Agios Pharmaceuticals Q2 2025 Earnings Report

Agios Pharmaceuticals EPS Results

• Actual EPS: -$1.93
• Consensus EPS: -$1.74
• Beat/Miss: Missed by -$0.19
• One Year Ago EPS: N/A

Agios Pharmaceuticals Revenue Results

• Actual Revenue: $12.50 million
• Expected Revenue: $9.46 million
• Beat/Miss: Beat by +$3.04 million
• YoY Revenue Growth: N/A

Agios Pharmaceuticals Announcement Details

• Quarter: Q2 2025
• Date: 7/31/2025
• Time: Before Market Opens
• Conference Call Date: Thursday, July 31, 2025
• Conference Call Time: 8:00AM ET

Agios Pharmaceuticals (NASDAQ:AGIO), a biopharmaceutical company, discovers and develops medicines in the field of cellular metabolism in the United States. Its lead product includes PYRUKYND (mitapivat), an activator of wild-type and mutant pyruvate kinase (PK), enzymes for the treatment of hemolytic anemias. The company develops AG-946, a PK activator for treating lower-risk myelodysplastic syndrome and hemolytic anemias; and AG-181, a phenylalanine hydroxylase stabilizer for the treatment of phenylketonuria. Its preclinical product is siRNA for the treatment of polycythemia vera, a rare blood disorder. Agios Pharmaceuticals, Inc. was incorporated in 2007 and is headquartered in Cambridge, Massachusetts.

Agios Pharmaceuticals Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: De-risked multibillion dollar opportunity with first-in-class PK activator PyraKine and key near-term catalysts including FDA PDUFA for thalassemia on Sept 7, Phase III sickle cell RiseUp readout by year-end, and Phase 2b MDS data early next year.
• Positive Sentiment: Strong second quarter performance with $12.5 million net revenue (up 45% YoY), a partnership to commercialize PyraKine in Europe, and $1.3 billion in cash and equivalents to fund growth.
• Neutral Sentiment: Agios expects modest full-year 2025 net revenue growth versus 2024, with quarter-to-quarter variability driven by ordering patterns and a sales focus shift to thalassemia.
• Positive Sentiment: Pipeline advancement includes dosing the first patient in the Phase II tebapivat sickle cell disease trial and IND clearance for AG-236 siRNA targeting TMPRSS6 in polycythemia vera.
• Negative Sentiment: Increased expenses in Q2 with R&D at $91.9 million and SG&A at $45.9 million, driven by a $10 million milestone payment to Alnylam and launch preparations for thalassemia.

Presentation

[Operator]

Good morning and welcome to Agio's Second Quarter twenty twenty five 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 Agio's request. I would now like to turn the call over to Agio. Please go ahead.

[Morgan Sanford, VP - IR at Agios Pharmaceuticals]

Thank you, operator. Good morning, everyone. I'm Morgan Sanford, Vice President of Investor Relations at Agios. Thank you for joining us to discuss Agios Pharmaceuticals' second quarter twenty twenty five financial results and business highlights. You can access the slides for today's call by going to the Investors section of our website, agios.com. Please move to the next slide. Today, we'll be making certain forward looking statements. 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. Next slide, please. On the call with me today from Agios are Brian Goff, Chief Executive Officer Cecilia Jones, Chief Financial Officer, Sveta Milanova, Chief Commercial Officer, and Doctor. Sarah Hewens, Chief Medical Officer and Head of Research and Development.

[Morgan Sanford, VP - IR at Agios Pharmaceuticals]

Following prepared remarks, we will open the call for questions. With that, please move to the next slide, and I am pleased to turn the call over to Brian.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Thanks, Morgan. Good morning, everyone, and thank you for joining us on today's call. Next slide, please. 2025 is shaping up to be a breakout year for Agios, and we believe we have a clear path to deliver sustainable growth and unlock long term shareholder value. First, we have a de risked multibillion dollar opportunity with our first in class TK activator, PyraKine.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Second, momentum is building as we approach multiple near term high value catalysts. We hope to add thalassemia as the second approved indication for pyrokine in The US, pending FDA approval, and we are now less than forty days from our September 7 PDUFA goal date. We expect to read out the Rise Up Phase III trial for pyrokine in sickle cell disease before the end of the year, and early next year anticipate phase 2b data for tebapivat, our more potent PK activator in patients with anemia due to lower risk myelodysplastic syndromes. And third, we are well capitalized to develop and launch pyrokine in thalassemia and sickle cell disease, and to continue to advance expand our pipeline through internal efforts and business development activities. Please move to the next slide.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

