All right. Welcome, everyone. I'm Tiago Fauth, I'm a biotech analyst at Wells Fargo. We're joined today by Disc Medicine. We have Jonathan here from the team. Thank you so much for making the trip.
Appreciate it.
A lot to discuss. I usually like to give you a couple of minutes for just some intro remarks. What are the main assets, where they are from a clinical development perspective, and we'll get to the detailed discussion thereafter.
Yeah, perfect. So just to orient everybody, Disc Medicine, as the name implies, is a company that is focused on, developing therapies to treat serious hematologic disorders, disc being the shape of a red blood cell. We now have a pipeline consisting of three mid-stage clinical assets, and the approach by which we went to build our portfolio is to build, to have tools that can manipulate, fundamental biology of the red blood cells. So we have programs that control how heme is synthesized, and we also have programs that control how iron is metabolized. So heme and iron, like, these are fundamental to the red blood cell biology, and that is the platform by which we're able to address a wide range of diseases, from anywhere from very rare orphan diseases to large blockbuster-type diseases. Just briefly, our p...
Our pipeline, our lead program is a molecule called bitopertin. It is a heme synthesis inhibitor. It is currently... We're wrapping up a phase II program, and getting ready to enter a phase III trial next year in a rare disease called erythropoietic protoporphyria. We had EHA. We presented data at EHA just this past year that showed really encouraging and transformative levels of efficacy, so we feel really great about that program. Our next program is DISC-0974. It's our lead program to control iron homeostasis. That is currently in two phase 1b/2 studies, in different forms of anemia of chronic disease.
The first in anemia of myelofibrosis, very severe, very serious, difficult to treat condition that is driven by high levels of hepcidin, and a second study in phase 1, in a phase 1b/2 study in anemia of chronic kidney disease, in the non-dialysis dependent segment. And those are both ongoing. We will have data updates on both of those there this year. And then the third program, DISC-3405, also controls iron homeostasis in the other direction. This is a program designed to increase hepcidin and restrict iron. There's a range of diseases you can go after there as well, but the lead indication we're going after there is a disease called polycythemia vera.
Each of our programs has demonstrated clinical activity, and so, looking very much forward to discussing our plans to push forward into the next phase of development.
Perfect. And just briefly for Bitopertin in erythropoietic protoporphyrias, let's talk about the mechanism of action, because again, this is a drug that was formerly developed for different indications, and we don't have to go necessarily that deep into the biology, but can you just describe the mechanism, why it is appropriate for this particular indication?
Yeah. So this indication, these porphyrias, are a family of rare diseases, genetically driven diseases. And they're basically diseases of dysregulation of heme synthesis. There's various mutations that occur in the genes that govern heme synthesis, and when you have, generally loss-of-function mutations in each of these steps in heme synthesis, what results in is a buildup of immature forms of heme, which are toxic. These are called porphyrins, and that is what causes all the different forms of the disease. In the case of erythropoietic protoporphyria, the last step in heme synthesis is governed by an enzyme called ferrochelatase. Patients with EPP have a loss-of-function mutations in ferrochelatase, and what results as a consequence of that is a buildup in the intermediate before a mature heme called protoporphyrin IX.
That is a highly photoactive toxic molecule, and that's what drives all the issues around the disease. The thesis around Bitopertin is that, so this is a small molecule that inhibits a transporter of an amino acid called glycine. Now, glycine is the initiating step for heme synthesis. You cannot make heme without glycine. So the thesis here was that if you can inhibit GlyT1, inhibit glycine uptake in. That slows down the entire heme synthesis process, and that allows you to bring down this toxic metabolite. So it gives you a disease-modifying way to address a disease of heme synthetic dysregulation, and that is what we've shown in our phase II trial, and that our drug does a very good job at reducing these levels of toxic protoporphyrin IX, and that results in pretty profound improvements in photosensitivity.
