Disc Medicine, Inc. (IRON) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to Disc Management Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, John Quisel, CEO. Please go ahead.

Good morning, and welcome to the Disc Medicine Management Call. This is John Quisel speaking, CEO here at Disc, and I'll be joined by Will Savage, our Chief Medical Officer; and Jonathan Yu, our Chief Operating Officer. We are presenting from Orlando, where the 67th Annual Meeting of the American Society of Hematology is underway. We presented an exciting first look at data from the RALLY-MF trial at the ASH Conference yesterday, which will be the focus of today's call, along with a couple of broader corporate updates on the progress of our portfolio. Before we get started, I'll cover a few preliminaries. We will be making forward-looking statements, and these should be taken in context with respect to materials that we have filed with the SEC and have posted on our website. Additionally, Bitopertin, DISC-0974 and DISC-3405 are investigational agents and are not approved for therapeutic use in any jurisdiction worldwide. Turning to the agenda. I will give a brief introduction and provide a status update on Bitopertin, which is currently under FDA review for accelerated approval for treatment of erythropoietic protoporphyria, or EPP, under the new Commissioner's National Priority Voucher Program. Then we'll get into the ASH updates. Will is going to present the first interim data cut from our Phase II RALLY-MF study of DISC-0974 in patients with anemia of myelofibrosis. We first showed our proof-of-concept data for this program at ASH last year. And as you'll see, the results continue to point to this being a potentially transformative treatment for anemia of MF. And then Jonathan will discuss how these data position DISC-0974 in MF care and our view of the commercial opportunity. Finally, Will and Jonathan will discuss our third program, DISC-3405, providing an overview of our vision in iron restriction and study designs for the first 2 inpatient studies that we've initiated this year in polycythemia vera and sickle cell disease. I will close with a preview of where the company is headed in 2027. So on this slide are some of the key messages for today's call. With respect to Bitopertin, I'm delighted to announce that the NDA has officially been accepted for review. We were notified of this over the Thanksgiving holiday precisely on schedule. This has been a rigorous and intense review process to date, and we are planning for an approval decision and potential launch by the end of January 2026. This is consistent with the 1 to 2 months review period that is expected under the CNPV following NDA acceptance. However, to be clear, there is no statutory obligation for this time line, and I expect that the regulators will take whatever time is necessary to ensure a thorough review. Our commercialization efforts have been accelerated significantly, and we are well on our way to launch readiness. On DISC-0974, the highlight today is the RALLY-MF data. Like in the Phase Ib study, this initial data cut shows consistent and substantial decreases in hepcidin, leading to iron mobilization, and these translate to durable benefits on clinical meaningful measures of anemia, including hemoglobin, transfusion burden and symptoms like fatigue. Importantly, we will show that these results are consistent regardless of whether patients are on an underlying MF-directed therapy and regardless of which therapy they're on, including ruxolitinib, momelotinib and other JAK inhibitors. This is the lead indication for our second program and is shaping up to be a strong beachhead for Disc's second act in the myeloproliferative neoplasm hem/onc space. Then we have our third program, DISC-3405, which entered its first proof-of-concept study this year. We started the Phase II polycythemia vera trial around midyear and saw immediate interest and rapid enrollment from the community, prompting us to expand the study. These physicians are many of the same treaters who have been involved in our MF trials. So there's a great synergy between these programs from a development and commercial perspective. More recently, we started a Phase Ib trial in sickle cell disease. We expect initial data from both indications in 2026. So now let's get into the Bitopertin updates. As a reminder, we submitted our NDA for Bitopertin in EPP on September 29 of this year. And then a couple of weeks later, we were awarded the CNPV as part of the program's first pilot cohort. The CNPV grants a review time of 1 to 2 months from the NDA acceptance as well as increased engagement and enhanced communication from FDA reviewers. We have seen that engagement play out over the last several weeks, and we're actively collaborating with reviewers and responding to information requests. The FDA officially accepted our submission at the 60-day mark, so we anticipate an approval decision by the end of January 2026. We are preparing for a potential launch accordingly. And additionally, I can confirm that we've made great progress in accelerating our CMC readiness for launch, and we now expect to have drug supply available by the end of January 2026, coinciding with our anticipated launch time line. So really great progress across the board on this Bitopertin effort here. And aside from supporting the FDA's review for our application and preparing for launch, we are also continuing to drive enrollment in the ongoing APOLLO trial, with our focus shifting now to the ex-U.S. sites, which are currently being activated. As a reminder, APOLLO is intended to support full approval in the U.S. as well as a standard MAA application in Europe. We plan to present more detail on our U.S. launch strategy at the JPMorgan Healthcare Conference in January. And so with that, I'll hand it over to Will to provide ASH updates.

