Agios Pharmaceuticals, Inc. Q2 2026 Earnings Call

Good morning and welcome to Agios Pharmaceuticals Second quarter 2026 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 this call is being recorded at Argos. Request. I would now like to turn the call over to Morgan Sanford, Head of Investor Relations at Agios.

Thank you. Operator. Good morning everyone. Thank you for joining us to discuss Agios Pharmaceuticals second Quarter 2020 financial results and business highlights. You can access the slides for today's call by going to the investor section of our website. agios.com. Please note, we'll be making certain forward looking statements today. Actual events and results could differ materially from those expressed or implied by any forward looking statements because 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 On the call with me today from Agios are Brian Goff, Chief Executive Officer. Cecilia Jones Chief Financial Officer, Tsveta Milanova chief commercial officer and doctor. Sarah Gheuens, chief medical officer and head of research and development. Following prepared remarks, we will open the call for questions. With that, I am pleased to turn the call over to Brian. Thanks, Morgan.

Good morning, everyone, and thank you for joining us. Before we review our second quarter results, I'd like to take a step back and highlight the strong position from which Agios executing. As we continue advancing toward our goal of building a multibillion dollar rare disease business We are executing against multiple drivers of value creation, including the launch of activism and thalassemia. The potential expansion of Mitapivat into sickle cell disease, and a pipeline that continues to grow through both internal innovation and disciplined business development. During the quarter, we further strengthened our portfolio with the addition of a next. Generation, highly selective oral SYK inhibitor that expands our rare hematology franchise into immune thrombocytopenia. Or ITP. We also advanced AG 236 into an operationally seamless phase two three program in polycythemia Vera, adding another potential growth driver within hematology. Beyond hematology. AG 181 continues to progress, and we expect phase one B proof of mechanism data in phenylketonuria patients in the second half of the year. We also continued to apply a disciplined approach to portfolio management, making focused investment decisions and directing resources toward opportunities with the greatest potential to create value for patients and shareholders. As you'll hear throughout today's call, our progress this quarter reflects the strength of that strategy.

Combining commercial execution pipeline advancement, disciplined capital allocation, and strategic business development to position Agios for sustainable long term growth. Turning to our second quarter highlights on the next slide, we delivered a quarter marked by strong commercial performance. Meaningful pipeline progress and continued portfolio discipline. First, we delivered sustained commercial momentum with $44.7 million in total net revenue, including $40.9 million in the U.S. and 442. Cumulative activism prescriptions from Rems certified physicians. Second, we further diversified our pipeline through the in-licensing of. A next generation, highly selective oral SYK inhibitor for ITP progressing toward phase three and strengthening our rare hematology pipeline. Third, we advanced mitapivat toward a potential new indication in sickle cell disease. During the quarter, we received FDA acceptance of our send a with priority review and were assigned to goal date of November 1st, bringing us one step closer to delivering a first in class medicine. In an area of significant unmet need And finally, we ended the quarter with approximately $1 billion in cash, cash equivalents, and marketable securities, providing financial flexibility to support both commercial growth and pipeline progression. Overall, we entered the second half of 2026 with strong commercial delivery of more diversified pipeline, an important near-term regulatory catalyst, and the capital position to execute on our strategy.

With that, please advance to the next slide, and I'll turn the call over to Cecilia to discuss financials.

Thank you Brian. Next slide please. Turning to our second quarter financial results. Total net revenue was $44.7 million, including $40.9 million in the US. And $3.8 million outside the US Cost of sales for the quarter was $3 million, and research and development expense was $100.8 million, compared to $91.9 million in the second quarter of 2025. Primarily due to an increase in growth in process research and development of $15 million, driven by the $25 million upfront payment associated with the agreement of Operator. Selling, general and administrative expense was $51.5 million, compared to $45.9 million in the prior year period, reflecting an increase in commercial related activities. As we execute our launch of advancement in 17 net. For the second quarter of 2026 was $100.7 million, compared to a net loss of $112 million for the second quarter of 2025. We ended. The quarter with approximately $1 billion in cash, cash equivalents and marketable securities, which we believe provides financial flexibility to support commercial execution. Advancement of our pipeline and continued investment in opportunities to create long term value. Turning. Now to our outlook for 2026. We continue to expect. Approximately 45 to $50 million from PK deficiency revenues in the US. Full year. Operating expenses are expected to remain approximately flat versus 2025, excluding the $25 million upfront payment associated with the semi in licensing transaction recognized in the second quarter.

