Hello, everyone. I'm Jay Olson, one of the biotech analysts at Oppenheimer, and it's a pleasure to welcome you to Oppenheimer's 35th Annual Healthcare Conference and our discussion with Q32 Bio. It's a pleasure to introduce Jodie Morrison, CEO, Lee Kalowski, CFO, Sheila Violette, founder and CSO, and Jason Campagna, Chief Medical Officer. Thank you so much for joining us here today. Great. Thanks so much for having us. We really appreciate the opportunity to present the Q32 story. As we get into the slide deck here, we're going to focus highly on our lead asset, bempikibart, which is our bifunctional antibody that provides IL-7 and TSLP inhibition. We believe there's broad opportunity across TH2 and TH1-mediated diseases, which is supported by the biomarker data and safety data that we've amassed to date, which we'll share today. Our proof of concept in alopecia areata has us pretty excited here. We've already shown meaningful hair regrowth and durability in response, now out to 36 weeks in this study. We've shown a strong reconsent rate across our post-week 36 data sets, where we're now seeing patients coming back looking for open label expansion, which we will open very soon. Within these data sets, we're already seeing potential signs of what we believe is a remissive effect in patients after seven months after their last dose, and we'll present some of that data today. Collectively, this data has built high conviction for Q32 on the opportunities for the AA sector, and we think we can really amass a paradigm shift here. AA is a disease with a high unmet need, where the only available treatments are JAK inhibitors, which have classified safety warnings and no durability of response. For those that know the space, the hair begins to fall out as soon as you take off the drug in that setting. We're showing something that's very different within the data set here, which is why we're really doubling down on this indication and focusing on it as we move forward. We continue to have high conviction on our novel tissue-targeted complement platform. At this time, to conserve resources for our de-risk bempikibart program, we're halting continued development and clinical for that platform, and we're going to look into opportunities for strategic considerations there as we move forward. The near-term value creation is going to be focused on bempikibart. Over the course of this year, we look to recruit new patients into Part B of the clinical program, as well as re-enroll patients from Part A into the open label expansion. We expect that data to culminate in readouts over the first half of 2026, and we'll look for opportunities across 2025 for that open label data to be presented early as well. With that, I'm going to hand it off to our team to walk you through the data sets that we're seeing here. Pipeline is presented here again with alopecia and then our complement platform with ADX097, which is a phase II asset, as well as the 096 asset and our platform, all of which we are going to look for strategic opportunities for. With that, I will hand it to Sheila, and she can walk you through the data sets we are seeing for biomarkers, PK/RO, and beyond, and Jason will walk you through clinical data. Yeah, so bempikibart really provides us with a unique opportunity to inhibit signaling that's mediated by two different cytokines, that being IL-7 as well as TSLP. The reason is that bempikibart binds to a region on the IL-7 receptor alpha subunit that's shared for binding by both of these cytokines. IL-7 really provides the fuel for the generation and maintenance of pathogenic T effector memory cells, causing those cells to become autoreactive T cells responding in a low-antigen microenvironment. TSLP, different mechanism here, is predominantly responsible for the differentiation polarization of TH2 cells, leading to the production of classic TH2 cytokines and driving an inflammatory allergic reaction where you have an epithelial barrier. From our phase II studies in atopic dermatitis and alopecia, we were able to demonstrate that bempikibart dosed at a 200 mg flat dose every two weeks by subcutaneous administration led to really favorable PK and PD properties. What I'm showing you on the right-hand side are biomarker data that came from our atopic dermatitis trial looking at classic TH2 biomarkers that include readouts such as TARC, IgE, and eosinophils. The reductions that we saw were very robust and indicating that not only were we getting to drug levels in circulation, where we were achieving full receptor occupancy throughout the entire dosing in greater than 90% of the patients, but that we could also see changes in biomarkers that are reflective in inhibiting these inflammatory biomarkers that are predominantly being produced by the disease tissues. We were also able to evaluate other markers that are demonstrating blockade of the IL-7 cytokine. The PD marker that we evaluated here were changes in T cells and T cell subsets, and as shown here on the right-hand side, this is CD3 positive T cells from our alopecia trial. Similar data in atopic dermatitis, we