Welcome everyone to the 41st annual J.P. Morgan Healthcare Conference. My name is Tessa Romero. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Taylor Hanley and Atoraj Shah from the team. We are pleased to welcome Agios to kick off our Wednesday here. Speaking on behalf of the company, we have CEO Brian Goff. Before I turn it over to Brian, I just wanted to remind folks that there will be a Q&A after the formal presentation. There is an Ask a Question button in the portal. I'm happy to ask the question on your behalf, and then we'll also have a mic runner to take live audience questions. With that, Brian, over to you.
All right. Well, thank you, Tess, good morning everyone. Agios' mission is to develop transformative treatments for patients living with rare diseases, it's truly my pleasure to speak with you today about our strategy for significant growth and value creation by 2026. Now, before I get started, I'd like to remind everyone that some of the statements I'll be making today will include forward-looking statements that are based on our current expectations and beliefs. Please refer to our SEC filings for additional details. Agios is the pioneering leader in PK activation with unmatched expertise in cellular metabolism. We have a track record of successfully translating that expertise into the discovery, development, and commercialization of novel therapies for areas of profound unmet need.
This is evidenced by approvals for two first-in-class targeted oncology therapies in 2017 and 2018, as well as the first approval just last year for our first-in-class PK activator, PYRUKYND, for adults living with PK deficiency in the U.S., EU, and Great Britain. By 2026, we have the potential to meaningfully expand our rare disease portfolio across connected diseases that share a common underlying pathophysiology, with additional potential PYRUKYND indications in thalassemia and sickle cell disease, as well as the advancement of additional clinical and pre-clinical programs. Now, let me briefly summarize the three key reasons I believe Agios is poised for significant growth by 2026. First, we're focusing our PK activator molecules on hematologic diseases that have a common underlying pathophysiology, meaning the data we generate in one disease area has direct implications on the probability of success in other areas.
The data we've generated to date is striking. We've seen compelling and consistent data across multiple disease areas, suggesting that PK activation has the potential to transform patient function, quality of life, and long-term outcomes in each of these indications. Second, we have the potential to realize meaningful commercial opportunities by 2026 that may have a transformative impact for historically underserved patient communities with significant unmet needs. The FDA approval and US launch of our PK activator, PYRUKYND, in PK deficiency is enabling our team to build strong commercial capabilities to support anticipated product expansion into meaningfully larger patient populations. Specifically, we anticipate additional PYRUKYND approvals in thalassemia and sickle cell disease by the end of 2026.
We're in an enviable cash position with approximately $1 billion on the balance sheet as of the end of third quarter 2022, which we expect to support the completion of our ongoing programs, including our five ongoing pivotal studies, as well as enable us to expand our portfolio. The hematologic diseases we're targeting are united by shared pathophysiology, limited treatment options, and profound unmet patient need. Our goal is to transform the treatment of each of these diseases and significantly improve how patients living with these diseases feel and function. In PK deficiency, PYRUKYND is currently approved for the treatment of adults living with PK deficiency, and we aim to deliver the first approved therapy for children living with this disease.
In thalassemia, there is no approved therapy available for approximately 60% of patients, and we aim to deliver the first therapy approved for all subtypes of thalassemia. In sickle cell disease, our goal is to deliver an oral therapy that both improves anemia and reduces sickle cell pain crises or VOCs. In lower risk myelodysplastic syndrome or MDS, our goal is to deliver the first oral therapy that addresses the underlying cause of ineffective erythropoiesis. Through our ongoing clinical development efforts in each of these disease areas, we aim to significantly expand our PK activation franchise with two additional indications by 2026.
Specifically, we're driving towards successively larger near-term expansion opportunities for our PK activation franchise in thalassemia, for which we're aiming for a potential U.S. approval in 2025, sickle cell disease, with a potential U.S. approval in 2026, and in low-risk MDS, for which we're evaluating our novel PK activator, AG-946 . In each of these disease areas, we believe there is a significant opportunity in both the U.S. and E.U. markets, as well as beyond. Our clinical development strategy is underpinned by a robust yet focused clinical pipeline of programs across these three areas.