And include investments to prepare for a potential sickle cell disease launch aligned with our November 1st. Date Our priorities for the remainder of the year remains clear. Driving the advancement launch. Preparing for a potential sickle cell disease approval. Advancing our pipeline and maintaining financial discipline. Please advance to the next slide, and I'll turn it over to Sara to cover commercial highlights. And let news launch progress. Thanks, Cecilia. Next slide please. With six. Months of launch experience now behind us, we are encouraged by the underlying drivers of performance. What we have. Seen so far continues to reinforce our confidence in the long term, especially opportunity in the leukemia Importantly, the strong execution across our commercial and patient focused organizations. Further strengthen our confidence in future launch opportunities. In the US. Performance reflected continued growth in the leukemia demand and solid commercial execution net. In the quarter, reflected approximately $5 million of one time benefit related to stocking Antileukemia, along with modest growth to net Favourability. We. Expect growth to net within our previously guided 10 to 20% range with quarter to quarter variability. Outside. The US. We delivered $3.8 million in net sales, reflecting anticipated demand for thalassemia in Europe. Owing approval and continued consistent early demand for leukemia in the GTC.

As we have seen consistently across rare disease launches, the shape of new patient starts naturally moderate as adoption broadens beyond the earliest wave of highly motivated patients and prescribers. We continue to expect quarter to quarter revenue variability, reflecting order timing, inventory movements, and growth to net dynamics Next slide. Please. I'm very pleased with the continued US launch performance of FSC. During the second quarter. We generated an additional 200 prescriptions from Rems certified physicians, bringing cumulative prescriptions to 442 as of June 30th. As a reminder, this. Metric captures unique prescriptions for patients with completed start form from rent certified physicians and serves as an early indicator of underlying demand Importantly, the underlying launch dynamics remain healthy. While demand continued to come from highly motivated patients. We saw a growing proportion of non-transfusion dependent patients in the second quarter, a profile consistent with the therapy moving beyond the earliest, most motivated cohort of transfusion dependent patients. We. To see strong conversion from prescription to treatment initiation. Time to start is naturally trending toward our anticipated 10 to 12 week range. As adoption broadens across the NTD population, where treatment decisions often involve more deliberate clinical discussions and patients may have less frequent interactions with the healthcare system.

Access. Continues to strengthen, and we now have approximately 75% of the leukemia lives covered under payer policies Additionally, physician ran certification continues to progress in steps with prescribing activity, and it's not a barrier to patient access, as the. Launch matures, prescriptions with completed start forms become a less informative measure of performance. Whereas revenue increasingly reflects both new patient starts and persistence on therapy For that reason, in anticipation of a potential FDA approval for me to pivot in sickle cell disease. We plan to discontinue reporting prescriptions from certified physicians after the third quarter and transition to revenue as our primary measure of commercial performance. Upon a potential sickle cell disease approval. We will assess the most meaningful metrics to communicate the progress and outlook of the broader Mitapivat franchise. Next slide please. I wanted to take. A few moments to highlight the launch considerations in the second half of this year. The. First half reflected a distinct initial phase of the launch. The first quarter benefited from a strong prelaunch anticipation and momentum built in the period leading to approval. Following the more than three month delay. Second quarter demand continued to reflect adoption from highly motivated patients and prescribers.

With time to treatment initiation beginning to approach our anticipated 10 to 12 week. At launch, maturity. Looking at. Ahead, we expect the shape of the launch to naturally evolve. Adoption is expanding into a broader non-transfusion-dependent population, where patients are typically seen less frequently and treatment decisions may take more time as. The patient mix continues to shift toward non-transfusion-dependent patients. We expect time to. Treatment initiation to move well within the 10 to 12 week range. We consistently discussed. We are also mindful that the first cohort of patients who initiated therapy in the earliest month, month of launch is approaching six months of treatment. A natural point at which physicians assess clinical response. This is an important part of the treatment journey, and it is the period during which we will begin to build a broader real world understanding of how physicians and patients evaluate response and integrate mitapivat into long term care. Taken together, these dynamics reinforce that access Me is delivering a healthy launch that is successfully progressing beyond the initial wave of adoption and into a broader expansion phase. As we move through the second half of the first launch year, our focus remains on expanding reach across the thalassemia community, expanding adoption in the Non-transfusion-dependent segment.

While continuing to add new prescribers. We. Remain highly confident in the long term opportunity for access. And in our ability to build a durable, growing thalassemia. Franchise. Over time. Please move to the next slide. We are actively preparing for a potential sickle cell disease launch in the US, and are encouraged by both the commercial opportunity and the unmet need we see in this community. Our initial launch focus is on approximately 25,000 patients who are actively treated or in need of therapy. Today. We believe that population alone represents a meaningful opportunity for me to pivot with potential to expand beyond the initial segment. Over time. Importantly, we are leveraging the capabilities. Relationships, and insights we have developed through the thalassemia launch while continuing to invest in market access, education and community engagement activities. Ahead of the goal date. Pending FDA approval. We believe this efforts position us well to support the successful launch and to deliver a to patients in need of innovative treatment options. Please move to the next slide. And with that, I will hand the call over to Sarah to cover key R&D highlights from the quarter. Thank you. Sarah. Turning to our pipeline on the next slide following recent portfolio prioritization decisions, we remain focused on advancing a diversified rare hematology portfolio with opportunities across multiple stages of development Mitapivat continues to anchor the portfolio with approved indications in pyruvate kinase deficiency and thalassemia, and a potential accelerated approval in sickle cell disease later this year.