saw the expected 35%-40% reduction. It is this data set that allows us to demonstrate that we're achieving pharmacology that's associated with receptor occupancy and engagement of the target that's associated with changes of blocking both of these cytokines and with minimal effects on ADA with no impact on PK. I'll hand over to Jason, and we'll talk about the data from our alopecia trial. Thanks, Sheila. What you're looking at here is a representative image of the proof of concept efficacy that we showed in the phase II clinical trial. This is a patient with severe alopecia areata, and for the purposes of the discussion here, the trial enrolled both severe and very severe patients, which range in SALT score from 50-95 and 95-100, respectively. The efficacy you can clearly see on the left-hand side of the baseline imagery, we dosed for 24 weeks, as Sheila had mentioned, and you can see that between baseline and week 24, she had a fairly robust response, achieving a SALT score in this case of less than 20, so more than 80% of her scalp coverage. Importantly, the second element of the efficacy response that we saw in the trial is that between weeks 24 and week 36, after treatment was discontinued, we continued to preserve the hair that this subject had regrown. If you look at the graphic to the left, the investigator scored this patient as having a deepening effect. Difficult to determine that in the photographs, but the point is that the proof of concept efficacy that we showed here was that through week 24, which was the sort of bare minimum time when we believed that we could be looking for an effect given it takes some time to regrow hair, we see very clear evidence of hair regrowth and a maintenance of that effect independent of pharmacology. We're sort of building a story here around that remissive potential that both Jodie and Sheila had mentioned. If you look to the far right, you can see the subject at week 42. The trial had ended at this point. We'll come back to how we got these images in a moment, but you can see that now out to week 42, approaching a year, which would be six months off treatment, that the patient is continuing to maintain the hair that she regrew in the trial during the 24 weeks of dosing. Why don't we go to the next slide? Now these are graphical representations of the entire per protocol population, middle modified ITT population on the right, the tabular view of the same data on the left. You can clearly see that across both populations, we are, one, growing hair, and two, maintaining that hair regrowth through the entirety of the follow-up period through week 36 off drug. Obviously, these data were very exciting to us, and I think had the data sort of flow stopped here, I think our excitement level would have been very high, but what had happened was it got even higher. That is because at the end of the trial, week 36, we received an inbound request from a single subject in the trial letting us know that after 36 weeks, she had had additional hair regrowth and was asking for the opportunity to explore expanded access for the drug. This is obviously despite the fact that there are approved therapeutics on the market. We wanted to understand that request a little bit better, so we got in contact with the clinical trial site and asked them to bring the subject back to the site, even though the trial had been over for her at that point for a period of about three months. Why don't we go to the next slide? What you're looking at here is imagery from two subjects. I want to focus first on the one at the top. This is the subject I'm referring to who reached out to us asking for expanded access. This is a very severe patient. Again, that's defined by SALT of 95-100. You can see her baseline images on the left. Through week 24, consistent with her email, she did not have much in the way of hair regrowth. By week 36, also consistent with her email, she had had some regrowth. We went from a SALT of 98 down into the 80s, but you can clearly see at the image on the right, this is what the investigator was able to capture. When When the subject came back to the trial site after her email, she had really quite explosive, that's the investigator's words here, hair regrowth. This is long after treatment discontinuation, which again, by way of reminder, was week 24. We, of course, reached out to all of the clinical trial sites after this, and we received, of the 22 patients that made it through week 24 to week 36, we've heard back from 10 of those patients. All 10 of those are reporting maintenance of hair regrowth, but this particular subject is one that noted that she was having continued hair regrowth. Once again, we asked the subject to come back to the trial site. You're looking at the imagery now on the far right of week 55, and you can see following her from left to right, she's had almost complete recoverage of that left portion of her scalp, all of which has happened after the cessation of dosing, now out to at least six months afterwards. What do we think is happening here? Next slide. Sheila mentioned earlier, Jodie