Our pipeline has grown dramatically since we announced the divestiture of our oncology business and focused exclusively on rare diseases just two years ago. This is a true testament to the dedication and expertise of our development team. Let me now spend the next few minutes providing a bit more detail on the compelling and consistent data we've generated in the PYRUKYND development program to date and why we're so confident about the future. While the clinical manifestations of the diseases we're targeting differ to some degree, they're united by shared underlying pathophysiology of red blood cell metabolic stress. At a high level, this metabolic stress is caused by an imbalance of energy supply and demand in red blood cells, which ultimately leads to disease. In a healthy red blood cell, energy produced in the cells in the form of ATP meets demand.
However, in the case of PK deficiency, energy production is defective. In other anemias such as thalassemia and sickle cell disease and lower-risk MDS, there can be a defect in both energy production as well as significantly increased energy demand. In each case, ATP supply does not meet demand, which leads to red cell metabolic stress, anemia, and reduced patient quality of life. With PK activation, we aim to correct red blood cell metabolism and restore the balance between energy production and demand in red cells, thereby reducing hemolysis and ineffective erythropoiesis and improving how patients feel and function. Now taking this one level deeper, this red cell metabolic stress can lead to both chronic hemolysis, the destruction of red blood cells, and ineffective erythropoiesis, the reduced production of healthy red blood cells.
These defects in red blood cells lead to similar clinical complications and comorbidities, including anemia, the need for transfusions, iron overload, reduced bone mineral density, and long-term organ damage. Ultimately, these clinical consequences significantly reduce patients' quality of life and how they feel and function. For instance, patients often experience chronic fatigue, susceptibility to illness, challenges with school and work, pain, fractures, and a significant financial burden to manage their disease and its complications. The goal of our current PK activator development program is to correct red cell metabolism and address the underlying pathophysiology of red blood cell metabolic stress in each of these diseases. By doing so, we aim to reduce the clinical impact of these diseases and again, improve how patients feel and function. Let me now provide a bit more detail on the PYRUKYND clinical data we've generated to date across these disease areas.
These data were generated in the phase three program in PK deficiency, for which PYRUKYND is now approved in the phase 2 study in thalassemia, and in our phase 1 studies in sickle cell disease. In each of these studies, we've observed improvements in hemoglobin, hemolysis, and ineffective erythropoiesis. Importantly, these data show that PYRUKYND is not simply increasing hemoglobin levels in otherwise dysfunctional red blood cells, nor is it simply spurring the increased production of dysfunctional red blood cells. Instead, PYRUKYND is correcting red blood cell metabolism and is thereby making each red blood cell work better, improving its health and energy, which leads to consistent benefits in downstream markers of disease. We've observed improvements shown in diseases characterized by both mutant PK as well as diseases characterized by wild type PK.
These improvements have been shown on clinical endpoints as well as in measures of how patients feel and function. Just back up here. In the next few slides, I'll tell you a bit more about how we aim to translate these compelling clinical data into meaningful commercial opportunities by 2026. Our U.S. launch of PYRUKYND in PK deficiency is currently ongoing, and while it is a modest but important revenue generator for our business, it primarily serves as an important foundation for our anticipated near-term expanded franchise in PK activation into meaningfully larger patient populations. Over the first quarters of launch, we focused on optimizing the patient and provider journey by building capabilities in four key areas: awareness and education, diagnostic efficiency, therapy onboarding, and access and adherence.
To improve disease awareness and education, we launched a disease education program to drive awareness and urgency to manage PK deficiency among both healthcare providers as well as patients. To improve diagnostic efficiency, we launched our Anemia ID program, which offers free genetic testing to help providers confirm diagnosis of hereditary anemias. We're also using claims-based targeting and AI or artificial intelligence to help identify those who may be living with PK deficiency. To facilitate therapy onboarding, we're leveraging our compelling clinical data to activate physicians to prescribe as well as help eligible patients advocate for their own treatment. Through myAgios, our customized patient support services program, we're providing insurance coverage support, co-pay assistance, and free product eligibility for underinsured patients to improve access and adherence.