In the second quarter, we reported $12,500,000 in net revenue, reflecting the strong value proposition of Pyrokine. We entered into an agreement with Avanzanite Bioscience to commercialize and distribute Pyrokine in Europe. This is a capital efficient deal, allowing us to focus our investment on commercial launches in The U. S. We exited the second quarter with approximately $1,300,000,000 in cash, cash equivalents and marketable securities and intend to be disciplined in our investment behind the commercial build out of PyraKyme and advancement of our pipeline.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

In the second quarter, we dosed the first patient in the Phase II trial of tebapivat in sickle cell disease and received IND clearance for AG-two 36, our siRNA targeting TMPRSS6 intended for the treatment of polycythemia vera. We are at an important turning point in our growth story. Near term, we have the potential to transform the treatment of thalassemia and sickle cell disease with pyrokine. And beyond, we have the opportunity to deliver additional medicines to rare disease patients waiting and in urgent need of innovative treatment options. Please move to the next slide, and I'll turn the call over to Cecilia to provide additional commentary on our second quarter performance and the future trajectory for Pyrokine.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Thank you, Brian. Next slide, please. Our second quarter twenty twenty five financial results can be found in the press release issued earlier this morning, and additional details can be found in our 10 Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Second quarter net Pyrokine revenue was $12,500,000 an increase of 45% compared to $8,600,000 in the 2024 and an increase of 44% compared to $8,700,000 in the 2025.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Sequential net revenue growth reflects continued commercial execution in PKD, as well as an extra week of ordering in the second quarter and an increase in the number of units processed directly by the specialty pharmacy. In the second half of the year, we expect continued quarter on quarter variability in net revenues due to ordering patterns. Pending approval for thalassemia in The U. S, we expect softer PKD demand as a sales force transitions promotional focus to thalassemia. We still anticipate the fourth quarter to reflect partial demand for thalassemia given timing of a PDUFA goal date due to the expected time to convert patient enrollment forms to treatment initiation.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Taken together on a full year basis across indications, we expect net revenues in 2025 to show modest growth compared to 2024. Cost of sales for the quarter was $1,700,000 R and D expenses were $91,900,000 an increase of $14,500,000 compared to the 2024. This increase was primarily driven by a $10,000,000 milestone payment to our partner Alnylam related to the development of AG-two thirty six. SG and A expenses were $45,900,000 in the second quarter, an increase of $10,400,000 compared to the prior year, driven by continued investment ahead of the potential commercial launch of Pyrokine for the treatment of thalassemia. We ended the second quarter with cash, cash equivalents and marketable securities of approximately $1,300,000,000 Next slide, please.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Our strong balance sheet supports our focused capital allocation strategy, us to invest in our next wave of growth and pipeline delivery. First, we have executed a capital efficient commercial build out, prioritizing investment in potential U. S. Launches, which present the largest commercial opportunity. Last year, we announced our partnership with Newbridge Pharmaceuticals to commercialize Pyrokine in the GCC, and last month we entered into an agreement with Avance and BioScience to commercialize and distribute Pyrokine in Europe.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Both agreements are structured as revenue sharing arrangements that favor Agios over the long term. We will record our share of VexUS sales as net revenues. Second, we are strategically investing in our pipeline to advance our early and mid stage clinical programs. Third, we will opportunistically look for ways to expand our pipeline through internal efforts or externally sourced assets. In closing, I am confident that our balance sheet will enable us to continue to execute from a position of strength.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Please advance to the next slide and I will turn the call over to Sveta to share commercial highlights for the quarter.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Thank you, Cecilia. Next slide, please. Net revenue growth in the second quarter reflects strong execution by our commercial team. However, we continue to anticipate quarter on quarter variability due to ordering and inventory dynamics typical for rare disease medicines.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

As of the second quarter, two forty eight patients completed prescription enrollment forms, up six percent from the 2025. One hundred and forty two patients are now on active biokind treatment, an increase of four percent on a sequential basis. Please move to the next slide. With less than forty days to our PDUFA goal date, our commercial team is fully prepared for a launch in thalassemia pending FDA approval. We believe in ViralKind's strong clinical profile shown across two phase three studies, ENERGIZE in non transfusion dependent patients and ENERGIZE T in transfusion dependent patients.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

