Agios Pharmaceuticals Inc. Q1 2023 Earnings Call

Speaker 2: Participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised this call is being recorded at Agios' request. I would now like to turn the call over to Agios' chief financial officer, Cecilia Jones. Please go ahead.

Speaker 3: Thank you, operator. Good morning everyone and welcome to Agios First Order 2023 conference call. You can access slides for today's call by going to the investor section of our website agios.com. diverse More than 100,000 users are now bunched in Ivan Ins Cormac year by year.

Speaker 3: On today's call, I am joined by our Chief Executive Officer, Brian Gough, Dr. Sarah Humes, our Chief Medical Officer and Head of Research and Development, and Svetlana Novar, our Chief Commercial Officer.

Speaker 3: 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.

Speaker 3: Actual events and results 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 FCC and any other future filings that we may make with the FCC. For more information, visit www.fema.gov

Speaker 3: With that, I will turn the call over to Brian .

Speaker 4: Thanks, Cecilia. Good morning, everyone, and thank you for joining us. Agios is the pioneering leader in PK activation and is dedicated to developing and delivering transformative therapies for patients living with rare diseases.

Speaker 4: We continue to generate consistent and compelling data with our PK activators across multiple disease areas, highlighting the potential of this differentiated mechanism of action.

Speaker 4: to transform patient function, quality of life, and long-term outcomes in PK deficiency, fallacy, mea, sickle cell disease, and lower risk NDS.

Speaker 4: Driven by the enthusiasm of our clinical investigators and the operational excellence of our research and development team, I'm pleased to report that we have closed screening in our phase III studies in thalassemia, which together encompass the entire thalassemia population.

Speaker 4: expect to complete enrollment of these studies later this month.

Speaker 4: On behalf of the Agios team, I'd like to thank the patients, caregivers, and physicians for their continued participation in these trials.

Speaker 4: As Sarah will describe in more detail, the rapid enrollment of these studies highlights the significant unmet need in these areas and bolsters our conviction in our broader clinical development strategy.

Speaker 4: In this context, we continue to advance our robust clinical stage pipeline and are on track to announce the data readout from the Phase II portion of the operationally seamless Phase II III rise-up study of pyrokind and sickle cell disease and the go-no-go decision that Phase III in the middle of this year.

Speaker 4: Echaling deposit reception of both Pyrokine and AG-9 or Stix from investigators at our clinical trial sites.

Speaker 4: We continue to receive positive feedback from both patients and clinicians on the impact that Pyrokine is having on individuals living with PK deficiency in the real world.

Speaker 4: We're encouraged to see that the efficacy of PyraKind observed in the clinical trial experience is translating to persistency on therapy in the real world, and we believe this has positive implications for the potential long-term impact of PK activation on how patients feel and function.

Speaker 4: in not just PK deficiency, but also valesemia, sickle cell disease, and lower risk MDS.

Speaker 4: SETTA will provide a detailed update on our commercial performance in just a few minutes.

Speaker 4: As you'll hear from Cecilia, we ended the first quarter of 2023 in an enviable cash position with approximately $1 billion on the balance sheet. As a reminder, as part of the divestiture of our oncology business to survey in April of 2021, we retain lights to a potential milestone.

Speaker 4: upon FDA approval of boracidinib and royalties on potential U.S. net sales.

Speaker 4: We were therefore pleased to see that Cervi8's phase 3 trial of Boracidinib in patients with residual or recurrent IDH mutant low-grade glioma met both its primary endpoint and key secondary endpoints.

Speaker 4: These data underscore OJOs' strong track record in the discovery and development of therapeutics for disease areas with high-end metadine, which to date span five approved indications across three separate products.

Speaker 4: In addition to the upcoming Phase II data read out of Pyrachine and Sickle Cell Disease, we're expecting a number of additional milestones by the end of the year, including...

Speaker 4: completing enrollment of the phase three studies of pyrucine in thalassemia.

Speaker 4: Enrolling more than half of the patients in the phase 3 Activate Kids and Activate Kids T studies of pyrukyne in pediatric PK deficiency

Speaker 4: completing enrollment of the Phase IIa study of AG946 in lower risk MDS, and filing the IND for our PAH stabilizer for the treatment of PKU.

Speaker 4: Finally, looking forward to what we expect to be a catalyst for which next few years, we anticipate redouts from the Phase III studies of pyrachyne and dallosemia in 2024, and redouts from the Phase III studies of pyrachyne in sickle cell disease and pediatric PK deficiency in 2025.