During the. First half of this year, we achieved an important milestone with thalassemia approvals in Europe and the UAE completing regulatory approvals across all four. Priority launch geographies. Following prior approvals in the US and KSA. Since. First quarter results, we filed and received acceptance in the US for the Mitapivat NDA in sickle cell Disease with priority review and a goal date of November 1st. We remain committed to bringing Mitapivat to patients with sickle cell disease and recently dosed the first patient in reignite. Our phase three confirmatory trial, an important milestone in advancing the program We also strengthened the pipeline during the quarter through the in-licensing of a next gen. Cystic inhibitor that expands our reach within rare hematology and adds a compelling opportunity in immune thrombocytopenia. Beyond mitapivat and nib, we. Continue to invest in future growth drivers, including 82. 36 in polycythemia, Vera and 8181 in phenylketonuria. They. Together, we believe the pipeline reflects a focused allocation of capital and resources towards programs where we see the greatest potential to create long term value for patients and shareholders. Please move to the next slide. As. We discussed when we announced the in-licensing of our interest.

In the program is grounded in its potential to address some of the limitations that have historically constrained the thick inhibitor class. Was designed to optimize both selectivity and pharmacokinetics, supporting sustained target inhibition while maintaining a tolerability profile suitable for chronic use. The. Data generated to date are encouraging and support this design rationale, demonstrating dose dependent activity. No dose limiting toxicities through phase two and evidence of durable platelet responses. Taken together, these data support a rationale for advancing NIB as a next generation, highly selective inhibitor. We're looking forward to engaging with the FDA in the coming months to align on progression to phase three. Next slide. Please. At Issi in June, we were pleased to share a broad body of data across both Palestinian and sickle cell disease that continues to strengthen our confidence in Africa across the portfolio. We have sent. Abstracts accepted, including the rise of phase three study, which was selected for the Iha oral plenary session. In sickle cell disease rise of demonstrated hemoglobin responses consistent with the mechanism of PK activation with hemoglobin responders experiencing clinically meaningful improvements in sickle cell pain, crisis related and points in fatigue. At Iha, we presented new data showing clinically meaningful reductions in transfusion burden and red blood cell units transfused across the total trial population, exceeding historical experience with Hydroxyurea Importantly, outcomes from the subgroup of patients with at least one transfusion in the 52 weeks prior to enrollment directly informed the treatment effect.

Empowering assumptions for the ongoing reignite confirmatory trial supporting accelerated approval We also presented additional patient reported outcomes data showing clinically meaningful improvements in hemoglobin responders, feel and function, including reductions in physical pain. In addition, 56 week follow up data from the satisfied phase two investigator sponsored trial in related Membranopathies show robust hemoglobin response rates and mean hemoglobin improvement, as well as suggesting decreased iron burden. In non-transfusion-dependent thalassemia, we shared open label extension data showing that 60% of patients continuing on Metallica met criteria for hemoglobin response, and 60% of patients who switched onto metabolism in the open label extension achieved hemoglobin response Additionally, subgroup analyses indicate high hemoglobin response rates for non-transfusion-dependent patients with high baseline hemoglobin levels, indicating that less severely anemic MPD patients achieve improvements in hemoglobin levels and fatigue These data were received very favorably by the Talassemia community and reinforce the value of Mitapivat in Non-transfusion-dependent patients, which comprise the majority of the diagnosed adult patients in the US. Taken together, these data reinforce the consistency of Mustafa's profile across indications and further strengthen our confidence in the long term potential of mitapivat in hemolytic anemia. While we. Continue to advance and expand the sacrifice opportunity, we're also focused on building the next generation of potential growth drivers within rare hematology. 8236 is an important example of that strategy.

Next slide please. Following encouraging phase one data, we're advancing 8236 into an operationally seamless phase two three development programme in polycythemia Vera. What continues to differentiate AG 236 is its potential profile with an evolving treatment landscape The molecule demonstrated hepcidin induction through day 67 and favorable effects on iron parameters in extended follow up, supporting the potential for an every six month dosing regimen without titration. The phase two portion of the study is designed to identify the optimal therapeutic window across multiple dose levels, while enabling efficient progression into the registration portion of the program. More broadly, the seamless phase two three. Strategy reflects our commitment to disciplined execution while advancing development as efficiently as possible. With phase two initiation planned for the second half of 2026. We believe AG 236 has the potential to further diversify our rare hematology leadership and contribute to our long term growth beyond mitapivat. With that, please move to the next slide and I will hand the call back to Brian for closing remarks.

