Good afternoon, everyone. Happy to have Alumis with us this afternoon, Martin Babler, CEO, and John Schroer, CFO. I guess maybe we're going to have Martin go through a few slides as an overview of the company, and then get into a Q&A. Maybe, Martin, over to you.
Alex, thank you for having us, for you and the entire organization. Let me just briefly share a couple of thoughts on Alumis with all of you. I will be making forward-looking statements, so I'm going to ask you to look that up on our website. Just as an overview overall, we are a company that's about four and a half, almost five years old now, and are close to reading out our phase 3 for our first lead program, which is Envudeucitinib in psoriasis. Behind that, we also have a second program with Envudeucitinib, which is a lupus trial, systemic lupus erythematosus. That is a phase 2b trial. It is designed as a pill trial, so it might enable us to just have one additional trial to get this drug approved. We have created a second TYK2 inhibitor. There's a brain-penetrant TYK2 inhibitor behind Envudeucitinib.
That molecule is going to enter phase 2 in MS in the first half of next year. We made really nice progress with this molecule, have now completed the chronic tox so that we could possibly run also an extension to that three-month trial for Envu. From the merger with Acelyrin, we have Lonigutamab in our portfolio now, which is a clinical stage asset in the phase 2. We are looking to how to move that forward as we speak. Last but not least, we do have an active research effort ongoing at Alumis. We have shared in the past that we are pursuing the IRF-5 pathway, and we're pursuing additional pathways. We have decided as an organization that we will only communicate what these things are once we have phase 1 results.
As I mentioned, the most important thing for us is 2026 is going to be a very active year. There are several transformational events happening, the first one being in early Q1. We will read out our phase 3 psoriasis data. We'll read out both the 16 and 24-week data for both our trials. In the third quarter, we plan on reading out our phase 2b in lupus. There are also quite a few external catalysts with readouts in multiple indications from our competitors in the TYK2 space, and also in psoriasis, some additional launches and efforts ongoing. I would say the most important thing about us right now is that, especially in the TYK2 space, we have conviction that TYK2 can work in many different indications based on early work that we have done.
The question next year, about a year from now, we will really know how broad TYK2 might be used as a mechanism across many immune indications. Just going to Envudeucitinib and psoriasis to start, why are we excited about this? Why do we believe that there is a need for additional medications in this field? We do believe that there's a significant unmet need for high-efficacy oral drugs. Most patients, in fact, over 75% of the patients actually tell us that they prefer an oral over injectable. It turns out that today, despite the fact that the dollar share is actually very high of the injectables, less than 10% of the patients do get an injectable drug. So 90% plus of patients actually are looking for an alternative. They get topicals, they get light therapy, they get orals.
Today, actually, the two drugs with the highest patient share in psoriasis are Otesla and methotrexate, which really tells you that there's a very significant opportunity here for better and more better tolerated and better and more efficacious drugs. One of the interesting aspects about TYK2 is that actually it has a very strong effect on itch. If you ask patients what the most important side effects are that they would like or symptoms are that they would like to control, itch will come up as the number one symptom. Now, in psoriasis, the itch symptom is an interesting one because it's not triggered by or caused by the disease, but it's actually caused by the patient basically rubbing their plaque. The reality is you can't stop a patient from scratching when they're itching, and so it just gets worse.
We do believe that actually, as you will see, it manifests in our data that we have a very strong and profound effect that ultimately also shows that it has a very strong impact on quality of life for patients. As you all know, safety is really critical in psoriasis. You only have to have a very safe drug to participate in this market. So far, we see a very nice safety profile from our drug. I think the most important thing here is that we have now data in over 2,000 patients, some of them more than two years, and we have not really found any safety signal with this molecule. Last but not least, I think it is really important to understand that in this market, simplicity is important. Many physicians are trying to have a high-throughput practice.
The simpler we can make this with an oral drug, the better off we are ultimately in the long term for patients and physicians. This is just one reason laying out here on this slide why we are very keen on seeing our phase 3 results. From the get-go, when we did genomic data analysis, we always felt like it is very important that TYK2 actually is inhibited very, very strongly to get the best possible outcome. What you see on the very left here is genomic data that shows you that if you are a homozygous carrier of a mutation of TYK2 that only affects the kinase function, you actually have about an 80% protective effect from TYK2 to get an autoimmune disease, despite the fact that you have no phenotype.
You see that the heterozygous carriers of this gene mutation actually have still a protective effect, but it's a lot weaker. That tells us that probably affecting the kinase function here is extremely important. When you look at our preclinical data and then phase 1 data, you can see that Envudeucitinib is able, because of its tolerability profile, to not dose-reduce and stay above IC90, even at trough 24/7. You can see then when you look at biomarkers that measure the inhibition of TYK2, when you have full inhibition of this target where you really slam the biomarker in red on the right side there, you get about a 20% jump compared to about an 80% inhibition of the target with the second highest dose.