Speaker 5: With that, I will now turn the call over to Sarah. Sarah? Thanks, Brian . In the first quarter of the year, our team made tremendous progress executing across our industry-leading pipeline of PK activators. And we were pleased to receive the 2023 SiteLine Award for Excellence in Rare Disease Drug Development.

Speaker 5: This award recognizes pyrotechnical approval in BK deficiency and its significant potential impact in other ballistic enemies, including sickle cell disease and talcemia.

Speaker 5: Let me now provide a brief update on each of our programs, beginning with TALASIMIA, where pyrotechnics have the potential to become the first oral therapy to improve immunosimulitis and ineffective erotopolitis across all TALASIMIA subtypes. Specifically, the phase 3 TALASIMIA program comprises two randomized placebo-controlled trials, each of which is enrolled in patients with both ALSA and VEDA TALASIMIA. Energized is enrolled in patients who are not regularly transfused with a primary endpoint of hemorrhag...

Speaker 5: Turning to sickle cell disease, our goal is to address the high unmasked patient's need with an oral therapy that improves anemia, reduces sickle cell pain crisis, and provides a durable improvement in how patients feel and function. To meet this differentiated target product profile, we are advancing the operationally seamless safe 2-3 rise up study of pyrucyte in adults with sickle cell disease.

Speaker 5: to find Gono, Gokra, Syria in the face to portion of Ryza, including any additional data from the face to secondary end points, and longer term data from the ongoing extension studies of the investigator and sponsor trials at the NIH and the University of Pytrecht. Finally, we continue to advance the face to three active tips and activate tips.

Speaker 5: studies of fire time in pediatric decay and deficiency as we aim to deliver the first approved therapy for children living with disease.

Speaker 5: We expect to enroll at least half of the patients in each of these studies by the end of the year.

Speaker 5: Turning to the development of AG9 for 6 are novel decay activator that has potential to strengthen our decay activator franchise and enable once-a-day building.

Speaker 5: As a reminder, low risk NDS can counter approximately 70% of NDS cases and share the underlying specific physiology with other disease areas in our pipeline.

Speaker 5: Based on the data we have generated in the Phase 1 study of AG946 in healthy adults, we look forward to progressing this study and expect to complete enrollment of the Phase 2 by the end of this year.

Speaker 5: As we continue to advance the development of our PK activators, we also end to expand our portfolio beyond PK activations through both business development and advancements of our earlier stage pipeline.

Speaker 5: In this context, we continue to progress our small molecule, phenylalanine hydroxylase, or ph-stabilizer program, to directly address the underlying cause of phenylchentinaria, and we are targeting an IMD filing for this program by the end of this year.

Speaker 5: Overall, I'm excited by the tremendous progress the team made executing across our portfolio this quarter and look forward to a number of important milestones over the next several months. With that, I will now turn the call over to Sara.

Speaker 5: the tremendous progress the teammates executing across our portfolio this order and look forward to a number of important milestones over the next several months. With that I will now turn the call over to setup. Thank you Sarah.

Speaker 5: Our commercial organization is laser focused on executing a comprehensive strategy that addresses each phase of the patient journey, from disease awareness to reimbursement, adherence and persistency. By doing so, we aim to maximize the opportunity in the current launching PK deficiency.

Speaker 5: and build the capabilities needed to fully realize the potential of anticipated future launches in Telathemia, sickle cell disease and lower risk MDS.

Speaker 5: A foundational element of any successful launch is a clear, damage manager's proof file.

Speaker 5: Consistent with the positive feedback we received from patients, providers, we are pleased that the compelling data we observe with Pyrokine in the PK Dekfficiency Clinical Trial Program has continued to translate into persistent treatment news in the real world.

Speaker 5: Specifically, our market research data indicates that nearly 100% of our target healthcare providers are likely to recommend pyrokine to their adult patients with PK deficiency.

Speaker 5: For clinicians, key drivers of these recommendations include improvements in antimoblubing levels, reduction in transfusion frequency,

Speaker 5: an impact on long-term disease complications and comorbidities.

Speaker 5: While we remain focused on patient identification and improving disease awareness, launch to date, discontinuations have remained low overall. Reauthorizations have not been a barrier, and persistency of treatment has remained strong.

Speaker 5: beyond six months from treatment initiation. Together, we believe this reflects both the positive impact of pyrocyan on how patients feel and function and the strength of our commercial capabilities, including market access and patient services.

