Welcome everyone, to the 42nd annual J.P. Morgan Healthcare Conference. My name is Tess Romero, and I'm one of the biotech senior analysts here at J.P. Morgan. Our next presenting company is Agios, and speaking on behalf of the company, we have CEO Brian Goff. Brian, over to you.
All right. Well, thank you very much, Tess, and good morning, everybody. Really delighted to be here. I'm gonna start with introductions on who is with me. We have Cecilia Jones, our CFO, Sarah Gheuens, who is our CMO and Chief Medical Officer and Head of R&D, and also Tsveta Milanova, who is our Chief Commercial Officer. So before I get started, just want to remind everybody that I will be making forward-looking statements that include our expectations and beliefs, going forward, and so I would refer you to our SEC filings. Now, Agios is entirely dedicated to developing and delivering transformative therapies for patients who are living with rare diseases, and I am particularly excited to share with you our strategy for significant growth and value creation, particularly over this catalyst-rich period of the next 12-24 months.
So to get started, Agios is well positioned to deliver multiple clinical and regulatory catalysts, and these are gearing up to position us to enter into multi-billion dollar categories, namely thalassemia and sickle cell disease. We're very proud of the fact that we are the pioneers of this core mechanism of pyruvate kinase activation. We also are experts in cellular metabolism, and this has led us to PYRUKYND, or mitapivat, which is the first and only approved therapy for patients with pyruvate kinase disease, and this is a disease-modifying therapy or deficiency, I should say. Now, the mechanism is playing out to be particularly unique because I think many understand that there are benefits with hemoglobin that come from pyruvate kinase activation. But increasingly, what we're learning is the benefits for patients go well beyond hemoglobin alone.
And with each step forward that we make on delivering data based on this mechanism, we're increasing significantly the probability of success for our programs going forward. And we were particularly delighted just last week to announce the very positive results from our pivotal Phase III study known as ENERGIZE, which was targeting non-transfusion dependent thalassemia patients, and I'll share more about that in a little bit. But that certainly creates more momentum again for these catalysts going forward. The last thing I'll say is that we are well-capitalized, and we continue to grow our pipeline. We've done this in two different ways.
One is with our internally, organically developed programs. A good example of that is our PAH stabilizer. That is really a great feature of the expertise in cellular metabolism from Agios. With this, we are targeting phenylketonuria or PKU.
And another example is from externally in-licensed products, and a great example of that last year was our in-licensing of an siRNA from Alnylam that inhibits TMPRSS6, and this is targeting polycythemia vera or PV. Now, as we prepare for these launches to come, we have a wonderful backdrop of already having PYRUKYND, again, as the first and only disease-modifying therapy approved for an ultra-rare condition known as PKD. And the commercial capabilities that we've built over the last couple of years to deliver on this launch, we will be leveraging for sure into our potential future launches in thalassemia and sickle cell disease. But these opportunities actually have some very interesting and compelling features that are actually quite different from PKD. The most obvious of which is these are significant, significantly more prevalent diseases on a global basis.
More importantly, both thalassemia and sickle cell disease are readily diagnosed, and that's thanks to the ubiquity, particularly in the U.S., of newborn patient screening. The other feature is that on a global basis, both of these diseases have very well-recognized burden of disease at the patient level, and that certainly helps with the motivation to adopt a novel treatment therapy. Now, the mechanism of pyruvate kinase activation is very unique, and at the core, this is all about addressing the imbalance of energy that cells under metabolic stress have. In essence, there is an imbalance of both the supply and the demand, and by increasing or activating pyruvate kinase, the last step in the glycolytic pathway, we're looking to normalize that balance and increase the level of energy for the cell.
The benefits, as I mentioned, that we see are not just hemoglobin improvements, but also ineffective erythropoiesis improvement, markers of hemolysis, and increasingly, what we're starting to see are the benefits directly to the patient in terms of, in the case of sickle cell disease, improvement in vaso-occlusive crises, also feel and function, and we saw this again just last week with the readout of our ENERGIZE data, showing improvements in fatigue at the patient level. On the left-hand side of this slide, though, you can see another unique feature of the pyruvate kinase activation mechanism unique to our franchise, mitapivat, and our other PK activator, AG-946. Specifically, not only-...
