I guess we will kick things off. So thank you very much, everybody. Thrilled to have with us Disc Medicine, represented by the company's CEO, John Quisel. It's been a very eventful period for you as a public company. Maybe just as a starting point, just provide a quick overview of the company and sort of your lead program before we dive into the specifics. Yeah, great. It's great to be here. So yeah, exciting second half of the year or last few months of the year for us at Disc Medicine. As you referenced, publicly traded company under the ticker IRON, about $2 billion market cap as of today. Focused entirely on red blood cell biology, treating diseases that arise in the red blood cell compartment by manipulating the metabolism of iron and heme. So our lead program, bitopertin, is in license from Roche. We've read out of phase two, and about a year ago had an end of phase two meeting with the FDA where they invited us down an accelerated approval path. That was followed by about three more interactions, kind of defining different aspects of that pathway. Now we're projecting, with a high degree of confidence at this point, that we'll file our NDA in October, setting up then, presumably, if all goes well, a PDUFA date sometime in the second half of next year. So that's the lead program. A lot of interest in the regulatory pathway. We've also started the confirmatory trial called the Apollo trial. So that's underway and enrolling as we speak. Turning to our pipeline, which is quite well developed, we're in phase two on two different programs in myeloproliferative diseases. So we're manipulating iron up or down, up with our second program, DISC-0974, in myelofibrosis anemia and anemia of chronic kidney disease. Read-outs coming at ASN or ASH as we come into the end of the year. And then our third program, DISC-3405, manipulating iron down to manage hematocrit and overall kind of well-being in polycythemia vera. That's the quick snapshot of the company as we sit. And maybe we'll start with bitopertin. Clinically, one of the things that you sort of discussed recently was sort of that you had some evidence from, I think it was the Beacon study, that there was some improvement in some of the patients' iron or liver enzyme in some of that normalization there. And we know that that's not necessarily a great proxy for sort of protection from overall liver damage, but it is certainly better than nothing. And I'm just curious what the reception from KOLs has been. And is there any avenue to get liver protection onto the label? And what would you necessarily need to do, if not for the accelerated approval, but potentially for once you read out Apollo? Yeah, great question. So the data you're referring to came from The OLE long-term extension study, which we presented at EHA. Yeah, yeah. And the question about, is our drug going to be protective for liver disease in these patients is one where we have a high degree of confidence that it will be. That's based on epidemiologic data that's been published now, long-term natural history studies that show very clearly that Protoporphyrin IX, toxin that drives the disease, the higher that level is, the worse the liver outcomes are in these patients. And we know that reducing it by the 40%-50% that we see on average, that based on that data should provide significant protection, if not complete resolution. We also have now mouse data published. I mean, we did a one-year mouse study with our collaborators at Boston Children's Hospital and showed great data, tremendous protection from liver disease in those mice. So I think a lot of good reason to think this drug is going to work in that way. And I would say the KOL viewpoint is highly supportive of that. I think the general view there is, if you're reducing PP9, it is going to improve liver health. It's almost like inevitable is the viewpoint. Now, showing that is a long-term effort. And the studies we've designed so far are not designed to show that. We've generally been excluding patients who have evidence of severe liver disease. So we're working in a population that's by and large, their livers are unaffected or only very mildly affected. The data you referenced, though, we did look in patients who received the highest dose of drug and continued on that for the long term. We did see a reduction in ALT levels in those patients. So that's encouraging, directionally positive. But if you put all that data together, we have no expectation that that will be a label claim for us. I think that's going to be something that would have to come out of some longer-term or additional study work at this point. I'm just curious, when you talk to KOLs, do they think that's important or do they think this is sort of an outstanding question or do they intuitively get it just given the mechanism of action? Does that, given that intuitive sort of the mechanism of action and why it should have a protection effect on the liver, put bitopertin ahead of sort of Scenesse, which by definition should not or mechanistically did not have any protection of the liver? Yeah, I think there's general expectation that lowering PP9 is going to treat all aspects of the disease and a strong degree of belief in that premise from the KOL community. So I do think we'll have substantial advantage over Scenesse from that point of view, setting aside the obvious advantage we have, which is it's a once-daily pill, which is extremely convenient compared to a surgical implant. I'm just curious because this is a