Appreciate you guys coming out, and I'm pleased to be joined by Aclaris Therapeutics, who are gonna be running through some slides. Over to you.
Hi, good morning. I'm Hugh Davis. I'm the President and COO for Aclaris Therapeutics, and thanks to Bank of America for having us at their healthcare conference. The normal disclaimer and cautionary notes regarding forward-looking statements. Aclaris Therapeutics is an innovator in immunological assets for important unaddressable disease. Addressing validated targets is key to success while we are really understanding how to take innovative approaches to our portfolio. Two examples would be bispecifics and ITK oral inhibitors that'll be best in class. We have a research lab in St. Louis that is state-of-the-art scientific platform in kinase biology and world-class scientific acumen across the company. In 2026, we have a quite a catalyst calendar that I'll speak to later.
As I mentioned, addressable I&I diseases of dermatologic, immunologic in terms of respiratory and IBD disease is important, with, you know, an impact in millions of patients just in the U.S. alone. In Aclaris, we are going after these respiratory and dermatologic conditions with first in class types of molecules. It's unusual for a smid-cap to have such a strength in large and small molecule development in therapeutics, and yet we have both ITK franchise that has JAK-like efficacy that we're looking to expand on with a broad ITK selectivity, as well as in biologics, where we have potential first-line therapies. Really what we're looking to achieve is very, was a higher efficacy ceiling in these patients with derm and respiratory disease.
We also have the opportunity for extended dosing intervals with our biologics portfolio, leveraging our biology and our drug design. Our pipeline, we have a phase II bosakitug anti-TSLP mAb that's currently going to read out by the end of this year. It's a 100 subject placebo-controlled study in AD with moderate to severe. Following is ATI-2138, which is our ITK JAK3 inhibitor. This completed a phase II-A study in atopic derm as a POC, and now we're pursuing lichen planus as our phase II-B indication that will initiate by the end of this year. ATI-052 is the bispecific that targets both TSLP and IL-4R. We've completed the healthy volunteer portion of that, I will go over that momentarily, and we have two phase I-Bs ongoing in severe atopic derm and moderate to severe asthma.
Our ATI-9494 molecule is going to be moving toward an IND submission by the end of this year. Regarding bosakitug, our TSLP antibody, TSLP is extremely important because it has a pleiotropic, broad set of activities, where we hit dendritic cells, mast cells, fibroblasts, and even ILC2s, innate side of the immunity, and it's the master regulator of Th2 pathway indications. When we consider going after TSLP and inhibiting it's really with this pleiotropic activity in mind. We have a best-in-class molecule in our mind with over 400 hours of residence time on TSLP.
We bind and it dissociates very slowly, with 400 hours of residence time relative to other clinical development candidates that we've tested, and it's about 25 to 30 time longer residence time than tezepelumab, the only approved anti-TSLP antibody to date. When we compare to tezepelumab, the structural crystal structure work that Amgen put out years ago and published, you can see that we have three CDRs on the heavy chain that's binding to the C-terminus of TSLP. It's an affinity-based interaction. Whereas bosakitug has all six CDRs in both the heavy chain and light chain that are contacting the TSLP molecule all the way from the C-terminus to the N-terminus. It's binding and it's not letting go.
This molecule has already completed a POC study in atopic dermatitis, where the data showed over 90% of subjects had an EASI 75 response, and an IGA 0/1 88% response, IGA 0/1. We've taken this forward into a phase II-B, or a phase II, sorry, in atopic dermatitis, as I mentioned, that'll complete by the end of the year, and that's in moderate to severe patients. The same anti-TSLP antibody is a component of our bispecific, this time we have the TSLP and also ScFvs that bind IL-4R.
What we've been able to show is that this molecule is about 4x more potent than the combination of dupilumab and tezepelumab in inhibiting chemokine secretion from PBMCs that have been activated with TSLP and IL-4. In the healthy volunteer portion of the phase I, we've shown extended PK duration out to 20 weeks after the last dose, at week four, so 16 weeks of coverage at the 480 and 240 milligram dose.
