Protagonist Therapeutics, Inc. (PTGX) Earnings Call Transcript & Summary

Thank you for joining the Protagonist Therapeutics Research and Development and Corporate Update Conference Call. The company will give a presentation followed by a Q&A session. Directions for the Q&A will be given at the appropriate time. With that, I'd like to turn the meeting over to Dinesh Patel, CEO of Protagonist Therapeutics.

Thank you. Good morning, everyone, and welcome to our Research and Development Corporate Update Event. As a reminder, Protagonist is a publicly traded company, and today's discussion will include forward-looking statements about the company's future expectations. Let us start with the agenda for today's event that is listed on Slide #3. I'll be providing a general corporate update after which we will focus on the data presented for our hepcidin mimetic PTG-300 at the recent American Society of Hematology Conference or the ASH Conference. This year's ASH meeting was the first opportunity for Protagonist to share detailed findings on PTG-300 for polycythemia vera or PV at a major medical conference. Our presentations at ASH will be summarized by our Chief Medical Officer, Dr. Samuel Saks. We are also very fortunate to have Dr. Andrew Kuykendall from Moffitt Cancer Center, Florida, join us for today's event. Dr. Kuykendall will highlight the data that was presented at ASH from the ongoing Phase II study of 300 for polycythemia vera. Following Dr. Kuykendall's presentation, Dr. Sam Saks will summarize the next steps towards the registrational study that we envision for 300 in PV. We will then open the meeting for Q&A and will be joined by other members of the Protagonist team, namely Dr. Suneel Gupta, our Chief Development Officer; Tracy Woody, our Executive VP of Commercial Strategy and Dr. David Liu, our Chief Scientific Officer. Let us go to Slide #4. Protagonist is focused exclusively on the development of peptide therapeutics. We have a highly innovative, complex and proprietary technology platform that allows us to discover novel peptides in a de novo fashion against almost any biological target of interest. Our technology is like a toolbox with very unique tools ranging from the precision of computational design to randomness of phage libraries for de nova discovery and a very deep-rooted understanding of multiple peptide drugs and mechanisms existing in our gastrointestinal tract to enable us to engineer oral stability characteristics into this peptides. The true validation and strength of our platform and our capabilities is best illustrated by 5 different assets, including PTG-300 that have progressed from discovery to clinical development for multiple indications, and these are shown on the right-hand side of this schematic. The platform and the discovery engine are very much alive at Protagonist, and you can anticipate new peptides entering our pipeline in the coming years. On Slide 5, we are summarizing our pipeline of multiple peptides, and they fall in 2 broad categories of diseases. The first is hematology and blood disorders, and our principal asset here is PTG-300. And it is currently in 2 different indications. The first is a 50-patient Phase II proof-of-concept study in patients with polycythemia vera, which is our major focus and the main subject matter for today's event. The second indication being pursued is hereditary hemochromatosis, a disease which results from the absence or deficiency of hepcidin in the body. In the future, we do intend to pursue other indications with 300 that are characterized by erythrocytosis and iron imbalance. And finally, we are also working on an oral hepcidin mimetic and preclinical proof-of-concept data was presented at the ASH Conference. The second category is inflammatory and immunomodulatory diseases such as inflammatory bowel diseases or IBD. Here, we are developing orally stable and orally administered peptides that work through intervening those biological pathways that have already been validated by injectable drugs on the market, thereby derisking the biology, offering a strong differentiation and addressing a prominent unmet need of oral targeted therapy in these indications. One such validated mechanism is the Interleukin-23 pathway as exemplified by the IL-12 and IL-23 antibody drug Stelara from Janssen. Stelara is approved for both IBD and non-IBD indications, and it generated over $6.5 billion in revenues last year. Protagonist is pleased to have a partnership with Janssen, and we currently have 3 oral development candidates, PTG-300, PN-235 and PN-232 in our IL-23 program. Another validated pathway for IBD is alpha-4-beta-7 integrin as exemplified by Entyvio from Takeda Pharmaceuticals, which generated over $3 billion in revenues last year. PN-943 is an oral gut-restricted alpha-4-beta-7 integrin-specific antagonist peptide that is fully owned by Protagonist and is currently in a Phase II study in patients with ulcerative colitis. Finally, I'm very glad to report that we are fortunate to have a good cash runway lasting us through the middle of 2023, and that should enable us to complete the ongoing clinical studies to our satisfaction. Now let us go to Slide #6 and turn our attention to hepcidin. Hepcidin, as you know, is a natural hormone and a master regulator of erythrocytosis and iron homeostasis in our body. From a drug-development perspective, hepcidin in itself is a good starting point for drug discovery rather than a drug in its own right. It is a synthetically-complex peptide and lacks drug-like properties. Starting with hepcidin and using a scaffold hopping tool of our platform, we were able to discover 300 as a structurally novel synthetic mimetic of hepcidin with favorable drug-like properties all across the spectrum, spanning from potency and half life to solubility, stability as well as ease of synthesis. We believe that such a de novo approach is a unique attribute of our technology platform and poses a significant challenge and barrier to entry for others in the field. With that introduction, let me now ask Dr. Sam Saks to talk briefly about PTG-300 in polycythemia vera and the data we presented recently at ASH Conference. Sam?