noted it in the introduction, that this idea of remissive potential is sort of intrinsic to the mechanism of bempikibart and what would happen if one were to be able to effectively modulate pathogenic effector memory T cells. The snapshots of these manuscripts that we show here are simply intended to say that this is something we were aware of. This is a very interesting field of literature, and when we acquired the rights to bempikibart from Bristol-Myers Squibb back in 2019, it was something we were particularly interested in. It is the reason why we built the 12-week follow-up into both the atopic dermatitis and the alopecia areata clinical trials. If we go to the next slide, Sheila, we are happy to tag team this, but I will just keep going here. These are representative data that existed both in the, some of those manuscripts, those papers that I showed you on the prior slide, and also the BMS data sets that came to us as part of the transaction. They span the gamut of various preclinical animal models. You are looking at type 1 diabetes on the far left, a collagen-induced arthritis model in the middle. Both of those are in rodents, and they both show basically a flavor of the same thing, that a short interval of dosing with the drug leads to long-term tail efficacy. In the case of those rodent models, something on the order of three-ish months. Interesting and very compelling. It is the data on the right that came from OSE, which is a company that has a competitor molecule to ours. We believe that our pharmacology is better, but that's not the point here. The point is that OSE, who recently reported out positive proof of concept data in ulcerative colitis, when they took their antibody into a non-human primate model, in this case, a tuberculin challenge model, what they were able to show is that a single dose of their drug can give long-term, meaning a year in this case, effect in the tuberculin challenge model. Two really critical things emerged from those data. One, it's absolutely selective to the T cell variant in play. This is not a general immunosuppressive phenomenon. It has nothing to do with an overall reduction of T cell. That's just a biomarker. This is a very specific event. Second, that you could restore that impact of the remissive effect by just re-challenging the animal with BCG again and bring it back completely. These were the kinds of data that we were familiar with at the time we built our clinical program. Why are we sharing all of this with you? We think that what we're seeing here with the efficacy profile of the drug, the durability of the effect, and the continued hair regrowth after treatment cessation is exactly, it's consistent with and sort of exactly what was predicted by those remissive data sets at the time we had licensed the product. In summary from our efficacy, we've clearly shown proof of concept, and we have shown two differentiating features from currently approved therapeutics. We would say highly differentiating that unlike with JAK inhibitors, when one discontinues treatment and generally speaking, within a couple of weeks, hair begins to fall out, that is not what we're seeing at all. We're seeing the exact opposite, a maintenance of effect. Even more interestingly, we're seeing patients that after we have maintained the effect, we're getting even deeper and more profound hair regrowth afterwards. I think we're very excited about these data, and we're looking forward to moving ahead in the next stage clinical development here. With that, I think, Lee, we can go to the next slide. I think this is a summary of everything that I've just said. I think we can go to the final slide here. What are we doing next? Jodie mentioned this at the beginning of the presentation. The gray is our completed Part A trial that I've just shared data with you for. The blue at the top is the open label extension that Jodie mentioned that we're opening in the first half of this calendar year. This is an opportunity for us to get these patients in Part A of the trial back on treatment and to see what happens over even a longer period of time. The bottom is the clinical trial that we're opening now. We imaginatively have called it Part B. We will name it at some point, which is not today. Part B differs from Part A in three really important points. One, we're going to provide a loading regimen. Two, we're going to treat for longer out to 36 weeks. Third, we'll follow the patients for longer to explore that remissive potential out to week 52. This trial is a practical trial for us. It's open label, and what it allows us to do is understand the nature of the efficacy that we're seeing here more completely so that we're able to more effectively engage with FDA in an end-of-phase II meeting and build out what that phase III program looks like. It's pretty practical questions. What is your effect at week 24? How does it compare in the absence to what we see now in the absence of a load? When you treat people to week 36, how does it compare to the remissive data that you are showing us now with week 36? Importantly, when