Got it. No, and I think that's a fair point. And one of the questions we were getting is just related to how validated the mechanism of action. So what is the literature that indicates the correlates PPIX to either disease severity presentation? You also have always established that 30% lowering that could lead to clinical benefit. Where does that come from?
Yeah. So there's a lot of literature out there, both in terms of and patient cases as well. The first thing is that protoporphyrin IX, it's not just a biomarker, it is what causes the disease. If you look at the structure of it, it's a it has lots of these double bonds. It's very similar to chlorophyll, and it's a very photoactive molecule. And the primary manifestation of the disease is, patients can't go outside without, in sunlight, without developing these very severe attacks. And that's caused by sunlight hitting protoporphyrin IX, activating it, and the releasing of these reactive oxygen species, causing all sort of downstream effects. So that is very well known, and so the biology should map extremely well because PPIX is what is causing all these issues.
But then, you know, from correlating it, there is very good evidence in the literature and patient case studies showing that patients who have higher levels of PPIX have more severe level of disease. Those with lower levels of PPIX seem to have a milder form of the disease. And there are also very interesting case studies where, for instance, in patients who become pregnant, for whatever reason, it's not clear what the mechanism is, they have decreased levels of PPIX. It doesn't go to zero, but they have a partial decrease in PPIX, and that is enough for them to have complete resolution of their disease while the patient is pregnant. And then once the baby is born, PPIX levels go back up, and the disease returns in full form.
So that told us that, you know, we know the biological basis of EPP, that PPIX is important to reduce, but this is also... This basically told us that if you can reduce PPIX, and you don't need to reduce it all the way to zero, that could have this transformative effect. So that was what motivated the entire development program.
Got it. So just to recap again, so you have a biomarker that is actually causative of the disease.
Correct.
How has Bitopertin performed on that biomarker in terms of reduction? How consistent it is? Is it dose proportional? What have you guys found out from a PK/PD perspective so far?
Yeah. Yeah, we know that the drug, and this is what we had always expected, because the preclinical data and the clinical data that we saw from Roche, we knew that this would slow down heme synthesis. The primary thing we were looking at in our phase II program, we ran two different phase II studies, one open label study looking at two different dose levels, and then the AURORA study, which was a placebo-controlled study, also looking at different dose levels, and very consistently, we were able to see statistically significant reduction of PPIX levels from baseline, order of magnitude to anywhere from 40%-50% levels of reduction. So that we felt checked a very important box that does your drug reduce PPIX levels in a meaningful way? The answer is yes.
Does it do it in a dose-dependent way? The answer is yes. So we feel very, that was maybe the most, one of the most important readouts from both of those studies. And then what led from that then is what does this mean in terms of photosensitivity? And then we can get into greater detail.
Yeah.
But then you measure photosensitivity through a variety of different ways, and I think each of those gives you one piece of the overall picture. But what was most encouraging from our phase II program is independent. There are nuances of how you measure it, but independent of which measure you look at, we are able to see that reduction in PPIX translates into meaningful improvement in photosensitivity.
Got it. And perhaps before we start talking more about that, let's talk about what you had in terms of regulatory comps and standard of care, right? Because you do have one treatment alternative that was approved on photosensitivity and hours under sunlight, so on, so forth. So can you just kind of recap what the competitive landscape was and how that informed the AURORA trial design?
Sure, yeah. So there is one drug that is approved on the market. It is in a surgically implanted pellet that elutes a form of alpha-melanocyte-stimulating hormone. Basically, it's a once every two-month implant that causes you to tan, and the thesis here is that by creating some level of barrier in the skin, that prevents sunlight from activating this PPIX. So it is not a PPIX-reducing agent. It is not what we would call, you know, disease-
Modifying
... disease- modifying, but it did get approved, and the endpoint that that company used was a very specific endpoint looking at cumulative time and light. That is one way you can measure efficacy. There are other ways to look at this as well. Another company, Mitsubishi Tanabe, is developing an oral tanning agent. Again, does not reduce PPIX. They're looking at a measure called time to prodrome event. But then you can also look at attacks, these photosensitivity, phototoxic attacks, which are really what govern what a patient on a day-to-day basis lives with and tries to avoid. So we looked at a whole host of different measures in our phase II trial.