Thanks, Dinesh. It's been a busy week for Protagonist and our clinical team led by Suneel Gupta. Days after receiving Fast Track status with the FDA, we were involved in 5 presentations at the Annual ASH Meeting. An oral clinical presentation of data from our Phase II study and high and low-risk PV patients was discussed. Four poster presentations were made, including our mimetic reversing iron deficiency in our clinical study, preclinical data on PTG-300 was presented, as well as our work on an oral hepcidin mimetic. Importantly, we were able to characterize the current state of real-world treatments, showing the unmet need for these patients. Next slide. Let me summarize what we have observed with this mimetic of a natural hormone that regulates iron. We have seen encouraging durability in controlling the hematocrit, while reversing iron deficiency in PV patients. Reversing iron deficiency may have an effect on symptoms. We have not seen serious off-target adverse events to date. In the real world, patients are not having their hematocrit in control to clinical guidelines that was demonstrated. Fortunately, today, we have Dr. Andrew Kuykendall here. He's one of our leading investigators from the Moffitt Cancer Center and has been involved in our study treating patients actively. Dr. Kuykendall?

Thanks, Sam. So I have the opportunity today to review the presentation that was presented at ASH this past week entitled PTG-300 eliminates the need for therapeutic phlebotomy and reverses iron with low and high-risk polycythemia vera patients. Next slide. And so before going into the trial design, I wanted to do a quick background on polycythemia vera as far as what it is and our goals with therapy. And so polycythemia vera is a chronic myeloid malignancy that is driven by a mutation in JAK2 protein, which is involved in blood cell production. And it leads to basically the switch being turned on to overproduce blood cells and leads to an overproduction of red blood cells as well as some white blood cells and platelets. And what this clinically leads to, in addition to numbers that are higher than usual, is also an increased risk of thrombotic events, such as blood clots in the veins and the arteries, which would include strokes, heart attacks, DVTs, PEs. And we know patients are at high risk for suffering these consequences, which obviously can impact morbidity and mortality. Additionally, these diseases can also progress to worse stages or worse forms of leukemia, including myelofibrosis and acute myeloid leukemia. Our treatment paradigm for polycythemia vera is really to attempt towards the risk of thrombotic events as we know this is one of the leading causes of death and morbidity for these patients. And so we do that by a number of different manners. So first, we treat all patients with aspirin in addition to phlebotomies or taking blood from patients to keep their hematocrit at a level that's optimal. And then in some high-risk patients, we'll add on a medication that we term cytoreductive therapy, and this can include interferon, ruxolitinib or hydroxyurea. Unfortunately, what this leads to is in the majority of patients we induce -- we performed phlebotomy to keep hematocrit to a good level, but what this leads to is result in iron deficiency. And it's almost what we're going for with the phlebotomies because we -- by reducing the levels of iron, they can't make red blood cells appropriately, which thereby reduces their need for phlebotomies. However, the iron efficiency results in adversary of symptoms and reduces quality of life. So we're kind of in a little bit of a challenge there because our treatment induces more symptoms that we're not really ready to alleviate because that would lead to more need for phlebotomies. So that's a quick background. So now I'll introduce the Phase II study of PTG-300 in polycythemia vera patients, and this was a study that enrolled patients with polycythemia vera that were requiring phlebotomies, and they had to be requiring at least 3 phlebotomies over the 6 months prior to going on study, so about 1 per every 2 months or so. And they could be on cytoreductive therapy, too. They could be on hydroxyurea, interferon, ruxolitinib or they could just be receiving phlebotomy alone. And in the first portion of the study, Part 1, was a dose-finding phase where patients were started on a lower dose of PTG-300 and slowly escalated on a monthly basis in order to achieve a hematocrit less than 45% which is our goal in these patients. And then the subsequent 12 weeks was an attempt to titrate this dose to find the optimal dose for each individual patient that could keep their hematocrit in that goal zone. This was followed by Part 2 where the -- which was a blinded withdrawal phase where patients are randomized to either continue on their optimized dosing strategy or to be taken off of medication, and closely monitored thereafter. And then patients then rolled over to the open-label extension phase, where they were either continued with therapy or put back on