you follow those patients out to week 52, does the effect go even deeper? We believe that with those efficacy data coupled with the pharmacology safety and biomarker, we'll be well positioned to open a registration program here in alopecia areata with some very, we'll say, differentiating efficacy signals than what's present in the currently approved therapeutics. Let's go to the next slide and speak to the market here, right? We're really excited about alopecia areata as a market opportunity for this asset. Ultimately, there's 700,000 patients living in the US with alopecia areata, and these patients, I think, manifest before the age of 50. You're talking about patients on average in their 40s who get diagnosed, and their only treatment option at this point are JAK inhibitors, which have black box warnings related to safety concerns. Ultimately, they can't take any time off the JAK inhibitors because if they do, their hair falls out, right? That's the profile that exists now. In most of the indications where JAKs are present, RA, AD, there's biologics that take a front-run position. In AA, JAKs are the only ones there. It's flipped on its head. There is no biologic in the setting. It is ripe for the opportunity of a biologic to step into this market, and we believe we'll be very well positioned with the safety profile we're seeing here. It's really transformative efficacy finding that we're starting to see in these later months. We're pretty excited about the opportunity here. On the next slide, just looking at the market opportunity overall, right? 700,000 patients, 300,000 of those are severe, greater than 50 SALT, and only 30,000 are appearing to be JAK treated based on the data we've pulled. The market opportunity here is expected to grow from $1 billion in 2026 up to $2.6 billion. Again, no biologic entries here, so we really have a great opportunity to be a front-run position coming into this. With the remissive data that we're seeing and our status on the IL-7 compared to the other IL-7 assets that could be developed in this place, we think we're really well positioned to be the front runner here. Let's go to the next slide. This was an independent review that was done by Guidepoint following the data release that we had in December. This was before the emergence of the week 36 data or any of the post-week 36 data. Already you're seeing from an independent review the potential side effect profile here being something that could be a game changer in the space and that patients would prefer an injection if it was safer in the end. Given the safety we're seeing here, we think we're well positioned to meet some of the guidance that's provided here. With that, we certainly think we have a great opportunity in AA. We're doubling down there and focusing our resources on expanding this data set as we move forward. It's not lost on us that with the biomarker data, the safety profile, and what we're seeing here, we really have great opportunities beyond alopecia areata in other TH2 and TH1 diseases. Something we can look forward to in the future as we look to expand the kind of opportunities for Bempi as we move forward. Our tissue-targeted complement platform is certainly still near and dear to our heart. We think there's a lot of opportunity with these programs, ultimately making the decision to refocus our resources on AA given the proof of concept data that's emerged there. We also think the opportunities within the renal sector have gotten fairly crowded, and so that played a role in our decision to table the renal basket program here. We will be seeking strategic opportunities and expansion opportunities for that with partnership, and we'll look forward to updating as things emerge there. With that, why don't we go to the last slide, Lee, and present the financials, and then we can circle back for Q&A. Sure. Our cash balance as of the end of September, as we reported in November, was $89.1 million runway to the second half of 2026. That gets us through a series of milestones, including initiating enrollment and getting through data in the SIGNAL-AA Part B, as well as the OLE that we're initiating in patients who are in the SIGNAL-AA Part A. With that, Jay, we can leave some time for questions. Okay, great. Thank you so much for the update. Really appreciate catching up on the progress you're making. Really exciting data in alopecia areata. Maybe just to start with, can you talk about any biological hypothesis around what's driving the continued hair regrowth after stopping treatment? Yeah, Sheila, you want to start there? Yeah. There's been really some beautiful work that was done really over a decade ago. It originated in the type 1 diabetes models and then extended to a number of different preclinical studies. It's really through these direct effects on the pathogenic T effector memory cells. These are cells that basically become autoreactive to responding to antigen. The data that we showed you, particularly like that tuberculin challenge, there's been some nice characterization of this. Those memory cells are long-lived, so we don't