We do believe inhibition level matters significantly here and hope that this will ultimately translate into a great outcome in phase 3. Certainly in phase 2, that manifested itself in a PASI 75 between 80-90%, in a PASI 90 between 60-70%, and in a PASI 100 between 35-45%, which we believe are very competitive numbers for an oral therapy. I talked about this briefly. What you see here on this slide is basically just how strong the impact on itch was. On the right, you can see there even after just 12 weeks, we had more than 70% of patients who had a very strong itch reduction of at least four, below four, sorry.
What you see on the right is resulting the DLQI, which is actually very strong on this drug, even at 12 weeks, and actually almost reaches maximum effect already at 12 weeks. You do not have to go to 52 weeks to get the maximum effect. We believe that is a key differentiator because that is actually very different from what you see with IL-23. It is actually one domain where when you look at the oral IL-23, it did not beat the TYK2 inhibitor statistically. This just shows you how we are positioned against the competitors in this field. This slide basically is a very complicated slide, but actually the message is very simple. Every line here represents one arm of a clinical trial in psoriasis over the last couple of years. It is a total of 79 studies that are represented on here.
What you see is that basically over time, you'll reach a certain plateau. We do believe the plateau that you see for our molecule is actually very significant for an oral drug. You see that the lower line of the two really fat lines up there is our NRI analysis. The upper line is actually as observed. The truth is probably somewhere in between there. What you see is that you have between 80-90% PASI 75 efficacy in our phase 2 long-term extension, which we believe is higher than we've seen with any other oral drug today. The other opportunity that is really a transformational opportunity for us next year is lupus. Here there really is no approved oral therapy for lupus. We do believe there is a real high unmet need for that.
A lot of patients wish they had a very safe and efficacious oral option. We do believe that interferon is already proven as a key pathway for lupus. We are basically with TYK2 affecting not just IL-23, but the interferon pathway. I'll show you some data in a second there. What we do believe is that something that is very selective that affects interferon and that is not associated with a lot of side effects and is not a broad immunosuppressant would be extremely helpful for these patients. The market opportunity here is actually quite significant. As you all have hopefully seen, anifrolumab, which was launched a couple of years ago, is on a run right now to reach $1 billion in sales. We do believe that there's a very significant opportunity here. Here's just some data on the interferon side.
Think of this as an oral version of anifrolumab where you basically affect the interferon pathway very, very significantly. You can see here on the left the different doses and the amount of interferon impact that we have. You can see at the highest dose, we really just eliminate type one interferon complex or basically score quite significantly. We have shown since also that in the skin of patients with lupus, you see very much increased interferon. In the psoriasis patients, we actually have shown that when you have increased interferon levels in the lesions, we can bring that back with our drug to non-lesional levels. We compared non-lesional levels at the beginning of the therapy to lesional levels at the beginning of therapy to lesional levels at the end of the therapy after 12 weeks.
We're bringing back interferon levels to basically non-lesional levels, which we believe is important, especially in lupus where there is some skin association present. Not only do we have good evidence from the genomics and from our competitor TYK2 and from anifrolumab that lupus is a very attractive indication for TYK2, we also have basically an ability here to drive a trial pretty fast and well. We have designed this trial as a pivotal trial and basically are executing in a way that we believe we have done everything we can to minimize the placebo effect. We are adjudicating every patient in a panel that looks at every patient to make sure they have active disease. We're also making sure that the concomitant meds are very well controlled.
We're watching carefully how the physicians and investigators actually apply the tools that we use to assess lupus to make sure they're doing a great job there. With that, we hope that we will have a positive readout in the third quarter of next year. The last two molecules, just a brief overview here. A-005 is, as we said, our brain-penetrant TYK2 inhibitor. With this molecule, what we've shown is basically that the exposure in the blood is exactly the same. The free exposure in the blood is exactly the same as in the brain. We have 100% brain penetration. We are going into MS first with a lesion reduction study, three-month lesion reduction study. We'll see what other indications we're going after. Last but not least, lonigutamab. Lonigutamab came to us with the merger.
We do believe lonigutamab is a drug. We're working through how to best realize the value of this drug. The one thing I want to leave you with is that one of the most important things about lonigutamab is the way it actually processes IGF-1. It actually internalizes it. There is a lot less free-floating IGF-1 in the blood with lonigutamab than with some of our competitive products. We do believe there is actually an advantage, especially from the safety standpoint. Now it is just a matter of how do you best identify the best risk-benefit ratio for this molecule. With that, again, key year next year with many different readouts that could really be transformational for us as a company.
Great. Thanks, Martin. Yeah, I think there is a lot of threads to pull here in particular.