disease that has a very early onset. I would think sort of some of the patients that are most significantly affected are children, right, just because they want to run outside in the playground, et cetera. What's your plan for pediatrics? At what point do you think you'd be in a position to sort of discuss that? Yeah, so we did include in our 100 patients' worth of phase two work, four adolescent patients in the Australian open label study. Broadly speaking, the response to drug was the same as we saw with the adult population. So there's a strong argument that the adult data is predictive of adolescent benefit. So that went down to age 12. So our objective in our approval process is to include those adolescents on the label. But let's be realistic, with four patients of data, that is somewhat at risk, right? So it may well be that we have an adult label at launch and have to do additional pediatric work, which we are enrolling adolescents in our Apollo confirmatory trial. So it shouldn't be too far behind if we have to have some additional evidence. And that talks about going into adolescents, but is there a plan or thought into going? Oh, yeah, sure. Yes. Below adolescents, right? Because that should be a fairly significant marker for you. Yeah, we do have a plan there as well. Small, younger patient study, probably post-approval, post-first approval. Yeah, high degree of interest there. I think most patients, it takes a long time to get diagnosed, so eight or nine is when you start to see kind of the prevalent population increase demographically. To your point, there's no greater demographic representation in any particular age decile. But the adolescent and pediatric populations are extremely sympathetic because it's often the sort of moment of agony for patients as they first come to grips with the diagnosis and the way it's going to limit their activities through the school ages, and so we would very much like to provide something that can alter that for these patients. When you anticipate going, so obviously you feel comfortable with the dosing going into adolescence. When you go into sub-adolescence, even if it is just a few years younger, would you need to do some sort of dose ranging work to sort of identify whether you've got the right dose? I mean, we have excellent theoretical underpinnings for our dosing. So I don't think we'd have to do dose finding, even in the adolescent. Dose confirmation, I guess. Yeah, yeah. Even in the adolescents, we did do kind of an initial starting dose of 30 milligrams and then ramping up to the 60 that we view as the optimal dose, so there will no doubt be a lower dose just based on weight for younger people, but figuring that out shouldn't be complex. Okay. And maybe just an update on where you are from a commercial standpoint, because obviously the good news of getting accelerated approvals are going to be on market sooner. The bad news is that you were probably planning to launch this drug in a few more years down the road. And so you have to squeeze a lot of work into a short amount of time. We have indeed, yeah. And actually, I think as I've referred to in prior conversations, the CMC part of that was actually probably the hardest. But I think we've gotten that well under control now. And by the way, it's not hard because the drug is hard to manufacture. It's just there's kind of an exhaustive process to getting a commercial supply ready. That's under control. And yeah, we're full steam ahead on building the commercial team, Chief Commercial Officer on board. Many of the key leaders under her are in place, experienced team, lots of rare disease launches under their belts. We have a medical affairs team, MSL team now fully hired. And they're out in the field with the key mission at this point being taking our claims data, which we know has identified 14,000 diagnosed patients in the U.S., basically going rank order through sites by the number of through accounts by the number of patients identified in the claims data, going and validating those. And it's going very well. We're still in the early days, but if you go through the top handful of accounts, the numbers are basically broadly in aggregate matching up with what the claims data tells us. So starting to feel more and more confident about what that claims data predicts for us. Do you think that there's I think you've indicated in the past that the claims data suggested there were patients who sort of fell out of the system, just given the fact there wasn't a great treatment available? How much work do you think it will be to sort of find them and bring them back into treatment? Yeah, like you say, of those 14,000, we've identified about 6,000 to 7,000 who we view as highly engaged or engaged in their medical care for this disease. And we've sized our field-facing force, 25- 35 people, including MSLs, to access the accounts for those 6,000-ish patients. The rest of the patients, so-called 8,000, had only one claim against EPP in the seven-year lookback we did. So we view those as patients who, in all likelihood, got their diagnosis, felt that there was not much of a care system for them, and have simply gone and adjusted their lives to their diseases. So our approach to those is going to be more through patient advocacy work, social media type work, what we view as conventional launch things. I think what's great is that for those 6,000, with the claims data, I think, some very active patient advocate groups, we feel very good about being able to