Importantly, each of these capabilities is aimed to prepare us for potential future launches in successively larger patient populations, including thalassemia and sickle cell disease. Transitioning now to these larger potential opportunities and beginning with thalassemia. There are approximately 20,000 patients living with thalassemia in the US and EU five. Importantly, there exists a significantly larger or significant opportunity outside these geographies as well. For instance, the prevalence of thalassemia in Saudi Arabia is among the highest in the world. If approved, we believe this geography could represent an important future market for PYRUKYND and thalassemia. Importantly, approximately 60% of patients with thalassemia have no approved therapies. Our goal is to deliver PYRUKYND as the first therapy that addresses all thalassemia subtypes and thereby transform the thalassemia treatment paradigm.
Turning to sickle cell disease, this would represent another step change in the size of the patient population with approximately 120,000 patients across the US and EU five. Just like thalassemia, the significant opportunity exists beyond these geographies as well. With no novel oral therapies that both improve anemia and reduce the vaso-occlusive crises that plague patients with sickle cell disease, we believe there is a significant opportunity for PYRUKYND to deliver benefits in each of these areas and transform the course of care in this devastating disease. Finally, I'll provide more detail on our strategy to drive long-term growth and value creation through the advancement and expansion of our portfolio.
As I mentioned, Agios has a strong cash position with approximately $1 billion on the balance sheet as of the end of the third quarter of 2022, which we expect will support the completion of our ongoing clinical programs and enable us to expand our portfolio beyond PK activation through both disciplined business development and advancement of our earlier stage pipeline. In terms of our clinical pipeline, I've had the opportunity to tell you about PYRUKYND and AG-946 in their development programs, as well as their potential to drive near-term growth over the next few years. Within our preclinical pipeline, we're excited about the progress we're making on our lead research program, which aims to address neurocognitive impairment in phenylketonuria, or PKU.
Approximately 15,000 patients suffer from PKU in the U.S. alone. We aim to file an IND for this program by the end of this year. In addition to our current programs, we have the ambition to further strengthen our pipeline through disciplined business development within our areas of core expertise, where we believe Agios is uniquely positioned to maximize value. In this front, we recently expanded the size of our BD team to enhance both the quality as well as the quantity of our diligence capacity. Our approach in BD is to leverage our deep expertise in rare disease biology, development, and commercialization in order to identify opportunities that are aligned with our rare disease focus, are transformative for patients with an identified regulatory pathway, and the potential for us to be able to de-risk early.
Obviously, what we're looking for ultimately is a clear path to value creation. Importantly, our activity within each of these buckets is aligned to the same core objective to deliver transformative therapeutics for rare disease patient communities with profound unmet need. Now in the last few minutes, let me highlight our roadmap of key clinical and regulatory milestones that we anticipate will help fuel our growth over the next few years. Starting with 2023, we're expecting a number of important milestones across our programs, including, first, completing enrollment of the phase 3 studies of mitapivat in thalassemia. Secondly, enrolling at least half of the patients in the phase 3 studies of mitapivat in pediatric PKD. Third, readout of the phase 2 portion of the RISE UP study of mitapivat in sickle cell disease, as well as a go, no-go decision for phase 3.
Fourth, completing enrollment of the Phase 2a proof of concept study of AG-946 in low-risk MDS. fifth, filing the IND for our PAH stabilizer for the treatment of PKU. Now, throughout the year, of course, we'll continue to strengthen our commercial capabilities through our ongoing launch of PYRUKYND in PKD, and we'll continue to evaluate BD opportunities to expand the pipeline. Let's look ahead now to 2024 to 2026. We anticipate a catalyst-rich period with the potential for two additional PYRUKYND indications in this timeframe. In 2024, we're expecting the readouts of the Phase 3 studies of PYRUKYND in thalassemia, as well as the readout of the Phase 2a study of AG-946 in low-risk MDS.