Now, you know, to answer your question about how we went about designing the phase II, our phase II program, the primary endpoint was reduction in PPIX, because that mechanistically and was what was most important for us to demonstrate, and then we looked at a variety of secondary measures. We did look at the cumulative time in light endpoint, but we have also done analyses on a longitudinal basis. We looked at phototoxic events and also quality of life measures as well.
Got it. And the light tolerance for this patient population, is it fair to say that it's somewhat subjective? Because I'm curious how to think about the relevance and how consistent some of these endpoints are, 'cause that will help us kind of disentangle the debate on the AURORA results, right, for cumulative time and light, also time to prodrome. That feels like there's some degree of subjectivity here. So how should we think about the key efficacy endpoints that you've looked at?
Yeah. I think these are robust measures, but different degrees of robustness, and they each only give you a piece of the picture. And, you know, you can definitely design robust development programs around these endpoints, but you have to just be mindful of each of the idiosyncrasies of each of these endpoints. You know, I think, you know, one theoretical construct that everyone sort of would like to see is, well, can't you just do a challenge study? And that's what everybody wants to see, right? But there are, you know, ethical and operational limitations to that. So then what do you have that's left?
Well, you have these other endpoints that, you know, give you a piece of the picture that may have their own things you have to control for, but then also have to stand to regulatory scrutiny. So, you know, one of the measures we looked at was cumulative time and light, because that was what that was one regulatory precedent, but of course, it's one of several measures we looked at.
Yeah, and even in that endpoint, you did outperform placebo. It wasn't that significant, but I think taking those data in light of the longitudinal analysis, it becomes very interesting, especially because it was only, correct me if I'm wrong, but four months, correct?
Exactly.
So how do we reconcile that? Because there seems to be an early placebo outperformance, which you sort of saw with the Scenesse trial as well.
Yeah.
I'm curious how to paint the overall picture.
Yeah, exactly. I think this shows sort of the limitation of... One limitation is if you look at things from a cumulative, you know, in a cumulative basis, it obscures a little bit of what's happening as the data is being collected. So when we did our top-line analysis in April, you know, we did show a numerical difference from placebo, but because we didn't have the deeper analysis, and we're like, "Well, why is this difference not greater?" We weren't able to explain what was happening.
What we were able to show at EHA and what gave us just greater confidence in the drug's profile and, you know, a path forward in phase III, was what you saw is like early on, even before the drug is taking effect, every arm went out into the sunlight, you know, because, you know, that was just part of the study is you want to go see how much time you're able to spend in sunlight. You know, and nobody knows which drug they're on and, you know, so then you have this sort of an initial behavioral component in the study.
But then over time, what we were able to see longitudinally is that the placebo arm, their time in light regressed, but the active arm, in each case, they were able to continue to spend significant amount of time out in the sunlight. So compared to baseline, you know, we were able to double, you know, longitudinally, we were able to double the time that patients were able to spend in light, whereas placebo, it was like, you know, just 10% improvement. That nuance is showing, and then we were able to show that, you know, by the time that your PPIX levels have dropped, because it takes a little bit of time for the drug to take its full effect.
By the time the PPIX levels have taken effect, you're able to see in full flight later on, you know, from a longitudinal basis, that the patients were definitely having an effect, and this is, of course, different from the placebo side, from the placebo arm. The other element of this is that we were able to do a longitudinal analysis of what was happening in terms of pain attacks. This was quite striking in that by the time the drug took effect, patients basically were not experiencing any attacks in either the 20 milligram or the 60 milligram arm, whereas the placebo arm, you can see we have this chart in our slide. In our slide presentation, you can see that those patients continued to experience attacks.
So that was very important because in the totality, when you look at the totality of the data, what does it tell you? As our drug takes effect, patients on our drug are able to spend meaningfully more time in sunlight and are not experiencing any attacks, whereas placebo, they start spending less time in sun, and even that time that they're spending in the sun, they are experiencing attacks.