Thanks, John. As a reminder, DISC-0974 is an anti-hemojuvelin or HJV antibody that works to inhibit hepcidin, leading to an increase in iron availability and greater red blood cell production, which is why we are studying it in several anemias of inflammation. The focus today will be the data shared at the ASH Conference from our ongoing Phase II RALLY-MF study of DISC-0974 in anemia of myelofibrosis. In this study, patients received DISC-0974 every 28 days for 6 months and then have the option to roll into a continuation phase. As of the cutoff for ASH, we had enrolled a total of 47 patients in the study, and you can see these patients are spread across transfusion categories as well as a good mix of patients on and off JAK inhibitors, including 13 patients on momelotinib. Looking at pharmacodynamics, we can see the drug is working exactly as expected with significant decreases in hepcidin, which translated into increases in serum iron, and these impacts were seen consistently across transfusion cohorts. Here, we are looking at the nontransfusion-dependent and transfusion-dependent low cohorts, which represent the majority of patients. We see durable hemoglobin response in the overall population in the blue line in each cohort and even greater response in those patients who qualify as major responders. When looking at FACIT-Fatigue scores, where a 3-point change is seen as the threshold for clinical significance, we're seeing meaningful improvements in nTD and TD Low cohorts, particularly in the major responders. And this is encouraging because it shows us that the improvements in anemia are translating into improvements in anemia symptoms for these patients. Continuing with the nTD and TD Low cohorts, we are getting great hematologic responses, consistent with what we saw in the Phase Ib study. In the nTD group, we see a 63% overall response and a 50% major response rate. For TD Low, 71% of patients had both an overall response and a major response. As a reminder, historical response rates have been around 30%. So what we're seeing here is very encouraging. Moving on to the TD High patients, which represent the minority of MF patients and a small portion of the patients enrolled to date, we are seeing a 67% overall response rate in the 3 patients who had been on study for a sufficient duration and no major responses as of yet. On the right, you can see an additional 3 patients who have been on study for slightly less than the cutoff of 85 days for determination of a response. And these patients have excellent responses so far in terms of reduced transfusion and have not received any transfusions while on therapy, with all of them trending towards a major response of transfusion independence for at least 12 weeks. So of course, these are small numbers right now, but it's encouraging data. The data shown so far demonstrate meaningful response across transfusion cohorts. And here, we are also showing a consistently strong response regardless of concomitant use of JAK inhibitors. On the left, we show that regardless of which JAK inhibitor is used, DISC-0974 significantly lowers hepcidin, including in patients on momelotinib who actually start with the highest baseline hepcidin levels. This hepcidin reduction consistently leads to increases in iron, and then that translates into strong overall hematologic responses of at least 50% across all groups. These data continue to give us confidence that DISC-0974 can improve anemia no matter what other therapies patients are on. Finally, looking at safety, the profile is consistent with background adverse events typical for the MF population. DISC-0974 continues to be well tolerated with no treatment-related SAEs. So overall, we're very excited about this data set where DISC-0974 continues to show strong responses across a broad range of patient types with anemia of MF. And now I'll hand it over to Jonathan to review the MF anemia market.

Thanks, Will. As we've discussed previously, anemia is a serious unmet need when it comes to treating MF patients. And when we think about anemia of MF, there are really 5 key treatment objectives. Very important is a treatment that can work across the spectrum of MF patients with anemia. So first, patients need a treatment that works independent of the transfusion burden. Second, patients also need a therapy that can work as a monotherapy or on top of their backbone JAK inhibitor with the potential to optimize their JAK inhibitor regimen. DISC-0974 has shown similar strong efficacy as a monotherapy and in the combination with a range of JAK inhibitors, including ruxolitinib, the current standard of care as well as newer JAK inhibitors such as momelotinib and pacritinib. And we shared data on the latter for the first time at this conference. And most importantly, patients need a therapy with high response rates, something that DISC-0974 has demonstrated to date with overall response rates of over 60% and have also shown that this activity is durable. Moving on to the next slide. The implication of this profile is that DISC-0974 has the potential to address a very significant market opportunity. As we noted before, anemia of MF is a serious condition that affects approximately 22,000 patients in the U.S. alone. And these patients suffer from severe symptoms that negatively impact their prognosis, outcomes, optimal treatment and quality of life. This is a very clear and top-of-mind unmet need for both patients and physicians who contend with a lack of good existing or emerging treatment options for this burdensome condition. It's a well-characterized market with established treatment pathways and also that enables us to find -- that makes finding patients and connecting with HCPs fairly straightforward. So our goal then is to enter this market with a truly differentiated product that maximizes anemia benefit and has the potential to be used across the spectrum of anemia of MF patients and particularly in conjunction with the underlying JAK inhibitor therapy.