Thank you Sarah. Next. Slide, please. As we look across the business, we continue to make meaningful progress against the strategic priorities we established for 2026. We're building commercial momentum with acquisition thalassemia reaching 442 cumulative prescriptions as of June 30th. We're advancing mitapivat toward a potential approval in sickle cell disease, which represents an important opportunity to expand our PK activation franchise. And a potential next growth driver for the company. We're also advancing AG two three six, our siRNA ten six inhibitor for polycythemia vera. Into an operationally seamless phase two three program. Expected to begin in the second half of this year. And during the quarter, we further diversified our portfolio through the addition of a next. Generation. Highly selective SYK inhibitor in ITP, progressing toward phase three. Importantly, our progress this year reflects both execution and discipline We're investing behind the opportunities where we believe Agios can have the greatest impact for patients and create the strongest long term value for shareholders. Next slide. Taken together, we enter the second half of the year with a growing commercial foundation, a meaningful near-term regulatory catalyst, and an increasingly diversified pipeline in the financial strength to execute on our strategy.

Next slide please. Today. Agios is anchored by a growing commercial business and supported by a pipeline spanning multiple development stages and disease areas across the portfolio. We are pursuing opportunities where differentiated biology, meaningful patient, unmet need, and disciplined execution can support durable long term growth Collectively, these opportunities represent rare disease markets. Estimated at more than $10 billion in 2030. Before we open the call for questions, I'd like to thank the entire Agios team for their unwavering commitment to patients and their continued dedication to executing on our strategy. Their passion, resilience, and focus have been instrumental in the progress we've made this year. And with that, thank you all for joining us today. Operator, we're ready to begin the question and answer session.

Thank you. Ladies and. Gentlemen, to ask the question, please press star one one on your telephone. Then wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Alex Stranahan with Bank of America. Your line is open.

Hey guys, thanks for taking my questions and congrats on the really strong quarter here., two questions from me. First, on time on treatment in the commercial setting. Do you think the energize studies are a good barometer here. Just trying to think about how the dynamic of patients potentially coming off their T could could play into second half sales. And then. You know, when you look at the time on treatment,, did this change at all between one Q to two q. Did it move closer or further away from that 10 to 12 week average range that you're setting out and I guess, are you starting to see any repeat prescriptions under the Rems program at this point? Thank you.

Thanks, Alex. So two parter. So Tsveta, you can take the first one. Actually, you'll take both of these on time, on treatment and energize as an analog. And then the second one, I think Alec you're asking about not time on treatment, but time to treatment from the demand to initiation. So do you want to take that ?.

Absolutely. We are very pleased with the strong initial start of the launch. Alec. And as we mentioned, we have in total 442. Prescriptions from RAM certified physicians for the first two quarters of the launch., as we look ahead in the first couple of quarters, we benefited from faster than anticipated times. Treatment initiation. So it was faster than the 10 to 12 weeks. Weeks., given that we had prescriptions coming from highly motivated patients and physicians, keeping that in mind, we will start kind of the natural to reach the natural point of the six months at which physicians and patients are going to evaluate benefit for the product and continuation rate. But that's going to be more in the second half of the year. And we'll monitor that closely., currently, what we see from the market is a very,, kind of strong., feedback. And a positive feedback from the community. So we expect continuation rates to be in line with the energize study., and,, you know,, you know, we'll continue to monitor that, but, the product performance is very strong., in the market when it comes to time to treatment initiation., we start seeing that as we penetrate into the entity setting to move closer and closer to what we initially expected, the 10 to 12 week range., and as we move into the second half of the year,, we will,, we will continue to monitor that, but we expect to be well within the 10 to 12 weeks given the strong penetration in the entity setting ., and your third question was around repeat prescriptions., for the Rams., when we look at that, of course we have patients who have been on therapy for multiple months.

So we do start seeing the repeat prescriptions and patients and physicians are going through the process very, very smoothly.

Thank you.

Thank you. Our next question comes from the line of Andrew Berens with Leerink. Your line is open.

Hi. Thanks and congrats on the strong execution ., I guess I just want to expand a little bit on the,, the persistence rate since it's so important going forward. Is there anything that you can tell us about maybe the expanded access program at all?, what the experience will be like for these patients in the real world. And then the other thing that's obviously very important is going to be the sickle cell label, whether it's on a or pirate kind What, what factors will go into that? And is there anything you can tell us in these early days? Ahead of the November 1st? For that business confidence that you won't have a Rems or have to potentially reduce the pricing, or. In thalassemia. Thanks.