As shown on this slide, data generated across this robust clinical program means upon potential approval, we are set to deliver a series of firsts in the treatment of thalassemia in The U. S, all of which are profoundly meaningful to thalassemia patients. Next slide, please. We are confident in our ability to deliver on The U. S.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Launch of PyroKind in thalassemia, pending FDA approval for several reasons. First, thalassemia is well diagnosed due to widespread prevalence of newborn patient screening in The U. S. In addition, given the availability of claims data and ICD-ten codes, these patients have an established record of engagement with healthcare services. Second, the burden of disease is high, meaning symptomatic patients are actively managed and the associated cost of care is significant.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Despite this, treatment options are limited, especially for patients with non transfusion dependent disease, and most patients still rely on supportive therapy. Third, this is a community with a high level of engagement across key thought leaders and robust patient advocacy representation. Just this month, we attended the first Thalassemia International Federation Pan American Conference, where we engaged in meaningful conversations with patients and physicians that reinforce our understanding of their needs. Lastly, robust preparedness supports our ability to deliver a successful launch. Our disease state education is tailored to address the diverse multicultural aspects of thalassemia, and we have leveraged our connections with top leaders to provide additional disease education for community based physicians.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Last year, we doubled our sales force to approximately 40 employees and have focused our launch planning on non treatment centers. Initial conversations with payers have been encouraging, reinforced by the compelling benefit risk profile of ViralKind. Please move to the next slide. We have focused our capital investment on The US, which represents the largest commercial opportunity globally with six thousand diagnosed adult thalassemia patients. Our initial launch is focused on the 4,000 patients that are actively managed due to their symptomology.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

This patient segment includes both transfusion and non transfusion dependent patients who experience complications and or are living with debilitating fatigue. Next slide, please. Our agreement with Avandin BioScience and Newbridge Pharmaceuticals allow us to provide sustainable tailored access to pyrokines outside of The U. S. We anticipate the first potential regulatory approval in the GCC in the coming months and I will share additional detail on the commercial lung dynamics in the region shortly.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

In Europe, we anticipate a potential regulatory decision early next year. Here, we will work with our partner, Avandinize, on a focused country by country launch strategy aligned with the Latino disease prevalence. Please move to the next slide. I would like to take a few minutes to double click on the opportunity in the GCC. There are an estimated seventy thousand adult and pediatric thalassemia patients in the GCC, regardless of genotype and phenotype, and the majority of this estimated prevalence is concentrated in Saudi Arabia.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

However, due to the lack of National Registry data, we have been working with our partner Newbridge to refine our launch strategy. Since accessing the region is fragmented, we are focused on targeting all patients actively managed as an institution, and this target launch population represents a smaller proportion of the seventy thousand estimated prevalence. Importantly, we see potential to expand access by securing national procurement agreements, which can take roughly two years from approval, during which time access is granted on a patient by patient basis. Once procurement agreements are secured, we expect to further expand access agreements at an institutional level. We are thrilled to partner with Newbridge, a company with extensive experience commercializing medicines in the GCC, to potentially transform the treatment of thalassemia in Saudi Arabia and The United Arab Emirates.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Please move to the next slide. And with that, I will hand the call over to Sarah to cover key R and D highlights from the quarter.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Thank you, Sveta. Next slide, please. Pyrokines, our first in class PK activator, has demonstrated consistent, meaningful clinical data across multiple hemolytic anemias, reinforcing the strength of its differentiated mechanism action as an allosteric activator of both PKR and PKM2 and the broad applicability of this unique mechanism. In pyruvate kinase deficiency, our first approved indication, treatment with pyruvate kinase resulted in statistically significant improvements across multiple endpoints, highlighting improved hemoglobin levels, reduced hemolysis, and improved patient reported outcomes. At the end of last year, we submitted a supplemental NDA for pyrokine pyrokine for the treatment of alpha or beta thalassemia regardless of transfusion burden.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

