Good morning and welcome to Agios' webcast and Conference Call from EHA 2024. At this time, all participants are in a listen-only mode. Following opening remarks, there will be a question-and-answer session. Please be advised that today's conference is being recorded by Agios' request. I would now like to turn the conference over to Chris Taylor, VP Investor Relations and Corporate Communications of Agios.
Thank you, Michelle. Good morning, everyone, and welcome to Agios' webcast and conference call to review data from the phase 3 Energize study presented this weekend at the 2024 European Hematology Association Congress in Madrid. You can access slides for today's call by going to the Investors section of our website, agios.com. On today's call, you'll hear from our Chief Executive Officer, Brian Goff, Dr. Sarah Gheuens, our Chief Medical Officer, and Head of R&D. We are delighted to be joined by Dr. Ali Taher from the American University of Beirut Medical Center and Dr. Kevin Kuo from the University of Toronto. Agios' Chief Commercial Officer, Tsveta Milanova, will join for the Q&A. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements.
Actual events and results could differ materially from those expressed or implied by any of the forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. With that, we'll turn the call over to Brian.
Well, thanks, Chris, and good morning and good afternoon, everyone, and thank you for joining us on Father's Day. At EHA this week, we were pleased to present a total of seven abstracts, including two focused on data from the positive phase 3 Energize study of mitapivat in non-transfusion-dependent thalassemia. Earlier this month, we were very pleased to announce positive top-line data from the complementary phase 3 Energize-T study of mitapivat in transfusion-dependent thalassemia. We believe mitapivat is well positioned to become the first therapy approved for all thalassemia subtypes, which includes both alpha and beta thalassemia and both non-transfusion and transfusion-dependent thalassemia patients. We plan to file a marketing application encompassing data from both Energize and Energize-T to the FDA by the end of this year, which is similar to the approach we took with PKD, which led to a supportive label.
At EHA this week, data from the phase 3 Energize study were presented by Dr. Ali Taher and Dr. Kevin Kuo, two leading KOLs in thalassemia, who were also investigators in the study, and we are delighted to have both of these distinguished physicians joining us today. Each of them will briefly review the key data from their presentations, and then we'll open the call for questions. First, I will turn it over to Sarah, who will contextualize these presentations within our broader phase 3 program of mitapivat in thalassemia. Sarah?
Thanks, Brian. Next slide. Thank you. PYRUKYND or mitapivat is an oral small-molecule allosteric activator of pyruvate kinase with the potential to correct red blood cell metabolism through its novel mechanism of action, leading to more effective erythropoiesis, reductions in hemolysis, and improvements in how patients feel and function. Next slide. Mitapivat thereby has the potential to address the underlying pathophysiology of all subtypes of thalassemia, and we have advanced two global phase 3 studies, Energize and Energize-T, that together encompass all forms of thalassemia, including alpha and beta thalassemia and transfusion-dependent and non-transfusion-dependent thalassemia. It represents the most comprehensive development program in thalassemia to date. It also truly reflects a global population because patients were enrolled globally, and this is important as thalassemia can now be found globally everywhere, really in every country due to migration.
Also important is that both Energize and Energize-T studies have met the respective primary endpoints as well as all key secondary endpoints. Based on the positive data we have generated in both Energize and Energize-T, we believe that mitapivat is poised to become the first therapy approved for all thalassemia subtypes, and we look forward to submitting an SNDA based on all available data for both studies to the FDA by the end of this year. On today's call, I'm very happy to be joined by Dr. Taher and Dr. Kuo, who will be walking you through the data that was presented at EHA just now. The data, of course, gives an overview of the study that we have run in a non-transfusion-dependent thalassemia patient population. Without further ado, it's my pleasure to turn the call over to Dr. Taher.