Thanks, Jonathan and Will. It's a very exciting data set in a rich market where we think DISC-0974 has real potential to address significant unmet need and reach blockbuster status. In anemia of MF, we will continue to progress this Phase II study with data planned for the second half of 2026. Following this, we are planning for an end of Phase II meeting with the FDA to align on the registrational trial design before proceeding into a pivotal trial, likely in the first half of 2027. We are also continuing to progress efforts around DISC-0974 in other anemias of inflammation with plans to initiate a Phase II study in anemia of IBD early next year. And we also have a long-acting version, which we call DISC-0998, and we are moving that molecule quickly into IND-enabling activities. I'll now hand it back over to Jonathan to discuss our third program, DISC-3405.

Thanks, John. DISC-3405 works in exactly the opposite direction from DISC-0974. So it works by increasing the endogenous production of hepcidin, thereby limiting iron availability, and it does so by inhibiting a well-validated target called TMPRSS6. We believe this approach to restricting iron has numerous therapeutic applications in diseases associated with erythrocytosis like polycythemia vera, ineffective erythropoiesis like sickle cell disease and other indications where iron overload is an issue. We presented healthy volunteer data at ASH last year, which showed this mechanism is working as expected and have now advanced the program into 2 proof-of-concept studies in polycythemia vera and sickle cell disease. We have also explored DISC-3405's potential role in treating conditions of iron overload as shown in our iron pulse study at EHA earlier this year and are continuing preclinical work in some of these indications. This program is an exciting growth driver for Disc, offering a differentiated product profile starting in 2 indications, which have been derisked and both represent attractive market opportunities. Starting with PV, this is a larger orphan indication with around 150,000 U.S. patients alone. This is a serious disease with uncontrolled hematocrit leading to significant risk of potentially life-threatening thrombotic events, among other debilitating symptoms, and many patients are not achieving optimal hematocrit control with current treatments. The role of therapeutic iron restriction in PV has now been well validated based on the clinical trial experience of Rusfertide, an exogenously administered hepcidin mimetic that has achieved significant phlebotomy-free hematocrit control and improved negative symptoms associated both with the disease itself and with frequent phlebotomy. We believe our approach can improve on this by using a monoclonal antibody to induce endogenous hepcidin production and which would allow dosing that is less frequent and has shown favorable safety and tolerability and no injection site reactions to date. Importantly, there is also significant synergy here with our NMF program, which we have already benefited from in terms of clinical development efficiency. So these 2 programs together form the beginning of a strong MPN hem/onc franchise. On the other side, sickle cell disease is another larger orphan indication, where there has been a lot of advocacy, KOL interest and R&D activity, but still very few effective treatment options. We believe iron restriction is a very promising approach based on clinical evidence, phlebotomy is increasingly being used as a treatment in clinical practice, especially in European countries and has shown evidence of disease modification. Mechanistically, we anticipate restricting iron to decrease hemoglobin S concentration would decrease the red blood cells propensity to sickle and therefore, may have benefits on hemolysis and VOCs or vaso-occlusive crises. This is a different approach from many mechanisms in development, which aim to increase hemoglobin, but it's fundamentally linked to the mechanism of sickling, which is directly driven by hemoglobin S concentration. I'll hand it back to Will to talk through our ongoing development program.

Thanks, Jonathan. Here's a look at our Phase II polycythemia vera trial, which we are calling RESTORE-PV. This is an update from what we have shown previously. In the early days of the trial, we saw such strong interest in enrollment that we amended the protocol to increase the sample size to 40 with 20 patients in Cohort A and 20 patients in Cohort B. Cohort A will have an initial dose escalation period before moving into first maintenance period, dosing DISC-3405 at 300 milligrams every 2 weeks, followed by 300 milligrams every 4 weeks. Cohort B will receive dosing of 300 milligrams every 4 weeks for the entire study period. We'll be focusing on safety, PK, hepcidin, iron, hematocrit and phlebotomy rate and expect to present initial data in 2026. And here's our Phase Ib sickle cell trial design. The main cohort of 12 participants will include people with hemoglobin SS and hemoglobin SC genotypes. There will be 20 weeks of dose escalation from 75 milligrams to 300 milligrams, followed by an optional maintenance period for up to 12 weeks. We will measure safety, PK, hepcidin, iron, hematologic parameters and hemolysis markers as well as explore additional efficacy endpoints, including PROs and changes in frequency of sickle cell complications. We expect to present initial data in 2026. Now I'll hand it back to John for closing remarks.