I think the start of the conversation here I want to have is about what is the path for these next-gen TYK2s, Envu, in particular, becoming a real large class across inflammatory diseases. What should we take away from what happens with TYK2 and looking forward to over the next year or two with new phase three readouts across different indications, et cetera, to sort of see a path here where so far empirically we have not seen one?
Yeah, I think this is a really good question because we do believe, based on our data that I just showed you where we go from all the genomics to the preclinical data to the clinical data to the readout, I think we need to first really check whether TYK2 is a very strong, very effective drug across these multiple indications or whether it really is a secondary class of drug. Based on the genomic data, we actually believe TYK2 is a very viable asset in immunological diseases. We do believe that the data is very clear that the level of inhibition of the target is critical. And so we haven't run that experiment yet. We've run it in our phase 2 extension. But given that this is extension data, people put a little bit less credibility to it, although actually no 2 three is even placebo-controlled after 16 weeks.
We have certainly had to explain that a little bit more to people. I think ultimately our phase 2 data in psoriasis is very strong. If we can repeat that, I think it would become obvious that TYK2 actually was misunderstood because you just had less active drugs. I think the readouts we will have from some other areas where companies have pushed the dose will also help us. From our viewpoint, our own lupus data, we believe some IBD data that will come from the competitors, some Sjogren's data, some lupus data from competitors will really answer the question. Is it the target or is it the molecules and/or is it the dosing? I think ultimately a year from now, we will have a lot more clarity about that because fundamentally the underlying science is extremely strong.
We just have to really now show that that translates into the clinical efficacy that we're all seeing, at least in our phase 2, but hopefully we'll see in other instances as well.
Maybe zooming in a little bit more on psoriasis is the more proximal data sets here. What are the key differences between Envudeucitinib and the Nimbus now Takeda molecule as we should think through phase three updates for the next six months or so?
I think that the most important thing that we always go back to is the PK/PD profile. We have a very linear PK. We have very tight PK. We have really strong translation into PD through that. I think the other TYK2 inhibitors have more variability and have a little bit less linear PK. We do believe, especially with kinase inhibitors, that is critical because at the end of the day, our suspicion to a certain degree is that with TYK2, we have a strong amplification. When you have that amplification, we do believe actually that level of inhibition is really critical. The PK/PD profile ultimately translates into the right clinical outcome. On top of that, I think when you look at the selectivity, we have spent a lot of time as a class talking about JAK selectivity.
Rightfully so because we do not want a JAK black box. I think the selectivity across the entire kinome is probably as critical. When we look at the fact that we did not have to dose reduce, but we get this maximal inhibition, it tells you that it is probably some other kinase selectivity that plays a role with these other compounds because both the Takeda molecule and the carbamazepine have had to dose reduce from their phase one to their psoriasis data just because they had some tolerability issues that we have not seen really with our molecule to the same extent and actually to a very low extent.
The other molecule that's hard to avoid in a conversation here is deucravacitinib. It's not a TYK2, and I think that's important. How do you compare and contrast Envu to deucravacitinib?
The hardest part with an oral peptide always is whether the clinical data will translate into the commercial data. We all know that it's a great molecule. It works really well. The question really is, is that going to translate into the same outcome in the commercial market where patients might not be as compliant with the fasting requirements that are associated with oral peptides? We might actually already have seen a little bit of a hint of that because when you look at the 52-week data in the lead trial, there's already a pretty substantial reduction in efficacy. We just don't know whether that's actually associated with it or whether that's another reason. For us, that is probably the one thing. The other one is we clearly see additional benefits from going beyond IL-23.
Yeah.
I just talked about the edge. There might be additional special areas where it seems like we see maybe a little bit more efficacy with TYK2. I think the other aspect really is that besides the edge and besides special areas, is really is there a difference in patients that actually have an interferon component to their disease? If you look at the latest derm meetings, actually that interferon story around psoriasis has actually gotten a lot more airtime. I think there is going to be some interesting work that we hope we can do once we have our phase three data sets to just look at whether there's a way to distinguish those patients that had an interferon component to their psoriasis or not. Is that a subset? Is that a segment? Et cetera, et cetera. We don't know yet.
There definitely are areas where there is not just an efficacy or a safety difference from the IL-23 component, but where we believe there might be a different segmentation or a different possibility for differentiation from that molecule as well.
You're framing up your phase three top-line data next year. It's somewhat unique to have both the 16 and 24-week endpoints included in the top-line. I guess how would you frame up what good looks like for that readout?
I want to be very thoughtful when we say what good looks like because there's a couple of components that I don't know yet. I do believe if we can repeat our phase 2 and be between 60-70% for a PASI 90 at week 24 to 52, and if we can be in the 80% range for a PASI 75, that is a highly competitive molecule. Is there still a drug if it's slower? Yes, there probably is. There's a point at which we probably would say we're not pushing forward with this, but we can find a specialty pharma that could possibly take care of that. I want to be very clear. We have our internal bars. One of the pieces we don't understand yet is where Xazo is.