Thank you, Sarah. Next. Energize is a phase 3 double-blind randomized placebo-controlled global study of mitapivat in adults with alpha and beta non-transfusion-dependent thalassemia. This study is conducted in 70 sites across 18 countries. Eligible patients were randomized in a 2-to-1 ratio to oral treatment with mitapivat 100 milligrams twice daily or matched placebo for 24 weeks double-blind period. Patients who completed the 24-week double-blind period could receive mitapivat and for an additional 5 years in an open label extension period, which is currently ongoing. The study, as said, enrolled adults with alpha and beta non-transfusion-dependent thalassemia with a hemoglobin of less or equal to 10 grams per deciliter. You could see also that randomization was stratified by baseline hemoglobin and thalassemia phenotype. Next. These are the endpoints. I will stress only on the primary endpoint and the key secondary endpoint.
The primary endpoint is hemoglobin response defined as an increase of equal or more than one gram per deciliter in average hemoglobin concentration from week 12 to 24 compared with the baseline. The key secondary endpoint is a change from the baseline in an average fatigue scale, fatigue score from week 12 through 24, and we will see this in the second presentation with my colleague Kevin Kuo. Next. This is the patient flow chart. We started with 235 patients assessed for eligibility, 194 patients randomized between 2 to 1, 41 did not meet the eligibility criteria on screening, and we've ended with 130 patients included in the mitapivat arm versus 64 included for full analysis in the placebo arm. Next. The baseline demographics and disease characteristics are clearly seen on this slide, and they were balanced. For example, the mean age was around 40 years.
There were slightly more females than males. The median baseline hemoglobin was 8.4 grams per deciliter. Approximately one-third, as you see, of the patients had alpha, and around 40% were splenectomized. What is important is that most had received no transfusion during the 24 weeks prior to randomization. Next. This is our primary endpoint that was met. Most patients in the mitapivat arm, as you could see on this waterfall plot, most patients in the mitapivat arm experienced an increase in hemoglobin as shown in this plot. 42% met the threshold of hemoglobin response as defined in the endpoint versus 1.6% in the placebo arm. Among patients who achieved the clinical response or the hemoglobin response in the mitapivat arm, mean change from baseline in average hemoglobin concentration from week 12 through 24 was around 1.6 grams per deciliter. Next.
Hemoglobin response rates were higher, as you could see, in the mitapivat versus placebo across all pre-specified subgroups. I will not go through the detail, but it was higher in the mitapivat versus placebo. Next. Now, the key secondary endpoint, which was a very important part of this study, also demonstrated a statistically significant improvement in this key secondary endpoint, change from the baseline average fatigue score from week 12 through week 24 compared to the placebo. The FACIT-Fatigue questionnaire is a validated PRO tool used to assess the impact of fatigue on individuals with chronic illnesses. Higher scores, less fatigue, and my colleague Kevin Kuo will be discussing this in his next presentation. Next. This is an interesting slide that shows that the hemoglobin levels improved early in the mitapivat, you could see at week 4, and were sustained all through the 24 weeks. Next.
Also, as you know, the pathophysiology or the pathology in the disease relates on hemolysis as well as ineffective erythropoiesis. So improvement in the markers of hemolysis were observed in the mitapivat arm by a reduction in indirect bilirubin and a reduction in LDH versus the placebo. Next. Similarly, improvements in markers of erythropoietic activity were observed in the mitapivat arm versus the placebo arm with an increase in reticulocyte count. Next. Now, that was the efficacy, and if we look into the safety, the mitapivat was generally well tolerated. The proportion of patients with adverse events of any grade was similar between the two treatment arms, the mitapivat versus the placebo. 8 patients in the mitapivat arm had serious adverse events and were considered not to be treatment-related. No serious adverse events or adverse events leading to treatment or discontinuation in the placebo arm.