In our phase three ENERGIZE and ENERGIZE T studies, we showed statistically significant improvements on measures of anemia, including hemoglobin level, transfusion reduction, and reduction in fatigue. We continue to partner with global health authorities on our regulatory filings and work towards our PDUFA goal date in The U. S. In sickle cell disease, we have reported compelling Phase two data from the operationally seamless Rise Up Phase twothree trial in 2023 and are on track to deliver top line results from the Phase three trial by the end of the year. Please move to the next slide.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Last month at the European Hematology Association Congress, we had a combined 14 abstracts that led to multiple oral presentations, posters and publications focused mostly on pyrokines and sebativa. These data add to the robust body of efficacy and safety data, reinforcing the promise of PK activation and the therapeutic potential of mitapivat and sebapivat across a range of devastating rare diseases, including pyruvate kinase deficiency, thalassemia, sickle cell disease, and myelodysplastic syndromes. Please move to the next slide. Our rise of phase two data reinforce our confidence in the potential to deliver a statistically significant improvement in hemoglobin response and reduction in analyzed rate of sickle cell pain crises, which are the dual primary endpoints for our Phase three trial. As the occurrence and severity of sickle cell pain carry variability, we kept consistency across our Phase two and Phase three trials by using the same inclusion and exclusion criteria, same definition of pain crises, same adjudication committee and methodology, and by including sites from the phase two in the phase three trial.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

We hope to deliver data that can speak to the positive impact pyrochem can show on the totality of the disease, for example, hemolytic anemia and vaso occlusion. Additionally, as fatigue is important to patients, we will look at the improvement in the Frommitt's Fatigue Scale as one of our key secondary endpoints. We believe our robust trial design provides multiple pathways to deliver clinically meaningful data and a differentiated profile with pyrokine. Next slide, please. We continue to advance our pipeline and are now investigating our potential best in class PK activator franchise comprised of pyrokines and cepapivac across four rare diseases.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

We are also excited to progress the multiple ascending dose Phase one trial for AG-one hundred eighty one intended for the treatment of phendylketonuria and the single ascending dose Phase one trial for AG-two thirty six intended for the treatment of polycythemia vera. As Brian mentioned, in the second quarter, we delivered on the two planned corporate objectives for mid year with sevapivat and AG-two thirty six. These achievements reinforce our consistent strong track record of delivering on our pipeline milestones. I look forward to bringing you additional updates on our pipeline as we look to develop a robust portfolio of medicines to transform the treatment of rare diseases. With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Thank you, Sarah. Next slide, please. In the second quarter, we made strong progress against our 2025 priorities. We achieved important milestones to advance tebapivat and AG-two thirty six, two assets with potential to expand our reach into new rare disease indications. We believe 2025 will be a breakout year for Agios as we make strides towards the potential launch of pyrukinin thalassemia in The US, phase three rise up readout in sickle cell disease, and continued advancement of our mid and early stage pipeline.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Please move to the next slide. In closing, Agios has necessary ingredients to deliver innovative medicines to rare disease patients in need, driving sustainable growth and unlocking long term shareholder value. At our core, we are fueled by our connections with the rare disease communities we serve, enabling us to deliver clinical benefits that matter to patients with a tailored commercial model to best meet patients where they are. Importantly, we're on our way to building a diversified rare disease portfolio. We are rapidly advancing a best in class PK Activator franchise with potential across four indications, and we look forward to providing future updates on our early stage pipeline with the opportunity to accelerate our growth outside of hematology.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Before we move to Q and A, I'd like to extend my appreciation to the investigators and patients whose participation, partnership, and trust have been invaluable to our development work. And of course, the Agios team who continue to inspire me every day. We look forward to what's ahead as we strive to redefine the future of rare diseases. With that, I'd like to open the call for questions. Operator, please open the line.

[Operator]

Thank you. To ask a question, please press 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. We ask that you please limit yourself to two questions. One moment while we compile our Q and A roster.

[Operator]

And our first question is going to come from the line of Eric Schmidt with Cantor. Your line is open. Please go ahead.

[Imogen Mansfield, VP - Biotech Equity Research at Cantor Fitzgerald]

Hi. Good morning, everyone. This is Imogen on for Eric. I think in the past, you've said that you would update investors on any change to ometipivat safety profile, including any cases of liver toxicity outside of thalassemia. Is there anything new that you have to report there?

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Good morning, Imogen. It's Brian. Thanks a lot for the question. I'll have Sarah comment on that first one with respect to any updates in the safety profile.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So, good morning. So no no updates to the safety profile. That that's it, really.

[Imogen Mansfield, VP - Biotech Equity Research at Cantor Fitzgerald]

Okay. Great. Thank you. And then one quick follow-up. On the GCC approval dates, is there any more color you could share on that?

[Imogen Mansfield, VP - Biotech Equity Research at Cantor Fitzgerald]

Are you expecting it maybe just after The U. S. Approval?

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Well, I will say, just reflecting on what we had announced in December, I'm really proud of the fact that the team has submitted, this was the first for Agios, submitted simultaneously across four different regions. And, all we can share at this point is that we're, actively in discussions across all four regions and we look forward to having the opportunity to give updates on the status of those reviews. And I I will also say that Steta and her team are certainly ready from a commercialization standpoint.