In 2025, we're expecting the potential approval of PYRUKYND in thalassemia, as well as the Phase 3 readouts of PYRUKYND in sickle cell disease and in pediatric PK deficiency. In 2026, we're expecting the potential approvals of PYRUKYND in both sickle cell disease and in PK deficiency with pediatric patients. With this slate of potential near-term catalyst, we aim to realize our 2026 vision of Agios, an established hematology franchise with approvals spanning three hemolytic anemias. An expanded portfolio fueled by business development and advancement of our internal pipeline that is aligned with our core expertise in rare diseases. Lastly, cash flow positive with a view towards profitability. Thank you very much for your time, and we now look forward to taking your questions.
Great. Thank you, Brian. I'm gonna welcome the rest of the Agios team up onto the stage.
Okay. While we're doing that, I will introduce who is here in the room with us. Joining me is Sarah Gheuens, who is our Chief Medical Officer and Head of R&D. We have Cecilia Jones, our Chief Financial Officer, and in her first week at Agios, joining at J.P. Morgan, I'm really pleased to have Tsveta Milanova, who is our newly named Chief Commercial Officer.
Great. Welcome everyone. I thought we might start the discussion with PYRUKYND and PKD. While still in the early innings here, where has the launch performed well, and where have there been some headwinds?
Yeah. I'll start. Actually, I might even conclude because this is Tsveta's first week. where PYRUKYND has really done exceptionally well is in the most important aspects of a launch, which is PYRUKYND itself is performing well clinically for patients. We know that from really two different directions. One is the anecdotal feedback that we're receiving in these early days from both patients as well as the prescribers who have had experience now with PYRUKYND. Secondly, almost as an indirect measure of excellence for the product, payers have been very supportive launch to date. We've not really experienced headwinds for patients starting on therapy. So far, again, in the early days for continuation, we've really been able to see payers navigate through patients on a continuation beyond the six-month mark.
That said, in terms of headwinds and the way to think about this launch generally, this is an ultra-rare disease launch in PKD, and it is among the most challenging of launch types in my experience and with the rest of the management team who has deep experience with rare disease launches. The journey will be slow and steady. As I mentioned, the most important thing is this launch is a capability-building platform for us for all of these meaningfully larger launches to come. The dynamics of the PKD launch are such that PYRUKYND is the first ever approved therapy for adult patients with PK deficiency in the 60-plus years that PK deficiency has been identified. That's one aspect.
Secondly, there is diagnostic intensity that's involved because it's not natural for a physician, a hematologist, who's not had a therapeutic option to go looking for PKD. That's a lot of the heavy lifting that we're doing right now is to motivate that diagnostic throughput and efficiency. Lastly, while it's devastating individually for the patients from a chronic fatigue and some of the downstream complications of hemolysis, it's not imminently life-threatening for patients. In a launch like this, another big heavy lift that we are focused on is increasing the sense of urgency, both with the provider as well as importantly for the patients to advocate on their own behalf.
Yep. Brian, can you talk a little bit about what your early market research suggests about if patients that are on therapy, are they staying on for more than 6 months? Kind of how is that looking in, like, these early days here?
Yeah.
I know you're probably still.
Yeah, it's a good question. I mean, just to anchor on where we are in the launch journey, we were approved at the end of February in 2022 in the U.S. In the clinical trials, the pivotal trials for PYRUKYND in PK deficiency, they were 6 months in duration. We knew from that, from the clinical trial that about 40%-45% of patients would meet the endpoint. It still is relatively early, as you noted, Tess, in the early quarters of launch. So far what I would say is it's been encouraging to see that patients have crossed over that 6-month mark. That suggests to us that not only is PYRUKYND very effective, but also it can also transcend beyond just markers of hemoglobin.
If the patient actually feels well and there are other benefits that they're experiencing, we've seen patients continuing in therapy. Again, importantly, we don't expect this to be a managed category from payers, and payers so far have been quite supportive in that dynamic.
You know, any further detail on kind of what types of patients are coming on to PYRUKYND? I think in the past, you've kinda talked about it being a pretty.