Does this mechanism activate PKR, which essentially controls energy at the red blood cell level, but also another isoenzyme known as PKM2, and this is important because it regulates cellular energy at the tissue level, and we believe that this could be important for downstream organ damage. Our intent to bring that to life is to study renal impairment in sickle cell disease patients. You can see at the bottom the growing stack of late-phase trials that we've reported out, and the most important thing is that this data has continued to be consistent and compelling across these hemolytic anemias.
Now, if I take a step back, just a couple of years ago in 2021, Agios made the decision to divest our oncology business, which was really, the way the company started, and we made a complete pivot to a focus on rare diseases. And I think what's striking is to just reflect on what our pipeline looked like in rare disease and PK activation at that point in time. We had a total of three programs underway, and if you advance to today, you can see the dramatic, enhancement and depth of our pipeline. In fact, with just our PK activation franchise alone, we have nearly triple the number of programs that we had at that time.
You can note at the bottom, not only have we advanced the pipeline, but we've expanded and diversified again, noting our PAH stabilizer that we're advancing for phenylketonuria, as well as, the asset that we in-licensed from Alnylam, where we're focusing another very high unmet need in polycythemia vera. 2023, on every dimension, was a tremendous year for Agios. We put forward a very ambitious list of goals, which was largely geared towards advancing our pipeline, and, you can easily see just across the board, a bunch of check marks, which we're very proud of. We delivered on every goal that we put forward, and to name a few, looking again at thalassemia and the opportunity we have in front of us, we fully enrolled earlier last year, both of our ENERGIZE and ENERGIZE-T Phase III pivotal studies.
We actually did that ahead of schedule, and that obviously positioned us very well for the readout that we announced just last week, the very positive readout of our ENERGIZE phase 3 study, targeting non-transfusion dependent patients. Additionally, in sickle cell disease, at the midpoint of the year, we were delighted again to read out a very positive phase 2 study. This is part one of the operationally seamless phase 2/3 design. And what we're very proud of is just three months after we read out that data, we were already enrolling our pivotal phase 3 portion of the RISE UP study for sickle cell disease. I'll also note that our other PK activator, AG-946, we have been advancing in low-risk MDS.
This is a disease that is very much about ineffective erythropoiesis, and we enrolled that phase IIa proof of concept study, again, well ahead of schedule. And then we were delighted in the Q4 of last year to announce positive results of our pre-specified proof of concept endpoint of transfusion independence. We achieved 40%. The last thing I'll just say again is we're really excited about advancing the earlier stage of our pipeline, namely, the PAH stabilizer for PKU, as well as the in-licensing agreement from Alnylam. Now, the first potential launch in front of us is thalassemia, and this is a very profound and severe disease for patients around the world who suffer from the chronic hemolysis that comes with this genetic mutation, affecting both the alpha and beta globin genes.
What you can see on this slide is on the left-hand side, there are really two segments of thalassemia, and I'll note our intent is to deliver for all forms of thalassemia. But nearly 70% of the patients, as noted in orange, are non-transfusion dependent thalassemia patients, and this was the focus of the ENERGIZE study that we just reported out last week. Unfortunately for these patients, they have no currently approved therapeutic options in the U.S. And then the other blue section of this pie chart is the remaining patients, and these are so-called transfusion-dependent patients. This is the depiction in the U.S. These transfusion-dependent patients are the focus of the other pivotal Phase 3 study known as ENERGIZE-T.
