Q1 2024 Agios Pharmaceuticals Inc Earnings Call

Participants

Christopher Taylor; Vice President, Investor Relations and Corporate Communications; Agios Pharmaceuticals Inc

Brian Goff; Executive Vice President, President - Hematology; Agios Pharmaceuticals Inc

Sarah Gheuens; Director; Agios Pharmaceuticals Inc

Tsveta Milanova; Chief Commercial Officer; Agios Pharmaceuticals Inc

Cecilia Jones; Chief Financial Officer; Agios Pharmaceuticals Inc

Greg Renza; Analyst; RBC Capital Markets

Presentation

Operator

Good morning and welcome to RGA's First Quarter 2024 conference call. At this time, all participants are in a listen only mode. There will be a question and answer session at the end. Please be advised that today's conference is being recorded at Agios' request. I would now like to turn the call over to Chris Taylor, Vice President, Investor Relations and Corporate Communications for IGM. Please begin.

Christopher Taylor

Thank you, operator. Good morning, everyone, and welcome to Agios' conference call and webcast to discuss first quarter 2024 financial results and recent business highlights. You can access slides for today's call by going to the Investors section of our website at Agios.com.
On today's call, I'm joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Hughes, Chief Medical Officer and Head of R&D that I know Nova, our Chief Commercial Officer, and Cecilia Jones, Chief Financial Officer.
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 results and events could differ materially from those expressed or implied by any 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.
And with that, I'll turn the call over to Brian.

Brian Goff

Good morning, everyone, and thank you for joining us. Our mission at Agios is to develop and deliver transformative medicines that elevate and extend the lives of patients living with rare diseases, and we are off to a fast start in 2024. Our foundation today leverages mitapivat novel mechanism of action, which focuses on overall red blood cell health and has been a key driver for our recent clinical results.
On January third, we reported positive data from the Phase three energized study of our lead P activator, mitapivat marketed this pilot time in patients with non-transfusion dependent thalassemia. This study met both the primary endpoint of hemoglobin response rate as well as both key secondary endpoints associated with change from baseline in Facet fatigue score and average hemoglobin concentration. And we look forward to presenting these data at an upcoming medical meeting as a reminder, non-transfusion dependent thalassemia accounts for approximately two thirds of Dallas SENIOR in the US and has no FDA approved treatment options despite not requiring regular transfusions. It is increasingly understood that these patients experienced a significant impact on their quality of life, a wide range of serious morbidities fees and an elevated risk of premature death due to chronic analysis and ineffective erythropoiesis. Based on these data, our team is actively preparing for a potential launch in thalassemia in the U.S. complementing the energized study in non-transfusion dependent thalassemia. We continue to advance the Phase three energized T. study of mitapivat in transfusion dependent thalassemia. We expect to report data from this study in the second quarter, a slightly more refined timeframe than previously communicated and we plan to submit a single regulatory filing encompassing data from both energized and energized team to the FDA by the end of the year. In parallel, we look forward to near term milestones across several additional clinical programs in our pipeline, including completing enrollment in the Phase three portion of the rise up study of mitapivat in sickle cell disease by the end of this year and reporting data from four additional Phase three studies by the end of 2025. Sarah will provide a detailed update on our progress in upcoming milestones across R&D in just a few minutes. Given the consistent positive data we've generated across the mitapivat development program and the high unmet need in our target disease areas. We believe mitapivat has the potential to transform the course of multiple hemolytic anemias by improving red blood cell health and to become a multi-billion dollar franchise to help realize the full commercial potential of mitapivat and based on the strength of the energize data, our commercial organization is laser focused on building upon the infrastructure established through our current launch in pyruvate kinase deficiency or PKD to prepare for potential U.S. launches of mitapivat in thalassemia in 2025 and in sickle cell disease in 2026. Satya will provide greater detail on the market opportunity in Dallas, Aimia and the team's robust preparation for launch as well as an update on our current launch in PKD. in just a bit.
Finally, as you'll hear from Cecilia we ended the first quarter with a strong cash position with approximately $714 million in cash and investments on the balance sheet. Importantly, we have the potential to further bolster our cash position in the near term, as Servier announced FDA filing acceptance and priority review for a new drug application for more aside, nib for the treatment of certain IDH mutant diffuse Cleo. You'll recall that as part of the divestiture of audiences, oncology business to Servier, a POD yields retains rights to a potential $200 million milestone upon FDA approval of worksite nib and 15% royalties on potential U.S. net sales. If approved board aside, it would become a first-in-class targeted therapy for patients with IDH mutant gliomas and we look forward to the due for action date of August 20th, 2024.
With that, I'll turn the call over to Sarah.