Speaker 5: In the first quarter of 2023, which represented the fourth-two quarter of lunch, we generated 5.6 million dollars in net-pire-kind revenue.

Speaker 5: A total of 127 patients have now completed a prescription enrollment form or PES, including 22 in the fourth quarter of 2023. A 21% increase versus the fourth quarter of 2022.

Speaker 5: This has translated into net 89 patients on therapy, a 14 percent increase over last quarter. Patients on therapy continue to stem from a growing and diverse provider base of 113 physicians.

Speaker 5: and represent a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population.

Speaker 5: I am confident that strengthening the commercial capabilities we are prioritizing today, including our ability to identify providers likely to treat patients appropriate for pyrokine, enhance the agnostic efficiency.

Speaker 5: Activate a broad range of prescribers and maintain long-term adherence and reimbursement.

Speaker 5: We will help maximize the potential of the current launch and lay the foundation for potential launches in a meaningful, larger patient population.

Speaker 5: Our next potential launch is in Telotimia, where approximately 60% of patients do not have an approved therapy in the US.

Speaker 5: Importantly, phyrochym has the potential to become the first oral therapy to improve hemolytic anemia and in effective erotropoezis across the full range of telotemia patients.

Speaker 5: including both, Alpha and Beta-Athelosemia. Alpha-Athelosemia currently has no approved treatment options and will therefore require a particular focus on patient identification and disease education.

Speaker 5: leveraging the capabilities we are building in the current launch in PKD efficiency.

Speaker 5: Base at the leukemia on the other hand is the more common form of the disease, constituting approximately two-thirds of the leukemia cases in the US.

Speaker 5: Given its greater prevalence and more competitive landscape, we believe adoption in data telesemia will require a greater emphasis on market access and Pyrochine's overall product profile including efficacy, safety and route of administration.

Speaker 5: Taken together, each of these potential launches will require a tailored commercial strategy, and we aim to leverage capabilities from our current launch to address the needs of each of these populations. The full range of telacemia patients is comprised of approximately 18 to 23,000 patients in the U.S. and...

Speaker 5: capabilities to meet the unique needs of our target diseases and deliver transformative new treatment options to these areas of profound and met patient need.

Speaker 5: With that, I will now turn the call over to Cecilia.

Speaker 3: Thanks, Vera. Our first quarter 2023 financial results can be found in the press release we issued this morning, which I will summarize. More detail will be included in our 10Q, which will be fired later today.

Speaker 3: First quarter 2023 Net Pyrocan revenue was $5.6 million, an increase of $1.3 million compared to Q4 2022. As Pyrocan is the first therapy for this ultra-rare patient population, we continue to gather data and insights on the launch trajectory and will not be providing guidance at this time. For more information, visit www.plastics-car.com

Speaker 3: were $67.3 million for the first quarter, a decrease of $2.8 million compared to the first quarter of 2022.

Speaker 3: This decrease was primarily driven by the 1.5 million of reversible transition related expenses we provided to Serbia in the first quarter of 2022 related to the sale of the oncology business.

Speaker 3: SCNA expenses were 28.4 million for the first quarter, a decrease of 3.1 million compared to the first quarter of 2022 that was primarily driven by a reduction in workforce-related expenses.

Speaker 3: As a reminder, TIPSOLVO Royalty, which was recorded under Royalty income from gain on sale of a quality business on her income statement, has ceased, given the sale of a right to 5% Royalty's on US net sales of TIPSOLVO to cigar.

Speaker 3: for a one-time payment of 131.8 million in October 2022. As part of the divactature of our apology business to survey, we retain rights to a potential 200 million milestone upon FDA approval over a side-and-if.

Speaker 3: and 15% royalties on potential US net sales.

Speaker 3: We ended the quarter with cash, cash equivalents, and marketable securities of approximately $1 billion. We ended the quarter with cash equivalents, cash equivalents, and marketable securities

Speaker 3: We expect our cash, cash equivalents and marketable securities together with anticipated product revenue and interest income will enable us to execute our operating plan.

Speaker 3: including funding the current-replanned development program for Metapeva, AG946 and our P-AIDS stabilizer, and commercialized Metapeva outside of the US through one or more partnerships.

To maintain our strong cash position, we will remain focused on proactively managing our cost base and deploying a disciplined cash allocation approach. I'll now turn the call back over to Brian for his closing remarks.

Thanks Cecilia, given the rapid enrollment of our ongoing studies of pyrokinin valesimia, the persistence of real-world pyrokin treatment in our current launch in PK deficiency and our strong balance sheet, our team is energized and focused on advancing our industry-leading pipeline of PK activators.

to address the profound unmet needs of patients suffering from rare hematologic diseases.