[Imogen Mansfield, VP - Biotech Equity Research at Cantor Fitzgerald]

Okay. Great. Thanks very much.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

You're welcome.

[Operator]

Thank you. And one moment as we move on to our next question. Our next question is going to come from the line of Mark Fram with TD Cowen. Your line is open. Please go ahead.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Hi, thanks for taking my questions. Maybe just with the thal review ongoing, are you able to comment on if you're maybe in labeling discussions yet? And obviously, safety information is going to need to be at least somewhat updated just to account for the fact that thalassemia is now well, hopefully going to become an approved indication. So what's the latest thoughts on kind of how you're anticipating that part of the label to read? And then I'll probably have a follow-up question.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Yeah, thanks, Mark. So Sarah can start.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Sure. Thanks, Mark. So well, maybe just a recap, but as you know, we've submitted to, as Brian just mentioned, four different regions for the indication of thalassemia based on our two well controlled trials that met the primary and key secondary endpoints in both. So that's the benefit part. You mentioned on the risk side, we have of course the hepatocellular injury, which you can already see reflected in the PKD label that was based on the thalassemia observation.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

And so we do at minimum anticipate there the updates in the PKD label to reflect the indication statement and the dose to be changed to, you know, to thalassemia and one hundred milligrams BID. But the process and the review are of course ongoing, and the FDA only provides you an end date of the complete review. So the final label, that's what we will know at PDUFA date.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Okay. That that's helpful. And then this is Morris for Sveta and Celia. Just the SG and A spend has you have been ticking up, obviously, as you build out and and prepare for that thalassemia launch. Should we view this as fully built out now and this is kind of the run rate or are there still kind of meaningful step ups that we should be expecting going forward as the launch actually starts?

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Yeah, maybe Cecilia can start on the financial aspects and then Steta always loves the opportunity to be able to talk about how well prepared her team is for potential launches ahead.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Thanks, Mike. Yeah, from a financial perspective, we do expect to see a little bit more growth on the SG and A side for thalassemia. You're right, we built the bulk of the infrastructure with the sales teams and customer facing teams starting last year after the trials read out. But we do have some launch related expenses that would obviously only happen upon approval. So, we do see some more coming potentially after that.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Yeah, absolutely. And the team I can tell you, the team is ready for a potential launch in thalassemia. As Cecilia mentioned, we've deployed the field facing organization late last year, and that includes the 40, about 40, people in the sales organization, but also a cross functional team that is going to run the different customers. We are excited, about having the potential provide, pyrucans in thalassemia, of course, pending FDA approval in The US, and we're looking forward to give updates when possible.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Great. Thank you.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

You bet.

[Operator]

Thank you. One moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open. Please go ahead.

[Salveen Richter, Biotechnology Equity Research at Goldman Sachs]

Good morning. Thanks for taking my question. As you look to the upcoming PDUFA here for ZAL and focus on the launch, could you just help us understand the initial target patient population that you'll be addressing or just be targeting here initially?

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Yeah, thanks a lot Salveen, and, again, I'll turn that one over to Sveta.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Absolutely. So, from a commercial perspective, thalassemia is really an attractive indication for us to potentially launch next. And the reason for that is, is that the patients with thalassemia are actually diagnosed and well known to the healthcare system in The US. There is a great data based on the ICD 10 codes, in The US, which we have been able to validate through our interactions with healthcare professionals. And that gave us a lot of clarity, not only where patients are currently being managed, but also what the patients potentially we should prioritize and focus at launch.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

When you think about which patients are really the most appropriate for our initial launch target, These are about four thousand patients out of the six thousand diagnosed adult patients in The US. And the way we prioritize these patients is based on their symptomology, the fact that they're engaged with the healthcare system, and they potentially will require additional management and treatment. And in this group of patients, you see both transfusion dependent patients who might be looking to reduce their transfusion burden, as well as non transfusion dependent patients who are symptomatic, they're experiencing fatigue and other complications of the disease, and both the patient and the physician might be looking for additional management and treatment. As I said, the team is very well prepared for the launch, and we have the opportunity to actually engage with these accounts, in advance of the launch. Very importantly for us, it's important that to remember and recognize that thalassemia is a disease with high unmet needs.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