think that we're depleting them, but rather silencing them, dampening their response. There's direct effects on those cells, but when you suppress the function of those cells, you're then also allowing the T regulatory cells to impart their immunosuppressive properties. The direct effects are probably on the T effector memory cells. Okay. Recognizing that with JAK inhibitors, the hair regrowth is lost upon treatment discontinuation, has this sort of sustained hair regrowth after treatment discontinuation ever been observed in any other studies with other treatments? Not to our knowledge, and certainly something in speaking with KOLs is a unique opportunity and truly transformative to the paradigm here if we can continue to see more of this as we move forward. Okay. Is it correct to think that there's no spontaneous remission of alopecia areata or like a placebo effect in the natural course of this disease? Yep. Go ahead, Jason. The placebo effect is generally pretty low, Jay. I mean, it's single digits low, and those are called big trials. The disease is a sort of lifelong chronic affliction, and they think about the disease in terms of duration of a current episode. Patients will have this sort of patchy hair loss that can last anywhere from months to years. The average in the JAK inhibitor trials, which matter because they were the pivotal trial that first sort of illuminated this, is roughly four years, meaning the patients in that trial had an average duration of current hair loss of about four years. We, in our trial, enrolled patients that were much higher than that. We are showing hair regrowth in patients that have had a shorter duration of current episode, which is what the JAKs have done, but also patients that have duration of current episode out to nine years. You might say, when that episode resolved? They do not fully regrow their hair, but the episode does wane a little bit. They may regrow some of the patches and have others lost. If patients have alopecia totalis or alopecia universalis, which is truly complete hair loss, they may regrow small patches of hair. Take that woman that we showed you in our imagery, the one that triggered with the email. She had been like that for years and had no appreciable movement at all in her hair regrowth. You saw what happened while we were on treatment. Although you may get some waning of the disease when those intervals sort of lapse, they never have a truly complete regrowth of their hair. Okay. Makes sense. Does this sustained hair regrowth, does it suggest that bempikibart is having a disease-modifying effect in the scalp? Yeah. You have asked the question, Jay, and I would say that I'll answer it with maybe sort of a bit of an observation. If we know that you lose the hair in alopecia because you've collapsed that immune privilege environment, period, that's what happens. If you're regrowing hair and maintaining it, one thing must be true. You've restored some degree of immune privilege to the hair follicle, or you couldn't have those clinical effects. To the extent that that restoration of immune privilege is the language you used, sort of remissive or remission or curative or disease-modifying, it strongly suggests that that's the case. How would we be able to confirm that? More efficacy data will be helpful for sure. The opportunity potentially later to get more tissue-level biomarkers is something that's on our mind to be able to explore that more fully. Right now, I would say, yeah, we think that we're having a disease-modifying element to what's happening in alopecia. Otherwise, you wouldn't be able to maintain the hair after you've discontinued treatment. There's just simply no way around it. Yeah. We do think that a maintenance dose is probably something we'll have to think about over time to continue to keep patients in that state. One of the things we'll be looking at between the OLE and the Part B will be thinking about what that maintenance dose looks like, be it quarterly or otherwise as we move forward. Okay. Sounds good. I can't remember if you mentioned collecting biopsies from these patients. It's something we did not build into the clinical programs here, just given the nature of getting these up and running, but it is something we're thinking about that we could do in the future, certainly for confirmation studies. Right now, we're focused on getting more patients on as quickly as possible in that data set, but we're looking at potentially adding some additional stuff in the future. Okay. I guess, given these encouraging results in alopecia areata and the potential for sustained durable disease modification, I know you mentioned type 1 diabetes. What are some of the other diseases where you think bempikibart could have a similar durable effect? That's Sheila and Jason tag team this one. Yeah. We We have the wheel slide that we put up there. There are a number of diseases where we think RA is one of those diseases. That's where there were some preclinical data that showed those sort of long-term durable responses. Ulcerative colitis certainly could be one of those