Sarah Gheuens

Thanks, Brian. As we approach top line data readout for the Phase three energize the study of mitapivat in transfusion dependent thalassemia. I would like to highlight a few key elements of the lease-up of our development program and policy as a reminder, the Phase three program of mitapivat in thalassemia, namely energized and energized T. was designed to deliver data across all subpopulations of balancing, yes, including alpha and beta-thalassemia and populations with different transfusion needs. As Brian mentioned, only patients with transfusion-dependent beta-thalassemia, which represents one-third of US patients, have an FDA approved treatment option. The other two thirds of patients in the U.S., including all patients with alpha thalassemia. And those patients with beta-thalassemia who are non-transfusion dependent have no approved three, it is a common misperception that non-transfusion dependent or NT. T cells. Cf patients are less sick when the reality is that these patients suffer from a poor quality of life and a high rate of serious morbidities, including thrombosis and premature death this population, which represents approximately two thirds of the total counseling patients in the U.S. as a high unmet need for any treatments. The unmet need was strongly reinforced through our Phase three energized study by the speed of enrollment, the total number of patients enrolled in the high completion and rollover rates we observed. We were very pleased to announce positive results from this study in January and are eagerly awaiting the opportunity to present more complete results at an upcoming medical meeting.
Turning to those results, our goal was to build on our Phase two findings with a more rigorous way to measure a hemoglobin response in the Phase three energized trial, which we defined in the primary endpoint as an increase of equal or more than one gram per deciliter in average hemoglobin concentrations from week 12 through week 24 compared to baseline. But in a much larger trial, we were excited to be able to announce success in this trial as treatments with 100 milligrams we talk about BMD demonstrated a highly statistically significant result on the primary endpoint of hemoglobin response rate with 42.3% of patients in the treatment arm, achieving a hemoglobin response versus 1.6% of patients in the placebo arm. In addition, treatment with mitapivat also resulted in statistically significant improvements in both key secondary endpoints, including change from baseline in average Facet fatigue score, an important patient report. This measure of how patients feel in line with its novel mechanism of action that improves overall red blood cell health up about is the first molecule that has shown in a randomized controlled trial that it does not only improve hemoglobin that actually makes people without seeing a few less 50. In addition across the primary and secondary endpoints, all prespecified subgroup analyses favors myself. If I compare to placebo, suggesting that no single subgroup was responsible for driving results, which supports our aim to file for a broad label covering all CELsignia, thanks.
Turning to the energized team, let me highlight three key reasons why we are excited about the upcoming readout in transfusion dependent thalassemia. First, it is important to recall that regardless of a patient's transfusion needs something in the hemolytic anemia by up-regulating PK activity and improving overall red blood cells. Help me talk about a novel mechanism of action directly addresses the underlying pathophysiology of hemolysis in all seven senior sub-debt. Second, this is a similar approach to the one we took for our PK deficiency program in decades in the Phase three ACTIVATE-T study of mitapivat in regularly transfused adults with pyruvate kinase deficiency missed up about demonstrated a statistically significant and clinically meaningful reduction in transfusion burden. These data, together with positive data from the Phase three efficacy study in patients with PK deficiency who are not regularly transfused led to FDA approval of mitapivat for adults with PK deficiency regardless of transfusion status. And we look forward to the potential to achieve the same in Cell C and third, in line with Mr. Professor <unk> mechanism of action, we have seen consistency in the data with improvements in hemolysis and ineffective erythropoiesis in clinical studies across three hemolytic anemias namely PK deficiency, sickle cell disease and non-transfusion dependent thalassemia. As a reminder, the primary endpoint of energy I see is a transfusion reduction response, defined as a 50% or greater reduction in transfused red blood cell units with a reduction of equal or more than two use of transfused red blood cells in any consecutive 12-week period through week 48 compared with baseline. This definition allows us to wait for patients to achieve a reduction in transfusion burden. First, see an increased time interval between transfusions or second through the use of fewer units or both in order to standardize as much as possible, the standard of care in this large global trial, each patient had a specific hemoglobin threshold value that was calculated based on their individual transfusion history prior to enrolling in the trial. If patients' individual hemoglobin threshold value determines the hemoglobin value by which they will receive a transfusion in the trial as the mechanism of action of mitapivat focuses on increasing red blood cell health and decreasing hemolysis. We are hoping to maintain hemoglobin levels above this threshold and reduce the need for transfusions We designed this study by incorporating learnings from prior studies as well as agency feedback and believe the primary endpoints dynamic assessment periods reflects what matters to patients and physicians as well as regulators. We now look forward to the readout of this study in the second quarter and are planning to submit a single regulatory filing to the FDA and combating data from both energized and energized team by the end of this year, seeking a label that covers people living with all subtypes of CELsignia.
Turning to sickle cell disease, enrollment in the Phase three portion of the ramp-up study of mitapivat continues to progress, and we are on track to complete enrollment by the end of the year. We have increasing conviction about the role of mitapivat in sickle cell disease, where we believe we have the potential to be both best-in-class and first-in-class. We look forward to reporting top line data from this 52-week study next year and believe firmly in mitapivat potential to address the high unmet need in this disease by improving anemia, making patients feel better and reducing sickle cell pain crises. We also remain on track to deliver on all milestones across the rest of our advancing pipeline. This quarter, we commenced dosing in the Phase one study of AG. one H. one, an oral phenylalanine hydroxylase or PAH stabilizer for phenylketonuria, abbreviated as PKU patients population with limited treatment options. We are excited about the potential to introduce a novel mechanism of action for PKU treatment and look forward to providing an update on next steps as enrollment progresses.
Based on the data generated in the Phase two A. study of our novel PK activator, AG nine four six in lower-risk MDS. We plan to increase the doses evaluated in the upcoming Phase IIb study, which we expect to initiate in mid 2024. And in pediatric PK deficiency we expect to complete enrollment of the Phase three efficacy study in the middle of this year, and we also now expect to report top line data from the Phase three activated T study in mid 2024 sooner than our original projection of year end. This is a very exciting time at Agios, and we look forward to providing additional readouts and progress as we proceed through the year. In particular, we are looking forward to share with you the status of submissions for E, how when they are made public in a couple of weeks.
With that, I will now turn the call over to Satya.