About two thirds of the patients have no available treatment in The US. And that unmet need was really reinforced through our interactions with both patients and physicians, earlier in the month, where we had the opportunity to actually attend, CEMA International Pan American, Conference, which gave us a lot of energy and excitement, about the potential launch in the future.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Yeah, that's great. And Salveen, just to go back to the numbers for a second, Sven made the point that a lot of times we get asked about how solid are those numbers, the 4,000, patients. It is a pretty important point that these ICD-ten codes have been in place for quite a long time in thalassemia. So there's a lot of rigor around those numbers. And I'll just point out that's in contrast to PKD, where literally the codes were established right before launch.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

So it's a very different dynamic. And maybe I'll just ask Cecilia to comment on the look ahead for from a revenue perspective with a potential launch, what fourth quarter could look like.

[Cecilia Jones, CFO at Agios Pharmaceuticals]

Yes, thanks, Brian. So given the expected goal of PDUFA in September and the time it takes between a and patients initiating treatment from a revenue perspective for this year 2025, we don't expect the Latina revenues to be material.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Thanks.

[Operator]

Thank you. And one moment as we move on to our next question. Our next question comes from the line of Emily Wagner with H. C. Wainwright. Your line is open. Please go ahead.

[Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.]

Hi, good morning. Thanks for taking the questions. I guess for the first one, maybe if you could talk about the pediatric opportunity for thalassemia and if you have any timing, for potential FDA filing there. And then just maybe if you could confirm that you haven't had any changes to either access or I guess tone of speaking to the FDA in kind of recent weeks given some of the news going on there? Thanks.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Sure. Thanks, Emily. How about Svetlou can start on pediatric from a commercial perspective, and then Sarah can reflect on, the trials and the pathway ahead?

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Absolutely. So, are about eight thousand thalassemia patients in The US. As we said, about six thousand of those are down, so the remaining two thousand, are pediatric patients. Of course, it is a genetic disease where the patients are diagnosed at birth. There is availability of newborn screening.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

So, there is a high diagnosis rate in that disease, And there is always a high unmet need and an opportunity for us to provide value in pediatric patients. But with that, I'll hand it over to Sarah.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

The way we would the way we are approaching pediatric development is we wait for the benefit risk profile in adults, which we now have. And so the plan for thalassemia indication is doing exactly the same what we have done for the pyruvate kinase deficiency indication with an expansion by running the trials in the pediatric patient population. And then once that data is available indeed, deliver that to regulators for review.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

And I think, Emily, if I heard the second part of your question, Dawn was about FDA interactions. Of course, we're not going to talk about specifics, but anything you want to add, Sarah, about our engagement?

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

No, we always pride ourselves on collaborative engagements and relationships with all of our all of the regulators that we interact with. So, I know the the disruption in the news, and we have not experienced, like, major disruptions in our team engagements with the FDA, and it remains like a collaborative engagement.

[Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.]

Alright. Thank you.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

You're welcome.

[Operator]

Thank you. And one moment for our next question. Our next question comes from the line of Alex Shanahan with Bank of America. Your line is open. Please go ahead.

[Matthew Guggenbiller, Equity Research Analyst at Bank of America]

Hey, guys. This is Matthew on for Alex. Thanks for taking our question. Maybe first from us. I know the initial focus of the launch is on higher frequency of visit patients.

[Matthew Guggenbiller, Equity Research Analyst at Bank of America]

Curious for those outside the initial focus, what the key points of education are to drive uptake and whether that differs US versus ex US? And then maybe a second question on the early stage pipeline. Curious if there has been any change to your development plans in PKU after the approval of PTC's second.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Okay. So thanks, Matthew. So Sveta can start on the question about beyond the initial higher frequency clinical touch points, what does segmentation look like?

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Absolutely. So, we said, our priority segments are patients that are transfusion dependent, or non transfusion dependent patients that require additional management because of their symptoms, of the disease. When we look beyond that patient segment, we'll continue to expand into the non transfusion dependent patients, who might be experiencing symptoms, but might not be ready to initiate therapy immediately. It's also important for us to remember that as patients age, the burden of their disease increases, so they might be actually developing complications of the disease as well. The key educational elements there will continue to remain the same.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

We know that the unmet need in thalassemia is well characterized, but it is also an evolving field and additional data on the unmet need, especially in the non transfusion dependent patients is emerging. So, a lot of our educational efforts are actually disseminating that additional information and continue to engage both with patients and physicians. We're also stressing the importance of continuous monitoring, for those patients, given the long term disease complications and the pathophysiology of the disease, which is an important element for us. So, once we are ready to expand, we'll have more engaged both patients and physician community on that front. That will be consistent, in The US and ex US, of course, our priority and segmentation across the globe will remain quite consistent.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