Now that we have the positive readout of ENERGIZE, as we just reported, we are delighted to have, very soon, at the midpoint of this year, the expected readout of the ENERGIZE-T study. Again, the intent of our pivotal Phase III design is to encompass all subtypes of thalassemia, transfusion-dependent patients, non-transfusion dependent patients, and also as well, the subtypes, including both alpha and beta thalassemia. To go a little bit deeper on the unique nature of thalassemia, it is uniquely geographically concentrated, very large population worldwide, 18-23,000 patients in the U.S. and EU5. On the previous slide, I should have noted approximately 6,000 patients in the U.S. alone are already diagnosed and active in the system.
But if we go outside of the U.S., one geography in particular, GCC or the Gulf region, has a shockingly high prevalence of thalassemia, and in fact about 70,000 patients, which is roughly 8-9 times the size of the U.S. alone. So like, when you look at the disease impact at the patient level on the right-hand side of this slide, there is a disconnect in a way, in that these patients are subdivided, as I noted, in non-transfusion dependent thalassemia, as well as transfusion dependent thalassemia. And unfortunately, non-transfusion dependent thalassemia patients have historically been thought to be less severe, less at risk for all these disease impacts. And increasingly, what we're learning is that they are subjected to hemolysis every day, and hemolysis is deadly because free heme in the body is toxic.
And so in many ways, they're even more undertreated and even more vulnerable, and that's why we're delighted to have this ENERGIZE data to directly address what these patients are so in need of. The data itself that we reported is just amazing on many levels. First of all, we were highly statistically significant with our primary endpoint of hemoglobin improvement, and in fact, the p-value was less than 0.0001. But as I noted, the benefits for this mechanism of pyruvate kinase activation were really showcased in this study because beyond hemoglobin, we also hit statistical significance in both of our key secondary endpoints.
One is average hemoglobin concentration improvement, and the other, which is I think the one that was a real pleasant surprise to many, is that the average FACIT fatigue score, and fatigue is a very profound element of unmet need for these patients, also met statistical significance. Again, reinforcing these benefits that go broadly beyond hemoglobin alone. The safety profile demonstrated that the adverse events were very balanced between both mitapivat as well as the placebo group. Four patients in the mitapivat arm had AEs that led to discontinuation.
There were none in the placebo group. And the last point I just want to make is at the very bottom, which is that all of our pre-specified endpoints favored the mitapivat arm. And so another way to think about that is there were no subgroups that skewed the results one way or the other.
A very balanced profile, which again, fits beautifully with our target of addressing all dimensions and all subtypes of patients with thalassemia. So the next steps, as you can see on the right, is our tradition, is we top line the data, and then we look ahead to a major medical meeting to feature the totality of the results, and we look forward to doing that. As I noted, we're delighted that ENERGIZE-T is not that far away, so we'll look forward to those top-line results at the midpoint of the year. This data then will be packaged as one submission, as an sNDA to the FDA, and that'll be by the end of this year, and then pointing towards a potential launch in 2025, which we are very excited about.
The commercial aspects of thalassemia are also very different and very appealing, but quite different from PKD, where we've currently been commercializing. And just to name a few of these features, for one, the diagnostic intensity is very different. There are already, as I noted, in the U.S. alone, 6,000 adult patients who are already diagnosed with thalassemia. We've already talked about the fact that 70% of these patients approximately, have no therapeutic options. And, and then the providers themselves, and where these patients are treated is much more concentrated than we have faced with PKD. And the example here is that about 50% of these patients are actually being treated in approximately 150 hem/onc treatment groups across the U.S., which is a very favorable situation for us. And then even the advocacy groups are much more established.
This is more of a patient-connected community, and Cooley's anemia is one example, and TIF is another. And then again, looking outside the U.S., in just the Gulf region alone, you have 8-9 times the prevalence that we have in the U.S. So the summary is, we're targeting an all-inclusive design for PYRUKYND. We already have now the backdrop of very positive, energized results. We're looking ahead to the ENERGIZE-T readout. We submit all this data, have an opportunity for best in class, and ultimately foundational therapy for these patients, and a launch next year. Now, if I move to the other key significant near-term launch opportunity, sickle cell disease, I think this is very well known, certainly in the U.S. and around the world, another devastating hemolytic anemia with very high unmet need.