Exactly.
That told us this drug is active.
Got it. No, perfect. And again, really high expectations, too, that first AURORA update. And then again, folks started to regain confidence in the treatment effect and the mechanisms of action, both the ASH analysis. So what's the status now? There are some questions. Again, I don't think the base case would be that AURORA plus BEACON is potentially fileable. So I'm assuming you're in regulatory discussions with FDA right now for the phase III. What, what's the timeline for that, and what are some of the potential scenarios?
Yeah. So we're getting ready for phase III. And so what we've guided is our plan is to start a phase III first half of next year. The first, the step before, very, very important step before that, of course, is for us to engage with regulatory authorities. So, what we've guided is in Q4, we will have feedback from our end of phase II discussions with the FDA, so that we can provide guidance on, you know, what endpoint are we choosing and what does a phase III study look like?
Got it.
Yeah. And then, you know, we haven't provided, we're not providing specifics right now about our plans, you know, as we engage with regulatory authorities. But I think one of the things that came out of our EHA analysis was now that we have a deeper understanding of the data, we feel very good in that we have a range of options we can present the FDA with. In that, you know, even when you look at that cumulative time in light, if you look at it from a cumulative perspective, that numerical difference, that's real now. You know, it's not just a matter of chance, but then you can look at it analytically from a different number of ways or, you know, we know how to design a study to be able to handle that endpoint.
But we also showed statistically significant improvement in pain attacks. Pain attacks is very meaningful to patients, and we also showed stat sig improvement in a quality of life score. So we... All to say, I think we have a pretty good hand to be able to go into our discussions with the FDA.
Yeah. And again, I guess based on initial investor feedback, the efficacy endpoints, besides just the cumulative light, they have a much clearer signal that would have been very easy to power to show a clinical benefit. But the cumulative light tolerance, to your point, so it was a four-month trial. From the longitudinal data, you saw some greater separation the longer you follow this patient. So worst case scenario, if it is cumulative, how should we think about either length or just-
Yeah
... upsizing the trial to get the powering? Like, it, it sounds like you have some flexibility there.
Yeah, exactly. And we, if that is the endpoint, then we know now more how to design the trial. You know, things we can do to balance the study, you know, even going from four months to six months. You know, that longitudinal analysis showed you that separation is happening later... maybe that gets picked up if you go from four to six months, and then, of course, you can brute force it by having a larger sample size.
Yep.
So, you know, all of that was what came out clear from our EHA analysis and presentation.
And again, you don't have what the phase III design is, so hard to talk about timelines, but can you just give us context on the execution for BEACON and AURORA? How many patients, how quickly can you enroll these trials?
Yeah.
Enroll, right.
Exactly. Like, not having, you know, not with, without that feedback yet. But, you know, to give you a sense of these trials and the dynamics of how they recruit, they. This is a very well-networked, very engaged patient population, and so these trials, you know, ours or our competitors, they've all recruited extremely well. To give you a feel, you know, we ran our phase II program, you know, altogether was about a hundred patients between BEACON and AURORA, and about a year or two to enroll, and without a huge number of sites either. So that gives us great confidence that, you know, that's not a bad timeframe to think about enrollment for the phase III trial.
Perfect. And again, we spent a lot of time talking about the data. But let's talk about just the patient population, the addressable market real quick, just to wrap up the conversation. But from a prevalence perspective, what are some relevant comps? What are some relevant numbers? Is there upside to current estimates? Again, whenever better treatment options are available for rare diseases, you do tend to find more patients. How are you guys thinking about the commercial opportunity overall?
Yeah, I mean, that's absolutely the pattern for orphan diseases, you know. So when we started thinking about what is addressable. You know, one of the things about this disease, about this patient population is, like, EPP is not a silent disease. You know, if you go out into the sun and you have an attack, it's a constant reminder of the disease. And it's really just a question of, you know, how long does it take for you to get the definitive diagnosis. So there is a pool of patients out there, and what's more important is there's excellent patient advocacy groups that are already out there. They're very highly networked. They're tapped into key centers of excellence.
