Q32 Bio Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Yeah. Sure. Sheila, want to take that?

Thanks very much for hosting us today. Q32 Bio was formed back in 2017, just about nine years ago. It was really formed based on the concept of developing therapeutics that would target pathways that were fundamental to driving a number of inflammatory and autoimmune diseases. We were keenly interested in those pathways that if you inhibited them, would allow you to restore or remodulate the immune system, really providing homeostasis as opposed to general broad immunosuppressing agents. Initially, we brought forward tissue-targeted regulators to the complement system. Those are now in clinical development. But two years into the company, we had the opportunity to in-license a second asset that is known now as bempikibart. It is an IL-7 receptor alpha subunit antibody. We were particularly drawn to this asset for a couple of really important reasons.

One was the underlying biology, and the other was because we recognized at that time that this was likely a best-in-class asset because there were other companies that were going after this receptor pathway. What we knew about it was that bempikibart binds to the IL-7 receptor alpha subunit at a region that is shared and required for binding and signaling by two very different cytokines. That includes IL-7 as well as TSLP. IL-7 is a really important mediator of T cell biology. It regulates the generation of pathogenic T effector cells, and it lowers the threshold for T cell receptor signaling on these cells in the context of autoimmune disease. Essentially what it is doing is it is causing these T cells to now respond in what should otherwise be a low antigen microenvironment.

It's also a pretty important cytokine for regulating the proliferation and survival of antigen-specific T memory cells. TSLP is on the other side of the inflammatory cascade, where it's a modulator of TH2 responses, particularly where you have an epithelial barrier. We knew that this one antibody had bifunctional activity, and if it worked, it could generally probably go pretty broadly.

The other thing that was unique about the biology was that we could see from the data that had been generated at Bristol Myers Squibb and what was in the literature, was that it had been shown that you could dose in preclinical animals for a period of time, allow the drug to wash out of circulation, and have these long-term durable responses. The biology looked really intriguing to us. The other side of things was that it looked like it was a best-in-class asset.

I say that for a few reasons. One was that we looked at the PK/PD properties. We could see that this was an antibody that you could probably administer low doses by subcutaneous administration, get good coverage of the target in circulation and in the tissue. As we've taken the program forward, we've actually illustrated that this is really the case, so it continues to be a best-in-class asset, in large part because of PK/PD properties, but also because it was engineered to be effectorless which we felt was important for this class of therapies.

The other important point was that it was a fully human antibody. There was concern in the field back when we were in-licensing this that there was a class effect, and you wouldn't be successful developing an antibody that had low ADA, and we're experiencing very, very minimal ADA, especially you can see in our alopecia trial. That's the history of how we brought the program in. We took it forward in a phase I study in healthy volunteers, then we took it forward in phase II studies in atopic dermatitis and alopecia, and it was in that initial alopecia Part A that we could see that we were seeing some really interesting signal. We were seeing that we were regrowing patients' hair, but also that there were really strong indications that there was a durable response.

That led us to then complete our Part B trial. Where we are landing today is that now that we see that we have such profound efficacy in alopecia patients, which is a T cell-mediated disease, it really opens up the door for us to think about indications where similar biology is in play.

Yeah. It is a good question. When we think about alopecia, I think we all think about this as largely a T cell-mediated disease.

A lot of that comes from actually looking at the histology of the hair follicles in these patients. There is quite a bit of work that has been done where if you look at the immunostaining of cells that are infiltrating the bulb of those hair follicles and leading to that cellular destruction, because normally the hair follicle is in an immune-privileged environment, but that gets broken down. The T cells are infiltrating and producing these pro-inflammatory cytokines. You get destruction of the hair follicle and then the loss of hair. What is it that you can do here to restore that? Quite a bit of data that has been generated, with JAK inhibitors, that have showed that if you take biopsies from patients before and after treatment, you can see that you resolve that inflammation.

It is concordant with the regrowth of hair, the restoration of the anagen phase follicles, as well as the resolution of inflammation. We do consider this to be a largely T cell mediated disease, and when we thought about where we might take bempikibart, it was a natural tendency to go into indications where there was a large T cell component. Having said that, it cannot be ignored that there are data that we hear of anecdotally with patients that have been treated with DUPIXENT, as well as data that has been published with DUPIXENT trial, that show that there are a subset of patients that are atopic by nature. These could be patients that are high in IgE. It could be patients that have comorbidities like atopic dermatitis or asthma, for instance, that do show a response to DUPIXENT.

It may take them longer to get there, maybe more in that 48 weeks after treatment. But it argues that in a subset of patients, there may be this TH2 component that is contributing to this inflammatory environment that is further driving those cytotoxic T cells. For us, we think this is really important because we have demonstrated in atopic dermatitis as well as in alopecia, that we are having really profound effects on TH2 biomarkers, really showing robust reductions in classic things like IgE, eosinophils and TARC. If there is a component, we think that we would be covering both the TSLP as well as the IL-7 side.