit.
That program is ready for an MS phase II, which we plan to initiate later this year. We have an active research platform where we plan on having an additional molecule going into the clinic potentially by the end of the year. If you look at TYK2, why are we excited about TYK2? TYK2 has been a class that had a really was a very hot target a couple of years ago, and then some things happened with our competitive molecules that were not quite as people expected. There is a little bit of a cloud over the class, but I really want to make the case to you why TYK2 is such an interesting target. The first part is that it is probably one of the most genetically rich targets that there is in immunology.
It's very interesting because TYK2 actually has several mutations in humans that can tell us a lot about where TYK2 should work and how TYK2 should work. The data on this slide really tells you a little bit more about this story. The first one is there's a mutation, which is this P1104A mutation, which is a mutation in about 5% of Caucasians and a little bit less in other ethnicities that really is making these people have a lot less of the kinase function of TYK2, which is exactly what we're doing pharmacologically. If you have that mutation, there are two things that are interesting about you as a human being. The first one is that you actually do not know that you have this mutation because there is no phenotype for this mutation.
You don't have increased risk in terms of safety, in terms of infections, et cetera, et cetera. The other one is that you're actually protecting from getting autoimmune diseases. You can see a list here on the top right where you have about a 40%-50% protection to get psoriasis. You have about 40%-50% protection to get lupus, et cetera, et cetera, as you go down this list. Even more interestingly, actually, the data from that genetic mutation also supports our claim that one of the most important things about TYK2 as a target is that you have to hit the target hard. What you see at the bottom here is actually what happens when you have a heterozygous mutation versus a homozygous mutation.
What you see is that that protective effect that we talked about in the heterozygous mutation is actually not as pronounced as in the homozygous mutation. If you are a homozygous and you have two alleles, you can see that that protection level is actually about 80%, which is very, very significant. That means your kinase function of TYK2 is actually reduced to a stronger degree, and that really protects you better. For us, this is part of what created the hypothesis that you really have to hit this target hard. Ultimately, our clinical data panned out on that, and you'll see in a moment. What did we do? We developed two molecules that have hit this target extremely hard.
With ESK-001, we have maximum target inhibition, and I'll show you data that we currently are the only molecule that is in global studies or launched that basically is above IC90 247. With A5, we were able to accomplish the same thing and also do that in the brain and not just in the periphery. We get maximal target inhibition with ESK-001. We have a high oral response, and we have long-term safety now with over 2,000 patients on this drug. About 150 of those patients actually have been on the drug for more than two years. We know that we have a great safety profile at this point in time. There could be some very spurious things, but we do believe that we have a pretty good understanding of the safety profile of this molecule at this point.
With A5, we have the full penetration into the brain, also maximum target inhibition, not just in the brain, but also in the periphery, and we are ready for phase II. This is the data that confirmed for us why maximum target inhibition matters. What you see here is on the left side is basically different doses of our molecule, and you can see that there is a couple of doses that basically hit trough levels that are between IC50 and IC90. The top dose actually is above IC90, not just as an average, but also you can see that even the confidence intervals rarely cross that IC90 threshold. What you see on the right is the consequence of that. When you look at the dose in red, that is the dose that always stays above IC90.
When you look on the blue, that's the doses that are between IC50 and IC90. You can see that doses between IC50 and IC90 are actually very consistent with some of the other TYK2 inhibitor data in this disease, versus the red one is really stand out because you get about a 20% improvement. What this really tells us is that unless you hit TYK2 extremely hard and you get maximum target inhibition, you have probably some kind of amplification or other effect that really reduces the efficacy of this target. And our molecule is the only one so far that is in a global phase III or launched that actually is able to do so.
That is really, in our minds, the key differentiator and should lead to a very different outcome in the long run, both in terms of efficacy and ultimately also in terms of safety because we have actually shown that we have a safe molecule. This is the data from psoriasis that confirms that. This is 52-week data. I think the most important takeaway here is that we are starting a new paradigm. Both oral IL-23s and TYK2s can reach what we call the 80-60-40 paradigm: 80% PASI 75, 60% + PASI 90, 40% + PASI 100. That is really a new achievement that we have not seen with all drugs in psoriasis before that we believe is highly competitive with other molecules and also competitive with even injectable molecules to a certain degree.
When you look at how we ran this trial, I want to point out to you that we actually didn't just run this experiment once. We actually ran it several times because after the 12-week phase II, we moved all these different doses to the highest dose, which is this 40 milligram b.i.d. dose. What you see here is that the data outcome, no matter where you started, is actually very consistent. Once you get on a 40 milligram b.i.d. dose, you're always at 80% or above in terms of your outcome. Even the placebo patients ended up in the exact same space. The data is very internally consistent. We've ran this experiment now multiple times, and we get exactly the same outcome.