study if they were assigned a placebo and then monitored thereafter. At this point, as of November 18, 2020, 18 patients have been dosed and duration of exposure had been between 5 and 54 weeks. Next slide. So here is a little bit of a background on who was in some of the demographics of the patients included on the study. And this is a fairly consistent with what we see routinely in patients with polycythemia vera. You can see there's a male predominance, about 2/3 of patients were male opposed to 1/3 that were female. And you could see as far as patients requiring phlebotomies, the majority of patients were receiving 3, 4 or 5, phlebotomies with a small subset that was heavily phlebotomy-dependent requiring 6 or greater phlebotomies. And then you could see there's a diverse array of prior treatment. So about half patients were on phlebotomy alone, while just over half were on some sort of cytoreductive therapy in addition to phlebotomy, interferon and hydroxyurea. And then as far as risk category, about half and half between low and high risk, although we've kind of separated high risk due to age and then high risk due to thrombosis. As a background, patients are considered high risk if they have polycythemia vera, if they have a prior thrombotic event or if their age is greater than 60. And so that's why we broke it down into high with thrombosis versus just high. And then I'll give a little background on allele burden, what that means. So I briefly alluded to that virtually every patient with polycythemia vera has a JAK2 mutation. However, the degree to which they have this mutation or the amount of cells this mutation is present, that varies. And so patients with a related disease, essential thrombocythemia, which is considered to be kind of a lesser intensity myeloproliferative disease, will have allele fractions or allele burdens between 5% and 20%. Those patients with polycythemia vera will have allele burdens, meaning the amount of cells that have this mutation present and over 30% of their cells -- you can see here that the majority of patients on this study had allele burdens that exceeded 50%. And what does allele burden mean? Well, we know that the higher the allele burden, the more that associated with maybe higher blood counts and maybe an increased need for phlebotomy. So that's kind of what we would expect from this patient population that was phlebotomy-dependent. Next slide. And here's the money slide because as you can see here and looking at the slide right in the middle, the dotted vertical line is the start of treatment. And preceding that is kind of the phlebotomy history for each individual patient prior to going on study. And so each horizontal line represents a patient, and you could see the red droplets represent the occurrence of phlebotomies preceding the study. And then after the study starts, you can see a dramatic reduction in the incidence of these phlebotomies, meaning that patients once they started on treatment, really required much fewer and virtually eliminated the need for phlebotomy. You can see a few phlebotomies there, 3 that are evident on this graph. And that's not uncommon. Once again, the dose is being titrated up to achieve this goal hematocrit level. So there's a phlebotomy here and there, but overall a dramatic reduction in the frequency and incidence of phlebotomies. Next slide. And accordingly, we could see that the hematocrit or the percentage of blood volume that's made up by red blood cells was reduced associate -- reduced effectively to keep in the zone between 40% and 45%. And so hematocrit is really our gold standard for how to keep patients safe from thrombotic events, and this is based on a previous study called the CYTO-PV study that showed that patients with hematocrit less than 45% were at an increased risk for cardiovascular events and vascular events compared to patients who had a hematocrit that was between 45% and 49%. And so that's really what we're aiming to achieve is that threshold between 40% and 45%, and that was done fairly effectively with PTG-300 treatment. Some will also argue in the field that maybe red blood cell count is a better measure of relevance. However, it's not something that we often use. However, for those folks that are interested, you could see that PTG-300 also consistently reduces red blood cell counts and is able to keep those at an adequate threshold as well. Next slide. Now intriguingly, one of the rationales behind this is also to try to normalize iron levels or get the ferritin to come back up in patients who are sufficiently iron deficient. So you could see that at baseline, the ferritin level is significantly in that iron deficient range, so right around 5, suggesting clinically significant iron deficiency. And then soon after treatments initiated, you could see the ferritin levels begin to increase and then level out after week 20 or so. And so this is suggesting that iron stores are able to be normalized with this treatment. Transferrin saturation, which is a measure of the amount of