Thanks, Andy. And I will just say again and thanks for the comments about the strong quarter. I am really pleased and proud with the continued execution from Tsveta and the team. I think on the persistency. Andy, maybe we'll start with Sarah. Just reflecting on the the clinical trial, the open label extensions and what we saw. Because it still is early days for us to quantify persistence, but we always look at the trials and oils as a proxy Yes. Thanks, Brian. And I think ,, Andy, here we can really look at the open label data that we presented at Iha recently as well. So as you know, we have very high continuation rates for people who finish the clinical trials and then go into the open label extension. And now we have the benefit of being able to have followed them for a period of time. Post randomized control trial, where you see there is a good maintenance of response. So the patients do continue on the drug., and you see that maintenance of hemoglobin, the maintenance of anti-hemolytic response and people feeling, feeling good., another point there. What was exciting to see at the Iha data set was that people with a higher hemoglobin also had good response to the treatment, which is important, of course, as we continue to expand, the patients, we capture in the launch for them and non-transfusion patients.

And so yes, so I think the clinical trial data is actually the best way to look at that question right now. And.

And just wanted to end that. We I have been spending a lot of time with clinicians in the field. Had the opportunity to hear their feedback on the Iha data., and as we enter into the second half of the year and we start experiencing, kind of the real world evaluation of persistency and very confident that,, you know, we will see the repetition of what we see in the clinical trials in terms of continuation rates for six months.

And then. In regards.

To. Sorry, I'm going to ask, can you give us a, can you give us a number, a percentage that you saw in the open label extension study of patients who stayed on.

So for for energize, we had like an over 90% continuation from the clinical trial., in regards. Yeah. And then of course, it always, you know, as time continues, clinical trials are burdensome. It drops a bit, but it's very, very good persistence. Both both for PKD for Talassemia for sickle cell disease and the clinical trials What was interesting there is also the response rate with longer exposure, which it's important for talassemia from ,, in the early 40%, we had some Non-responders convert into responders. So we got to a 60% response rate there. So the clinical trial data is,, is, is very good.

And we know obviously that's, that's an important metric, for us going forward. And,, but we're still early days, we're, this is our second full quarter of launch, which in a way. Matches the,, the period of time for the energize trial. So we'll continue to monitor and of course, implement appropriate patient services support to help patients continue on therapy. And Andy, maybe you can just repeat the second part of your question.

Yeah, just I mean, obviously, I don't think anyone expects sickle cell pricing to be as resilient as thalassemia or PKD ., so it really depends on whether you get sickle cell. Or pirate kind. What do you think is going to drive that decision? And any insights? Now that we're several months away from the Paducah about which which brand sickle cell may be added to, if approved Yeah. So,, the Paducah is indeed November 1st priority review. So we're very excited about that., we have not further discussed which brand name., is. Going to be used, but as you know, the clinical trial data looked very good. We did not have the hepatocellular injury. observed in the sickle cell disease patients. So therefore it may not warrant a Rems. Either way our teams are ready to execute a launch with or without a Rems. So more to come.

And as always we'll provide more specifics at the time of launch. Once we have the label ,, we'll price the product., for that indication. And across the portfolio to maximize the opportunity based on the clinical data., and of course, the market environment at the time, I must say we are in a very strong position given that it's our third indication. There is a very high unmet need in sickle cell disease., and,, we do have a very strong market access team. I'm very proud of the progress they made in thalassemia with the payer policies. And we'll continue to learn and build from here.

Thanks for answering the questions and congrats again on the strong quarter. It looks like it's going to continue Thanks, Andy.

Please stand by. For our next question. Our next question comes from the line of Gregory with Truist Securities. Your line is open.

Hi, team. This is. Congrats. Let me add the congrats to the team too. On on an excellent quarter., so my, my question is two parts as well. If I may., so as we enter the second half of 2026 and we move beyond the initial wave of highly motivated transfusion dependent patients, how should we think about the run rate of, of new patient starts, particularly in the, in, in the broader non-transfusion dependent population. And the second part is where are you at in terms of grocery? I know it's favorable this quarter. Where are you at in you know in within the range of the 10 to 20%.. Expected target. Now you're at 75% of Covid life. Thanks and congrats again.