Thanks, Will. While the main update today was around the new MF data, I want to step back and acknowledge the transformative year we've had at Disc. A little more than a year ago, we learned that the FDA was open to an accelerated approval path for Bitopertin in EPP using PPIX as a surrogate endpoint. And now we are anticipating a potential approval and launch of Bitopertin before the end of next month. We have also today presented strong initial data from RALLY-MF, which further increases our confidence in the path forward for our second program, DISC-0974. And we expect to engage in discussions with the FDA about the registrational path for that program over the next year. We have outlined our next phase of development with 3 new trials in PV, sickle cell disease and soon in anemia of inflammatory bowel disease. And we continue to work in a highly focused way on exploratory research that will pave the next wave of pipeline development. We completed 2 follow-on offerings this year, which fund the company into 2029. And importantly, to note, that runway does not include any revenue projections from Bitopertin. So it's a very conservative runway statement. And this should take us through the launch of Bitopertin as well as several key pipeline milestones, all of which position us well to become a self-sustaining commercial stage biotech company with multiple levers for growth in the long term. And on the next slide, we have all that summarized in a pipeline chart. This chart is focused on what we view as the key value-driving trials. As you all know, there are other smaller exploratory trials going on with each of these molecules and the full pipeline chart is available on our website. But this set of key drivers for the company is going to drive multiple catalysts over the next 18 months. And we will be back presenting at JPMorgan next month. And at that meeting, we plan to give additional detail on our launch plans for Bitopertin as well as a view of key milestones for the company running into 2027. So with that, thank you all for your attention today, and I will turn it back to our moderator to open the Q&A session.

[Operator Instructions] Our first question is going to come from the line of Roger Song with Jefferies.

Congrats for the data. I do have 2 questions related to the poster. So the first one is, given the momelotinib anemia sparing effect, what should we expect the incremental anemia response on top of momelotinib? And then can you give us some reasonable benchmark? And then the second question, interesting. So you have a couple of patients pausing dose because they reached the upper normal range of the 12 gram deciliter for the hemoglobin. So how should we interpret that? And then can you give us some color around the frequency of such incidents and the kinetics of the pausing and resume the therapy?

Yes. Thanks for the question, Roger. As to point number one, yes, the effect of DISC-0974 to manage anemia on top of momelotinib in these patients, that's actually one of the exciting parts of this data. And I think what we see in the hemoglobin results when we break it out by the momelotinib group is great. It just shows essentially the same level of response as we see -- from a hemoglobin perspective as we see in all the rest of the patients. Interestingly, we see the same kind of decrease in hepcidin, and we see the same kind of iron mobilization. So essentially, patients who are receiving momelotinib, which as you say, it's an anemia-sparing JAK inhibitor, we get basically the same type of anemia response as we do with all other background therapies that we tested so far. So that's great to see. And it's a pretty robust data set at this point. Greater than 10 patients have come through on momelotinib. So we have a high degree of confidence around the robustness of that data. As to your second question, yes, we're delighted to see some patients reaching targets such that we had to pause the drug, and I'll hand it over to Will to comment further on that.

Sure. So we wrote in the protocol to hold the dose if hemoglobin gets into the near normal range just for common sense reasons. There's no need to continue treatment if they're not anemic. So we hold doses where applicable for hemoglobin and patients are evaluated on a monthly schedule for the protocol, and they just resume their monthly -- their dosing once the hemoglobin goes down below 12.

Our next question is going to come from the line of Thomas Smith with Leerink Partners.

Congrats on the data and all the progress. Just first on Bitopertin. It sounds like really great progress with the agency and ongoing engagement with FDA. But because you're one of the first companies going through this process, I was wondering if you could just comment on the acceptance notification and how it compares versus other typical sort of acceptance notifications. Is there any indication of review types like priority review? Or was there any explicit acknowledgment that the FDA would be proceeding under a more accelerated review process? And then a second question, if I could, just on 974 and the competitive landscape in myelofibrosis. Like you're clearly seeing consistent activity on top of JAK inhibitors with 974, including momelotinib, could you just comment on the mCALR targeted agents and how you think 974 fits into the treatment paradigm with those agents?

