Disc Medicine, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Great to be here. Excellent.

Yeah, it's a great place to start. DISC-3405 is a monoclonal antibody against TMPRSS6 designed to restrict iron, which is a mechanism that has already been proven out to be effective in managing excess red blood cell production in polycythemia vera patients. What's been exciting about this program is just the rapid progress. We honestly, our guidance was that we wouldn't have data till the end of the year, but the trial enrolled far ahead of schedule. We were able to pull in or really needed to pull in our initial data disclosure. The trial is 2 cohorts, cohort A, cohort B. Cohort A is designed to probe essentially our max dose, Q2 weeks dosing, but there's a dose run-in kind of adjustment, just checking that we've got the right dose for these patients at the beginning of the trial.

The data just shows a complete snapshot of all the cohort A patients that we have on board as of the data cutoff back in the summer. It looks really promising. I think as our first experience in these patients, we can see for sure, as expected, the drug is restricting iron, engaging all the mechanisms that are supposed to be engaged. The real goal here is to achieve really the most kind of side effect-free control of hematocrit that you can achieve for these patients. That's really the objective. It is a competitive space, and I think we expect all of these iron restriction agents to end up with about the same efficacy level. That's assessed by looking at the rate of phlebotomy, right? Typically, these patients are being managed by simply bloodletting, which it turns out makes them feel miserable.

So the idea of replacing that with a drug that allows people to keep their iron in their bodies, which makes them feel a lot better, no surprise, but still retain that kind of stable hematocrit around 45%. That's the objective. So we've seen recent approval of rusfertide, which is the pioneering product in this space, showing about 70%-80% phlebotomy-free, reduction in phlebotomy rate. That's pretty much exactly what we see. We see a reduction in the phlebotomy rate from about four per unit of time down to about 0.6, which is right in the same neighborhood as we've seen with other agents. If you look at the rate at which patients from time zero are phlebotomy free, that's a little bit north of 60%.

Now, that's a little low compared to the comparators, but the relevant apples to apples is actually look once you're on a stable dose that's been maintained for a while. There we had about nine patients who'd been on long enough to achieve that, and seven of those nine were phlebotomy free as well during that kind of later stable dose interval. That puts us in the high 70% range for phlebotomy free, which is right in amongst all the other compounds with the iron restriction mechanism. So side effect wise, we see almost no anemia, almost no injection site reaction. I think that is if we're able to prove that out in a larger set of data that is actually distinct from, I think, what some of the other agents have been able to show.

Because sometimes you get anemia, apparently, if you restrict iron too much or too long, it pushes down too hard on hematocrit, and we believe that with the only antibody being developed here, we'll be able to achieve a kind of a tailored effect on iron and hematocrit that may be able to give patients a really clean experience.

Yeah, I think you want to achieve. Clearly everyone can achieve a very significant effect on hematocrit with this mechanism, which is no surprise given the power that iron has on erythropoiesis, and even some evidence of kind of direct interaction with the JAK pathways that tend to be hyperactive in this disease. No surprise that all these agents are able to achieve that, a kind of a similar level of efficacy. I think then really it just becomes about giving the best possible product experience for the patients, which is a mix of ease and convenience, and avoidance of any side effects. If you look across the landscape, there's some evidence of injection site reactions with some agents, some anemia with other agents. I think those have been the places where different molecules may be able to distinguish themselves.

Yeah. The trial fully enrolled 2 20-patient cohorts, which are designed to kind of probe the Q2 weeks dosing regimen and Q4 weeks dosing. That'll come in cohort B. That was fully enrolled by the middle of the summer. We'll be able to have data from cohort B by the end of the year. From there on, the trial will wrap up, and I think our plan is to move to an end of phase II meeting and get that going into phase III. With gratitude to the rusfertide program that came before us, I think the pathway has been pretty well established in terms of what a trial looks like, what the endpoints are going to look like.

Somewhat different for us, where everything else we are doing is breaking open new ground, there is a pretty well-established path here, and we think we can move fast.