Thanks. Super. What?, so Tsveta. Maybe you can. Start with. And I think you said it the right way as we extend further into the broader reach and the NTD population study, you want to take that and then we'll do gross to net separately., absolutely. I'm very pleased with the progress so far. we are really seeing a very healthy start of the launch, both from penetration into the community setting where the majority of,, of prescribers are,, as well as the penetration into the entity setting, which is the bigger commercial opportunity., as we mentioned in the second quarter, we added 200 prescriptions from Ram certified physician physicians. As we move into the second half of the year,, prescriptions, growth and revenue growth are not going to be directly correlated., you know, on a perfect basis, given that we're moving into the more mature phase of the launch., and the really also depend on time to treatment initiations, Ramzan and., as. We've discussed,, moving ahead,, as we move into the entity setting, we expect the time to treatment initiation to move well into the 10 to 12 weeks.. Given the fact that these patients have less frequent visits to the health care professionals,, and they all need to go through the insurance verifications,, as well as the, the Rems process as well.

But we are really, really,, encouraged by the, the rate of patient adoptions, the progress that we are making, the way the patients are converting and staying on therapy at this,, part of the launch and most importantly, the really positive feedback from what I'm hearing from the clinicians on the product profile in the real world.

Great. And then,. I think the second part of your question was around the 10 to 20% guidance that we've given on gross to net Cecilia. Do you want to comment here?

Yeah. So we expect that to continue to be in that range of 10 to 20% as we guided before. There's always some quarter over quarter variability. But in aggregate, that's that's a range we still expect to see.

Thank you. Please stand by for our next question. Our next question comes from the line of Mark Frahm with TD Cowen. Your line is open.

Hey, thanks for taking my questions and completely get, you know, the kind of pushes and pulls on turning a TRX into ,, into actual revenue and, and,, and of course, there will be some drop off of patients on the back end starting in the second half. But do you view that 200 patients at the top of the funnel?. As now kind of a sustainable rate or does that still reflect a little bit of that bolus that you kind of talked about for Q1 of the backlog of Rems certifications and kind of the, the highly, highly motivated patients.

Yeah, I'll maybe I'll start and I'm going to turn it over to Tsveta. I think, Mark, a good way to think about a comment. We've made several times in terms of engaged patients engaged clinicians is that's a gradient. And we know that we're still on the front end of that gradient., as we instead of just commenting on the two as we move further into the NTD population,, by definition, these patients tend to have less frequency of clinical interactions. And so that's, that's essentially the dynamic that we're up against. Tsveta. What would you add?

Yeah. No., I absolutely, and as I also mentioned in my prepared remarks., looking into the entering a new phase of the launch in the second quarter, we expect prescriptions, growth and revenue growth not to correlate directly in every single quarter due to the timed treatment initiation., the patient patient conversion rates, persistency and kind of inter quarter ordering. Variability. That's why we actually move away from this initial indicator of demand., after the third quarter, which is prescriptions to something that we believe is more reflective of the underlying health of the business, which is going to be revenue. When you think about how the the first half is going to transition into the next phase of the launch, which is the second half. In the first half in Q1, and partially in Q2. We really benefited from this,, early adopters, highly motivated patients and physicians. The delay in the Padua, which created a anticipation of the launch in the for the launch and patients and physicians who are ready to, to start as quickly as possible as we move into the second part of the launch, what I'm looking for is really the underlying dynamics of the launch, which allow us to further penetrate into the community, setting a very strong adoption into the entity, setting across alpha and beta thalassemia patients and moving into that more steady state of 10 to 12 weeks treatment initiation., so we are very encouraged of, of the way the launch is going., and the way the team is executing..

Okay. That's all helpful. And then maybe just on the other end of the funnel, on the discontinuation rate, do you, do you view these initial kind of very highly motivated patients and clinicians that are using, you know, we're starting therapy in, Q1 and early Q2. Are those patients do you think more likely to stay on drug because of that motivation or ,, are they perhaps the very hard to treat patients? And maybe they'll have a somewhat higher discontinuation rate than kind of the long term number might end up being.

As we.

Progress into the next phase of the launch, we'll provide more color onto onto what we see in the real world. My suggestion for now. And what are we hearing from the clinicians is that the core period in the clinical trial, trials. Is is a very good proxy for continuation ., and we'll continue to learn more., I'm very pleased with the pair policies that have been issued., they really allow a lot of flexibility for patients and physicians to make informed treatment choices on continuation., the policies are really,, managing for managing patients to clinical trial criteria or better. So let's use for now the clinical trial as a proxy.

Okay. Thanks.

Thanks, Mark.

Thank you. Our next question comes from the line of Samantha Semenkow with Citi. Your line is open.

Hi. Good. Morning. Thanks very much for taking the question. And let me on my congrats on the strong quarter. Wondering if you could just speak a little bit more to the dynamics of the clinical evaluation at six after six months of treatment that you were speaking on in your prepared remarks, what are physicians viewing as acceptable clinical bar for continuing treatment? And is this six month clinical mark? Is that pretty strict or is there some flexibility where it could vary? When a physician would be looking to assess the clinical progress for a patient? And I have a follow.

Up.