However, ex US will need to deal with different market dynamics and patient access, which we'll address with our partners appropriately on a country by country basis.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

And just as a point of emphasis to Sveta's point about ex US, we're really clear on the geographic priorities. US clearly is our number one priority, that's why Asveta and the team have designed, for direct commercialization, and we're really proud of the partnerships that we have already established, and updated, in fact, this morning with Europe with, Avandanite Biosciences, as well as Newbridge in GCC. And that's a, as I noted, that's a very capital efficient approach, but it also leans on localized expertise, in those geographies accordingly. And then, to the second question about PKU, maybe I'll have Sarah pick up on that.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Yes. So we have not made any changes based on the recent approval. We are very excited about that approval to be able to monitor what happens and of course, learn from them as well as progress. But fundamentally, the same principles around our program remain intact because we have a drug of phenylalanine hydroxylase stabilizer basically which is completely a novel mechanism of action, oral therapy with the potential to really deliver another therapy to patients who still have a dire need. Even with this recent approval, there will remain a dire need for other options because these patients, can be in the position that they don't respond to the therapies or they have, you know, if you think about Palynziq, there may be anaphylaxis or things like that.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So there will remain a big, big gap there to address. And you even see that reflected in the current label that they received on the new drug because the stopping criteria when there is no treatment response, observed means that there effectively will be people who are not responding to this therapy and will need other options.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

And PKU is right in the sweet spot for Agios as a company that takes a lot of pride in, innovation to address diseases with high unmet needs. So just like across thalassemia, sickle cell, PKD, any of our diseases that we're pursuing, Any innovation is important and, you know, we like to read that news that you referred to and we're very excited about the progress that we're making with, our own, pH hydroxylase stabilizer with one a one. So thanks a lot.

[Operator]

Thank you. And one moment as we move on to the next question. Our next question is gonna come from the line of Andrew Burns with Leerink Partners. Your line is open. Please go ahead.

[Andrew Berens, Senior MD - Targeted Oncology at Leerink Partners]

Hi. Thanks, and congrats on all the progress. This is a follow-up to Mark's earlier question. Has anything changed in the sickle cell trial protocol since you identified risks and liver injury of ASH twenty twenty four. Interested in whether the consent forms and the monitoring requirements have changed.

[Andrew Berens, Senior MD - Targeted Oncology at Leerink Partners]

And then I have one on tebipivat. We noticed that the tebipivat trial is using markedly lower doses than the MDS Phase 2b trial is being conducted. Can you discuss the dosing protocol in this trial and the rationale for going lower in the sickle cell trial? Are there data at the relevant doses in MDS and sickle cell that you can share with us? Hello?

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Yes. Okay. So in regards to the sickle cell disease protocol, we've announced in the past that once we identified this risk in the thalassemia program that we had aligned all of our protocols to have monthly monitoring for the first six months, so including our open label extension trial. So for the sickle cell disease protocol, we aligned the open label extension study to match what happened in the first part of the randomized control trial because obviously, placebo patients get exposed for the first time in the open label extension study. So we made sure that they have the same type of monitoring.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

And so that is effectively reflected in the protocols. And we did update those informed consents as well, obviously. And in regards to your next question around the dosing differences between the sickle cell disease phase two and the MDS phase 2B, you are right, we are exploring lower doses within the sickle cell disease phase two. And that is because the sickle cell disease patients, their metabolism matches the healthy volunteer metabolism that was observed in the phase one. Reminder that we have sickle cell disease patients included in that trial as well.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

So we have that but then in the MDS trial in the 2A, we observed that the MDS patients metabolize the drug faster. So we adapted the doses appropriately. And so that's what you'll see that we are exploring. That's why we are exploring different doses between sickle cell disease and MDS.

[Andrew Berens, Senior MD - Targeted Oncology at Leerink Partners]

Thanks, Thank you.

[Operator]

Thank you. And one moment for our next question. Our next question is going to come from the line of Tess Romero with JPMorgan. Your line is open. Please go ahead.