However, four patients had adverse events leading to discontinuation in the mitapivat arm. Next. If you look at the most frequently reported, more than 10% adverse event, you'd see that they were headache, insomnia, nausea, similar to most of the studies, and they were mostly transient and did not affect neither the quality of life of our patients nor necessitating stopping the drug. Next. So in summary, this global study was the first to enroll patients with alpha thalassemia in addition to beta thalassemia. The primary outcome endpoints were met. The key secondary endpoints were met with statistically significant improvement in hemoglobin and fatigue with mitapivat versus placebo. And when we looked at the pre-specified subgroup analysis, it all favored mitapivat versus placebo. Improvement, as I've shown you in the markers of hemolysis and erythropoietic activity, were observed consistent with the mechanism of the drug itself or mitapivat.
Mitapivat was generally well tolerated in the study with low treatment discontinuation rate and a safety profile consistent with other studies. Thank you. I would like to ask my colleague, Dr. Kevin Kuo, to move into the patient-reported outcomes measures.
Thank you, Professor Taher. Now I'll be talking about the quality of life as well as patient-reported outcome measures in the Energize study. To recap, patients with thalassemia have serious long-term multi-organ complications. Anemia is associated with increased symptom burden such as fatigue and poor health-related quality of life. This is especially true in patients with non-transfusion-dependent thalassemias. This, of course, impacts on daily activities, physical functioning, as well as emotional and mental state. Now, this is, of course, regardless of transfusion status, and it's for patients with both alpha or beta thalassemia. Now, some domains within the health-related quality of life are worse or comparable in adult patients with NTDT versus those who are transfusion-dependent. Remember that for alpha thalassemia patients, there are no approved therapies. For beta thalassemia patients, there are no approved oral disease modifying therapies as well.
More importantly, there are no oral disease modifying therapies for thalassemia that's been shown to improve aspects of health-related quality of life. Next slide, please. Thank you. So as you can see in this slide here, Professor Taher has already described to you the primary endpoint and key secondary endpoint. Now I'm going to expand upon our key secondary endpoints here, which includes the FACIT-Fatigue score and also the 6-minute walk tiredness, as well as the patient global impression of change in fatigue, as well as the PGIC in thalassemia symptoms and PGIC in walking capacity. Next, please. And here, next, please. So let's have a look at the top table here. Patients, as you can see in both mitapivat and placebo arm, they're fatigued at baseline with a mean baseline FACIT-Fatigue score that is lower than the general population.
For reference, the FACIT-Fatigue score in the general population is 43.6. Mitapivat, and on the second row here, you can see mitapivat has demonstrated a statistically significant change from baseline in the average FACIT-Fatigue score from week 12 through week 24 versus placebo with an LSM difference of 3.4. So the next question is, how much of a change in the FACIT-Fatigue is considered to be clinically meaningful for a patient? And that's 4.5 points or higher. And we will call this MWPC or meaningful within-person change. Now let's turn our attention to the waterfall plot below that. In here, we see a higher proportion of those on the mitapivat arm, specifically 36.2%, met or exceeded the MWPC threshold compared with the placebo arm, which is 21.9%. Next, please.
On Figure 4, you can see that mitapivat led to early and sustained improvement in the FACIT-Fatigue score. Next, please. Now let's turn our attention to the 6-minute walk test, which is the litmus test for function. In healthy individuals that are aged 20-50 years, and which is a similar age range to our Energize cohort, a mean six-minute walk test distance reported in the literature is 593 meters for females and 638 meters for males. As you can see here in the table below, the baseline six-minute walk test is substantially lower in both the mitapivat as well as the placebo arm. Now, when we look at patients in the mitapivat arm, they had a greater improvement in their six-minute walk test compared to those in the placebo arm at week 24. Again, you can see it here in Table 2.
The least squares mean change from baseline at week 22 to week 24 is 30.48 meters in mitapivat arm and 7.11 meters in the placebo arm with an LSM difference of 23 meters between the treatment arms. So let's contextualize this. What does this really mean? Right? What we're looking at here is that in the literature, the reported MCID threshold, the minimum change important differences, clinically important difference is 20 meters. Mitapivat has clearly cleared that bar at 30.48 meters. Next, please. In Figure 5, we see that there is consistent reporting of greater improvement in the mitapivat arm as shown in the blue bar versus the placebo in the gray bar from week 12 all the way to week 24. Next, please.