These patients really suffer from anemia, from the risk of strokes, renal impairment, and ultimately, a shortened lifespan. Perhaps the most striking stat on this slide is the fact that the average lifespan for a sickle cell disease patient today is approximately 45 years. So we are delighted to have a very advanced program to address this significant opportunity. I just want to reflect back to the data that we were so thrilled to present at ASH just last month. This is the full data set for our phase 2 portion of the operationally seamless phase 2/3 RISE UP study. The first point is statistically significant improvement in hemoglobin against both of our doses tested, 50 milligrams as well as 100 milligrams. And secondly, again, moving towards benefits beyond hemoglobin...
Four out of four of the markers of erythropoiesis as well as hemolysis also met statistical significance, or sorry, improvements. Then again, a very surprising and very exciting feature was that with both doses, we also saw a positive trend in the devastating vaso-occlusive crises that patients are literally tortured with having this disease, and we were very proud of that result. Looking ahead now, this was a very efficient study operationally. We made no changes to the phase 3 design, with the exception that we picked our dose, and that is the 100-milligram dose. I'm very proud of the fact that Sarah Gheuens and her entire research team focused on this program. Within three months, we're already actively enrolling patients for this study. For Pyrukynd, the setup here is, again, an opportunity to become foundational, best-in-class, potentially first-in-class therapy.
What we're targeting is not just anemia, but the totality of symptoms and needs for these patients, which go into sickle cell pain crises, and again, fatigue, where if you talk to patients with sickle cell disease, they have management techniques for pain. They cannot adjust life for fatigue. And so having this entire profile is very special, and we, we look forward to that opportunity as well. We will deliver a full enrollment is our target of this study by the end of this year, data coming in 2025, and that puts us on a course for a potential launch in 2026, just a year after our thalassemia launch. Moving to the rest of our pipeline, we're in a very advantageous position to have not just one, but two PK activators.
So our second novel, PK activator, known as AG-946, we're currently pursuing in lower-risk MDS in a phase II study. We read out, as I noted, the phase IIa portion in the Q4 of last year, and we were very pleased that we met our pre-specified endpoint. 40% of the patients achieved transfusion independence, and that gives us the fortitude to advance thoughtfully with the phase IIb program at the midpoint of the year. We also have already submitted an IND, late last year for our PAH stabilizer for phenylketonuria. This is a very high unmet need category that fits in beautifully with our expertise in cellular metabolism, and we're looking to commence a phase I study this year with, with this PAH stabilizer.
Then the asset that we in-licensed from Alnylam for polycythemia vera, 100,000 patients in the U.S. Frankly, they're subjected to what we think of as medieval therapy. This is phlebotomy, and we're looking to revolutionize the way these patients are treated with this very novel mechanism of TMPRSS6 inhibition. So 2024, the setup for this year, we've already checked one very important box where we had targeted positive readout of our ENERGIZE thalassemia program for non-transfusion dependent patients. I mentioned we're also starting our phase I for PKU. The mid-year point, that's the important readout for ENERGIZE-T, which we very much look forward to. We are completing enrollment in the one remaining phase III program in pediatric PK deficiency. I noted we're looking to begin our phase IIb study of low-risk MDS with our AG-946 asset.
Then at year-end, we will be submitting the package for approval for thalassemia for Pyrukynd, sickle cell disease, our RISE UP phase 3 study we're looking to have fully enrolled, and then we will read out actually the first of our two pivotal phase 3 PKD pediatric programs. And that is a setup for. When I stood here a year ago, I said, "We are about to enter a catalyst-rich period." We are squarely right in the middle of that. So that's a setup for 2025. Here we're looking for the readout of the sickle cell disease phase 3 data. We will be looking towards a potential launch in 2025 with thalassemia, and then the second of our pediatric PKD programs will be reading out in 2026.