Yes. Thanks for the questions, Tom. Yes, I mean, it's really exciting to be part of this new Commissioner's National Priority Voucher program. And like you say, I think we and the FDA together are carving some new territory and procedures here. So I can tell you, it has been an incredibly rigorous and intense process. I don't know what the count on information request is at this point, but it's nearly daily. And there's an expectation that we will do some pretty complex analyses and respond within 24, 48 hours. So it's been a great process really to see the kind of speed and rigor combined and the sort of resources the FDA is able to bring to bear, all with the goal of bringing this therapy to patients as quickly as we can. So that's fantastic. In terms of the NDA acceptance, indeed, we did receive written communication around that. As a formal matter, it was designated as priority review. It is still considered under the accelerated approval pathway status, meaning the base plan here is approval based on a surrogate endpoint with indicators of meaningful clinical benefits and the APOLLO confirmatory trial. So that all is the basic premise here. And that's essentially what we know. Otherwise, the expectations around the 1- to 2-month review period are simply consistent with the public guidance that FDA has given around the CNPV program. And -- but like I said, it's clear that the intention here is to have it be a rigorous review that goes more quickly simply because the FDA is able to put more resources on it. And honestly, it would be great if this becomes a more broad widespread model for drug approvals here. So yes, then in terms of your second question, DISC-0974 with respect to the emerging mCALR targeted therapies, Will, do you want to speak to that?

Sure. I think 2 things to acknowledge regarding this exciting development in MF therapy. One is that those therapies are going to be potentially useful for a subset of MF patients. And we all hope that patients can benefit in many ways from new therapies, but it's only going to be applicable to those with mutant CALR. The second thing is that our mechanism of action is orthogonal to all MF-directed therapies, including mutant CALR. I think MF development has been trained to think about -- from other sponsors has been -- has trained everybody to think about single agent versus combined with rux. And there's kind of a legacy there that I don't think really applies to DISC-0974. And so we keep showing data that it doesn't matter what background therapy you're on in terms of a JAK inhibitor and expanding to other therapies as they become available, I anticipate the same response from patients.

Our next question comes from the line of Sean Laaman with Morgan Stanley.

Congratulations on multiple fronts. Just to clarify, the major hematological responses were achieved regardless of concomitant JAK inhibitors. But is there forward plans for specific combination strategies is the first question. And a similar question, opportunity for combination studies with ESA, luspatercept or other agents to further enhance efficacy or broaden the addressable population? And just lastly, first things first, of course, but beyond anemia and MF, what sort of other market opportunities might you observe with this mechanism?

Yes. Thanks, Sean. Yes, I mean, broadly speaking, the data again and again, both in the Phase Ib and now in the Phase II RALLY-MF study shows us a broad applicability of this mechanism. It just seems to provide benefit to all categories of patients that we're testing it in, in myelofibrosis. So while we could design trials and we have considered trials that would, for example, pair the drug, pair DISC-0974 directly with ruxolitinib on -- as soon as patients go on to that drug as a way of trying to buffer against the downward pressure that rux is known to put on hemoglobin levels. I have no doubt that, that would be an effective use of the therapy. But whether that's the exact trial design that brings this drug to the most potential patients, I think that's something that remains to be determined. I think right now, our bias, but let's wait until we get the full Phase II data, our bias is that this appears to be broadly usable in many different contexts in this disease. And we'll probably plan to study it essentially that way in the most generalized and broad way in our eventual pivotal trial. So that was the first question you had. The second question was going to studying with EPO and luspatercept. Will, do you want to speak to that?

Sure. So I'll say, Sean, despite John's comment about we want to develop this in the core development program for the broad range of anemic MF patients, there are interesting questions that are useful to answer like you bring up, like combination with EPO and luspatercept or upon initiation of rux, these are interesting questions that I think can be answered over time, but they're -- and certainly interesting to answer over time, but are not part of the core development program.

I will note we have presented at prior conferences, preclinical data showing the combination of the iron mobilization mechanism with EPO or luspatercept. And it's clear that these mechanisms do synergize. I think no real surprise there as you push red blood cell production with some of those agents, there becomes a demand for iron and that providing that by mobilizing with our antibody approach does appear to, at least in wild-type animal setting, drive additional erythropoiesis. So I think a lot of rationale why it would work, how we unpack that, we'll see over time. I feel like there was...

Market opportunity.