That is why we believe as we transition from phase II to phase III, we should actually see a repeat of that outcome as well, given that we have not really made any major changes to that. In terms of safety, this molecule has really not seen any significant safety signals. In fact, we have not seen any safety findings to date through week 52. We see some tolerability issues around infection. This is cumulative data now over 52 weeks. If you compare that with the general population, you are actually not seeing any change or major increase. The other piece that we have is the headaches and Covid-19, but these are really things that you see in the regular population at about the same rate. A very clean safety profile overall, and as I mentioned, no safety findings to date.
One important thing now is how are we different with IL-23? I just want to give you one example here and want to talk about a second example just verbally. That is that TYK2 is basically an IL-23 plus. What you get from the plus, which is basically the interferon inhibition, is that while you're basically competing with IL-23 in terms of efficacy, you actually get some additional benefits, one of them being that we actually have better effects on itch. What you see here on the right is basically the average itch score for patients on a TYK2. When you compare that with what you see with IL-23, these levels are actually higher. We achieve higher levels, and we achieve them faster.
For psoriasis patients, itch is actually one of the key symptoms or key things that they want to take care of. While in psoriasis, itch does not come like in AD from just the disease itself, but from the physical touch of your plaques, it is an issue for patients. We hear that from patients in our patient research, market research. For those patients, especially that have scalp involvements, and that's about 80% of them, this is actually a huge benefit by having a better effect on itch. The other piece that I want to just mention is that in diseases like psoriatic arthritis, actually TYK2 seem to, as a mechanism, seem to perform better than IL-23 as a mechanism. Given that about a third of patients in psoriasis do have psoriatic arthritis as well, that's another place where we believe we could potentially see additional benefits.
There is a differentiation profile that starts to emerge. What I would say basically is we have the chance to have a really great inhibition of IL-23, but we get additional benefits from the interferon inhibition as well. This just shows you how this stacks up against everything else in psoriasis. This graph basically depicts the key psoriasis trials over about the last 10-15 years. It includes about 79 studies. Every colored line basically represents an arm of a psoriasis study that was performed of relevant drugs over the last 10-15 years. Down here in the corner on the left, you see the placebos. They normally stop at week 16 or 24. All the colored ones are basically following those patients on active drug. We group them by color in terms of mechanism.
You can see that the IL-17s are always the fastest. If IL-17, if speed of onset would basically be the key driver for your treatment decision, you would only use IL-17. That is actually not the case in the market because the IL-23 mechanism actually performs better in the long run. You see that with the yellow and the red lines. Where you see our data, you see those two lines up there. One is the as observed. The other one is basically the line that shows you the NRI analysis. You can see the truth is probably somewhere in between there. What you see is that there are actually very few lines that are up there. We are actually up there where some of the biologics, the key biologics are. Are we as efficacious as the most effective biologics? No, we are not.
We understand that. There is a huge opportunity here for patients to basically have a drug that benefits most of them and does so very, very well. That is really what we are aiming for. Our goal is to ultimately go into this market and get patients that need an oral drug that is highly efficacious and is very safe. The market in psoriasis is very significant. There is huge opportunity. What we hear a lot is it is a very competitive market because you have quite a few of these injectable biologics. Interestingly, however, when you actually look at the patient distribution and the entire psoriasis market, the injectable biologics only make up about less than 10% of all the patient treatments. You have more than 90% of patients that are not treated by an injectable biologic. We believe that is actually really important to understand.
There is a very significant market opportunity here for effective oral therapies to go not just after the injectable patients that do not want to take an injection and want an oral drug, but there is also a significant opportunity amongst oral therapies and possibly at the top end of the topicals as well because we now know from some data that has been produced with other molecules that treating early and treating hard leads to a better outcome for the psoriasis long-term perspective on these patients. Getting some of this segment here and then getting at the top end of the topicals, getting some of the oral segment and maybe get some of the injectable patients that do not want to be really on an injectable, that is where we believe the market opportunity lies.
You need only a relatively small percentage of that overall market to actually have a very significant product. The only other thing that I want to point out to you, if you look at the systemics, the split between the injectables and the orals is about 50/50. Interestingly, on the oral side, methotrexate still has the majority of share. We do believe there is a need to re-educate folks and really get patients not on methotrexate because it does not work and it has some side effects and consequences. Why not put a drug where the patient can basically have an oral drug that ultimately will be effective and works in most of them and is safe. As I mentioned, we are now completing our phase III design.