Most importantly, there's an ICD-10 code already for this disease, so there isn't a lot of, like, grooming of the market that's required. What this also allows us to do is some very rigorous analysis. With this ICD-10 code, specifically for erythropoietic porphyria, we did some pretty detailed claims analysis, and we were able to identify that, you know, this is kind of what we suspected, but there can be up to 14,000 patients already in the healthcare system with a definitive diagnosis of EPP. Then if we want to go a little bit deeper, and we know that there's 3,000-6,000 patients who are actively engaged, who have other hallmarks of the disease that, you know, speak to their severity and have multiple interactions with the healthcare system and that are also recent.
So that tells us that, you know, you have this pool of patients that's immediately available, actively seeking, treatment. There's room for that to grow. And then, you know, the only genetic, rigorous genetic prevalence study that was done predicts that there's actually probably about 20,000 patients in the U.S. with the disease. So all that tells us is that there is a sustainable and, like, there's a sustainable business case here, and that there are patients that you can access day one, and that there's room for it to expand over time.
Got it. And to wrap up the beta discussion, DBA. So again, that's not a trial that you guys are active in. I think that's for NIH, correct?
That's right.
But what is the mechanistic rationale to explore between that indication? And again, if you do get positive phase II data, proof of concept, what could that look like going forward?
Yeah. So there's an excellent biological case in DBA. It's a little bit more complex than the EPP case. With EPP, it's just, you have high PPIX, if you can reduce the beginning step, it lowers the toxic metabolite, and the biology is translated very well. DBA is a little bit more nuanced. The case of DBA is that you have these genetic mutations that result in a mismatch of heme synthesis and globin production. And one of the causes of why you develop this very severe anemia in DBA is that you have too much of mispaired heme that accumulates in early developing red blood cells, and that causes toxicity.
Our thesis, and it has been proven now in preclinical studies, is that if you can reduce heme synthesis, that can help the net production of red blood cells. Now, there's a lot of things that have to happen biologically for that to work out in a patient. We're very fortunate in that the NIH was very interested in doing an IIT study with us. That's a great way, you know, as we focus on EPP, for a very skilled collaborator who, you know, who knows how to run trials in DBA, to sort of keep this thesis going. If it is, if we see a signal, then we can always step in and prosecute development more aggressively. You know, it speaks to the broader opportunity for heme synthesis.
I mean, EPP is our focus just because the biology matches so well, but theoretically, heme synthesis should have a role in multiple different diseases. So, I think once the tracks are set for EPP, then, you know, it'd be very interesting for us to explore other opportunities.
Just from a population size perspective, how comparable could it be to EPP, just to give us a sense?
Yeah, it's even rarer than EPP, but, you know, some North American registries, there's about a thousand patients already sort of-
Yeah
... captured in that, so.
Okay. Perfect. So yeah, I want to move on to the rest of the pipeline as well. So DISC-0974, so therapeutic hypothesis there, lower hepcidin, increased iron, that could address anemia. And you mentioned myelofibrosis and CKD anemia. Why do you think that mechanism could be appropriate for those two indications specifically?
Yeah. There's a whole host of different diseases where hepcidin is elevated, and in these different diseases, there are other things going on as well, but myelofibrosis is a highly inflamed disease. There's actually very rigorous studies showing that the anemia in MF patients hepcidin levels are elevated an order, two orders of magnitude, so you'd know that there's iron dysregulation happening there. In the case of CKD, there's also underlying inflammation driving hepcidin production, but, you know, hepcidin is also cleared through the kidneys, so as you lose kidney function, hepcidin becomes elevated, and in all these other, a host of other chronic diseases, you know, this underlying inflammation is driving high levels of hepcidin, and so you're having this functional iron deficiency that results in anemia, those are the commonalities between these different forms.