Tsveta Milanova

Thanks, Sarah. Today, a diagnosis of thalassemia can be daunting for patients and their families regardless of the disease subtype treatment options are limited and the burden of disease as well as the associated cost of care is significant. All forms of multimedia, including non-transfusion dependent thalassemia, bring higher rates of serious morbidities, reduced quality of life and a heightened risk of prevalence or events. There are approximately 6,000 diagnosed adults living with the leukemia in the U.S., approximately 4,000 of them are non-transfusion dependent and have no available treatment options today. As Barry mentioned, this patient population was studied in our energized clinical trial, which demonstrated the benefits of mitapivat in non-transfusion dependent thalassemia patients. The remaining 2000 are transfusion dependent and has no oral treatment option. We are eagerly awaiting the data from our energize the study in the second quarter, which is focused on the transfusion dependent patients. Our goal with mitapivat is to transform the treatment of Bolivia by becoming the first therapy approved for all subtypes of the disease, galvanized by the positive data from the NIJ study and the potential for positive data from energized team. Our commercial organization is actively preparing to address this high unmet need with a potential launch in India next year in the U.S. as we have highlighted, the lithium market in the US has more favorable commercial dynamics than the gain efficiency. In addition to the data, we are generating through the mitapivat clinical development program. We believe there are three key factors that have the potential to support adoption of mitapivat in thalassemia in the US for risk driven by the availability of newborn screening and well-established ICD-10 codes. The diagnosis rate in thalassemia is high with many patients diagnosed before others could. Second, both patients and providers are concentrated in a limited number of centers with approximately 50% of all diagnosed patients treated and fewer than 150 affiliated practices, providing a clear focus for our initial launch and learn our clinical trial sites in the U.S. are in some of the main centers of excellence. So many treating physicians will have first hand experience with me that the lab given these data and meet the above target product profile, we believe we are well positioned to provide a potential foundational treatment options for patients with hemophilia. Regardless of subtype. Our team is focused on four areas of the senior U.S. launch preparations for us. We continue to advance extensive market research and claims data analyses to further refine our market insights and our HCP targeting.
Second, we are rolling out a disease education campaign in the coming weeks designed for both patients and clinicians, highlighting the long-term complications and burden of disease across all deleterious subtypes. Particularly non-transfusion dependent patients who suffer from the misconception that they are at less risk.
You're right.
We are executing a disciplined expansion of our commercial and medical teams to right-size the organization for a successful launch in these larger, but still rare market and for our market access team is already engaging with payers on disease state education. I'm proud that our team has obtained broad market access for BiDil guidance in PK deficiency, and we look forward to the same strong outcome in thalassemia. In addition to the U.S., we aim to maximize the potential of markets outside the U.S. through coordinated regulatory filings, which we intend to pursue with Mark one or more partners. These markets include the Gulf region, which is home to approximately 70,000 unique patients and some of the leading treatment centers in our clinical trials.
Let me now provide an update on the current launch of BioTime in PK deficiency in the first quarter of 2024, we generated $8.2 million in net bio-implant revenue compared to $7.1 million in the fourth quarter of 2023 in the U.S., a total of 188 patients have completed a prescription enrollment form, including 10 in the first quarter of 2020 for a 6% increase versus the prior quarter. This has translated into net of 120 patients on therapy, a 10% increase versus the prior quarter. Patients on therapy continues to benefit from a growing and diverse prescriber base of 162 physicians and represents a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population in the US. We continue to be encouraged by the persistency of patients on treatment and remain focused on efficiently identifying providers likely to treat patients with beginning deficiency. We believe the capabilities we continue to strengthen through the current launch, including efficient targeting analytics, patient and HCP awareness and education and patient access, we'll provide a firm foundation to maximize potential future U.S. launches of mitapivat in thalassemia in 2025 and in sickle cell disease in 2026 above all. And you is once again, incredibly proud to be pioneering a potential new therapy for these two underserved patient population.
With that, I will turn the call over to Cecilia since our first quarter 2024 financial results can be found in the press release we issued this morning and more detail will be included in our 10 Q, which will be filed later today.

Cecilia Jones

Let me now take a moment to provide some context and highlight a few key points. First Quarter 2020 for net financing revenue was $8.2 million, an increase of $2.6 million compared to the first quarter of 2023, consistent with other rare disease launches. Gross-to-net has been and is expected to be in the 10% to 20% range on an annual basis. Cost of sales for the quarter was 0.6 million. R&d expenses were 68.6 million for the first quarter, an increase of $1.3 million compared to the first quarter of 2023. This increase was primarily driven by an increase in process development expenses, offset by a decrease in workforce related expenditures.
Sg&a expenses were $31 million for the first quarter, an increase of $2.6 million compared to the prior year quarter. This was primarily driven by an increase in commercial related activities as we prepare for the potential approval of Biocon in thalassemia. As a reminder, as part of the divestiture of our oncology business to Servier, we retain rights to a potential $200 million milestone upon FDA approval of Veracyte in it and 15% royalties on potential U.S. net sales. We ended the quarter with cash, cash equivalents and marketable securities of approximately $714.3 million. We expect that this balance, together with anticipated product revenue, interest income and the potential for upside in this milestone will enable the Company to fund our operating expenditure and capital expenditures through several value-creating milestones and at least into 2026. This guidance does not include cash inflows that could extend the runway beyond 2026, including the potential royalties or royalty monetization from vorasidenib commercializing mitapivat outside of the US through one or more partnerships or other potential strategic business or financial agreements. We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined cash allocation approach as we prepare to support potential future launches of Powercom as we move toward additional potential value-creating milestones in the near term. I am confident that our strong balance sheet will enable us to execute from a position of strength.
I will now turn the call back over to Brian for his closing remarks.