This pharmacokinetic profile also matches up with the pharmacodynamic profile in target engagement, where we've shown that TSLP activated whole blood from these subjects in the healthy volunteer portion of the study have 100% inhibition of the TSLP stimulated TARC, and up to week 20 after the last dose at week four. The IL-4 stimulated is inhibited for at least 12 weeks at 100% inhibition by the 480 milligram cohort. The PK/PD effect that we're seeing here actually gives us the potential to dose this drug up to every three months. The AE profile was very quite favorable, and we saw no SAEs and no TRAEs and no conjunctivitis. This molecule will be moving into an asthma study.
We're initiating that effort now and initiating the study by end of year. Ultimately, we would take this into both respiratory and dermatologic conditions listed here. On the other side of the therapeutic wall in small molecules, as I mentioned, Aclaris is quite adept at ITK therapeutic development. We have a number of best-in-class oral inhibitors in this space. Initially, an ITK inhibitor would cross over Th2 and Th17, as well as innate lymphoid cell biology, and with a TXK, a bispecific, it would also cross over into Th1. You're getting broad applicability with an ITK inhibitor.
Our first molecule that was in the clinic, that is an ITK/JAK3 inhibitor, this has a unique bispecific-like mechanism where we're inhibiting both the T cell receptor activation upstream and the effector cytokines downstream. We're able to hit where CD8 inhibiting the cytotoxic destruction of targets by the CD8 T cells, we're inhibiting the T cell proliferation, activation, and survival by inhibiting cytokines. ATI-2138 was also in a proof of concept study in atopic derm. It was a 12-week study. Our itch profile was particularly good. We saw a greater than four-point improvement in PP-NRS in 63% of subjects. This is, as you can see, on the slide, against other biologics and other kinase inhibitors, this is best in class.
On the skin clearance, EASI scores and BSA, we saw 77% drop in EASI score. This drug has shown in a POC study to have a significant itch relief, an improvement in disease severity, and extent of disease. In addition to the clinical output, we saw in this in the pharmacodynamic analysis, we saw that we had marketed and sustained target occupancy and functional ITK inhibition across the dosing interval. This is a BID drug at 10 milligrams, and so it's a very potent molecule. Ultimately, we're showing that we're seeing strong downregulation of these ITK-dependent pathways across Th2, Th17, and Th1.
The safety profile was also quite good, we also have the potential then to increase the exposure of this drug in future studies. The next study that we're looking to initiate by the end of the year is a study in lichen planus. Lichen planus is a dermatologic condition, where we see impact in both the oral and cutaneous portions of the body, as well as a lichen planopilaris, which is a scarring alopecia in the scalp with hair loss and scarring. You can imagine that this disease affects quality of life in these individuals. We're taking this on. The prevalence is between 0.1 and 1% of the population.
Interestingly, as we've seen in other diseases like HS, where the indication, is usually the prevalence is usually very low initially until drugs come on board that can treat it, and then you see that you grow that population over time, as there's relevant medications for it. We know that in this case, lichen planus does not have an approved therapy, so it's an unsatisfied market, and an opportunity for biologic-like pricing and even accelerated regulatory pathway, is being pursued as it's an orphan indication. With ATI-2138, we're taking that into lichen planus, and it's a basket study, with mucosal and cutaneous as well as lichen planopilaris, and that'll initiate by the end of the year. We have other dermatologic and respiratory indications that could potentially follow.
The other molecules, ATI-9494, are moving, as I mentioned, into an IND by the end of this year. We also have a third generation ITK selective inhibitor that would show up in 2027. As we're looking forward, the momentum in 2026 is really taking us with multiple clinical catalysts by the end of the year. With ATI-052, the bispecific, we currently have the 2 I-B studies ongoing, one in severe atopic dermatitis and one in asthma. Both of those we're gonna read out in the second half of this year with an initiation of the phase II-B program in asthma by the end of the year.
Bosakitug, the monovalent TSLP antibody is in phase II, as I mentioned, and we're expecting top-line results also by the end of this year. ATI-2138 is going to be initiated in a new phase II-B trial by the end of this year in lichen planus, as I mentioned, oral mucosal and lichen planopilaris. Our next gen ITK inhibitor is going to be filing an IND by the end of this year. We're able to do this with our cash runway out through 2028, covering all of the catalysts and efforts that I just enumerated. We currently have about $190 million on the balance sheet as of the end of March.
Thank you for your time, and I appreciate again the opportunity to present at Bank of America Healthcare Conference.