activate those patients. And in a sense, they're already activated. It's just a matter of confirming that with boots on the ground. Okay. And you may be turning to 974, which I think has sort of increasingly started to get attention with the investment community, certainly as that asset has made some progress. And one of the updates you gave somewhat recently was sort of the changes to the RALI-MF study and adding an arm of patients who are on momelotinib as well as pacritinib, I think. I guess, what do you think you will learn from that arm? And obviously, we see significant anemia associated with patients taking ruxolitinib. Does this sort of change in terms of the introduction of momelotinib change the dynamic at all for the market opportunity for 974? Yeah, I mean, that's been one of the big developments for the year is that, in a sense, a lot of the competitive stories have faded for us, and we feel like we're really the only drug in development anymore to manage anemia in myelofibrosis patients, and the reason I say that, momelotinib is very significant, so as you're saying, these JAK inhibitors, ruxolitinib is the mainstay therapy, has the side effect of exacerbating anemia, hence part of the reason why anemia therapy is important in these patients. Momelotinib, as one of the new JAK and newly improved JAK inhibitors, has launched very well, although interestingly, not taking market share from Jakafi so far, but it appears to be absorbing those patients who were deemed too anemic to even receive that best therapy, so those patients appear to have been kind of the target for momelotinib usage. I think if you look at the experience people are having, the notion that momelotinib is going to really treat the anemia in these patients, I think, is modest at best. And what it's really doing is providing anemia sparing, which is a very useful thing for these patients, right? You characterize Jakafi. This is the drug that I think everybody kind of wants to use, but it has this exacerbation of anemia. So then in your most anemic patients, I think physicians are hesitating about using that. Now, momelotinib gives them something that they can deliver it, and it's not going to make the anemia worse. And it may help a little bit, right? But what we saw as we opened our RALI-MF phase two trial with this exploratory cohort of 10 patients allocated to momelotinib and pacritinib, overwhelming demand from patients on momelotinib. You could not come into our trial unless you were anemic, right, so it was clearly that patients were going on to momelotinib, but not resolving their anemia, and hence, their care providers were still looking for an answer, and the only answer available is to try our trial, so we don't usually update on enrollment, but this was profoundly important, actually, to our trial design that we saw this extensive enrollment and actually over demand for that cohort of 10 patients, so what we did is we said, okay, well, look, we set that exploratory cohort aside because we wanted to know whether our drug actually would work on top of momelotinib. No reason to think it wouldn't, but it was an unanswered question. So we took a quick, and we shared this after EHA, a quick kind of non-quantitative assessment of the early data and saw that by and large, responses on top of momelotinib were similar to responses on top of Jakafi as well as on top of patients who weren't receiving any other therapy. So it felt like the rationale for treating this as a separate cohort didn't make sense anymore. So we rolled those 10 patients back into the three main cohorts based on their severity of anemia. And that allows us then to kind of enroll additional patients who are on momelotinib, give relief to the demand that we're seeing for enrollment into the study. And I think that'll be an important part of the data we shared ASH is really quantitatively now showing how does our drug perform on top of momelotinib. We already know from last year's data, it performs well on top of Jakafi. And I think our conclusion from all this is that our drug is going to be needed even in a world where momelotinib is being used. And moreover, our drug is going to work on top of momelotinib. And that's the preliminary assessment, real data to come at ash. And that's an amazing kind of resolution of a potentially competitive story back to the place now where we believe our drug is going to work on top of every available underlying therapy for these patients. I mean, I guess to your point, do you think that the availability of your treatment would drive some physicians to preferentially use Jakafi if you can address some of the anemia, right? Because that's the negative, and the preference for using momelotinib is that it is sort of anemia sparing, as you put it. There is a lot of interest in that approach, yes. I think physicians understand Jakafi very well. It's a therapy they like to use. We know head to head it is somewhat better at controlling spleen size and symptoms than momelotinib, so I think there would be a preference, and so if we're able to manage anemia early in these patients, right? We've seen very nice responses in kind of frontline, otherwise untreated patients where we can manage anemia with DISC-0974, and I think if you imagine us getting approved into that area, physicians would have the option of managing the anemia right out of the gate and then setting up the ability to use ruxolitinib as needed later as kind of the first line Jakafi. It would seem that, as I think