We do believe actually how we come out relative to that molecule is going to be as decisive of what good looks like as others. I want to be very thoughtful about it. I do believe if we replicate our phase 2 where we were between that 60%-70%, then we have a highly competitive molecule.
It's not clear, I guess, that we will see the actual clinical data before you have a top-line, though? If they only put out a success top-line, though, maybe?
We might have to wait for AAD next year to understand where things are. That is a possibility. That's not in my control, so I have to just speculate.
Yeah, but we'll see. On the lupus side, one of the elements here in the SLE space is obviously just a tremendous amount of interest and competition across a diverse range of drug classes. How has trial enrollment and enthusiasm been from your seat?
We enrolled our trial faster than anybody else. We enrolled over 400 patients. Especially towards the end, it was very fast. We do believe part of this had to do with the profile of the drug itself. Once investigators have put one or two patients on the drug, they felt really comfortable to put more. The drug, by investigators, both in the psoriasis and lupus side, is viewed as very simple, very safe. At least from what we hear from people, they believe something is working. In lupus, that's always very difficult to say because you have a high placebo rate as well. We do believe that simplicity is actually a key hallmark of the drug. Our enrollment has actually been really good. We hear a lot of positive feedback from investigators about this.
We do believe that if we have a successful phase 2b , actually an enrollment of a phase 3 could be relatively fast. It has helped us that we had such dramatic results in psoriasis and that we were able to go out there and show people, hey, look, this is what this drug does in psoriasis and here is the safety profile. That certainly has helped us. I think when you look at other treatment modalities, other trials, the complexity actually plays a key role in whether people are willing to give patients to your drug or not.
I think a broader strategic question, you check the box on phase three in psoriasis. What does the next step look like as you think about potentially launching this drug either by yourselves or with a partner? How are you framing up that decision-making process next year?
Our plan is to partner this asset because, as I said, we have a high level of conviction. We studied more than 10 diseases, closer to 20 diseases where we looked at what is the impact of this 1104 mutation on people that have this disease versus don't. It is very clear to us that there is a large opportunity here if psoriasis really reads out positive the way we believe it will, that to maximize the value of this asset, we have to have a partner. The one advantage we have because of the Alumis merger is that we can wait with that decision until we have a little bit of a better understanding of what the whole package looks like. Because by the end of the third quarter, you will know about IBD from the competitors. You will know about Sjogren's.
Potentially, you will know about other indications and our own lupus data. We are not saying we are going to do that, but I think one opportunity we have, if we do not like what we see in terms of partnerships, we can wait for that data as well until we make a final decision. Our goal is to partner. At the same time as we prepare for everything else, we have some people in place to help us really do all the critical elements for market preparation, and we can start to do the filing. We are waiting for a few more data points from the withdrawal study to make sure we have the durability and the maintenance information that will go into the label. Other than that, we are ready to file.
We haven't yet given any guidance to when, but we're preparing to file and we're preparing the market, but all in preparation to ultimately hopefully have a partnership for the molecule.
So then with A-005, so ultimately, if that's successful with Envudeucitinib, A-005 is kind of the future of Alumis, is that the right way to think about it along with Lonigutamab potentially?
A-005, I would say the plan is yes. There certainly is a case where A-005 gives you additional flexibility in the TYK2 space. We are aware of that, but A-005 is the next most advanced molecule besides Lani that we have. We are working very carefully to figure out what is the plan with A-005 and Lani ultimately. We are going to put one or two more molecules into the clinic next year from our pipeline. They could also be part of what the future of Alumis looks like.
When do you think you'll be in a position to make a decision on the go-forward with Lonigutamab?
We have some ongoing work. We have a plan. The question really here is, do you do this in TED, in TED only, et cetera? If you think about TED, the landscape in TED is shifting quite fast over the next couple of months. The question is, do you want to wait until you have some of that information? I do not believe that we know yet what that landscape ultimately looks like. The IL-6 probably just went away a little bit. We need to find out where the FCRNs are. We need to find out where some of the competitive molecules are. There is a lot of opportunity here. We believe Lani is a drug. We believe Lani has value. The question is, how do you realize that value in the most efficient way?
Yep. You mentioned the Acelyrin deal, obviously. Where are you now from a cash position perspective and where does your runway get you?
We will be reporting our third quarter later this week, and we will update the cash. On our second quarter, we had more than $480 million of cash and runway into 2027, which captures the two phase three pivotal trials for psoriasis and the top line for phase 2b lupus. With that cash runway into 2027, as we report this week, we're not expecting any changes.
Great. John, Martin, thank you so much.
Thank you.