Brian Goff

Thanks, Cecilia. Driven by a novel and differentiated mechanism of action that improves red blood cell health and a clinical data package that includes positive data spanning three hemolytic anemias. We believe mitapivat is poised to become a first-in-class and best-in-class treatment option for multiple indications and with potential to become a multi-billion dollar franchise. I'm very proud of our team for steadily delivering significant progress. And looking ahead, I'm truly excited about the catalyst-rich 24 months in front of us as we continue to take steps towards realizing our vision of becoming a leading rare disease company. We'll continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation.
And finally, I'd like to thank all of our employees for their hard work and dedication to our mission of developing and delivering transformative medicines that elevate and extend the lives of patients living with rare diseases and all of our partners, including the patients, physicians, caregivers and participants in our clinical development programs.
With that, we'll now open the call for questions.

Question and Answer Session

Operator

Thank you to ask a question, you'll need to press star one one on your telephone to Australia question, please press star one one. Again, we ask that you please limit your questions to one question and one follow-up, please stand by while we compile the Q&A roster. One moment for our first question. And our first question will come from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Greg Renza

Great. Thanks.
Hey, good morning, Brian and team. Congratulations on the progress and thanks for taking my questions.
Sure, I think Sure. Thank you.
Brian, we certainly appreciate them more precision and timing for the energize T data. Just curious, narrowing it at least from midyear to second quarter. It can just comment a bit on sort of the relevant factors now what needs to be done and maybe some of the influences around just getting it to that narrower earlier timeframe on the second quarter and maybe related to that, just remind us just the mechanics on patients rolling over to the open label pensions?

Brian Goff

Sure.
Thanks, Greg. I'm going to let Sarah talk about the mechanics, but I will say that we are very much looking forward to the data. It's a very special time at Agios because everyone who's followed us and I know, Greg, you certainly have been there knows that we were delighted to have the energize data back in January. And this study energize T is twice the length. That was a energized was a 24 week study. This is 48 weeks, and we know there's a lot of interest. And so we were delighted to be to give, as you said, a little more granularity on the timing. But Sarah, do you want to talk about some of the mechanics side?

Sarah Gheuens

And so the granularity of the timing is driven by the patient the last couple of patients in the study their decisions to roll over into open label extension or not because as you know is a patient would have decided to not go into open, then they would need to taper down the drug and then they have a safety follow-up visit, which could which really drives a timeframe to that. That creates basically a seven week difference between a potential readout. So now we have a much more precision around that type of information and so we can narrow our timeframe. So that's why we've updated our guidance today. We're very excited about about where we are right now. And the team is very focused on delivering the next are the next steps for this Pacific top?
Yes.

Brian Goff

So this was the exact same scenario that we faced last year when we read out the rise of that Phase two data for sickle cell disease and of course, the same for Energis in January, the big picture that I'll just end with here is that our intent, as we noted in our prepared comments, is to file both studies together to target a label that encompasses all fallacy mutations, all subtypes and done all that said course, we look forward to the data, but we're already in a significant position of strength given the energize data and the fact that as you heard from Satya, that addresses already two thirds of the population in the U.S. with non-transfusion dependent thalassemia.

Greg Renza

That's great, Brian, thank you very much. And maybe just a follow-up just broadly on the on the landscape, certainly PK activation competition and with the with telaprevir from from Novo, maybe having some timelines now established, what do you make of that? How do you think about the landscape longer term, you're certainly moving moving fast, but as you think about the jockeying between between the two two offerings per patient? Thanks again.