We have remarkably the potential for two launches, one in sickle cell disease and the other in pediatric PK deficiency. We are ultimately, I hope the takeaway here is extremely well-positioned to prepare for these meaningful growth opportunities. We have a very special and, remarkable, mechanism of action with PK activation. We're the world's leader with that franchise. It is advancing beautifully. This mechanism we're learning goes well beyond what people have traditionally thought, which is, beyond hemoglobin. And as I said, we continue to just stack up data readout after data readout, which only increases the probability of success of our franchise.
And we will continue in a disciplined way to look towards how we can advance and grow and diversify our pipeline. So with that, thank you very much. And, Tess, I'm going to turn it over to you for questions.
Great. Thank you, Brian, for the presentation. Yeah, please come on up. So, I thought I would start the discussion here on the ENERGIZE study results, which, Brian, thank you for articulating those right now for us. I did wanna just ask about helping to contextualize that hemoglobin response rate that was observed, and mechanistically, why might a patient not respond?
Yeah, well, first of all, I just want to reinforce that the results were as good as we could have imagined. The fact that we were highly statistically significant with the hemoglobin finding at the 100-milligram dose, and as well that we now have demonstrated once again that the benefits go well beyond hemoglobin. But I'll let Sarah comment on the second part of your question about hemoglobin response in general.
Yes. So thanks, Tess. I think it's also very important what you just last mentioned, the hemoglobin plus, so making people feel better is critically important in the context of a hemolytic anemia, where people are really suffering from fatigue. So we're very pleased with that because that also adds to the consistency of our data. It builds on the pyruvate kinase deficiency observations, in which we had a very similar package coming out of the Phase III trial, and now we see that again in thalassemia. In regards to so-called non-responders, it truly depends. So right now, we have given you an insight in the intent to treat analysis, hemoglobin response defined as 1 gram per deciliter over a period of time within the trial between week 12 and week 24 on average.
We do know, though, that there are also people who are maybe not necessarily reaching a clinical trial bar, but can still have some benefit on hemolysis and on patient-reported outcomes. So this is something that we will be talking about more with, you know, once we get through the first parts of the data presentation, but this is a very important thing, that there is more than just the hemoglobin component to feeling to demonstrating improvement. So mechanistically, why there may be some people that are truly non-responders, we don't know. We have analyzed that extensively in our PKD trial, of which for some people, there is a logical reason in the sense that they don't have enough enzyme left to be able to respond. From a wild type perspective, we haven't, we don't have that full insight yet.
This actually segues really nicely into my next question, which is: What should we specifically look for in terms of what we may see in that fuller medical meeting presentation? Of course, not what the data itself is, but the types of analyses that we might expect.
Right. So very consistent with how we have done this before, we always present our intent to treat analysis, so it will be our primary and secondary key, primary key, secondary endpoints, and other secondary endpoints, which are focused on hemolysis, and then, of course, the details around safety as well. And then from there, we typically do further analysis, digging in more into responder analyses, but that will come at a later, later time.
How should we think about the level of read-through between ENERGIZE and ENERGIZE-T?
Mm-hmm. So indeed, it's a different patient population in the sense it's that they need transfusions, ENERGIZE-T, which in ENERGIZE, they need an occasional transfusion, but it's at a different level. Now, the fact is that you can postpone transfusions if your hemoglobin stays up. So we do see a read-through there in the context that when you improve hemolytic anemia by improvement of hemoglobin, that should pull through to a trial in which you are studying transfusion independence or transfusion reduction. And we have seen that in our pyruvate kinase deficiency trial, so now we are very much looking forward to a mid-year readout of ENERGIZE-T.
Yeah, and maybe I'll just underscore that, too, because, again, if you look at the totality of all of the data that we've read out thus far with mitapivat, if you go back to PKD, ACTIVATE, ACTIVATE-T, I mentioned RISE UP, the phase II program, and now we have ENERGIZE and thalassemia. The data has been consistent, it has been compelling, and it's continued to show that there are these benefits beyond hemoglobin. So, you know, to the question about read-through and probability of success, I think I reinforced that a couple times in my prior comments. We have increased conviction with every study that this is a very significant mechanism, very novel, and is showing broad benefit for patients.