Thanks. And this is another good one for Tsveta. And also where we have important learnings from our experience already with PKD. Now over many years, in terms of evaluation., absolutely., so there is a variability of how patients and physicians,, define benefit. And I'm going to use the word benefit because it's quite often goes beyond what is defined as the primary end point in the clinical trials., of course for transfusion dependent patients,, both patients and physicians will look at transfusion reductions, both in terms of,, ability to expand the time between transfusions as well as reducing the amount of transfused blood and, and both of these aspects are important., what we hear from physicians and I had the opportunity to meet both with patients and physicians at recently at the Cooley's anemia, Foundation meeting is,, they really do that on a patient by patient basis. A majority of them mentioned the six months, but driven by the fact that,,, our clinical trials were within that time frame, but it's also a natural. Opportunity for them to, to evaluate initial benefit., and they'll make decisions based on that,, transfusion reduction in the TTP patients will be important. They are not necessarily going to stick to what was defined as a 50% reduction in the clinical studies going to be ,, on an individual patient basis.

And if they want to continue on therapy as well and how they feel between the transfusions,, is also important., on the entity., setting,, they're going to look on, on improvement in hemoglobin, the one gram per deciliter is not like a hard yes or no. There will also look at the improvement in hemolytic parameters and very importantly in the entity setting is how patients feel. The reduction in fatigue is a key driver both for patients and physicians to continue on therapy. Irrespective of the actual level of hemoglobin improvement. So we are very encouraged from what we hear from our customers and look forward to learning more in the second half of the year.

Great. Thanks very much. And then just a second question about the evolution of the prescriber base. Are you seeing physicians? Write scripts for multiple patients that they manage? And I'm wondering if there's any sort of ,, I. Guess, dynamic that you could share that you've seen over the first two quarters of launch? Thanks very much.

Absolutely., when I look at our prescriber base, the most important thing for me is to look for,, breadth of prescribing because the Leishmania majority of the. Patients are managed in the community and we don't have, that much better across the therapy area. And I see a very, very strong breadth of prescribing across the country., from, from, from, from different clinicians. So I'm very pleased with the healthy start of the launch., we do have,, a small number of key opinion leaders who have written for more than one patient., and we continue to see prescriptions coming from this prescribers,, and we expect that to continue. They do have a stable patient base., but really our opportunity is to continue to penetrate the community setting.

Thanks very.

Much.

Thank you.

Please stand by for our next question. Our next question comes from the line of Eric Schmidt with Cantor. Your line is open.

Thanks, Mike. Congrats on all the progress as well. And,, unfortunately, another question for Tsveta. She seems like she's on the hot seat today .. So I just want to be clear about what's in the 442. Cumulative prescriptions that you're reporting. You know, historically, I think you've said those are for individual patients., mapped to individual start forms and wouldn't include refills or anything like that. Is that is that still the case?

They are unique patient prescriptions in a way. That's kind of the equivalent of a start form. And it's written by a certified physician.

And I assume Tsveta you have some insight into how many refills have also been,, written thus far., so yeah, the refill rates on continuous as patients reach their second and third month of therapy., so the refills are continuing., according to plan. So depending on, you know, the patients that have started and are progressing to the Rems, the refills are coming in. We are not providing a specific kind of refill., and total patients on therapy. And as I said, moving forward, we'll move away from start forms and really start focusing on revenue more because it takes into account all of these dynamics that you're asking about. Eric, new patient starts time to treatment initiation refills and continuation..

Okay, you anticipated all of my questions. I've just got one left., which is,, conversion of patients from start forms to therapy. Do you have a sense of whether there have been ,, many or any patients who have dropped out of the queue as they await therapy? Thanks ., we, we have a very positive policies and we have no market access., kind of hurdles,, for, for now, at the beginning of the launch, but I'm very pleased with that., our fill rate, which is basically prescriptions to patients starting on therapy is very high and it's very much in line with other rare diseases. So not, not nothing. Unanticipated there. So I'm very pleased with that very high conversion rate.

Yeah. And Eric, I'll just add that this is again where our PCD experience. Smaller scale, but the experience really comes into play because it's usually a time element, not necessarily, you know, a loss element in, in the translation from a start form to a patient starting on therapy. And again, we know with these NTD patients, as we move deeper into that penetration, it, it could take longer., which is why the translational aspect of going from a start form to revenue gets harder and harder from your perspective.

Great. Thanks and congrats again.

Thanks a lot.

Our next question comes from the line of Emily Bodnar with H.C.. Your line is open.

Hi. Good. Morning. Thanks for the questions and congrats also on the positive quarter., I'll on your sales for thalassemia. Were any of the two key revenues driven by Europe, specifically?, and how do you kind of think about revenue growth for the remainder of the year?, and then maybe. Secondly, with the sickle cell disease coming in November., are you expecting to launch by year end? And should we be expecting any kind of initial revenues for the fourth quarter? Thanks.