Brian Goff

Yes, thanks, for the question. I mean, certainly, we take a lot of pride in the fact that we're the worldwide leader in PK activation from. And I think given some of the recent competitive updates that have been made public, but specifically with the other PK activator, topo pivot from Novo Nordisk, we took note of the most recent updated time lines, and that's why you heard in our prepared comments that we've often said we feel very confident in our best in class positioning. We feel increasingly confident now across both policy and certainly sickle cell disease with first-in-class potential And that all leads to this franchise having multi-billion dollar potential with mitapivat weren't a real significant position of strength.
Yes, absolutely.
And when we say the largely for CAD/CAM?
Yes, we are definitely very much as has our lowest third protocol is that they'll be reading out data in 2023 for their Phase two study. And we don't know about their commitment to Phase three. So fertility meal were very surprising to pioneer the way and handling and treatment options for growth and the senior patients in sickle cell disease of equally exciting are on our part. We are progressing well. The recruitment of our clinic Phase three clinical trial, everything going on plan, what we refer to as our dealers is they are expecting sickle cell disease data in 2027, which will be put them behind our anticipated launch in 2026, again, giving us that opportunity to basically bring the first in all of these products with the potential to even all the clinically meaningful and commercially meaningful endpoint of hemoglobin improvement reductions, you'll see an improvement in quality of life. So we're excited to be moving forward.
This is where we're taking full advantage of specialist expertise, deep expertise in rare disease launches. So this is what should lead for us a chance to change the lives of patients and thalassemia. Certainly that scenario and this launch has the potential to be next year or so coming soon.