The phase III design is that we have two parallel phase III. They are both completely enrolled with more than 800 patients each or 840 patients each. We will roll some of those patients over, most of those patients over into a longer-term extension. Our phase III program is actually completed when everybody has reached the six-month mark. We need 200 patients in the group over there in the open label extension to basically do the withdrawal process. That is all the data we need to submit to the FDA. We have agreement with the agency that we do not need to run a 12-month trial. We can actually do this with the six months because we have all these patients from the phase II that we put into the long-term extension where we get a lot of the long-term data that we need for the submission.
The next indication I want to briefly talk about is lupus. In our minds, this is actually one of the biggest indications in terms of value creation for us as an organization. There is certainly a huge unmet need. There is a lot less competition here. At the same time, we have really optimized this program for a good outcome. We have actually quite significant validation from lupus. We understand lupus has been an indication that has been really hard to manage. There are two pieces to lupus that matter. One is the great scientific rationale and validation. The other one is how do I avoid the big level of placebo effect in a phase II or phase III study? We really made sure we pay attention to both of those. In terms of validation, you can see here there is a very strong genetic rationale.
I showed you that rationale earlier in the 1104 mutation. A lot of these patients basically should benefit from a TYK2 inhibitor. The other reason is that we know that Anifrolumab, which is basically an interferon inhibitor, does really well for lupus patients. We basically have that component of TYK2 inhibition besides IL-23 that is interferon. When you look at our data that we published on the phase II and the phase III trial, we showed in that trial that we actually reduce interferon levels to normal levels in the skin and in the blood. We do believe we have that effect on the interferon that we need to have to be successful here. Last but not least, we also have data from one of our competitors basically that shows that TYK2 inhibition actually works in lupus.
We are able to go in there with more target inhibition. We hope that ultimately leads to a benefit not just from a safety profile, but also from an efficacy profile. The ongoing study, as I mentioned, is a study that is run as a phase II, but is basically run as a pivotal trial. It is basically designed really to show a significant delta between active and placebo. We did a lot to reduce the risk of a high placebo. When you look at past lupus trials that had placebo issues, the main things why their placebo rate was so high was because patients that were enrolled were not fully active patients because they had a lot of excessive concomitant medications and because people did not necessarily use the composite outcomes measures appropriately.
What we have done is we have made sure that basically we have an adjudication process for patients that come into the trial. We have also made sure that patients do not stay on steroids when they come into the trial and other concomitant meds. We have basically created a program that watches the data as it comes in. You could call it AI or whatever, but basically it watches the data that comes in for consistency so that if we see anything that is not appropriate, we can go back to the site, investigate, and re-educate if we need to. Again, this program is ongoing. This program will read out in 2026. Hopefully, we can then complete this development program with one additional phase III trial.
Certainly a key milestone next year and one that we want to make sure that we have a chance to read out before we make some key strategic decisions even around psoriasis, given that this is the second indication that we would come to market with. I also want to just point out to all of you that we do have external validation for ESK-001. We did a deal with Kyowa Kirin in Japan. This was a really nice deal for us where they basically worked with us to develop the drug in Japan, ultimately launched there because they're an expert. They're one of the larger immunology companies in Japan, one of the leaders in Japan for immunology and for psoriasis specifically. As you can see here, the deal that we actually did with them was specifically on dermatology and on psoriasis.
With the $40 million that we get that basically is unencumbered, that really, if you look at and multiply that up to a global basis, really values this asset close to a billion dollars already. This is the external validation and ultimately a reflection on where we believe the value of that asset is. The next one is lanigutamab. What I want to point out here because we're still doing a lot of assessment work, this molecule has a really differentiated mechanism. The one important thing to understand is that the other IGF-1R or anti-IGF-1R inhibitors or anti-IGF-1Rs, basically they are competitively binding to the receptor. This molecule actually binds and then everything gets internalized, which means that the blood levels of IGF do not go up as much with this molecule as with others.
The question really, now that we know that this is the key feature, the question now really is how this translates into the benefits for patients, for physicians, et cetera. One of the things that we believe is important is that we see a very different profile when it comes to ultra-toxicity and hyperglycemia. The question then really becomes, how do you take advantage of that and how are patients willing to make a trade-off? This is a PK/PD game. It's really important to understand that we need to understand the PK/PD well for this molecule and then decide how to move forward. As a team, one of the reasons why we were successful in TYK2 was because of PK/PD. Before that, many of us were at Principia where we looked at the same PK/PD issue with TYK2 inhibitors.