iron that's bound to a carrier protein in the plasma, can see -- remains relatively stable throughout treatment. Next slide. And then looking specifically at some of these markers of red blood cell size and some of the details regarding that, we could look at this measure called MCV, and MCV stands for mean cell volume. This is a measure that we get on normal CBCs and what we know is that red blood cells that are deficient in iron are typically very small. These are small red blood cells. And so they have a very small mean cell volume. And as expected, with PTG-300 as iron stores increase, you can see that the size of the red blood cells gradually enlarges suggesting these are getting closer to normal red blood cell size. Similarly, we have MCH, which stands for mean corpuscular hemoglobin, and this is the amount of hemoglobin, which is the oxygen-carrying protein that's within the red blood cells that's present within each red blood cell. And once again, iron forms the basis for hemoglobin and patients that have iron deficiency don't make as much hemoglobin, there's less hemoglobin in each red blood cell. And so those are relatively ineffective red blood cells or inefficient red blood cells. Here, you can see that the mean corpuscular hemoglobin also increases along with PTG-300 treatment over the first 28 weeks. Next slide. Folks will always be interested in what happens to white blood cell count and platelet count as these are also hematologic parameters that can be increased in patients with polycythemia vera. But as expected, PTG-300 really doesn't have much of an impact on the white blood cells or platelets as it is acting through the hepcidin pathway and going to be more associated with red blood cell production. Next slide. And very importantly, I think from someone who treats patients with polycythemia vera, this is something that I was very intrigued to see, which is what's the clinical impact of doing all of these things? Obviously, we are very focused on keeping our numbers where we want them to be based -- in an effort to reduce the risk for thrombotic events, but also these are diseases that patients live with for a long time. So it really matters what their quality of life is in addition just to meeting some number parameters. And what we gained a sense of was that certain symptoms that can be associated with both the disease or iron deficiency, did seem to be improving over time with the treatment with PTG-300. So here, we can see problems with concentration, which is a symptom that's often referred to in patients with polycythemia vera as well as iron deficiency. You can see that, that improved from baseline to week 28 from 2.2 down to 0.7, this is on a scale of 0 to 10. You can also see the fatigue and pruritus. Pruritus is an itching, is a common symptom of polycythemia vera. You can see that those symptoms also improve. So I think that's very encouraging that clinically we're getting some improvements in addition to meeting our criteria as far as numbers go. Next slide. So how is this drug tolerated? So very encouraging data here, greater than 90% of the adverse events reported were Grade 1. So very mild in nature and no Grade 3 or 4 side effects were reported. We did see some injection site reactions in around 3 patients, and those seemed to decrease in severity with continued treatment. No significant or severe adverse events were seen and no subject or patient stopped treatment due to adverse events. So once again, very reassuring as far as the tolerability of this agent. Next slide. So what are the conclusions that we have from this? So first off, I would say that safety is always paramount early in drug development, and we could see that this was a well-tolerated medication that had no Grade 3 or 4 treatment-emergent adverse events. And those adverse events that were reported were typically Grade 1 and mild in nature. PTG-300 may be an effective agent for reversing iron deficiency, and it was shown to dramatically reduce the need for therapeutic phlebotomy in polycythemia vera patients. They were those types of patients that were requiring a significant amount of phlebotomy prior to going on the study. A significant decrease of therapeutic phlebotomy requirements for 7 months in phlebotomy-dependent PV patients was significant, and this durability is very reassuring. And this emerging story of the effect of PTG-300 on PV-related symptoms is also something that we need to keep our eyes on because this reflects clinical significance for patients on a day-to-day basis. Continued patient enrollment is going to be very important. This is a study that's ongoing. And certainly, with this data, patients are going to be more motivated to come on study. And we'll need to get to see longer follow-up and an increased number of patients to really get a better sense of what this drug is doing. Overall, PTG-300 obviously looks very promising and eliminating the therapeutic phlebotomies in both low and high-risk patients. So with that, I'd like to turn it back over to Sam Saks.