Operator

Thank you.
Our next question will come from the line of David Round with PD. Cowan. Your line is now open.
Good morning. This is Debbie on for Mark. Thanks for taking our question. One on the calcemia, the transfusion dependent thalassemia trial coming up. Can you walk us through the powering assumptions for the primary endpoint?
And then I have a follow-up short review of.
Sorry, you want to take that?
Yes.
So we haven't spoken in detail about the powering assumption underlying the number. But we, of course, have leveraged all the information available to make sure that we have very good statistical justification for this trial. And so confident in the primary endpoint, then the sample size that we have selected the primary endpoint by itself, as you know, is a 50% reduction in any 12-week rolling period, which we believe can provide very meaningful assessment of the reduction in transfusion burden. And first, our senior patients kind of And then just quickly as a follow-up on further an app for 89%. So we still expect to see the full data from the Phase two A. trial on and sometime this year, but we haven't spoken about when we are going to release the Phase IIa data we have the team is assessing the best of the best opportunity on when to do so and the best conference and also in line of when we are getting sales to be up and running. So very focused on that very excited. We have a milestone around Phase IIb for this year. And so we're on track to deliver that.
Okay.
Thank you.
Thank you.
And our next question comes from the line of Eric Schmidt with Cantor Your line is now open.
Good morning, everyone. Thanks for taking my question and congrats on all the progress. Maybe just two quick ones. First for Brian and Sarah on this. So assuming a filing when I guess can you confirm whether it's going to be an NDA filing? It sounds like you're already preparing that filing. I'm just to be very specific If for some reason a beat TDT. study falls short, we would still be filing for non-transfusion dependent patients. Is that correct?
So and so thanks for the question. So our goal is to file the two studies together. As you know, we have already the first part of the data. So indeed, our filing preparations are completely underway and the team is on track to deliver another waiting for that second study. So the fact is that we already have great data for two thirds of the patient population. So we, of course, want the second study to deliver and make it, you know the great story. And if the study would fall short, then it truly depends on what the data would show how we would approach that. But our intent is to file for all balancing ambitions in get that broad indication.
And thanks for the clarification, Sarah. And just a second question on the sickle cell Phase three study that's enrolling. Can you provide any kind of color on how that's going and what percent of the study is already on board or maybe binary with your timelines for next year effects?
Sure. So we are very excited about the rise of study. Everything is going well and the team is doing an amazing job on getting that study completely up and running, and we are on track with our enrollment and so are completely expecting to be able to deliver towards full enrollment towards the end of this year. And we do not guide to them and no specific numbers expect that these specific weeks or months, these things are very rapidly changing are in big Phase three trial. So we feel we guide towards bigger milestones.
Thanks very much. Congrats again.
Thanks a lot, Eric.
Thank you.
Our next question will come from the line of Alok Stretta hand with Bank of America No, I’m is now.
Hey, guys. Thanks for taking our questions. And just a couple from us. First, a commercial question. Assuming both transfusion and non-transfusion and upon the label, any reason to think you'd need to maybe tailor your sales strategy differently between these two patient groups? Or will it be more or less the same given the likely seeing the same prescribers and then I've got a follow-up short.
Thanks, Alex, and welcome to the audio call and studying want to start off.
Absolutely.