As we look ahead to the clinical and regulatory milestones we expect in the balance of the year, we will continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation.

Finally, I'd like to thank all of our employees for their hard work and dedication to our mission of transforming the lives of patients living with rare diseases and all of our partners, including the physicians, patients, caregivers, and participants in our clinical development programs.

With that, we will now open the call for questions.

Thank you.

To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Gregory Renza with...

But perhaps if you could just remind us or provide some call around some of the scenarios that you are accounting for when it comes to factoring in your no-go decision. What is perhaps nested in there as you think about some of the potential outcomes of that data and how you think about the new information that's forthcoming.

And also as it relates to Brian , just the consistency of the data, as you have mentioned, you've been very pleased with that over time and how that factors into the outcome as well. Thanks so much.

Sure, good morning Greg and thanks a lot for the question. With respect to sickle cell disease, first off, I just want to again commend Sarah and her team for the excellent progress that she's made not just...

with Sequel Sal and getting us to the point of a data readout at the midpoint of the year, but as we noted on the call I'm especially proud of the fact that Thalassemia now with screening completed puts us in a position for a readout in that domain in 2024 and that's equally important as well.

For sickle cell, we have, of course, a number of scenarios that we're planning for. We are hoping and planning for success, of course, and that's why the trial was designed to be operationally seamless.

Phase 2-3. So with success in the Phase 2 readout, the great news there is that Sarah and the team would be ready to go quickly and leverage the same clinical site setup that we have in Phase 2.

And obviously this is a very high unmet patient need arena, and so we're eager on their behalf in that scenario to move forward. And also with respect to what we're looking for for the data.

We've talked about this many times that we're going to take a holistic approach as we look at the data. The primary endpoint, of course, in the Phase II Rise Up Readout will be focused on hemoglobin improvement. We have secondary endpoints, markers of hemolysis, and the like.

And then of course safety will be a key element. And that will also guide us on the dose that we would pursue with success. At a very high level, the way we're thinking about sickle cell disease is that we'll be looking for a hemoglobin plus dynamic. And so that could be...

hemoglobin plus a trend in VOCs, though it's a 12-week study, it's not designed for VOCs per se. It could also be patient feel and function.

And we know that having studied the sickle cell disease arena for quite some time, that is a very important dynamic. It's not just

Success for the patient with the short term is the ability to stay on a therapy chronically.

Which by the way is why we're so encouraged by the persistency that we're seeing so far in our PKD launch. So maybe I'll stop there and just see Sarah if you want to add anything with respect to the scenarios. No, I think it's covered. I think we're very excited about the way the study is designed because it does allow and gives us flexibility.

We have AG946 where we're looking for proof of concept in our phase 2A study and low intermediate risk MDS at year end. And then earlier in our research pipeline we have the PAH stabilizer that we're pursuing for IND at year end.

So it's a pretty busy time to come, but thanks again for the question.

Thanks, Brian . You bet. Our next question comes from Tess Romero from JPM. Your line is open.

Good morning guys. Thanks so much for taking the question. So you've laid out a number of factors that will contribute to the go no-go for midipatatin sickle cell disease.

Can you just remind us of the status of the phase one sickle cell disease cohort for AG946? And do any of the results there in patients on 946 factor into this decision, right? So, in other words, could there be a scenario in which you elect to move 946 forward instead of MIT to that? Thanks so much.

Thanks a lot Tess. I'm going to have Sarah weigh in on this one. Hi Tess. So for 946, the phase one is ongoing and we have not disclosed the time points at which we will be presenting data. In regards to the second part of the question...

946 and Mitapivat are the totally different phase of development and 348 has built a huge safety profile, has much longer exposure and is really, you know,

past the phase one development. So to substitute the one compound for the other is not something that we believe is doable, just in the context of each product needs to build up its own safety profile. And 946 in our view is

Let's advance that face point. And, again, I'll just reiterate that, and I started to call this way that with NGOs as the leader in PKR activators, we are pleased to have not one but two that we're pursuing in clinical trials. And that gives us, as you noted, quite a lot of optionality, that the near term readout that we're quite...

eager to see would be in the low intermediate risk MDS patient population. Again, that's at year end. But it is quite an advantage to even be able to stratify across different therapeutic areas with two PKR activators when we get into the data readout.