Yes
... group of patients. Is there any change in kind of how that's looking as you've progressed here?
No. As you noted, that's been consistent. I would say for where we are in the long launch journey of PYRUKYND for PKD, that's encouraging. I mean, we would look for breadth and heterogeneity of patient types. There's not any kind of particular niching. We're seeing, of course, all adult patients, but a wide range of manifestations of PKD, patients who are both transfusion-dependent as well as non-transfusion-dependent, splenectomized as well as not having had a splenectomy. Again, at this stage in launch, that's exactly what we would wanna see.
Yeah. What portion of patients who completed an enrollment form, which I think you provide an update on every quarter, actually convert to drug? Over how much time does that take generally?
Yeah, well, I'll just update the numbers as of the third quarter of 2022. The last report out of this data was 84 Prescription Enrollment Forms or PEFs. Those are patients who have been diagnosed, they've been identified as a great candidate for PYRUKYND. They've submitted that Prescription Enrollment Form to the myAgios system, and they've begun on that journey to actually transition onto therapy. Now, of those 84, we, as of the end of the third quarter, we had 56 patients who had started therapy. It's too early to say exactly what % of patients will ultimately wind up on therapy. I'll just say that we have no reason to believe that, over time, by far, the majority of those patients who have had a Prescription Enrollment Form would move on to therapy.
There's no, there's no inherent reason for a patient not to do so.
When do you expect to start guiding the street on sales for this, for this launch?
We have not identified specific timing on guiding for revenue. Hopefully, folks understand that it still is early. It's an ultra-rare disease launch. Our heavy focus right now is on the mechanics of the launch itself, getting that, as optimized as we can. Again, the bigger picture for us is building out that platform of rare disease capabilities across a number of domains. That's a great reason why I'm absolutely thrilled to have Tsveta on board with her deep expertise across a wide range of launches. As we make progress, and we hit the right time point, then I'm assuming we'll get to a place where we can guide on revenue.
Are there any commercial questions from the audience before I turn over to pipeline? Okay. Not seeing any. Okay. Let's move into pipeline a little bit here 'cause we've only got, you know, about 12 or 13 minutes. You know, you've got your Phase 2 portion of the RISE UP trial ongoing. Can you frame maybe for us here what the expectations should be for what you'll share midyear? What do you see as the profile you need to achieve here in the Phase 2 in order to move into the Phase 3 portion of the trial?
I will start with pausing just a moment to brag about Sarah Gheuens and her team with what they've been able to achieve, not just with the RISE UP study, but as I mentioned, with thalassemia and the incredible progress we've made on enrollment. To anchor, again, as I noted in my comments, where we are with RISE UP is, we had a goal to be fully enrolled by the end of 2022. We are delighted to have announced in our press release that we actually closed screening in December, and by the end of this month, January of 2023, we will have fully enrolled all of those patients. That puts us on a very meaningful glide path to data readout, as I noted, by the midpoint of the year.
It's really a mark of excellence from a clinical operations standpoint that Sarah and her team have been able to navigate through not just this trial, but as I noted, five different pivotal studies underway at the same time. I'll have Sarah comment on the profile itself.
Thanks, Brian. The profile itself for sickle cell disease, we're aiming to provide, as Brian had mentioned, a novel oral therapy that can hit both on hemolytic anemia improvements and on VOC reduction. The way our clinical trial is set up is to deliver exactly on that target product profile. The first component of the trial is a phase 2, which is a separate sample size. It's 69 patients randomized 1-to-1 to 1. Mitapivat 100 milligrams twice a day, 50 milligrams twice a day, or placebo twice a day. We'll be following those patients for 12 weeks.
The primary endpoint there is a hemoglobin response and safety. That will guide us to select a dose for Phase 3, together with secondary endpoints that will also highlight, you know, improvement on hemolysis and VOC reduction granted over a 12-week period, which is pretty short to follow that. Now, patients have an opportunity to roll over in an open label extension. We'll continue to accrue data on those VOCs as they, you know, gather more time on the trial. With that data set, we will complement that with data that we have gathered via other trials, via investigator-sponsored trials, where patients with sickle cell disease have been taking mitapivat for a longer period of time.