We are super excited with seeing the positive data from the energized study. And as I said, we are eagerly awaiting the data from the energized on TI as well on in terms of launch preparation, we are actively in a lower launch preparation mode. We believe that there is a high unmet need across best, both patient populations and student dependent and non-transfusion dependent. And we have a lot of data that we are basically our launch preparation strategy on including claims data availability as opposed to defined goals. And we have basically plan to approach in the same way in both patient populations because of the same underlying pathophysiology of the disease, the connection between the two patient populations. And as you said on the overlap in the prescriber base, of course, you see a little bit more concentration in the non-transfusion dependent patients in the well as centers of excellence setting and a bit more under the non-transfusion dependent in the community setting. But that would not change. The project deployments are in communication and education.
The only thing I would add is that with the transfusion dependent patients, there's obviously more regularity of clinician visits than you tend to see with the non-transfusion dependent patients. But I'm really proud of the fact that side of the team are prepared for all scenarios.
Okay, perfect. And then just one question on the ex U.S. opportunity. I know you said that the plan would likely be to partner in ex U.S. geographies, but any additional color you can provide around sort of timing or scope of the ex U.S. opportunity, just just from a modeling perspective for us. Thank you.
Absolutely.
Still in addition to active and actively preparing for launch in the US, we are also actively searching for the best possible partner for us to maximize the ex U.S. opportunity.
We've mentioned on several occasions that the Gulf region is a high priority for us, given that there are 70,000 patients with the lowest premium in that region. And Sarah and the team are preparing for regulatory submissions in these regions actively as well to submit as quickly as possible on that, that will allow us and we'll provide updates as soon as we have progressed the discussion and invested by the partner. But we are in a very strong position, especially now with positive data from energized. So have a very high quality discussions with partners who have strong expertise in the region, and we are excited about it because our clinical studies are also done in the region, and there is a lot of the KOL advocacy and experience with the lifting of mitapivat itself. And equally as exciting a place as the US launch as well.
Great.
Thanks again for the question.
Thank you.
And thank you.
Our next question comes from the line of Kash Romero with JPMorgan. Your line is now open.
Hi.
Good morning, Ryan and team. Thanks so much for taking our question. Andrew question for Cecilia here. I mean, just curious, can you walk us through what pushes and pulls on your balance sheet and how you think about meaning could potentially extend that runway and what your latest thinking is there as we notice you included in your release today and how interested specifically are you in potentially a royalty monetization for Horace Mann? And then on the partnering side outside of the US, just to clarify, it has comment here. Could that occur this year? Thanks.
Thanks, Stefan. And we can add on HS2. And so yes, we we have guided that we have our cash at least into 2026. We purposely left out a couple of things that you mentioned. So I'll cover some of those. But these are things that we obviously continue to manage our cost base it thoughtfully and in a disciplined way. We now are starting to prepare for the launch, but we waited to make sure we had the data before we went ahead with that on the voice side, and that's another option that we looked as we evaluate to extend our runway. We see that we had in the prepared remarks and certainly publicly announced that the FDA accepted the filing and they have a PDUFA date on August 20th. And as a reminder, we have CAD200 million milestone and FDA approval and 15% royalties on US net sales for that and we will evaluate opportunities to sell that the whole amount or a portion of that as part of our way to extend the runway as we would do with other things. The other option or the other piece that we left out, as you mentioned, is the ex U.S., a portion that can come in different shapes and forms and that's part of the reason we left it out and the timing. Obviously, the teams are working to make sure we have the best partner and that is reflective of whether patients are like I described, and we want to have tried to obviously do that as fast as possible to get access to those patients.
Thank you, sir.
Thank you.
And our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.