In Figure 6, in terms of the patient global impression of change in the thalassemia symptoms on the left-hand graph and in the PGIC of the walking capacity on the right-hand side, you can see at 24 weeks, you can see that in both of these measures that there's substantially higher proportion of patients with mitapivat versus placebo that reports a much better or a little better improvement. So in conclusion, in this 24-week double-blind period of Energize, there are significant improvements in fatigue as measured by the FACIT-Fatigue. This was demonstrated in the mitapivat arm compared to the placebo arm. A higher proportion of patients reported clinically meaningful improvements with mitapivat versus placebo. Furthermore, functional improvements in patients in mitapivat as measured by the 6-minute walk test exceeded a previously reported meaningful change threshold from the literature, which was 20 meters.
A higher proportion of patients with mitapivat reported improved fatigue, disease symptoms, as well as walking capacity, as was shown in the Patient Global Impression of Change with mitapivat versus placebo. So in conclusion, mitapivat is the first oral disease-modifying investigational therapy to show an improvement in fatigue as well as walking capacity in patients with both alpha or beta NTDT. Now I'm going to turn it to Brian Goff for the closing remarks.
Well, thanks a lot, Dr. Kuo, and thank you very much, Dr. Taher. This is really a special opportunity for us to hear directly from both of you. We really appreciate your perspectives, your insights on the data from this important study, and we're very thankful for your time. So with the positive data we've generated with mitapivat in thalassemia as well as in PK deficiency in sickle cell disease as well, we have great conviction in the potential for mitapivat to become a first-in-class and best-in-class treatment option for multiple indications and to become a multi-billion dollar franchise. Now, as a reminder, in addition to the two positive phase 3 studies in thalassemia that we've already reported this year, we're anticipating multiple additional catalysts over the next 12-18 months.
Specifically, by the end of this year, we expect to submit an SNDA for mitapivat in thalassemia, report top-line data from the phase 3 Activate Kids T study of mitapivat in regularly transfused pediatric patients with PK deficiency, and complete enrollment in the phase 3 portion of the RISE-UP study of mitapivat in sickle cell disease. Next year, we expect to report top-line data from the phase 3 portion of the RISE-UP study in sickle cell disease, as well as the phase 3 Activate Kids study of mitapivat in pediatric PKD patients who are not regularly transfused, and to launch mitapivat for thalassemia in the U.S.
Finally, I'll note that through the divestiture of our oncology business to Servier and the recently announced royalty agreement with Royalty Pharma, we have the potential to receive an additional $1.1 billion in payments upon FDA approval of vorasidenib, which has a PDUFA action date of August 20th of this year. We believe this additional cash will provide us with financial independence to prepare for back-to-back potential launches in thalassemia and sickle cell disease as we build a PK activation franchise with multi-billion dollar potential. Before we transition to Q&A, I'd like to take a moment to thank the entire Agios team and again express my sincere gratitude to Doctors Taher and Kuo for joining us today. And with that, we will now open the call for questions.
Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We do ask that you please limit yourself to one question and one follow-up. One moment while we compile our Q&A roster. Our first question is going to come from the line of Gregory Renza with RBC Capital Markets. Your line is open. Please go ahead.
Great. Thanks. Good day, Brian and team. Congrats again on the updates today and certainly over the course of this year. Thanks for taking my question. Brian, maybe for you, Sarah, of course, and for the doctors on the line, just curious if we could comment a bit on how the health-related quality of life measures and the FACIT fatigue, of course, correlate to hemoglobin improvement. And do we think that those quality of life improvements are driven by the hemoglobin increase, or are there other aspects of maybe mitapivat's biology that could also contribute? Thanks very much.
