Earnings call transcript: Agios Pharm Q3 2025 beats revenue forecasts

Agios Pharmaceuticals (AGIO) reported its Q3 2025 financial results, revealing a notable earnings beat with actual revenue surpassing forecasts. The company reported a revenue of $12.9 million against a forecast of $10.54 million, marking a 22.39% surprise. However, the company’s EPS came in at -$1.78, slightly better than the forecasted -$1.90. Despite the positive revenue surprise, Agios’s stock price fell by 3.38% to $41.96, reflecting investor concerns over broader financial metrics.

Key Takeaways

• Agios Pharmaceuticals beat revenue forecasts with a 22.39% surprise.
• EPS was slightly better than expected, at -$1.78 versus -$1.90 forecasted.
• Stock price declined by 3.38% despite revenue growth.
• Strong performance in PYRUKYND sales, with a 44% year-over-year increase.
• Ongoing developments in rare disease therapies and strategic partnerships.

Company Performance

Agios Pharmaceuticals demonstrated robust performance in Q3 2025, with its net PYRUKYND revenue reaching $12.9 million, a 44% increase compared to the same period last year. The company’s focus on rare disease therapies continues to drive growth, particularly in the U.S. market, where the potential for its products remains significant. However, increased R&D and SG&A expenses indicate ongoing investment in future growth and product development.

Financial Highlights

• Revenue: $12.9 million, up 44% year-over-year.
• Earnings per share: -$1.78, slightly better than the forecast of -$1.90.
• R&D expenses: $86.8 million, an increase of $14.3 million from the previous quarter.
• SG&A expenses: $41.3 million, up $2.7 million sequentially.
• Cash and investments: Approximately $1.3 billion.

Earnings vs. Forecast

Agios’s Q3 2025 results exceeded revenue expectations, with a 22.39% surprise over the forecasted $10.54 million. The EPS also showed a smaller-than-expected loss, at -$1.78 compared to the forecasted -$1.90, representing a 6.32% positive surprise. This performance highlights the company’s ability to deliver strong revenue growth despite ongoing challenges in the sector.

Market Reaction

Despite the positive earnings report, Agios’s stock price fell by 3.38% to close at $41.96. The decline may reflect investor concerns over the company’s increased expenses and the broader market sentiment. The stock remains within its 52-week range, with a high of $62.58 and a low of $23.42, suggesting room for recovery as the company continues to execute its strategic initiatives.

Outlook & Guidance

Looking forward, Agios anticipates top-line results from its RISE UP Phase 3 trial for sickle cell disease by year-end. The company is also awaiting a European Commission decision on PYRUKYND in early 2026. Agios’s guidance projects continued revenue growth, with significant developments expected in its rare disease pipeline.

Executive Commentary

CEO Brian Goff stated, "We are operating from a position of strength," emphasizing the company’s commitment to developing transformative medicines. Chief Medical Officer Sarah Gheuens added, "There is a huge unmet need for this patient population," highlighting the potential impact of Agios’s therapies.

Risks and Challenges

• Increased R&D and SG&A expenses could pressure short-term profitability.
• Regulatory delays, such as the extended FDA PDUFA date for thalassemia, may impact product launches.
• Market competition in the rare disease sector poses ongoing challenges.
• Macroeconomic pressures could affect healthcare spending and investment.

Q&A

During the earnings call, analysts inquired about potential REMS programs for thalassemia and ongoing liver safety monitoring. Agios also discussed its commercial strategies in Saudi Arabia and Europe, reflecting its focus on expanding global market presence.

Full transcript - Agios Pharm (AGIO) Q3 2025:

Operator: Good morning and welcome to Agios Pharmaceuticals third quarter 2025 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 Agios’ request. I would now like to turn the call over to Morgan Sanford, Head of Investor Relations at Agios. Please go ahead, ma’am.

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Am.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals Third Quarter 2025 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. Next slide, please. 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 and 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. Our third quarter earnings call agenda is shown on the next slide. Joining me on today’s call are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; Tsveta Milanova, Chief Commercial Officer; and Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development.