as well. Pretty much any one of these diseases on the right-hand side that are really these autoimmune-driven diseases could potentially have that effect. Jay, I won't add to the disease list, but I'll take an opportunity to re-emphasize a point we made earlier. Prior to our data, it was only in the world of animal data in which we knew that this mechanism impacted both TH2 and TH1. It was, in fact, one of the most common questions we received prior to the data readout. How do you know? And we would list all the things we knew, and you came up just shy of, but in man, you don't really know. I think now for the first time, we've definitively shown with our biomarker data that TH2 pathway engagement, and I think everyone, including us, is sort of settling around that reality that it's no longer hypothetical that these TH2 diseases are sort of available to us and that, in fact, they could be open for development. We are really honestly still getting our heads around what that would look like in, we'll say, an eosinophilic asthma trial or a COPD trial or eosinophilic esophagitis. Our biomarker data in many ways look consistent with, for example, what tezopelumab might be showing in some of those diseases for reduction. When you see data like that, it's, wow, that's really interesting. What could those indications look like? We are right in the middle of that right now. Okay. Great. I know you showed some initial KOL reactions to the data. Have you shown KOLs these images that you've shared with us here today? Can you tell us what KOLs are saying about the durability of the sustained hair regrowth beyond treatment? Yeah, I can start with that and say we're in the process of, if we're going to be opening this trial in the first half, you can all understand that we're obviously engaging with clinical trial sites right now. We will be adding some more sites to that. When we show those thought leaders, they are the people that know alopecia areata, the data, their only response is, when can we start? Yeah, there's a lot of excitement about the potential here and the idea that this could be really transformative for patients, especially patients that right now only have options of JAKs. We think that we're well positioned. The KOL support behind this is high. As we move forward, we are having an overread for eligibility of patients, and that's going to be led by some very key KOLs in this space who wouldn't be dedicating their time to this in the absence of the type of data we put in front of them. I think all signs point to high KOL support here. Okay. Yeah, I'm sure if the potential patients see these images, they're going to want to enroll in your study, and you're going to have high demand at the study sites. Any predictions on pace of enrollment? It's our expectation. We'll start recruitment in the first half of this year, and we're anticipating right now that we'll have the full readouts for the data sets in the first half of next year. I think that speaks to sort of our hope that this will be a quick recruiter, and there's nothing better than images like this, right? I think these types of studies, and certainly we've talked about the per protocol versus the MITT in the past, I think the recruitment of patients in a study where you have to wait to see your hair growth and nobody's shown it yet, I think leads to some dropouts in the studies. We're also hopeful that this will maintain patients in the study longer, given that they know what to expect now. Okay. Great. I guess maybe one last question. Are there any particular baseline characteristics or eligibility criteria you'll focus on that you think might be predictors of response to bempikibart? No, there's nothing in the biomarker data, but from an efficacy perspective, we feel like we have sort of broad latitude here. Definitely severe and very severe, same population. We will continue to focus on that duration of current episode as an important dividing line and potential additional differentiating factor. It turns out that we seem, Jay, I mean, it's small data sets. We're mindful of that, but the regrowing hair is real. It's happening. There's not much that biomarker selection will help you with there. If we're really regrowing hair in severe and very severe and duration of current episode short versus long, our only goal is let's enroll those patients. Severe and very severe, short and long duration of current episode and build out the efficacy story and move ahead in the phase III at scale and see what the drug can do. We will have an opportunity to really look at the biomarkers and understand where they may differ. I think the data sets are so small, we're not putting the biomarkers in front of us in terms of enrollment. Maybe we'll say it that way. Okay. Sounds good. We will stay tuned. Again, it's an area of super high unmet medical need. This is really encouraging news for our patients. Thank you so much for bringing us up to speed on the impressive work that you're doing in alopecia. Thanks so much, Jay. Thanks for having us. Thanks for having us. Our pleasure. Thanks, everybody.