Thanks. Emily. Cecilia. Can, comment on the European question and then we can come back to the question about sickle cell.

Yeah. So, Emily the ex-US revenue for this quarter is a combination of the consistent continued demand in GCC, as we have like early access. There, as well as anticipated demand for thalassemia in Europe. Following the approval in May, I'd say the vast majority of our revenues are still expected to come from the US for the upcoming quarters, as we're still kind of ramping up the other regions early access for both. So we don't expect either one to be materially contributors. And then the other question on on sickle, again, given the date being November, it wouldn't be a material contribution to a full year revenues for 2026 and.

I will I will just add, Emily, we're enthusiastic about the opportunity of a priority review in November 1st. For for sickle cell and none of you will know this, but we're actually at a pretty important sickle cell. Kol and community physician meeting. So the reason I bring that up is I'm really proud of the work that Tsveta and the team are doing to get ready for that launch. And we're certainly looking to amortize as much as we can from the progress we're making in thalassemia towards that launch, as well.

Thank you.

Thank you.

Please stand by for our next question. Ladies and. Gentlemen, due to the interest of time, we ask that you limit yourself to one question, please. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Good morning. This is Lydia on for Salveen. Thanks for taking our question and congrats on the progress., could you just speak broadly to the current breakout between transfusion and non-transfusion dependent patients? And when you anticipate the Non-transfusion population to make up a majority of patients on treatment. And then as a quick follow up, once you reach that 10 to 12 week range,, do you expect that to sort of be the run rate going forward? Thanks so much.

Thanks, Leah. Sarah.

Absolutely., what we're seeing now is a growing proportion of the entity segment, as we've always said, and as an anticipated,, in the first quarter and partly in the second quarter,, a significant proportion of the patients were the TTP patients. Even they have a more frequent interactions with the health care system and are in generally, the more engaged patient population. We've seen a significant growth of the entity patients in the second quarter, we expect that to continue., and if you look at our breakdown of the, our initial launch focus, we have about 4000 patients., that we are initially targeting and about 50% of them are the entity patients. So we'll continue to penetrate that segment. And we expect the 10 to 12 week, average time to treatment initiations to stabilize and remain constant over time.

Thank you. Please stand by for our next question. Our next question comes from the line of Tess Romero with J.P. Morgan. Your line is open.

Hi Brian and team, thanks so much for taking our question. So as a matter of quick housekeeping, can you just remind us what is the right way to think about the low for a pivot? And then second, to double click here. What is the right way to think about how cumulative scripts from Disney should evolve from end of two? Q to end of three Q and then when might you be in a position to guide to revenues if script count will no longer be reported after three? Q thank you.

Okay, thanks. Tess, first one will be quick. Mitapivat you can think of low as,, 2035 of composition of matter plus extensions. And there are additional potential for patent extensions beyond that, the second one, which of course, for where we go from two Q to to third Q will be directional, not we're not giving specific guidance, but qualitatively Tsveta I think this will be, you know, similar to earlier comments you've made about further penetration., absolutely. As we look into the second half of the year,, we're looking forward to continue to penetrate the entity segment., and as we know, these patients have less frequent visits to the health care providers., and with that in mind, we also anticipate time to treatment initiations to move,, into the 10 to 12 week range, which will be a key dynamic of the quarter as well. We are reaching this important six month point of,, of treatment benefit evaluation. And that's one of the main reasons we'll start transitioning beyond Q3 ,, into actually providing,, revenues rather than continued prescriptions. Very importantly, we have an important date November 1st with the addition of the sickle cell disease launch., and once we, we have,, hopefully that launch,, launch will provide more information of how we, we can characterize the evolution of the Mitapivat franchise across indications, but,, we'll do that at a time of launch.

In Cecilia. Tess snuck in a third question about,, guidance. And when. So do you want to comment on that one?

Yeah, yeah. So Tess, as far as mentioned,, also with sickle cell coming on board,, upon a potential approval in November, we look into the appropriate time to provide guidance for the franchise going forward.

Good. Thank you.

Thank you.

Thank you. And our final question comes from the line of Luca Issi with RBC Capital Markets. Your line is open.

Hi. Sam, this is Shelby on for Luca. And thanks for taking our question. Maybe on the commercial preparation for a potential launch of sickle cell. I believe this has a higher Medicaid mix versus thalassemia and PKD. So one is that correct. And two, how are you thinking about gross to net dynamics And net revenue per patient and sickle cell relative to your other existing commercial products, and also does the Novo competitive dynamic factor into your pricing approach at all. Any color there? Much appreciated.

Absolutely., we will provide,, definitely more specifics on pricing at the time ., of approval. And that's going to be driven by the label