I should have said, please wave your hand if you do have a question. I don't think my iPad is working. So can we talk a little bit about ENERGIZE-T in a little more detail here, particularly what you're looking to see around the primary endpoint, which is a 48-week read on transfusion reduction?
Mm-hmm.
What response rate are you looking for there?
So the primary endpoint in ENERGIZE-T is defined as a 50% reduction in any 12-week rolling period between week 12 to week 48. So basically, any consecutive 12 weeks that a patient has a 50% reduction in transfusions, then that means that that patient is a responder. So we're very much looking forward to that data. I think that is a really clinically meaningful way to look at data because we basically give patients multiple chances to have that type of reduction; we can highlight how a patient can be dynamic in the course of a period of time like this, and that is clinically very relevant.
You are enrolling a broader population here of both alpha and beta thalassemia patients.
Yes.
So, how do you think about the relevant clinical thresholds here to benchmark your results to, you know—and perhaps it might make sense to orient folks in the room on what is currently available for—
Right.
TDT, but not alpha thalassemia? Yeah.
So indeed, our program is set up in such a way that we are covering all of thalassemia. So with the two trials, we have a non-transfusion-dependent thalassemia population and a transfusion-dependent patient population. Both of those trials enroll different genotypes. So in each trial, a patient with alpha thalassemia can participate, or a patient with beta thalassemia can participate, and that is different from other clinical development programs. luspatercept is the only approved treatment in the U.S. for transfusion-dependent beta thalassemia. There is no approval for non-transfusion-dependent beta thalassemia, and alpha thalassemia patients weren't studied.
So this will be the first program that can deliver, if, you know, this, the first trial read out positively, if the second trial reads out positively as well, then we truly have a data package that can speak to the totality of, the patient population in thalassemia.
In regards to ENERGIZE, where we already have the results, as Brian mentioned in his presentation, both alpha and beta thalassemia patients participated. The way the trial enrollment occurred is very reflective of the general non-transfusion-dependent thalassemia population. And we also know that our primary endpoint hit statistical significance, and the pre-specified subgroup analyses showed that each subgroup, so the alpha thalassemia subgroup, the beta thalassemia subgroup, they all favored mitapivat against placebo, meaning there is not a single group driving the overall efficacy result. And so we're very pleased with that-
Mm.
Because that gives us a way to really talk to the totality of the data, overall thalassemia, but also speak to the subgroups specifically.
In the interest of time, I thought I would do a couple of quick hits on the pipeline and commercial year. On the mitapivat program in sickle cell disease, how comfortable are you that the sickle cell pain crises observations that you saw in the phase 2 portion of RISE UP, that there is a real signal there that you will discern in a longer phase 3 study?
Sure. So this is actually the third trial that we have with mitapivat in sickle cell disease. We have two investigator-sponsored trials that were open label, which already showed a signal on sickle cell pain crises in both those trials. But now we have the first placebo-controlled clinical trial data set with RISE UP. And what we are very pleased with is that you see a reduction on hemolysis, so a better reduction on hemolysis against placebo in the 50 milligrams, but an even better reduction in the 100 milligrams. And you see that same pattern and trend for sickle cell pain crisis reduction in 50 milligrams against placebo and 100 milligrams in placebo.
So for me, the fact that the hemolysis improvement and the sickle cell pain crisis improvement are moving in the same direction for each dose with a stronger pattern on the 100 milligram is very reassuring. And then the fact that we see similar evidence in those two investigator-sponsored trials, all of it is pointing in that same direction, gives me comfort for phase 3. And I think the fact that the phase 2 data set, the way we had set it up and the results, how they read out, that led us to just continue with the plan for phase 3, and that we didn't have to make any changes is a very good sign, too.
Okay. Please,
Just to understand... Oh, sorry. In thalassemia, there will—All patients would, will be eligible. There will be no eligibility criteria for the drug?
The way the clinical trial for ENERGIZE itself, patients did have to have a lower hemoglobin below 10 grams per deciliter-
Okay.