Sure. Thanks, Greg. First off, happy Father's Day. I think you as well.
Thank you.
Yeah, thank you.
Yeah, happy Father's Day to you as well. Yeah, it's Kevin here. That's a very interesting question. Definitely, we need to look at that, but we have not looked at that yet.
So if I can add to that, right now we have done the intent to treat analysis just as pre-specified in our protocol. We were very pleased with the results that we have obtained via our pre-specified statistical analyses and are now really focused on moving the program forward towards regulatory submission.
Got it. Got it. Thank you. Maybe just I'll use my follow-up. Just with respect to the primary endpoint and the secondary endpoint results, including that quality of life data, maybe for the doctors, what percentage of thalassemia patients would you believe could benefit from mitapivat in light of these data? Thanks again.
Yeah, Doctor.
In this data, you mean in non-transfusion-dependent thalassemia. These are a group of patients that do not require transfusion regularly. They might require transfusion every now and then, maybe not all their life, maybe a few times through their life. But the major issue that we have clearly shown is that if they have a low hemoglobin, they will develop at least three morbidities and more during their life from adolescence to adulthood. So increasing their hemoglobin is really something which is very important, not only to improve their quality of life, which you could see directly as a key secondary endpoint, but waiting for a few more years, you would see maybe that older morbidities will decrease and will not be there anymore. So I'm sure that the majority of the NTDT patients were requiring increasing their hemoglobin.
This is not, for sure, not those that have a hemoglobin of 10. We're talking about those that with a hemoglobin less than 10. But it remains to be that treating these patients should be a personalized treatment. Each patient is a different patient.
Thank you.
Thanks, Greg.
Thank you. And one moment as we move on to our next question. And our next question is going to come from the line of Eric Schmidt with Cantor Fitzgerald. Your line is open. Please go ahead.
Yeah, thanks. And let me add my congratulations as well. It's great to see some real innovation in the field of thalassemia. Maybe the first question for Sarah or the company, it's around the open-label extension. Do you have a sense of the number of patients who enrolled and are continuing on therapy in that OLE?
We have a lot of patients that elect to continue in open-label extension studies, which we see pretty consistently across our different programs. We have not highlighted the numbers yet or any data from the open-label extensions yet. But as we have done so for pyruvate kinase deficiency, this is something that we definitely will do at a later time point.
The majority.
The majority, yeah.
Yeah, the majority. Yep, indeed.
Then for Doctor.
Oh, Kevin, Doctor Kuo was adding something too.
I'm just echoing Sarah's statement. I was saying that patients on my site, they're very happy to be in this program and all the other programs as well.
Yeah, similar in our site also in Lebanon. All of them are happy. I don't think anyone is getting out. Most of them are going into the open-label.
That's great to hear. Maybe as a follow-up for Doctors Taher and Kuo, it sounds like mitapivat is probably going to get a pretty broad label for alpha and beta thalassemia as well as transfusion-dependent and independent patients. So maybe just can you give us a sense of which of your patients are going to be offered the drug, which are kind of the best candidates? And conversely, is there a subgroup of patients who you don't think are candidates? Thank you.
Now, that's a good question. And this is personally my opinion, okay? I'm going to tell you right now. Any patient who comes to me to clinic has clinically significant morbidities. So ergo, I would try everybody on the drug. That's the bottom line. Otherwise, they wouldn't be in my clinic to begin with, right?
If they have morbidities, it means that they need disease-modifying therapies to alter their outcomes and also to change their function.
Thanks, Kevin. Doctor Taher.
I follow a large number of NTDT patients around, let's say, 200 patients that I've been following over a long period of time, 20-22 years. As Kevin said, the majority of these, especially those that are moving into adulthood, the majority have at least three to four morbidities. Some of these morbidities are really hard morbidities like pulmonary hypertension and other more. So it is really my job to give such a product or such a novel therapy to most of the patients in order to reduce these morbidities or abolish them, hopefully, when we do a pediatric study.