Thanks. That was a great presentation. I want to start by thanking all the patients and investigators who have contributed to this work, really doing heroic work in difficult times. We couldn't do it without all of them participating and doing everything they can to difficult -- to navigate this difficult time. So what have we done with this study? We've expanded the study to 50 patients. We're enrolling patients both in the U.S. and ex-U.S., that's to get the full diversity of the patient population. To date, we've enrolled 24 patients, showing that we've continued to enroll patients during this difficult time. We've obtained orphan drug status both in the U.S. and Europe and Fast Track designation in the U.S. We're in the process of finalizing our pivotal design and we're working with KOLs and advocates to do that because we hope to take that final design to regulators in the first half of 2021. We expect future clinical updates at major medical meetings and our commercial planning is well underway in doing -- including doing important work to get ready for discussions with payers in the future. With that, I'll turn it over to Dinesh to make some closing remarks.

Thank you, Sam, and thank you, Dr. Kuykendall. On behalf of Protagonist, I would like to thank you all for joining us today and a special thanks to Dr. Kuykendall. We would now like to open the line for a Q&A session. Operator?

[Operator Instructions] Our first question comes from George Farmer of BMO.

Thanks very much for this update. I wonder, Dinesh and Sam, can you talk about the regulatory path a bit more? What does it take to get PTG-300 approved for PV? And perhaps to kind of put these results into some sort of real-world context, how much of an impact do you think these results can really ultimately have on patient quality of life and just thinking about how the drug could be used much longer term?

Thanks, George. Those are both very good questions. In terms of your second question of getting with that first, we'll be the first one to admit that the results we are seeing so far are very encouraging. We are clearly demonstrating effects on taking care of iron deficiency and maybe we are seeing signs of translation of that into symptoms as well. But admittedly, the data set is small. And I'm sure Sam and Dr. Kuykendall may have something to add to that. In terms of the first question, and again, Sam will elaborate on that, the regulatory path forward and the next study design, things of that nature, we are in a situation that could be as good as it could be. We have orphan drug status we recently bought from both sides of the portion and we recently received Fast Track designation from the FDA. Sam?

Yes. So as Dinesh said, that Fast Track designation allows for an expedited process with more dialogue. We intend to take advantage of that. We can't tell you the specifics of the clinical design until, obviously, we talk to the regulators. As soon as we can finalize the design and we've given time lines for that, we will tell the world and begin to initiate those studies. With respect to the potential use, I mean, the data is unfolding, we need to wait for all the data to come in. But I think, again, this is highly encouraging and suggests there may be a broad opportunity here. And I'll let Dr. Kuykendall say anything he wants to about the symptoms since he's the one who's really treating the patients.

Yes. Absolutely, Sam. So I mean, I think first of all, what's the clinical utility of this drug or what's the potential clinical utility? I mean, I think it's pretty applicable for patients, mainly because I think what we run into is that phlebotomy for patients is a really archaic way of treating them, albeit it's kind of the mainstay of our treatment. But the process of getting phlebotomies and taking blood and doing this on a regular basis is really challenging and leads to either kind of frustration with the patient on top of symptoms of iron deficiency and then also leads to non-adherence or non-compliance to the treatment plan. So I think that in many ways, this addresses something that's clinically very relevant and very important for a pretty significant proportion of PV patients.

