Dianthus Therapeutics 3rd Annual Guggenheim Healthcare Innovation Conference

Sure. Thank you, Yatin, and thank you to the Guggenheim team for this opportunity to be here with you today. Just quickly, I'm going to be making some forward-looking statements, so please, I refer you to our website and our SEC filings for all the appropriate risks, et cetera. So just very quickly on claseprubart, I'll just focus on our lead program, our very potent active C1s inhibitor. Our goal with claseprubart is to achieve a target product profile at approval that positions it as a first-line treatment across myasthenia gravis, CIDP, and MMN. The way we'll do that, we're aiming for best in disease efficacy. We're targeting very rapid, sustained, consistent efficacy, and I'll talk a little bit in a moment why we believe we may have best in disease efficacy with claseprubart. Secondly, differentiated safety. We'll be the only classical pathway inhibitor or complement inhibitor with no box warning and REMS program.

Finally, that patient-friendly DUPIXENT-like auto-injector. I urge you to understand how simple it is. Go to the DUPIXENT website, watch the patient video. Literally a five-second, super-fast auto-injector that patients can easily self-administer once a month in MG, once every two weeks in CIDP and MMN. Then finally, with these three markets in the U.S., it's about 150,000 total patients, with still opportunity to grow with the appropriate biologic that could be used earlier in more active, less severe patients. Right now, for example, the myasthenia gravis market, patient population in the U.S., despite having a decade now of complement inhibitors and FcRns available, still less than 20% of myasthenia gravis patients are on biologics. Why? Because you don't have the ideal biologic, that rapid, consistent efficacy, no box warning, with the super convenience of the SHL Molly auto-injector, which is exactly what DUPIXENT uses.

Why do we say we think we could have the potential for best in disease efficacy? This is a slide to summarize three elements. One, on the left, C5 inhibitors shut down the complement system. They shut down the complement system whether the classical pathway was triggered or the lectin pathway was triggered by encapsulated bacteria. They shut down everything, so that's why they have box warnings and REMS programs. The one thing they cannot do is prevent the formation of C3a and C3b, because that happens upstream of C5. We work upstream of C3. C3a and C3b are toxic split products. They are pro-inflammatory. In MG patients, C5s are doing nothing about this. We will prevent this. This may give us additional efficacy in MG over C5s.

The reason we work in CIDP and MMN is because we prevent C3a and C3b deposition. C5s don't. The middle graph is a reminder of our potency difference versus riliprubart, the active C1s inhibitor still being studied in one of the two phase III studies. They failed on one of them, but the other one passed futility and is still ongoing. We are seven times more potent at the IC90 using the CH50 ELISA assay than riliprubart. This is why, in our part A, we're seeing much higher response rates than they saw in their phase II open-label study. They had about a 50% responder rate in their phase II. We are seeing 75% responder rates in our first 40-patient interim responder analysis.

We just put out an update that we don't think we'll even need 200 patients in part A in order to recruit 128 patients into part B. That is a very clear signal that those high responder rates we saw on the first 40 patients are sustained now with more than double the number of patients having gone through part A. Finally, on the right, as an even more dramatic difference in terms of potency versus empasiprubart. There, at the IC90, using the Quidel MicroVue CH50 assay, the assay they published with to highlight their potency as a classical pathway inhibitor, we are 38 times more potent at the IC90. So even more dramatic of a difference in terms of potency. There is no more powerful, potent classical pathway inhibitor than claseprubart in development.

These are the data that give us confidence, including our part A 75% responder rate we saw with our interim responder, the first 40 patients, are what give us confidence that we will have best in disease efficacy across all three indications. Now, focusing on MoMeNtum, or our MMN phase II trial that's coming up in December, a reminder, this is a very small study. If the FDA and we had known what a phase III could look like in MMN, we would have probably gone straight into a phase III. But at the time, there was no precedent. Nobody knew what a phase III would look like. Nobody knew what the primary endpoint should be, so we went ahead and did a small proof of concept in phase II. This is a safety study. We have some efficacy measures, of course, in terms of muscle strength as secondary endpoints.

We have over-enrolled. We were targeting 12 patients. It's going to be about 15 patients per arm. We over-enrolled, and we have 46 patients who have completed the study, and we expect the results in December. A reminder, we do have two arms, 300 milligrams and 600 milligrams. We do not expect to see an efficacy difference between those two, just like we didn't see it in MG, and of course, a placebo arm. One big difference between the two trials I really need everybody to understand. argenx made a big deal about the 91% reduction in need for IVIG rescue in phase II. That endpoint is gone now. It's not even in phase III. It is irrelevant. We both decided which patients get IVIG rescue in very different ways. They had patients who had clinical deterioration and didn't get IVIG.

They had patients who didn't have clinical deterioration and got IVIG because they allowed for a patient to raise their hand and ask for IVIG, and they gave it to them, despite having no evidence of actually deteriorating clinically. In our trial, a patient gets IVIG only and when they have clinical deterioration documented, period. There's no asking for IVIG and you get it even though you don't have clinical deterioration, and if you have clinical deterioration, you get IVIG. Very, very different. It's really an irrelevant endpoint. I understand why they wanted to make a big noise with 91%, but it's not even something to look at in phase III anymore. The primary endpoint in phase III is grip strength, and for them, it's been changed now to the four-week average. That's what's going to matter in phase III.

Big differences between us and empasiprubart, and I'll wrap it up here. On efficacy or potency, we are 38 times more potent than empasiprubart at shutting down the classical pathway at the IC90. So reminder, if you like the data you see from their phase III, we should be able to at least achieve that. If you kind of have mixed feelings about their phase III data in MMN, we can do better. We really shut down the classical pathway. I'm not sure with their dosing if they're really shutting down the classical pathway. Secondly, they block the lectin pathway. It's a C2 inhibitor. We don't. We leave the lectin alternate pathway intact. Why is that important? The lectin pathway is a pathway that gets triggered by the presence of encapsulated bacteria.

That's the pathway that then allows the alternate pathway to rev up, and together they form the MAC needed to destroy the bacteria. If you shut down the classical and lectin pathway, there's really no way for the complement system to respond to the presence of encapsulated bacteria and prevent the potential for things like meningitis. They're very likely going to have a box warning and a REMS program. Finally, we're an auto-injector, the DUPIXENT, the same one, auto-injector, two milliliter low volume, once every two weeks, self-administered. They're an IV every month. Those are the major differences between us and empasiprubart.

Jan, there is almost nothing that we will see in our phase II that prevents us to go to phase III. This is a very small study. It is primarily safety, and I can tell you on a blinded basis, it looks exactly like the MG and the CIDP trials look. There is nothing going on on a safety front that we go, "Oh man, I hope that is a placebo patient," for example. Nothing. There is almost nothing preventing us from going to phase III. We know we shut down the classical pathway. We know MMN is IgM-driven and classical pathway-driven.