Right. Okay. Other market opportunities. Yes, I mean, this is something we're exploring. We had the readout from our study showing some activity in patients with a higher EPO level in that disease state. So we're still evaluating that. We have noted that we plan to open a trial in patients with anemia as a consequence of inflammatory bowel disease, and that's slated to start up in the first quarter of 2026. And that's what I would call sort of a pure anemia or -- well, definitely an anemia inflammation type disorder. And I think that remains the primary sort of expansion indication effort is into these anemia inflammation. Probably the right way to view that with DISC-0974 is that these are signal-seeking pilot studies and then we probably use our second-generation antibody to treat those wider indications. DISC-0974, I think at this point, with the success we're seeing in myelofibrosis, we'll keep it pretty focused there. We are probing MDS patients in a small cohort of this study as well. So that's an interesting neighboring indication that we're looking at, but we don't have any data to report out on that yet. So that's a sampling of where we're going. But yes, I mean, I think hepcidin and iron mobilization, it is a fairly broadly applicable mechanism.

Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald.

This is Rick on the line for Kristen. Congrats on the RALLY-MF data and progress across the pipeline. Just one question from us. On fatigue score, is there anything you can say even anecdotally about the TD High patients and the fatigue that they're experiencing and sort of relate that to the baseline that you see the patients starting at?

Sure. Sorry, the question was about fatigue and what the patients are feeling there.

Yes. Sorry, go ahead.

Yes. So we have only interim data on that. You noticed that we've reported out fatigue throughout the 6-month period for nTD and TD Low because we had data that far. We don't have complete data yet on TD High that's still in progress. But that is something we are evaluating.

Our next question comes from the line of Evan Seigerman with BMO Capital Markets.

So given the level of responses we've seen across both JAK and -- patients with both JAK and non-JAK background treatments, can you talk about what the FDA might need to see beyond this data in a Phase III to support a broad label across JAK usage and across kind of underlying hepcidin at baseline? And secondarily, for patients that are nonresponders or super responders, can you comment on how they've reacted to dose escalation to the 75 milligram, like how many patients have gotten to that level? And are they getting extra benefit from this escalation?

Yes. Thanks for the question. Will, do you want to go ahead?

Sure. Well, I don't -- from what FDA -- I think the key question is endpoint not so much population. So I think that we need to continue getting data from this study, come up with a Phase III design, engage with FDA and figure that out. But I think it's going to be acceptable to just take patients with -- continue to take patients with a wide variety of background MF therapy into a Phase III. This is precedented in other diseases where you're studying not the -- where they're receiving treatments that are not directed at what your drug is treating. So while other treatments are treating the spleen and symptoms, we're evaluating separately the anemia. So as long as it's balanced across groups, I don't think there's going to be much of a question of what the -- what kind of background therapy they're on. Regarding the dose escalation, I can say that it's a small number of -- it's a minority of patients who are receiving that dose escalation. We haven't reported out the results of that dose escalation because, of course, this is still an ongoing study. But looking at our Phase Ib portion with dose escalation, you can imagine that there's not a lot of iron benefit from escalating a dose, but we're doing the formal test of seeing what happens with dose escalation.

Our next question will come from the line of Tara Bancroft with TD Cowen.

So I'm curious if you could tell us if baselines, especially absolute hemoglobin levels, if they differed at all between enrolled versus efficacy evaluable patients and also by JAK use, if there's anything notable there at all if they were consistent. And then the clinical relevance of these hemoglobin increases you saw. I know that they experienced less fatigue, which is great, but it would be great to learn what you're hearing on how that impacts patient lives and their enthusiasm to continue or adopt therapy.

Yes. I'll start actually with the latter part. It's -- again, I don't want to put too much weight on anecdotes, but we've recently been hearing a lot of anecdotes about patients just feeling great on DISC-0974. I think the general reporting we hear is that there's not a lot of sense of side effect or anything -- any kind of negative feeling on the products. And we are starting to hear stories from investigators about how great some of the patients feel. But more rigorous, obviously, the data itself. Will, I'll hand it over to you to talk about the baseline hemoglobin levels and the other questions.

Yes. I'll just add one thing about the clinical meaningfulness of the increases that we're seeing. An important part of hemoglobin level is adding a buffer for patients. So if they get an acute on chronic problem, both physicians and patients feel some level of protection, like they're not on razor's edge with their hemoglobin and transfusion. So there's kind of a peace of mind aspect that's not captured in any endpoints that we're measuring, but it's certainly valuable clinically. Regarding the baseline hemoglobin difference, they are -- it is a mix across the board when you -- within each transfusion cohort. We're not looking -- there's no trend nor is there any inclusion/exclusion criteria that would bias the population. So it's still small numbers, but that's something that we may present in the future just to address the question.