We have a lot of experience on how to go about this and how to do this right. We're working through that right now with internal work, but also with market research to really understand what patients and physicians are willing to trade- off to get that additional benefit. If you talk to a patient with TED, they will tell you that, "I'm already losing my eyesight partially. Losing my hearing actually is really damaging to me." I think there's an acute understanding of hearing loss being a key issue for patients, even if it's only in the 10+% range for some of the competitors. If you're one of those 10% of patients, that's a real, real issue.
We believe there is an opportunity here, not just to have a better safety profile, but also possibly have a treatment option that can come in earlier before patients basically go to the ocular surgeon. We will elucidate on what our plan is here later this year. We committed to this summer. Our goal really is that as we go into the investor conferences in the fall, we have all of that laid out for you and can answer any questions you might have. The third molecule, as I mentioned, is A5. This is our brain-penetrant TYK2 inhibitor. It is a very unique and differentiated molecule. It is unique and differentiated because it has this maximum penetration into the brain, but also gets maximal target inhibition in the brain. If you think about this molecule, think about it as a BTK+.
Because we were involved in the development of tolerabrutinib, we have a pretty good understanding of brain-penetrant molecules that go after microglia. We know that the microglial effect of TYK2 is very similar to the BTK effect. However, what BTK lacked is a strong anti-inflammatory effect. You can see here in the EAE model, this molecule has an extremely strong anti-inflammatory effect. If you look on the left side here, that's the prophylactic model. You can see that if you're prophylactic, you give a mouse basically our TYK2 inhibitor that you cannot even induce inflammation in that animal, which is very rare. Very few drugs do that. You can see the comparator here that was the gold standard in this model so far is fingolimod, which is an S1P1 inhibitor.
You can see even in the therapeutic model, we actually beat the S1P1 in terms of anti-inflammatory effect. When I say BTK+, I mean the effect of BTK on microglia and therefore possibly on disability and also a very strong anti-inflammatory effect that should help ultimately with the relapse rate. Our goal here is to move into MS because that's the easiest way to get a readout for what the right dose is as fast as you can because you can run a three-month imaging trial. As I mentioned to you before, this is really one-to-one. You can see here on the left the plasma level and then the brain level. You can see that basically almost identical. This molecule is now ready for phase II. We are finishing up the tox. We have the material.
We're planning to start that phase II hopefully later this year. In terms of outcomes and milestones for the company, we will basically have the psoriasis finalization of the trial ongoing. We're planning to share with you all what our plan is for lanigutamab. We ultimately will initiate the MS trial. We actually have a third candidate or a fourth candidate, basically a third internal candidate that we basically plan on having ready for IND later this year. One of the things I haven't mentioned earlier is that we are working on a once-a-day formulation. We do have the formulation at this point. We're just finalizing and optimizing it. We'll announce later this year what that exactly looks like for ESK-001 so that we will have a once-a-day drug in psoriasis. Next year, we have the key readouts.
The ones that we're already clear about will be the readout for psoriasis early in the year, for lupus in 2026. Hopefully, we're going to add the readout for MS and for lanigutamab in the same time frame. As I mentioned, the most important thing here is with our merger, we have cash into 2027. No matter what we do, the one thing that is absolutely clear, that will not reduce our cash runway. Whatever we do with these other programs, we have money set aside to do that. If anything, we are trying to extend the runway rather than shorten it over the next 18 months to two years. With that, I have about a minute. If there's one question or so, I'd be happy to take it. Yes.
Could you say more about the program you're using for match checking the consistency of the data across your studies?
Yeah. In lupus, actually, if you think about it, there's a lot of data coming in. Because these are composite endpoints, we basically created a program that looks for outliers. That basically, you run it over the data on a regular basis. What you see is that if there's inconsistency in the data, for example, we have SRI-4, we have BILAG, et cetera, et cetera. If this data is inconsistent, then that gets flagged. Then we can go back to the site and we can see, is this a site operation issue? Is this a data issue? Or is it an entry issue? We can literally quality check the data as it comes in.
We believe that's extremely important in lupus because these are composite endpoints that have a lot of components to them. There often is little misstatements that we believe we can capture. We get a cleaner database at the time of when we basically have the total data available. Is that something you developed in-house? We did develop that in-house, yes. Part of what we do is we do, although we do not call ourselves an AI or machine learning company, we have a lot of those capabilities because we do a lot of precision immunology. One of the things that is not in this slide deck is actually that we did discover a biomarker for TYK2. That's part of our ongoing program.
This is a proprietary biomarker at this point and really will help us identify and correlates really nicely with outcomes that we see in patients in psoriasis. We're waiting to basically then analyze all of that in lupus as well, whether that helps us predict which patients will respond better in lupus or not will be seen. Okay. Thank you very much.