Hi, this is Whitney on for Salveen. Thanks so much for taking your question on just on the upcoming energized T readout. Could you just discuss the clinical bar for success here and what you're hoping to see in terms of that percentage of patients with a reduction in transfusion burden? And then what should we expect this readout to kind of take a similar form to the earlier energized readout?
Thanks so much.
Thanks for the question. So for in regards to the energized steel readout, of course, we are hoping to hit on our primary endpoint with the reduction of 50% reduction, any 12-week rolling period. It's we have not spoken about the exact difference. We are shooting for between placebo or at least talking about. But in regards to the trial itself, it is, of course, well designed to be able to hit on the primary endpoint with the assumptions that are underpinning that, that design. What we know though, is there is the clinical trial bar of what we're shooting for that 50% reduction on. But in the real world, we know that the bar actually may be lower because what the compound the product would do is basically remove some of the clinic visits for patients if they can skip transfusions. And that would have a big impact on quality of life for transfusion dependent thalassemia patients.
I think said, I can maybe add a little bit on on what we expect for the real world.
Secondly, you mentioned, et cetera, the clinical bar is obviously very important from a regulatory perspective. But what do we hear both from patients and clinicians in terms of utilization, they'll be looking to reduce the transfusion burden even at the lower rate is now considered as clinically meaningful because even extending the transfusion on kind of frequency by a week on a patient basis. It is very meaningful on a actually health care system basis as well as the initiatives within you get very meaningful. So we are super excited to and waiting to see the data and getting very actively for us.
And I'll just add maybe one last comment, which is that obviously, we're going for statistical significance in the energize T. study from past experience. We know that there could be the temptation for cross-study comparisons as well. And I just want to emphasize that the compelling totality of the profile of mitapivat means we don't necessarily need numerical equivalence. What we need is statistical significance from the endpoint. That's what we're targeting. But the fact that this is an oral therapy means the patients are already in a way to free up the clinic relative to other alternatives. Id was Patterson, and we see that as on top of all else, that's another real advantage at the patient level.
Thanks so much.
You're welcome.
Thank you.
And our last question will come from the line of Danielle Brill with Raymond James. Your line is now open.
Yes, good morning.
Thanks so much for taking my questions on. First, I wanted to ask a question about the expected placebo response for Energis T and Ms. Patterson, that trial, I believe the placebo response rate as you defined it for your primary was around 6%. Curious your thoughts on how the placebo population is able to achieve that level of reduction? And are you expecting a similar outcome and energized team? And then as a quick follow-up, I'm just curious how you plan to announce the data, will this be a top-line PR or is it possible that you presented at E. half?
Thank you.
Thanks.
Yes.
So there's always fluctuation when you measure transfusion. So 6% for the placebo arm in regards to the primary endpoint definition is a very reasonable observation. And that is also because in clinical practice, sometimes patients get transfused on based on symptom presence and things like that.
So in regards to how we are going to announce data, yes, we typically do to a top-line release of the our press release. We will not be able to present data at a point because the timeframe for submission of data there is long gone. So that will that is on indiplon.
Understood.
Thanks so much.
Thank you.
Thank you.
And this concludes today's question and answer session. I'll now turn the call back to Brian golf for closing remarks.
Thanks a lot, Norma, and thank you very much everyone for participating in today's call. I think it hope it's clear. It's a very exciting time at Agios. We believe that we're well poised to deliver transformative new therapies for patients as well as creating significant long-term value to shareholders. So thanks again, and we look forward to speaking with all of you again soon.
This concludes today's conference call. Thank you for your participation. You may now disconnect, and everyone have a wonderful day.