If positive for pairing for launch and then the economics that could surround that to have two is particularly advantageous versus having all therapies lined up within one.

and then the economics that could surround that to have two is particularly advantageous versus having all therapies lined up within one. So thanks again for the question.

Thank you. Thank you. And our next question is coming from Mark Breidenbach from Oppenheimer. Your line is open. Your line is open.

Hey, good morning guys. Thanks for taking the questions. Two quick ones for me. First with respect to the energize and energize tea trials, which are nearly completing enrollment. I'm curious if you've seen any.

trends in specific geographies that are enrolling patients fastest, given that these trials have so many X, U, S clinical sites. And is that trend potentially going to influence your plans for regulatory filings, which territory is to file in first?

And then the second question is just with respect to VORCID and maybe Serbia's plans for a future NDA filing. Do you have any clarity on when such a filing might happen? Thanks for taking the questions.

energized, energized tea in the clinical trial geographies.

where thalassemia is present and also reflecting how the distribution of thalassemia is between different genotypes because the program is developed to deliver a product for all thalassemia, meaning alpha and beta thalassemia, regularly and non-regularly transfused. And so the clinical development program is designed that way, but also designed in such a way that it is feasible to enroll these.

Cecilia for the question on the board side, Niv, that, you know, having Stata Milanova on board as our chief commercial officer is really advantageous, Mark, when we think about, with successful data, to your point, your question about launch sequencing, as Stata spoke about in her remarks, this is, Salicemia is a uniquely concentrated...

addressable market geographically. And so we will be particularly thoughtful about the sequencing in part, well of course, to address access for the most patients in those geographies as possible, but also with an eye towards the value maximizing economics.

with respect to pricing and so on. And again, this all comes obviously with positive data, but it puts us in a position of strength with respect to how concentrated that population is. And having sped on board as a world-class expert in globalization of rare disease products is a real advantage. Maybe we'll have Cecilia Common on board, Sidemen. Yeah, so we're very excited.

clarity on timing yet and we'll provide an update when we have it. And obviously this is in survey A shop but the original science and progress came out of AGOs and so I know we've got a lot of AGOs employees listening in as well and I just want to say we are off the charts proud of what that could mean for Puyoma patients.

where they haven't had any progress in the last 20 plus years. And this only adds to the track record that Agios has had across a number of fronts. And now we're leveraging all that great science into our progress in PKR activation.

Thanks so much. You bet.

One moment.

We have a question from Greg Harrison with Bank of America. Your line is open. Your line is open.

Hey, good morning. Thanks for taking the question. How would you say your PAH stabilizer is different from a drug like Kuvan? And where would you see it fitting in the PKU treatment landscape with enzyme replacement and gene therapy approved or under development?

So, Greg, first off, good morning. I will start by saying too early to give, too much on that front. However, we are keen to progress our pH stabilizer to IND, but I'm going to let Sarah comment further. And I think our program is really designed, like all of our programs are really designed to target unmet need in patient populations. And for this one specifically.

differentiation there. And that can be on the safety profile, but also on the amount of product people need to take to get to some meaningful difference, and to actually also shoot for further reduction of a better improvement basically of the phenylketonuria.

overall. And so more to come on that as we progress the molecule, of course it's early now and as with any phase Moving to IND and then phase one we will be learning as we develop the program. And it's another great example of Why are so passionate about rare diseases because Every single therapeutic area that we pursue is desperate for innovation and disruption and

You know, whether that's PKD or sickle cells, we've talked about already phallocemia, NDS, and a pH. That's the common thread of our focus. Got it. That's helpful. If I could sneak one, quick one on the sickle cell.

What forum will you use to announce that data would it be a press release or a conference? And then will you be announcing the go-to-go decision at the same time? Could there be a delay?

So in regards to how and when we will announce, it will depend on when we receive the data, but we are planning to do a press release which will...

We will not include all of the data because of course we do want to present at a medical meeting and so it's always a balancing act between those two but in typical, actual fashion I think you what we've done for our past programs like PKD, you can expect something in that similar vein. Yeah, our target will be...

to give our stakeholders enough clarity as to the why behind our decision, whichever way that goes based on the data.

to give our stakeholders enough clarity as to the why behind our decision, whichever way that goes based on the data. Got it. Thanks again.

You bet, Greg. Thanks. Thank you. One moment. We have a question from Divya Rao from TD Cowan. Your line is open.