[Tessa Romero, Equity Analyst at J.P. Morgan]

Good morning, Brian and team. Thanks for taking our question. So to double click back on a few of the earlier questions on the call, is it still reasonable to assume that the potential risk of hepatocellular injury will sit in the warnings and precautions section of the label as is currently reflected today? And relatedly, when do you expect to present your open label extension data that you have collected in this population that may be of interest to physicians and institutions as they begin to prescribe in thalassemia? Thank you.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Sure. Thanks, Tess. Sarah can take both of those. I'll just say on the open label extension, we're also interested in the data, of course, but we're to do things sequentially.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

Yes. Or maybe I can start actually with that one. Like, on the open label extension, you'll see us publish data of the open label extensions like we always do, just like what we've done for PKD. Obviously, right now, we're very focused on our ongoing reviews and prioritize the time of the teams there versus trying to get more publications out on the extension data. But that's coming for sure. We share that interest, obviously. And you're right, like everybody will continue to be interested in that. So more to come.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

And then in regards to your question around HCI and where it fits in the label, Brian mentioned it earlier. Obviously, we continue to engage with the agency as it goes. Like the benefit risk review is still ongoing with the agency. I think right now what you see, what is reflected in the PKD label to date is what we have observed in our program, right, which is you can see that language in another condition and at a higher dose is in the warning and precaution section of the PKD label. That language has to be updated at some point when we get to the final label for thalassemia.

[Sarah Gheuens, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals]

In regards to where it would end up or what would change, we don't comment on ongoing review processes with the agency. But as you know, our PDUFA date is September 7, at which point the procedure should be completed. And then you then we will all have the final label and can talk more about that.

[Tessa Romero, Equity Analyst at J.P. Morgan]

Thank you.

[Operator]

Thank you. And our final question is going to come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

[Theresa Robb, Director & Head, Global Client Experience Centre Regulatory Governance & Internal Controls at Scotiabank]

Good morning. This is Theresa on for Greg. Thanks for taking our question. I just wanted to see ahead of the launch, potential launch in thalassemia, if you could provide any additional color on the prescriber base for your initial launch focus and how you're planning to address any variability in care between academic centers and community hematologists.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Yeah, thanks, Theresa. Said I can reiterate a few of the points we talked about earlier in terms of in The US, the four thousand patients that are in our addressable target, and add a little bit more on community versus academic?

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

Absolutely. So, Theresa, as I mentioned, in The US, we really benefit from the fact that thalassemia patients are diagnosed, and they are well established ICD 10 codes. So, we have a lot of clarity of where these patients are currently being treated and managed. In addition to that, the team has been really focused on a very robust launch preparations where we had the opportunity to connect with the prescriber base and profile the accounts and really prioritize them appropriately based on the patients that have they have, and their potential willingness to manage these patients further. Of course, majority of the transfusion dependent patients are actually within the academic centers, where you would see a little bit more penetration in the transfusion dependent setting.

[Tsveta Milanova, Chief Commercial Officer at Agios Pharmaceuticals]

However, there is a very high unmet need in the non transfusion dependent patients, and that need is very well characterized and understood, even though if some of these patients are managed in the community, we've been able to actually engage with those prescribers, identify where these patients are managed, provide disease education, and prioritize those accounts, so we can pull them through launch as well at the beginning of the launch.

[Operator]

Thank you. And I would like to hand the conference back over to Brian Goff for any further remarks.

[Brian Goff, CEO & Director at Agios Pharmaceuticals]

Okay, thanks, Michelle, and thank you very much everyone for participating in today's call. As you know, we're halfway through yet another busy year. It's a very exciting time at Agios, and we truly believe that we are poised to deliver transformative new therapies for patients and to create significant long term value to shareholders. So thanks again, and we look forward to speaking with you again soon.

[Operator]

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.

Participants

Executives

• Morgan Sanford, VP - IR
• Brian Goff, CEO & Director
• Cecilia Jones, CFO
• Tsveta Milanova, Chief Commercial Officer
• Sarah Gheuens, Chief Medical Officer and Head of Research & Development

Analysts

• Imogen Mansfield, VP - Biotech Equity Research at Cantor Fitzgerald
• Marc Frahm, Biotechnology Equity Research Analyst at Cowen
• Salveen Richter, Biotechnology Equity Research at Goldman Sachs
• Emily Bodnar, Biotech Equity Research Analyst at H.C. Wainwright & Co.
• Matthew Guggenbiller, Equity Research Analyst at Bank of America
• Andrew Berens, Senior MD - Targeted Oncology at Leerink Partners
• Tessa Romero, Equity Analyst at J.P. Morgan
• Theresa Robb, Director & Head, Global Client Experience Centre Regulatory Governance & Internal Controls at Scotiabank