Now, MF is where we're most advanced, and so we've already been able to show what we showed at EHA is just really encouraging efficacy signal. You know, the first thing we saw, we showed at ASH at the end of last year, preliminary activity there, but it was very small patient numbers, early doses, and what we were able to show at EHA was in a more robust data set at higher dose levels, that efficacy was basically preserved. So we're seeing 60%-70% hematologic response rates in a very difficult-to-treat anemia patient population. And that's great translation of the biology. So if you can reduce hepcidin and make iron more available, this results in anemia benefit.
Got it. And you should have an update for that same patient population later this year, right? So what should we be looking for there? Just basically additional patients for the higher dose cohorts and longer follow-up. Is that,
That's about right.
Yeah.
What we've guided is we're aiming to start a phase II trial of MF at the end of the year. So, you know, in the 1B data set that we showed at EHA was fairly robust, but not every patient had been on the full course of treatment yet. So I think an update just to close out the 1B data analysis for MF.
From a safety perspective, anything noteworthy so far? If I recall correctly, there doesn't seem to be anything that is dose-dependent or anything like that, and we have some pretty good hemoglobin response. So I'm just curious about the product profile we've seen so far and that, how that might fit in the competitive landscape, 'cause MF-
Yeah
... is perceived to be very crowded.
Exactly.
There's a lot of debates. How should we think about that?
Yeah, it's very important that whatever drug we develop is highly compatible with whatever background MF therapy a patient might be on. So safety is paramount, and particularly for some of these other indications that we're looking at, like CKD and, you know, other anemias of chronic disease. But the biology has translated beautifully. We went after this target hemojuvelin because of the genetic evidence validating it, validating the target. So there are patients who have loss-of-function mutations in hemojuvelin, and by and large, the only phenotype they have is too much iron, which is the pharmacologic activity we're looking for. So that gave us confidence. But then everything from the preclinical studies to the healthy volunteer studies to our experience in MF has sort of recapitulated that expectation.
The drug, if you look at the phase I data, the drug has an excellent safety profile, and, you know, that just... As a drug developer, you feel very good about that because then you know you can just focus on the efficacy, and you don't have to worry too much about the therapeutic index.
Got it. And for CKD anemia, there seems to be a little less focus, but since we're gonna get updated data on that as well, much bigger potential addressable market, mechanistically could make sense. Well, what is the setup into the data update?
Yeah, the setup is, you know, at the end of last year, you know, we gave just, like, some initial data on the program. So CKD is running at a sort of a longer fuse. It's sort of a little bit behind the MF program. But at the end of last year, we showed that, you know, at the 28 milligrams, the first dose level, that the drug was engaging the mechanism. We're able to show that you're able to reduce hepcidin and increase iron, kind of like what we showed in the healthy volunteer studies. But, you know, it wasn't at a high enough dose level that we would have expected to see changes in like, you know, erythropoiesis.
So we have guided that we will give an update on the 1b CKD study, you know.
That's single ascending dose only?
Single ascending dose only. You will have at higher dose levels; we haven't provided specifics on that, but it'll be higher dose levels. And what we want to look at is, are you continuing to engage the mechanism? Is it dose-dependent? So is hepcidin; are we getting hepcidin suppression, iron increase? And then what would be very encouraging for us is, you know, getting to doses where we're starting to see changes in erythropoiesis. So that translation of hepcidin to iron to erythropoiesis, you know, red blood cells, reticulocyte, hemoglobin, you know, some signal of that would be like just very would be very encouraging for.
Yeah
... for this, condition.
That's something that we've got asked a couple of times. Like, again, it's just single dose. Is there a clear bar for what would be meaningful for a hemoglobin change, given that it's just single dose and still relatively smaller to work from a mechanistic perspective in CKD anemia?