So to really identify that hemolytic anemia concept in the trial. We had a very similar inclusion criteria for our other program, pyruvate kinase deficiency. Now, that, that, that did not translate to a label with that type of restriction on it. It's truly an all-comers indication statement there, and we're gonna take a similar approach for this indication.
Okay, thank you.
Okay. And, another update that, Brian, you talked a little bit about in your presentation was the decision to move forward AG946 and lower risk MDS. What underpins your confidence there? And it seems like mitapivat is-- or I'm sorry, 946 , is elucidating a benefit on transfusions, but not hemoglobin response. Is it possible that we might see that as the study moves forward?
... yes. So the phase 2a was our first endeavor in anemia that was slightly different from the other hemolytic anemias that we're studying. So this anemia more is driven by ineffective erythropoiesis, and there is only a very small subset of patients that actually has that hemolytic profile. So that's why we chose to really tread carefully with a smaller phase 2a, in which we could leverage the data to truly inform phase 2b and which doses to study and potential tweaks to make to the patient population. We did pre-specify the criteria that we wanted to see before moving forward to phase 2b, and the transfusion independence criterion was met.
We did have hemoglobin response in the trial, so we had one patient with a hemoglobin 1.5+ response and an additional one with a hemoglobin 1+ response. So it's there, but not to that same level as transfusion independence. So this is where we're looking forward to make more changes to the phase 2b, and then, as Brian mentioned, we are going to start that program mid-year, based on the lessons learned from phase 2a.
And, I'll just add one other point, too, because this was very thoughtfully designed to allow us to manage risk and learnings at the same time as we advance. One of the areas that we learned is perhaps the dose was not high enough, and we have latitude to make those adjustments as well as one example.
So maybe I'll squeeze in a commercial question, so that we're not leaving anybody out here. So PYRUKYND has been on the market in PKD for some time now. How do you think about where the next leg of growth comes from for that program? I think 100 patients are on therapy-
Mm-hmm.
as of your last update. We have noticed that there has been maybe a little bit of slowing of patient adds, so how do you think about the dynamic there, and what is a, you know, more than a 100-patient prevalent pool?
Absolutely. I'll take that, and thank you for asking the commercial question. So, as Brian mentioned, PKD deficiency is an ultra-rare disease in the U.S. and globally as well. And a very important characteristic of that disease is actually the low diagnosis rates. So the patients are not being diagnosed. There is actually a low urgency to monitor and treat these patients. So as a result of the and at the end of Q3, we had 160 prescription enrollment forms and net 100 patients on therapy on PYRUKYND.
As we've always said, because of the disease characteristics and the nature of this launch, we are very much focused on that first part of the patient journey, which is very heavy, involved on identifying prescribers and diagnosing patients, and would expect to continue to see slow and steady progress of this launch, because of the nature of this disease. And also variability quarter- over- quarter because the nature of the patient numbers is just so small. The very important aspect of this launch that we are looking towards is how PYRUKYND is actually performing in the real world. And what we are very pleased about is with the positive receptions of both patients and clinicians on the profile of the product and the strong persistency that we see in treatment use over time.
That gives us confidence for PKD deficiency moving forward, but most importantly, now with the positive data that we have from ENERGIZE, how that could translate into other hemolytic anemias, which are also chronic diseases. We are also building a foundational capabilities, as Brian mentioned, to move to bigger patient populations, such as thalassemia and sickle cell disease, and very different type of launches. The big difference between PKD and what's to come is the fact that the patients are diagnosed. These are better understood and well-known diseases. There is a higher concentration in the treatment base and established patient communities. We're looking forward to those launches and see the change in the trajectory there.
Thank you, Sveta. That was, that was great. Thank you, and I think we're out of time. I wanna thank the entire Agios team for being here as part of our conference, and thank you also for all the listeners for taking the time to join us. I hope everyone has a great rest of the week.
Thanks a lot, Tess. Thank you, everyone. Thanks.