Hi, guys. Thanks for taking our questions. This is Divya on for Mark. Given the commentary on needing to see this hemoglobin plus response, if the VOC trend isn't seen, is the view that the PRO analysis would be predictive of ultimately showing a VOC benefit?

or do you think the PROs themselves support this Humor Golden Plus commercial profile? And then I guess specifically are there any PROs that are particularly important?

So this is the Phase II readout, right? So the PRO analysis and VOC benefit, all of that will really come at the end of Phase III in line with our product profile. What we are doing now with the Phase II, it has primary endpoints of hemoglobin response and safety and then, indeed, secondary endpoints of hemoglobin response and safety.

that capture PROs, DOCs, hemolytic parameters, but we will be looking for trends in those datasets. We will of course be looking at the totality of the data generated to date across the different studies that are using MiTAF-IVAT in sickle cell.

of reauthorization? Are you seeing any trends or I guess changes in the way pairs are evaluating what would be considered a response or benefit? Thanks, Divya. I'm going to have Cecilia coming on stocking. And then Spetta is always eager to talk about launch dynamics. So, Cecilia. Thanks, Fred. So as a reminder, we only have limited distribution model. We have one specialty pharmacy and one specialty distributors. Our inventory levels are inventory.

comes to treatment initiation, but also we see that we reauthorize as well. Up until today, the reauthorizations have not been a barrier. Patients do utilize the inclusion and exclusion criteria as well as the primary end point defined in the clinical trial to assess reauthorizations.

However, the totality of the product profile is taken into account, and we see that both in the success of the reauthorizations and the strong persistency, we see even though early in the launch with small patient numbers, full patients will continue post-six months of reauthorization as well. Yeah, and we hope that, you know, on today's discussion, we hope that message really comes out.

our target list, which is inclusive of those who have actually prescribed plurkin share in that enthusiasm. So the lost dynamic really is not so much around access or enthusiasm for the product. It's really about education, diagnostic efficiency, and activating.

patients especially to begin therapy. That's really where it's fed as emphasis commercially is focused.

That's helpful, thank you. You're welcome.

That's all well. Thank you. You're welcome. Thank you and our next question.

It comes from Salveen Richter with Goldman Sachs. Your line is open. Hi. Good morning. This is Anu Mehtaon for Salveen. Just one on the PKD launch. Could you just provide an update on patient discontinuation rates and whether what you're seeing in the real world is consistent with what was observed in the clinical trials?

And then just on sickle cell, I guess you've walked us through what you're going to be looking at in terms of the data, but I guess are there specific deal breakers from the the factors that you're looking at that would lead to a no-go decision if you could just frame that scenario. Thank you. Sure, and we'll do that again in sequence so Sveta can start with PKD discontinuity.

With that in mind, the continuation has remained lower overall and so far, as we mentioned, reauthorization has not been a barrier and adherence for the product remains strong. And this is very much reflected, I think, of the pyrokind, the other proposition in PKD, but it really gives us...

Also, the encouragement that the importance of persistency, which is associated with pyrocyan, could potentially translate into other indications, future indications we are looking to expand into. And that can be a critical differentiator, knowing how important persistency and adherence in other diseases can be.

Yeah, and I think to that point of the clinical trial that persistency and adherence we've seen in the clinical trials which has allowed us to continue to follow patients in the long-term extensions, which has allowed us to continue to study maintenance of effect, impact on how patients feel and function. And then we're also very excited about our iron overload data that we continue to present.

And so it's that compelling data across the board, as Sarah mentioned, it's very important to us because we also look at that in the context of the other hemolytic anemia. And then turning to the other hemolytic anemia, sickle cell disease, in regards to the no-go scenarios there, there are some obvious no-go scenarios as what would be.

on the clinical trial as expected for a clinical trial when a clinical trial would fail. So, if you do not see hemoglobin response, for instance, in the primary endpoint, or we have a safety signal that tips the benefit-risk profile the wrong way, things like that are all proactively...

defined in our go-no-go scenarios, and then we have, as for any other clinical development program, clear goals, and then scenarios in which more data will need to be assessed. Thank you. Thank you.

Thank you, and I'm showing no other questions in the queue. I'd like to turn the call back to Mr. Brian Golf for any closing remarks. Well thanks a lot, and thanks everyone for participating in today's call. And of course, for your continued interest in Agios.

So as you heard this morning, we are making great progress across our portfolio. I am incredibly proud of the team for what they're doing on behalf of patients who count on us. And I'm confident in our potential to continue to deliver significant value for both patients and our shareholders. So thanks a lot. And we look forward to speaking with you soon. This concludes today's conference call.