Aclaris Therapeutics, Inc. ($ACRS)

Hi, everyone. My name is [ Matthew Guggenbiller ]. I'm an associate on Alex Stranahan's biotech team. Thanks for coming to the Vegas Conference, day 3. I appreciate you guys coming out, and I'm pleased to be joined by Aclaris Therapeutics, who are going to be running through some slides. Over to you.

Yes. 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 health care conference. The normal disclaimer and cautionary notes regarding forward-looking statements. Aclaris Therapeutics is an innovator in immunological assets for important unaddressable disease. And addressing validated targets is key to success while we are really understanding how to take innovative approaches to our portfolio. And 2 examples would be bispecifics and ITK oral inhibitors that will 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 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 an impact in millions of patients just in the U.S. alone. And so 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 and therapeutics. And yet we have both ITK franchise that has JAK-like efficacy that we're looking to expand on with broad ITK selectivity as well as in biologics, where we have potential first-line therapies. And really what we're looking to achieve is with 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 100-subject placebo-controlled study NAD with moderate to severe. Following this, the ATI-2138, which is our ITK/JAK3 inhibitor. This completed a Phase IIa study in atopic derm as a POC. And now we're pursuing lichen planus as our Phase IIb indication that will initiate by the end of this year. ATI-052 is the bispecific that targets both TSLP and IL-4R. We cleaned the healthy volunteer portion of that. I'll go over that momentarily. And we have 2 Phase Ibs ongoing in severe atopic derm and moderate to severe asthma. And then our 9494 molecule is going to be moving toward an IND submission by the end of this year. So in terms of 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 then it's the MAF regulator of Th2 pathway indications. So when we consider going after TSLP and inhibiting it, it's really with this pleiotropic activity in mind. And we have a best-in-class molecule in our mind with over 400 hours of residence time on TSLP. And so we bind and it associates very slowly with 400 hours of residence time relative to other clinical development candidates that we've tested, and it's about 25 to 30x longer residence time than tezepelumab, the only approved anti-TSLP antibody to date. And when we compare to tezepelumab, the structural crystal structure work that Amgen put out years ago and published, you can see that we have 3 CDRs on the heavy chain that's binding to the C-terminus of TSLP. It's an affinity-based interaction, whereas Bosakitug has all 6 CDRs in both the heavy chain and light chain that are contacting the TSLP molecule all the way from the C terminus to the end terminus. So it's binding and it's not letting go. And this molecule has already completed a POC study in atopic derm, where the data showed over 90% of subjects had an EASI-75 response and in IGA-01, 88% response IGA-01. So we've taken this forward into a Phase IIb or a Phase II, sorry, in atopic derm. And as I mentioned, that will 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. And this time, we have the TSLP and also scFvs that bind IL-4 receptor. And 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 4, so 16 weeks of coverage at the 480 and 240-milligram dose. This pharmacokinetic profile also matches up with the pharmacodynamic profile and 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 4. And then the IL-4 stimulated is inhibited for at least 12 weeks at 100% inhibition by the 480-milligram cohort. So the PK/PD effect that we're seeing here actually gives us the potential to dose this drug up to every 3 months. The AE profile was very quite favorable, and we saw no SAEs and no TRAEs and no conjunctivitis. So this molecule will be moving into an asthma study. We're initiating that effort now and initiating the study by end of year. And 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. And so we have a number of best-in-class oral inhibitors in this space. So initially an ITK inhibitor would cross over Th2 and Th17 as well as innate lymphoid cell biology. And with the Txk bispecific, it would also cross over to Th1. And so you're getting broad applicability with an ITK inhibitor. Our first molecule that was in the clinic is an ITK/JAK3 inhibitor, and this has a unique bispecific-like mechanism where we're inhibiting both the T cell receptor activation upstream and the effector cytokines downstream. And so we're able to hit where CD8 -- inhibiting the cytotoxic destruction of targets by the CD8 T cells, and we're inhibiting the T cell proliferation activation and survival by inhibiting cytokines. And so 2138 was also in a proof-of-concept study in atopic derm. It was a 12-week study. And what it showed was that our itch profile was particularly good. We saw a greater than 4-point improvement in PP-NRS in 63% of subjects. And this is, as you can see on the slide, against other biologics and other kinase inhibitors, this is best-in-class. Also on the skin clearance, EASI scores and BSA, we saw a 77% drop in EASI score. So this drug has shown in a POC study to have a significant itch relief and improvement in disease severity and extent of disease. And so 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. And this is a BID drug at 10 milligrams. And so it's a very potent molecule. And so 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. And so 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. And so lichen planus is a dermatologic condition where we see impact in both the oral and cutaneous portions of the body as well as lichen planopilaris, which is a scarring alopecia in the scalp with hair loss and scarring. And so you can imagine that this disease affects quality of life in these individuals. And so we're taking this on. The prevalence is between 0.1% and 1% of the population. And 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, and 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. And so with 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 will initiate by the end of the year. And then we have other dermatologic and respiratory indications that could potentially follow. The other molecules, 9494 are moving, as I mentioned, into an IND by the end of this year. And then we also have a third-generation ITK selective inhibitor that would show up in 2027. So as we're looking forward, the momentum in 2026 is really taking us with multiple clinical catalysts by the end of the year. So with ATI-052, the bispecific, we currently have the 2 Ib studies ongoing, one in severe atopic derm and one in asthma. Both of those are going to read out in the second half of this year with an initiation of the Phase IIb 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 IIb trial by the end of this year in lichen planus, as I mentioned, oral mucosal and lichen planopilaris. And then our next-gen ITK inhibitor is going to be filing an IND by the end of this year. And so we're able to do this with our cash runway out through 2028, covering all of the catalysts and efforts that I just enumerated. And so we currently have about $190 million on the balance sheet as of the end of March. So thank you for your time, and I appreciate again the opportunity to present at Bank of America Healthcare Conference.