We are hoping to be able to move forward into the phase 3. The phase 3 is set up in such a way that it can deliver on that target product profile with two primary endpoints. One is again focused on hemoglobin. The other one is focused on sickle cell pain crisis reduction to be able to deliver on that. We're also hoping with our secondary endpoints to be able to speak to how patients feel and function. That will be a trifecta of data, which should lead to an hopefully novel oral therapy for the treatment of sickle cell disease.
Just on the hemoglobin response rate endpoint here, I mean, is there a specific placebo-adjusted bar you'd like to hit?
We have indeed powered our phase 2 trial for the hemoglobin response. We have gathered, you know, looked at all of the data that is currently available across our program, but also across competitor programs, to make sure that we hit on a meaningful hemoglobin response. The hemoglobin response is defined as 1 g/dl change between week 10 and 12 compared to baseline, which is a bar that we know from a regulatory perspective is also important. That is where we start for the phase 2. We'll carry that on in the phase 3 as well.
That type of response, but over much longer duration because it is a chronic disease. We do believe delivering two endpoints at the end of a year is meaningful from a regulatory perspective, but also from a patient perspective.
Should we switch gears and talk a little bit about thalassemia?
Sure.
Brian, you made some comments on kind of the overall product profile that you're looking for in thalassemia. You know, ultimately, you know, where do you believe this drug could fit into the treatment paradigm in thalassemia? How do you think mitapivat could differentiate itself commercially?
Yeah. We're very excited about thalassemia. Just listening to Sarah's comments on sickle cell disease, in both of these diseases, we're really hoping that we get to the point where we have the kind of consistency and compelling data that we've seen thus far, because these are both diseases where patients desperately need new options. Now, in the case of thalassemia, as I mentioned, where you can read into how we could see this being positioned, just look at our ENERGIZE and ENERGIZE-T clinical program. The way it's designed effectively is it's all comers, adult patients who have both alpha thalassemia as well as beta thalassemia, transfusion-dependent, as well as non-transfusion dependent. As I noted in my comments, approximately 60% of these patients have no therapeutic option. Their therapeutic option may only be transfusions.
To have an oral product, if the ENERGIZE studies read out, that covers all of those subtypes, we believe is not a moment too soon for this population, which I mentioned around the world needs new therapeutic options.
Maybe just on ENERGIZE, maybe we'll start there. There's a 24 week primary endpoint of hemoglobin response. Again, similar question that I asked in sickle cell, but what is the bar that you need to hit there on hemoglobin response and what are the powering assumptions of ENERGIZE?
For the hemoglobin response, it's again identified as a 1 gram per deciliter increase. That's the bar that we are looking at in that period of time. In regards to power assumptions, we again looked at our prior data that was gathered to estimate a placebo rate and a response rate for that specific trial. We're looking for 171 patients to participate here in this trial over that time period. Very importantly, the hemoglobin response is aimed to be supported by a secondary endpoint that is focused on a patient-reported outcome to support that clinical meaningfulness of the hemoglobin response from the get go. That is something that we are very excited about.
We have observed that in our PKD trials, so which is pretty unique for hemolytic anemia, that we observed hemoglobin response that was supported by patient-reported outcome that actually made it into the label. We're very, very proud of that.
I'd like to just add on to emphasize a point that hopefully was clear in the slides. That is the ENERGIZE program, as Sarah noted, is 24 weeks in duration. ENERGIZE-T for the transfusion-dependent patients is 48 weeks in duration. To note the milestones that we're headed towards, both trials are expected to be fully enrolled by the midpoint of this year. Sequentially, because of the duration of the trials as we move into 2024, that's why we noted the data readout for ENERGIZE would be in the first half of 2024, and for ENERGIZE-T in the second half of 2024.
Is there a, you know, quantitative hemoglobin response rate there that you kind of give folks to sort of be thinking about as what would be, you know, a success?