Our next question will come from the line of David Nierengarten with Wedbush Securities.

I just had one left. When you look at anemia and IBD patients, are there any plans to stratify for baseline hepcidin or EPO levels in those patients, just thinking about the experience with CKD.

Sure. So in IBD, we know from the literature that it is a high EPO anemia like MF. And these have chronic kidney disease. In fact, in both MF and IBD significant in those trials, significant CKD is excluded from the study. The relationship between baseline EPO when you're -- and response is -- there's not a relationship in our study because everybody in the MF study because everybody has a high baseline EPO. And we expect the same in IBD. So it's not something we're planning. I mean we'll certainly evaluate as data come along, but it's not a stratification or enrollment criteria. Regarding baseline hepcidin, that as you may know it's a highly variable biomarker. It changes by the hour inside of a person. And so it's very sickle and not a good way to stratify patients nor when we look at our MF data, does baseline hepcidin matter for response. It's elevated in essentially everybody. And the key PD effect that we're looking for is increasing in iron, and that has been consistent regardless of what you're starting hepcidin.

Our next question comes from the line of Stephen Willey with Stifel.

Just a couple of quick ones on the Phase II PV trial. So what proportion of patients are you expecting to be on background standard of care therapy? And is there any mechanism in place to make sure you get a representative amount of monotherapy data? And then just based on the TPP [indiscernible], where do you think this best slots into the treatment landscape with respect to hydroxyurea?

Yes, good questions. Yes, we're certainly excited about the PV trial, but you picked up on that. We heard that enrollment was rapid. We've added another cohort. Yes, Will, do you want to speak about the plans for standard of care?

Sure. So there's there is not a protocol-specific way to ensure that we get representation of background therapy, but we do have the option to add a cohort into this study. So we can always add an attribute if we find out that there's some imbalance for an unexpected reason, we could always ensure that we get broader representation. But when you look at other sponsored studies, nobody has had an issue getting representative background therapy. We're not expecting that either. And regarding the TPP, I think we -- and hydroxyurea, I think people are going to -- one of the features of our TPP is the safety and tolerability profile. And if you're on hydroxyurea for hematocrit control, you have to compare what that looks like versus a once -- potentially once monthly antibody and that tolerability profile. So I think there's -- it's about giving options, and I think it would be an attractive option for patients and physicians.

Our next question comes from the line of Danielle Brill with Truist.

Congrats on the update. First, on the Phase II, I was wondering if you had the breakdown of response rates by background JAK use and baseline transfusion dependency status readily handy. If not, any qualitative comments you can share on whether there were deviations in response rates by the transfusion cohort when you look at background JAK use? And then I guess, looking at the optional continuation phase participation, only 68% of completers continued on. Any thoughts on reasons why others did not?

Sure. So regarding transfusion status and background, the question was on the transfusion responses and their background JAK status in the TD Low and TD High. We didn't present that. There's -- honestly, we haven't done [indiscernible] analysis. We have consistent results with the hemoglobin and overall response rate separated out by JAK inhibitor. As we get more data and particularly enrollment in the TD Low and TD High, looking specifically at transfusions will be more interesting. I think the question is -- it's really getting into finer and finer detail of a small data set. So I think it's something that could be forthcoming. Regarding those who -- only 68% of completers continuing, I don't know if it's only 68%, I think that's pretty good. But the -- we haven't collected the reasons. I know that one thing that has come up just in the study conduct is because of the appeal of the study, we do have a number of people who are flying to sites. There is a big travel burden for people for a number of participants, but we haven't collected systematically reasons for not continuing.

Our next question comes from the line of Rami Katkhuda with LifeSci Capital.

Congrats on the data. I guess do you think the slight differences in efficacy in the rux arm versus other JAK inhibitors is due to the small sample size? Or could it ultimately reflect a potential ceiling on anemia benefit from targeting this pathway? And then maybe secondly, on Bitopertin, the CNPV obviously accelerated the potential launch here. Could you provide a quick update on the status of your commercial readiness and sales force?

Yes. I mean I think the variations between the different JAK inhibitors are numerical small number type variations. Really, we're seeing consistent and similar responses across all groups regardless of background therapy. I think that's the take-home message from this data set, and that's how we expect it to evolve even as we get to larger numbers.