Our next question comes from Douglas Tsao of H.C. Wainwright. Mr. Tsao, your line maybe muted. Please unmute.

Can you hear me now?

[Operator Instructions] Your line is open.

Can you hear me now?

Yes.

Sorry about that. Dr. Kuykendall, maybe if you could -- I know it's early, but the company is obviously working on the development of an oral therapy. It seems like the injectable has been fairly well tolerated. So I'm just curious, maybe conceptually what you think of the value of that type of therapy? And then 2, in terms of the symptom improvement that we saw, I was just curious if there is one thing in particular that patients felt was most valuable or maybe said in other ways for PV patients, what's the sort of symptom that they find most problematic? Is it fatigue, lack of concentration? Or is it some of the things like pruritus, just your perspective on that would be most helpful?

Yes, absolutely. So to your first question, I think that most patients do prefer an oral formulation of medication, but that's not inherent. That's not necessarily the rule for everyone. With polycythemia vera, we are -- for cytoreductive therapy, we offer hydroxyurea or interferon as our mainstays. Interferon, a subcutaneous injection similar to this and hydroxyurea is the pill-form. And I would say in our practice, it's very -- for patients that are kind of between 50 and 65, I would say, it's pretty even split on what patients prefer. So I don't think that just because something is a subcutaneous injection that it's a nonstarter. I certainly think most patients prefer an oral formulation, but certainly once patients get used to subcutaneous injection, they don't really have too much of a problem with that either as long -- especially when it's once a week. To your second question about symptoms, I think it's an interesting question because when you look at data from countries that have large healthcare systems that they can interrogate and look at symptoms, that's really the main thing that bothers you on a daily basis with this disease. And then fatigue and itching and concentration issues, brain fog, bone pain, abdominal discomfort, all these things are symptoms that patients report in excess of 40% of patients. So I will say that the one -- from a personal aspect of patients on this study, I would say the one phrase they got back, itching improved, fatigue improved, but then one patient I remember just looked to me and said, I feel like this drug gave me my life back. And I feel like that's kind of encompassing a few different things: one, it took away that need for -- to constantly be checking hemoglobin going in and getting phlebotomies, but then it also gave a level of freedom and improvement in some of the other symptoms that I referenced earlier. So I think it differs patient to patient because the symptoms differ patient to patient, but we are seeing kind of an improvement in a variety of different things with each patient.

And just as a follow-up on that, Dr. Kuykendall, just curious, did you see as time -- patients who were on therapy, that their symptoms improved progressively or was it fairly immediate and then they sort of held at a constant level?

Yes. I mean, in my experience, it's been kind of a progressive improvement over time. I think that certainly that the first 4 weeks that you're on and when you're in the dose titration phase, there's still that -- there's still a little bit of hesitance about what is this drug doing, I'm on a trial, I still have to get my blood checked very frequently. But then as the iron levels seemed to come up over the course of the first and second cycles, patients seem to get more and more symptomatic benefit. And it's very -- it's hard to kind of put a number on it and we tried to in the slides. And within the MPN community, we tried to establish a scoring system that allows us to objectively measure this. But it tended to be something that occurred soon after starting, but also gradually progressively incurred while they were on study.

[Operator Instructions] Our next question comes from [indiscernible] of Jefferies.

Dinesh, Sam, Dr. Kuykendall and the team. This is [indiscernible] on for Chris. What are the key lessons you learned from the dose titration phase of the PV study that will shape the pivotal trial? And maybe for Dr. Kuykendall, how would you incorporate 300 into your clinical practice? And what proportion of your PV patients have high phlebotomy requirements?

Thanks for the wonderful questions. Sam, you want to answer the first one?

Yes. I want to say, basically, what we learned is that the response of the hematocrit is dose-related that we can in a dose-related fashion influence the hematocrit. I think it's fair to say, and Dr. Kuykendall can comment on the data, but we haven't seen a patient who's truly refractory yet, where we can't effect their hematocrit at all. But I would say that it requires titration, and this is a hormonal system. So those of you who are familiar with other hormonal drugs, insulin, cortisol, thyroid hormone, growth hormone, et cetera, they're all titrated to effect. In this case, the effect is a 100-plus-year-old blood test that is well entrenched as a way to treat these patients. So at the end of the day, as Dr. Kuykendall said, what we learned is you need a period of time to get it right. You may need to monitor it periodically to see if it stays right. But suffice it to say, again, like a lot of drugs that use indigenous hormonal systems, this drug is titrated to effect.