From the powering perspective, it aims for 35% hemoglobin responders versus 10% in the placebo. That's where we're powered for.
Okay.
That being said, our The Lancet data set. We have our Phase 2 data set that actually has shown a very good response rate over a 12-week period of time that has maintained over now a much longer stretch of time, 'cause we've just published that data at ASH as well. What is, to Brian's point, I want to reiterate that is very exciting about that, is that it's both observed in alpha thalassemia patients and in beta thalassemia patients, which is a very novel way to approach the development of these programs.
Okay. Should we frame ENERGIZE-T, just not to leave them out, quickly?
Yeah.
Just what the powering assumptions are there, and again, kind of what that, what the bar is that you're looking for there.
For ENERGIZE-T, The primary endpoint there is a 50% transfusion reduction response over any 12-week period observed between week 12 and week 48. Because to Brian's point, that trial lasts 48 weeks. That is supported by a bunch of different endpoints as well. There we have used again our PKD program to think about what we want to observe from a transfusion reduction from a response rate, but also what was known for Luspatercept for instance. It's always nice if there is other clinical development program data available for us to make these assumptions and look to what we need to observe. It's actually powered pretty similarly.
Great. Okay. Maybe just rounding out our session here, with the last couple questions. You reiterated the expectation to be cash flow positive in 2026. I think it would be helpful for folks to better understand what the key assumptions are underpinning that guide. Including any indication contributions, OpEx, things of that nature.
Great question. I'm going to have Cecilia comment because she's been patiently waiting for a great question around the strength of our balance sheet.
Thanks, Brian. Thanks, Tess. Yes, that's correct. Our balance sheet is very strong, and with that, we expect to support all the clinical trial work that Sarah just outlined. The five pivotal studies we have in PK deficiency for pediatric patients, thalassemia and sickle cell disease, as well as the proof of concept of 946, which we didn't talk much, but Brian presented as well. In addition to that, we do aim to advance the PAH program in PKU, and as Brian mentioned, the disciplined approach to potential business development as well.
Okay. You know, what is the stance on business development for the company? Is this kind of a key priority for the company near term, or is it really about developing your internal pipeline?
I'll start, and then Cecilia can certainly fill in. What I would like folks to take away from the presentation that we had today is we're in a very strong position. We have a pipeline that is advancing quickly. It is anchored on a set of data that continues to be consistent and compelling across hemolytic anemias. We're excited about the progress we're making in our five pivotal studies. We're excited, as Cecilia just noted, around our PAH stabilizer approaching IND the end of this year. All that said, we continue to have an ambition to advance and expand our pipeline. We will do that very carefully, very thoughtfully. We have put in place filters that I talked about, which is, first and foremost, rare disease focus.
Secondly, we will always look for opportunities that are truly transformative for patients, not things that are beneficial at the margins. We love opportunities that have a clear regulatory pathway, but we're not afraid to pioneer on that front as well. As I mentioned before, the opportunity to de-risk early is always beneficial. All that, we believe if we're disciplined in that approach, that will be value-creating. We will be patient to look for those opportunities. Anything you wanna add?
No, I think you covered everything.
Well, thank you.
Thank you.
I think that was a great session. Are there any other questions from the audience before we wrap up?
I guess just a quick one. Brian, could you talk about the impact of bringing Tsveta onto your leadership team as you prepare for commercial launches and get ready to expand the portfolio?
You wanna repeat that?
I didn't hear the last part of the question. About Tsveta joining the team.
Yeah, just as you prepare for commercial launches and expand your portfolio, what does that impact bring as you bring Sveta onto the leadership team?
This is a great example of experienced, seasoned talent that goes deep in rare diseases globally, not just in one country, is a moment not too soon for us, given the state of our portfolio, the launches that I talked about, the globalization potential. I can't say anything other than I'm thrilled to have a talent like Tsveta on board at this time.
Great. Well, I think we'll leave it there. Thank you, Brian and the whole Agios team for being here, and thanks for all of our listeners for joining. I hope everyone has a great rest of the conference.
Thanks so much, Tess. Thanks, everyone.