And Eric, as you noted upfront, we are targeting a broad label. I mean, here today, we're talking about the Energize data for the non-transfusion-dependent patients, which encompasses both alpha and beta thalassemia. But we were equally delighted last week to talk about the top-line results from the Energize-T trial, which now gives us firm footing for both of those cohorts as well, non-transfusion-dependent as well as transfusion-dependent patients. And this is a real advantage for the thalassemia patients broadly. And we were just delighted to be able to feature that data from Energize yesterday in the plenary session.
Thank you. One moment as we move on to our next question. Our next question is going to come from the line of Salveen Richter with Goldman Sachs. Your line is open. Please go ahead.
Hi, this is Lydia Ong for Salveen. Thanks so much for taking our question. Congrats again on the progress. Could you just help us understand the difference in hemoglobin response between the alpha and beta thalassemia subgroups and what might be driving this? Thanks so much.
Thanks, Lydia. Sarah, you want to start?
Yeah, I can start on that one. So we do not see that as a difference between the two subgroups, Lydia. So when you look at the pre-specified subgroup analysis, you can see that for both, and this is a standard way of doing an analysis on your stratification factors, it is each group that is tested for treated against placebo. They're not meant to be compared towards each other. So it is alpha mitapivat treated versus alpha placebo treated, or beta mitapivat treated versus beta placebo treated. And then the conclusion out of there is that in both of those subgroups, mitapivat was favored against placebo, which means that overall, in the overall primary efficacy results, there is not a single subgroup driving the overall efficacy result. And the conclusion that you can take from there is therefore that the drug worked in alpha thalassemia and in beta thalassemia.
That's really it. They're not meant to be number-wise compared to each other.
Yeah. So I would echo Sarah's statement. But this is what I tell my students in my methodology class, is that when we use forest plots like this in subgroup analysis, it's meant to look at the direction of change. That's more important than the magnitude of change. So as long as the direction of change is consistent, it means that we are seeing a consistent effect. It is only when the direction of change that are divergent, then we start to dig in and think about other causes as to why that is the case. But here, we see that in both alpha or the beta thalassemia subgroup is that the direction of change is consistent.
Great.
I feel like it.
Thanks, Lydia.
Thank you. One moment as we move on to our next question. Our next question is going to come from the line of Tessa Romero with J.P. Morgan. Your line is open. Please go ahead.
Hi, good morning. Thanks so much for taking our questions. So first one from us is, what were the reasons for the four TEAEs in the mitapivat arm that led to treatment discontinuation?
Thrombocytopenia, mild thrombocytopenia, increased in liver function test, abdominal distension, and arthralgias. I think these are the four. So I mean, these are four, to me, minor events, but these were the causes or the reasons for stopping the drug.
As we have said before, clearly, there are four different things. There is not a cluster of events that led to discontinuation within the study.
Okay. And then the second one or the follow-up from us is, you have talked about the objective for a broad label, and certainly, these were adult studies. What is your strategy in pediatrics? Thanks.
Yes. So we're very excited about the benefit-risk profile that we have generated in adults. So of course, pediatric development is now a top priority for us. And you can expect something very similar to how we've approached our pyruvate kinase deficiency program. However, we haven't guided yet to exact start date or the details of that program. But our intent is to really expand the patient population over time.
Okay. Thanks so much for taking our questions.
Thanks, Tsveta Milanova.
Thank you. One moment as we move on to our next question. Our next question comes from the line of Alec Stranahan with Bank of America. Your line is open. Please go ahead.
Hey, guys. Thanks for taking our questions. I want to just offer my congrats as well on the breadth of the positive data seen to date from the thalassemia program. First question, maybe one for Doctor Taher and Doctor Kuo. How do you view the overall convenience of mitapivat in regards to currently available treatments? I guess, how would a broad approval of an oral therapy change the way patients are managed from a logistical perspective in either or both transfusion-dependent and independent populations? And then I've got a follow-up.