Yeah, yeah. I mean, I think for the purposes of the SAD study, I think it's important for us to understand, like, are we engaging erythropoiesis as opposed to magnitude, you know? But, you know, I think, once you... I think downstream, as you sort of look at some of like the IV irons, for instance, that got approved, the order of magnitude of change in hemoglobin, which is what they got approved on, was about a gram.
Yeah.
But, you know, we're still in dose finding, and it is still single ascending dose, but it would be... I think being able to see those signs that the biology is translating would be, well, would be sufficient. Of course, if we saw like hemoglobin changes at that level, you know, then all the more encouraging.
... Perfect. And the last pipeline item, three, four, five. Again, much earlier, so what should investors be looking for there? There seems to be interest in the indication, interest in the target specifically.
Yeah.
We might get some ASH EHA data as well, right? What are some of the comps? What's the setup?
Yeah, the way we think about this is that the biology should be very well validated. I think that, you know, the, the pioneer in this field, if you will, was Protagonist Therapeutics with their hepcidin mimetic, rusfertide. They were able to show that, you know, hepcidin, their approach to hepcidin therapy, restricts iron, and that they found a really great application in polycythemia vera. Our approach is to increase endogenous production of hepcidin, as opposed to an exogenous form, and to do that through inhibiting a target called TMPRSS6. And again, this was driven or this target was selected based on genetic validation, genetic examples, and human genetic examples which validate the target, and that there are patients with mutations in TMPRSS6. And what is their issue with iron restriction? So that gives us great confidence in the target.
Then it kind becomes a question of what tool do you use to manipulate that target. We feel the best way to do that is an antibody, because the profile we are looking for is, can you induce hepcidin in a dose-dependent and meaningful way? Can you do that? Can you restrict iron in a dose-dependent, in a deep way, and can you do it in a durable and controllable way? For that, we thought, well, the best tool for that is an antibody. That's why we entered this field with our anti-TMPRSS6 antibody. What we showed at EHA was that all those attributes we're looking for, at least in the healthy volunteer setting, were intact with just a single ascending dose, with just a single dose.
We were able to show many-fold hepcidin induction. We saw reduction, restriction of iron in the 50%-60%, you know, level that was durable for several weeks. And so that-
Close to healthy volunteer reference, right? Like, that was striking from the data.
Exactly. And so, you know, and it translated well from what we saw pre-clinically, and so that makes us feel very good that we have... The safety was excellent and what we expected, so very encouraging. You could call that proof of mechanism, and then we're really putting through the paces now of the multiple ascending dose phase, and hope to provide an update on that end of the year. All of that is a setup for us to go into polycythemia vera as the first indication, but there are multiple other opportunities we can go after as well.
Perfect. And again, in our last minute, a lot going on, right?
Yeah.
So you have EPP, DBA could be something going forward, and that's more of a rare disease niche. You can probably execute on that by yourself. CKD anemia, larger market historically, larger trials to run, NPV. Like, what's your current capital position and how you're thinking about capital allocation and strategically about all those indications in the pipeline?
Yeah. Yeah. So we're excellent. We're very well capitalized right now. So our last Q, we had $501 million in cash and cash equivalents. That takes us well into 2027. In terms of what it can fund, you know, it allows us to be able to prosecute, be able to complete the phase three trial for EPP. We'll be able to get through all the phase II studies that we're looking for in MF and CKD. We should be able to get phase II, you know, catalysts on PV as well, in our third program. And all, you know, prosecuting fairly aggressively.
In terms of how we're thinking about capital allocation and deployment and how we're thinking about prioritization, we were very deliberate in choosing each of our lead indications, as these are things that we can take forward on our own from a development perspective and commercialize on our own as well. So, some of these larger expansion opportunities, there may be a role for our partner if we want to prosecute those more aggressively. But, we should... Those also have a longer timeline, and so we could potentially address those, you know, you know, a future version of this could potentially address those as well. So all to say that we have a lot of strategic flexibility and the ability to be able to prosecute our plan.
Perfect. That feels like a natural stopping point. So, Jonathan, appreciate the time.
Thank you very much. Yeah. Yeah, appreciate it.