Disc Medicine, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

It's great to be here.

Oh, sure. Yeah. We've been public for a few years now. As a company, we're focused on controlling red blood cell formation by controlling some of the fundamental building blocks. As you'll hear, our three different clinical candidates all focus on controlling either heme biosynthesis or iron metabolism. By doing that, we try to address a wide range of different disorders that arise in the red blood cell compartment.

Right. Yeah. bitopertin, designed to control heme biosynthesis and thereby control the accumulation of a toxic metabolite in these porphyria patients. To your point, one of the key readouts, the clinically meaningful readout, is looking at how long these patients choose to spend in sunlight. So essentially, a voluntary endpoint. Patients track how much time they go outside and expose themselves to light. They come into the study typically only able to tolerate 30, 40 minutes of sunlight in a day, which completely restricts their lives. In our phase II program, we had a 4-month placebo-controlled trial, with about 75 patients at 2 different dose levels. That was the key data set that we used to design the phase III APOLLO trial. It is reading out shortly.

In that data set, what we saw was all the groups improved their time in light during the first month or 2 of the study, and then you saw the placebo group trend back toward baseline while the active groups showed continued improvement over time. If you look at the last month of that study, the delta, the effect size, was an additional 14.9 hours of time in light. That kind of averages out to about a half an hour per day, which is about a 50% or more, actually greater than 50% improvement in the time in light. It does not sound dramatic, but the way it translates for patients is not so much that, oh, I get on average an extra half hour per day. It is that actually what they find, what they report, is that they are able to go and do capstone events.

Go out on the boat, go to the beach with their family, go to a wedding, things that they have never been able to do in their lives. That is what really matters to the patients, not so much the numerical average. But nonetheless, for powering the study and designing the statistics in that last month, it was a 14.9 delta. Actually, if you look at all the last 3 months, the average effect size was about 11 hours, and that is the number we used to power the study. In the APOLLO phase III trial, we are looking at the data, time in light in the last month. This time, it is a 6-month study, which we think that longer duration will allow a greater separation between placebo and active.

Rather than use the 14.9 that we saw in the last month of the AURORA phase II trial, we chose to give it about a 20%, 30% discount off of that, be more conservative, and use about 11 hours as our presumed effect size for powering the study. That also turns out to be the average effect size you get over the last 3 months of the 4-month AURORA trial. We feel like that's a very conservative and robust estimate of what effect size we can anticipate, and to use that as the basis for powering felt very comfortable to us.

Yeah. Patients are counseled about how the drug works, which takes a little bit of time, a couple of weeks, to start reducing the toxic metabolite protoporphyrin IX and really confer what we think are the benefits of the drug. I think it is essentially inevitable and kind of part of our planning now, right, that patients will come into the study with a lot of exuberance about the opportunity to change their lives, and they'll tend to experiment early on, and that's where you see this so-called placebo effect. It's actually every single group. You see everyone spending more time in light at the beginning of the study, at least in our phase II trial.

I think what we did is we said, "Okay, that's a natural behavioral element of coming into a trial, and we're just going to adjust our endpoint now to take that into account." That's why we focused on the last month of the study as our critical endpoint measurement.

Yeah. What we saw, the AURORA phase II trial was U.S.-based. That means you've got sites from Seattle to Boston, Texas to Miami. So a broad range of seasonal effects, right? You, in fact, might. I guess, behind all this, there's an assumption, which is that the best time to detect a drug benefit is when the weather outside is such that a person would like to go outside, would choose to spend time outside, but is perhaps prohibited by sunlight exposure. That would typically be summer in the northern latitudes, might actually be winter or spring in the southern latitudes. That's what we saw in the phase II, is that there's some effect of seasonality, but it wasn't dramatic. You see roughly the same drug effect regardless of season at different sites across the U.S.