Yeah, thanks, Alex. And maybe Dr. Taher could start because actually, this was some commentary at the end of the plenary yesterday.
So you mean what's the benefit of using mitapivat over other modalities? First, as Kevin said, this is an oral drug. It's for both alpha and beta, at least for now, non-transfusion-dependent thalassemia. The other alternative would be luspatercept, which is a subcutaneous injection every 3 weeks also to improve hemoglobin. The third alternative would be blood transfusion if needed, which is what we are trying as much as possible to minimize or even abolish from the management of this group of patients. So whatever is available now is luspatercept versus mitapivat. I think that, as I said at the beginning, that treatment is a personalized treatment. But as also Kevin said, I think that each and every patient with the NTDT, whether alpha or beta, would benefit from such a drug. Compliance is a major issue in the management of our patients.
And we have got a lot of compliance issues in the era of deferoxamine or Desferal in our patients where subcutaneous injection that was available to each and everyone, the compliance rate was 30%. So I do believe that taking an oral drug is really by far more beneficial, not for compliance, for school performance, for their daily life, for their work. I think this is the major benefit. Kevin, would you like to add something?
Yes. Yeah. And as well, we need to remember that there's really nothing out there for alpha thalassemia right now other than putting them on transfusion, which, as Professor Taher has noted, it is not desirable. And it's sort of the last resort. So for those patients, this would be the first go-to. The first disease-modifying therapy that we ever have. And more importantly, the fact that we saw improvements in both function as well as quality of life, I think, should be a great impetus for patients to at least try to be on this therapy first because the alternative really is nothing.
Yeah. That's true.
Yeah. Great. Thanks a lot.
All right. Great. One more quick follow-up, if I may. Just a regulatory question. How do you think the FDA will assess the totality of the data? Do you think they'll look at each study, Energize and Energize-T on its own, or is there maybe some read across they'll make for, say, biomarkers or the PRO endpoints? Thank you.
So well, obviously, we're not the regulator. So I can't comment on how they will look at the data. But our intent is to submit, of course, both trials supporting each other. We have now two trials that highlight that we can improve anemia with a trial that measures hemoglobin response and another trial that measures transfusion reduction response. So they are complementary to each other, highlighting that we can improve anemia in this disease. And then, of course, as always, it's a matter of ongoing review. Once we submit, there will be questions and answers provided back and forth. And then we are very much looking forward to start that collaborative process.
I think combining the two studies, not combining them, using them both will strengthen your file that you are going to be presenting. Although it's the same disease, but there is a lot of diversity in the severity of this disease. On the contrary, learning from experiences of other drugs and the way they were presented, I think this is the ideal way to present it both together, showing reduction in transfusion and increase in hemoglobin.
Great. Thank you.
Thanks. Thanks, Alec.
Thank you. One moment as we move on to our next question. Our next question comes from the line of Divya Rao with TD Cowen. Your line is open. Please go ahead.
Hi guys. This is Divya Rao for Mark. I will also add my congrats on kind of all the progress and the really great data. I just have two quick questions. One is, when can we expect a filing in the EU for thalassemia? And my second question is on the data itself. I know competitors have used PROs of test and weakness, I think, which is obviously a different endpoint from the SF-, FACIT, and fatigue score. Can you give us a little bit of color on kind of the difference in criteria and what kind of goes into each of those PROs?
Sarah, you want to start on the regulatory?
I'll start on the regulatory piece. And then I do think you might need to repeat the beginning of your second question because you broke up for a second. So let's maybe start with the regulatory path. So as you know, we try to always work as fast as we can. And so the team is in full-on filing mode. We have guided towards a submission for the FDA by the end of year. But as you know, we always work with core documents with a goal to be able to submit to other regulatory authorities as well. So we haven't provided the details yet on which regulatory authority when, but we're definitely in full-on global filing mode. And maybe I can ask Tsveta to comment as well.