I mean one thing to add is that anemia in MF is multifactorial. There's bone marrow fibrosis, there's splenic sequestration, splenomegaly are causes of anemia. With the hepcidin data that we've shown, we're essentially doing the scientific experiment of showing the full extent of anemia in MF that is driven by hepcidin because I think we are essentially completely correcting the hepcidin problem. So I think the ceiling that is really just based on the pathophysiology of MF. I think when it comes to hepcidin, there's no more meat on the bone, and we are completely fixing that problem.

Let's see, your second question was about the commercial preparation for Bitopertin. Yes, great question, huge occupation of the company these days is accelerating all of our launch preparations by roughly 6 months over our initial plan. And I would say, generally, it's going great. We are working on hiring our sales force. We're expecting to hire 24 reps across the country, and that's ongoing. And assuming a late January approval, that field force will be out in the field pretty shortly after that date. So really coming together there. Reimbursement and access conversations are ongoing. That's probably one place where this accelerated process leaves us a little shorter than we might have been otherwise. And to that end, I think I've been guiding expectation that there may be a higher degree of use of start-up programs initially where we provide -- we may provide some free drug initially out of the gate while we sort through some of the prior auth questions. And then drug supply, this is a super important, exciting development. I think this is always one of the longest lead time activities of a company. And at this point, we feel pretty good that we're able to meet FDA expectations on a drug supply that we can make available on that kind of late January time line. So really, all the elements are coming together well, and we feel good about that accelerated process from a commercial point of view.

Our next question is going to come from the line of Derek Archila with Wells Fargo.

Congrats on the update. Just a couple of questions. So just a follow-up to a couple of questions ago, but just any differences on the disposition of the patients on momelotinib and pacritinib relative to the Jakafi patients? Just kind of reconciling that slightly lower response rate, but it does sound like it's probably just small end. And also, what was the average Jakafi dose in the patients on Jakafi?

Yes. So I do think it's a small numbers issue right now. I mean we don't have any specific information on different disposition in the study, just they're all doing well. The average Jakafi dose, I mean, that's something ultimately that we will look at. I mean in an interim look, it's less fruitful, I think, to look at that because patients are -- many patients are still in the middle of the study, and it is a manual extraction sort of analysis, but it is a relevant question.

Our next question is going to come from the line of Martin Auster with Raymond James.

Curious if you guys had any observations in MF and the non-JAK inhibitor cohorts. I was just curious if there's any color on whether those patients were those who maybe didn't meet criteria for JAK inhibition or if they've maybe been patients who previously exposed and a discontinued drug? And then secondly, I know you'll be thinking a lot about the registration path in MF next year. But I was curious for now if you could comment on whether you're thinking about sort of a unified Phase III with multiple cohorts or if you'd be looking to maybe separate out the non-transfusion-dependent and/or low transfusion-dependent population from the high TD population and whether or not that can kind of meaningfully accelerate Phase III enrollment and maybe help get to market a little faster?

Yes, I can start tackling your second question about our pivotal trial design. I think our objective is to run a unified single trial, including whatever patient groups we can unify well under a single trial design and feel confident about enrolling. And I make that last comment because acknowledging that the high transfusion burden cohort, while preliminarily looks like the response rate is going to be pretty good. A small end, it was that way in Phase Ib, just a somewhat difficult to enroll, probably fairly rare patient group. So whether we're able to logistically incorporate those into the pivotal trial into the end or may pursue those through a separate trial, that remains to be determined. But your point about paying attention to time lines here, that is something we are absolutely going to pay attention to and try to make sure we're running a really efficient trial to get this drug to patients as soon as we can. Now your first question, I'll hand it back to Will.

Sure. So regarding the non-JAK inhibitor patients, we're not rigorously characterizing in the study why they are not on a JAK inhibitor, but we have surveyed investigators and most of them are -- most of these patients are people who just do not need a JAK inhibitor yet. There's a large population, a large minority of MF patients who don't have spleen or symptoms issues yet and anemia is their primary problem. There are some patients who have been previously exposed to a JAK inhibitor and have stopped, but that's fewer in the nTD cohort.

Thank you. And I would now like to hand the conference back over to John Quisel for closing remarks.

All right. Well, thanks, everyone, for your attention today. Again, really successful ASH Conference for us here. We're really excited about the quality and breadth of data that we're seeing at this interim look in the RALLY-MF trial for DISC-0974 and look forward to more updates next year. And then meanwhile, also excited about just the excitement and the pace of enrollment in our DISC-3405 polycythemia vera trial. So again, I appreciate your attention. Thanks a lot, everyone.

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.