one of the physicians says, one of the big value propositions of your drug is that you allow the sort of optimization of JAK therapy. Right, right. Maybe now turning to 974 for treating non-dialysis dependent CKD patients. Just maybe just a quick update on that program. I think one of the things that's been striking on the data that you've shown so far, which is not as mature as what we've seen in the MF patients, is sort of the effect on reticulocytes, which I think would ultimately bode well for what we'll ultimately see, right, in terms of improvements in hemoglobin. Whether you've talked about maybe that indication is one that you might pursue with a different asset. Where are you in terms of your thinking for developing that? I think it was 998. Correct. All correct. All correct. Yes. So with DISC-0974, I think it's now jets are on in myelofibrosis. I think increasing belief that the drug is working there. This is an important market, important unmet medical need that we're going to drive it with a lot of urgency. We also have been doing signal seeking with this molecule and other indications because we believe there's a broad anemia of inflammation world. And CKD was one of the CKD anemia is one of the obvious first indications. Everybody understands the hepcidin is elevated there. Hepcidin lowering drug ought to provide some relief from that anemia. The single ascending dose data that we shared a bit of last year at ASN was mixed, if we're candid, right? Some patients responded well, but there did seem to be some non-responders. So what we've been doing over this year is probing the full range of the doses that we had picked out for that study, as well as doing the multiple ascending doses. And we're gathering that full data set. We'll share it either at ASN or at ASH. We haven't committed to which conference yet, just based on timing as the data set comes together. And we'll see. I think the initial data showed that it's a somewhat more recalcitrant indication relative to myelofibrosis, where the responses have just been really great so far. And so the question on the table is, does increased dose or multiple doses give us a better response rate, a better average hemoglobin increase? If it does, we're going to plunge right into with great urgency into a kind of signal confirmation phase two trial. But if the data are more mixed and a little bit more questionable, we may take a pause and try to assess really the optimal use for that drug. A pause would also, as you mentioned, have the benefit of allowing the second generation molecule, which has an extended half-life, DISC-0998, to catch up, right? We're not yet in the clinic with that molecule, but we've learned a tremendous amount. I think we can move fast. And those patients do see their physicians less frequently. So having an extended half-life molecule, I think, provides legitimate benefit to that patient population. So that might be one of the ways this all comes together with what I call gray, dark gray data, if that's the way it comes out. We may pause, try to do some deeper understanding. We can continue to use DISC-0974 for signal seeking in other aspects of anemia of inflammation, where we've seen good preclinical data. But in the meantime, park CKD while we bring the second generation molecule on board. So that's a concept. Let's wait for the data. I guess as a follow-up on that, I mean, does it dent your hypothesis in terms of anemia related to inflammation, or are you still want to sort of invest in exploring things like IBD? Oh, yeah. Absolutely. CKD is somewhat unique in being a relatively low EPO form of anemia. And this is something we're curious about, whether baseline EPO levels have some influence on responsiveness to DISC-0974, to iron mobilization. We know in myelofibrosis, everybody has high EPO levels, everybody who's anemic, which is essentially everyone with the disease, which is a natural response to anemia. Your body makes a lot of EPO, but there's a problem, including hepcidin, blocking the formation of red blood cells. CKD is somewhat unique in that patients have declining EPO production, correlated with progressive kidney failure. So one thing we're watching carefully as we unpack this data set is there a tendency that patients with low EPO are poor responders? If that becomes the story, it doesn't really read through to other anemias of inflammation because essentially all of the forms of anemia have high EPO levels as a hallmark. Okay. And I know we're basically out of time. We're in stoppage time, as I refer to it. So if you could just really quickly touch on 3405 and just a quick update in terms of where that program is? Yeah, a super exciting program. We're in phase two, enrolling now, projecting data next year. The goal here is to chase the great data from rusfertide, showing that iron restriction is an enormously beneficial therapy for early to mid-stage polycythemia vera patients, and what we plan to bring to the table with DISC-3405 is an antibody rather than a peptomimetic. We think we'll be able to provide a better dosing regimen, and then part of our profile goal is to avoid any kind of injection site reactions. Haven't seen any in healthy volunteers so far, so we're optimistic about that. I think if we can bring that with a clean profile, it'll be a really exciting drug. Okay. Well, great. Well, I think we'll wrap it there. But thank you so much. And it's been a really busy time for the company. Yeah, great. Glad to be here. Thanks a lot. Thank you.