Absolutely. And Divya, as you know, we are in active launch preparation for the U.S. The team is progressing very, very kind of fast and steady there to make sure that we get ready, we educate the market, and we prepare for launch. As Sarah said, we've looked globally, and we have actually prioritized some of the markets for regulatory submissions. And Sarah and the team are working very closely with us to do that and have as quickly as possible submissions to the relevant regulators. From a commercial priority market, when you look at the prevalence of the disease, the Gulf region comes as a high priority for us. So we will definitely make sure that we prioritize that. And we are in active conversations to select partners with strong experience in the region so we can launch there as quickly as possible.
We will look into Europe as well. Again, in Europe, a regulatory submission and approval needs to be followed up with by individual pricing and reimbursement processes. That might take some time for us. But we are looking to assess what are the next regions that we'll enter after the Gulf.
Divya, do you mind just repeating the second part of the question?
Yes.
Because I think it related to the PRO.
Yes. Absolutely. Yeah, that was helpful. So I know competitors have used a PRO of I think it's tiredness and weakness, which is different from the FACIT-Fatigue score. Can you give us a little bit of color on kind of the difference in criteria and how each of those are evaluated?
So Divya, I think you're alluding to the Beyond trial where the PRO that was done was a so-called non-transfusion-dependent thalassemia PRO tool. That's the NTDT PRO. And in there, there's two different domains. There is the tiredness domain as well as the weakness domain. Is that what you're referring to?
Yeah, that's correct.
Yeah. Okay. And your question for that is?
Just in terms of the evaluation of how each of those are done, what are the criteria and how are they kind of different between the 6MWT, FACIT score, and that tiredness and weakness PRO?
Yeah. So these PROs are constructed with certainly some domains that have overlapping themes and some domains that do not have overlapping themes. All of them have been previously validated. It's not necessary criteria that we look at in these constructs. It's what we call it. Okay? So when we talk about PRO instruments, as they're called, surveys are essentially instruments. Within these instruments are different domains. Domains map to the different aspects of the patient-reported aspects of function as well as quality of life like fatigue, tiredness, etc. So what we have chosen, right, in this study is specifically to look at tiredness because this is what we found our patients were focused on. This is what they talked about most. The other thing that we chose, of course, is the 6-minute walk test.
Again, that alludes to the fact that many of our patients, especially during the phase 2 study, the 010, they talk to me about how they are not able to even, say, carry groceries or to do activities of daily living that we find to be simply essential or very common to us. And one patient, for example, described how she's not able to pick up her 3- and 5-year-old at that time before starting the medication. And she always has to take a nap because she was so fatigued. And she can't even walk to do any of the chores. And she has to rely on her mother-in-law to do everything in the afternoon.
From several questionnaires that we have done previously.
Yes, that's right.
Like 7 or 8 years ago, and we have published, fatigue is the most important and weakness, fatigue is the most important. What do you say?
It's a symptom.
Fatigue is the most important symptom in these group of patients.
This is something we have consistently heard also across all of our development programs, both for pyruvate kinase deficiency, thalassemia, and sickle cell disease, which is why the fatigue has been prominently featured in all of these development programs as well. So for PKD, we were able to highlight that improvement on fatigue or tiredness. Now we have the same type of results for thalassemia. Of course, we are still enrolling in our phase three study for sickle cell disease, but our hope is to be able to deliver a similar result there.
That's helpful. Thank you.
Thank you. I'm showing no further questions at this time. I'd like to hand the conference back over to CEO Brian Goff for any further remarks.
Well, thanks a lot, Michelle. Thanks to everybody for the questions this morning, this afternoon, depending on where you are. I just want to thank again, especially Doctors Kuo and Taher for joining us today. Again, happy Father's Day to all the dads out there. We look forward to speaking with all of you again soon. Thanks a lot.
This concludes today's conference call. Thank you for participating. You may now disconnect.