Yes. And to touch on the second question...

Go ahead, Dr. Kuykendall.

Yes. So just to kind of piggyback on what Sam said, it's been fairly predictable, definitely where as the dose goes up, the hematocrit comes under control, and we've gotten a good feel for that. It doesn't seem to have too many unexpected swings or anything like that. But from -- asking about its role within PV patients, I think, early on and -- PV is a really heterogeneous disease. And so I would say if you had to give a percentage of patients that this would be applicable for, say, at any given time, maybe 30% of my patients, but I think there's a time in each patient's PV journey where this is -- this could be a relevant approach. And I think especially for people that have a high-volume of disease, a high allele burden, those are patients that have high blood counts and require frequent phlebotomies, sometimes for years with their disease. And so this becomes a really interesting approach to try to keep those levels in a good zone while avoiding the iron deficiency that often comes with it.

Thank you. We have no additional audio questions at this time. Dinesh, I'd like to pass the floor back over to you.

Excellent. Thank you. So I'd like to make a few closing remarks. I think a number of messages have been conveyed over the past few days at the ASH Conference and then in today's call. With 300, we are in a wonderful situation. When we first disclosed the data in May, we had the data in 7 patients. When we released the ASH abstracts, we got the data in -- we submitted the data in 14 patients. At ASH, we presented the data in 18 patients. And as Sam mentioned, as of today, we have enrolled 24 patients. So we feel very, very good about the current study, the very important trends of solid hematocrit control and drastically reducing phlebotomy, that trend seems to continue. And we are very excited about that. Of course, now the patients are being treated for longer periods of time since we first announced the data in May. So the durability of the drug effect is in play and we very much like what we are seeing. The third thing is that if you look at the patients, the 18 patients, that is a diversity of patients, almost equal spread between low-risk and high-risk, treatment regimen diversity, we have 6 on phlebotomy alone, 6 on concurrent hydroxyurea, 1 on concurrent interferon. And then as we talked about today, we are clearly seeing reversal of iron deficiency based on ferritin as well as MCV and MCH measurements. And the safety component of the drug is very, very important. As Dr. Kuykendall mentioned and was presented at ASH, more than 90% of the patients, they have Grade 1 -- they recorded Grade 1 safety. There was nothing severe. Nobody has discontinued the study. Everybody continues to be treated with the drug. The retrospective analysis of the real-world patient treatment data gives us some alarming numbers. It's like the patients on current treatment therapy, we find that only 22% of the patients had hematocrit control below the 45% number. And I'm sure it is now amply evident the importance of keeping this below 45%. Because if you don't do that then the risk of thrombotic events increases significantly. In our analysis, what we found is that actually 49% of the patients, almost half the patients, had the hematocrit at least once about 50%. So that kind of demonstrates the "relative" ineffectiveness of the current treatment paradigm. And I would say the PV community is highly desirous of a good change over here. And we are able to offer that with a mimetic of the natural format. And as we also mentioned, we are starting with a subcu weekly injectable. The drug is looking very good. As Dr. Kuykendall said, it's like there is no strong preference for an injectable versus oral. But Protagonist is a company that knows that things are true about oral peptides. So at ASH, we also presented some preliminary but important data, a preclinical proof-of-concept data on the oral hepcidin mimetic. So that's about the science and the data and content around 300. Now in closing, I would like to thank all of you for joining us this morning. Again, our extended thanks to Dr. Kuykendall for his presentation and participation today. I would also like to thank the Protagonist employees who have worked tirelessly in discovering and developing PTG-300 and also other multiple assets that have enabled us to create a robust clinical pipeline. Finally, none of this would be possible without the healthcare providers and patients. So thank you and wish everyone a safe and wonderful holiday season.

Ladies and gentlemen, the call has ended. You may now disconnect.