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, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Morgan. Good morning, everyone, and thank you for joining us on today’s call to discuss our third quarter highlights. Beginning on the next slide. With steady progress and a focused strategy, we have a clear path to unlock long-term shareholder value. First, we have multiple high-value catalysts in the coming months that position PYRUKYND, our foundational PK activator, to achieve its multi-billion dollar potential across PK deficiency, thalassemia, and sickle cell disease. Following the FDA’s recent request for a REMS program, our PDUFA date for PYRUKYND thalassemia supplemental NDA has been extended to December 7. We are actively engaged with the FDA and are leveraging this additional time to strengthen our engagement with the thalassemia community and further refine our launch planning. Additionally, we look forward to sharing top-line results from the RISE UP Phase 3 trial of PYRUKYND in sickle cell disease by year end.

Meanwhile, we continue to advance our early and mid-stage pipeline, which includes our other PK activator tebapivat for lower-risk myelodysplastic syndromes, or MDS, and sickle cell disease, AG-181 for phenylketonuria, and AG-236 for polycythemia vera. Importantly, our strong balance sheet with approximately $1.3 billion in cash and investments positions us to invest in a disciplined manner to both support our potential U.S. launches and advance our rare disease pipeline. Our third quarter highlights are summarized on the next slide. In the third quarter, we reported $12.9 million in net revenue, underscoring the strong value proposition of PYRUKYND. In August, we announced approval for PYRUKYND in adults with thalassemia in Saudi Arabia, our first global regulatory approval for this indication. Earlier this month, we also received a positive CHMP opinion recommending PYRUKYND for marketing authorization in Europe for the treatment of adults with thalassemia.

Lastly, we achieved a key R&D priority by completing enrollment in the Phase 2b trial of tebapivat in lower-risk MDS, and we anticipate top-line data early next year. With continued momentum across our commercial portfolio and pipeline, our team has demonstrated strong execution and agility, keeping us firmly focused on our mission to deliver transformative medicines for patients. That agility is a competitive advantage as we work to transform the treatment landscape for thalassemia and sickle cell disease. Feedback from these communities through our recent global engagements reinforces the critical need for treatment innovation. Please move to the next slide and I’ll turn the call over to Cecilia to provide commentary on our third quarter performance and full year outlook.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Cecilia, thank you, Brian. Next slide, please. Our third quarter 2025 financial results can be found in the press release issued 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. Third quarter net PYRUKYND revenue was $12.9 million, an increase of 44% compared to $9 million in the third quarter of 2024, and an increase of 3% compared to $12.5 million in the second quarter of 2025. Third quarter net revenue growth reflects continued commercial execution in PKD ahead of potential U.S. approval for thalassemia. Looking ahead, fourth quarter performance will benefit from an additional ordering week compared to the third quarter, and we anticipate PYRUKYND net revenue will continue to reflect continued focus on PK deficiency ahead of potential approval for thalassemia in the U.S.

on a full-year basis. Given the strong execution of our sales force to date, we anticipate net revenues in 2025 to show robust growth compared to 2024, although we recognize this growth is on a relatively small revenue base. Cost of sales for the quarter was $1.7 million. R&D expenses were $86.8 million, an increase of $14.3 million compared to the third. This increase was primarily driven by increased clinical trial costs associated with our PK activation franchise. SG&A expenses were $41.3 million in the third quarter, an increase of $2.7 million compared to the prior year, driven by disciplined investment. Ahead of the potential commercial launch of PYRUKYND in thalassemia, we ended the third quarter with cash, cash equivalents, and marketable securities of approximately $1.3 billion. Next slide, please.

Our capital allocation strategy, backed by a strong balance sheet, enables strategic investment in future growth and delivery of our ongoing pipeline programs. First, we have built a capital-efficient global commercial model, prioritizing our investment in potential U.S. launches, which represent the largest commercial opportunities. We have executed partnerships with NewBridge Pharmaceuticals in the GCC and Avanzanite Bioscience in Europe, both of which are structured as revenue-sharing arrangements that favor Agios. Over the long term, we will record our share of sales as net revenues. Second, we will continue to invest in our ongoing early and mid-stage clinical programs. Third, we are opportunistically looking for ways to expand and diversify 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.

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

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Thank you, Cecilia. Next slide, please. In the third quarter, we delivered $12.9 million in PYRUKYND net revenues, up 3% sequentially, once again reflecting strong execution by our commercial team. To date, 262 patients have completed prescription enrollment forms, including 14 in the third quarter, representing a 6% increase. Sequentially, this has translated into 149 patients currently on therapy, up 5% from the second quarter. These results underscore the strength of our commercial model and the foundation we are building for future growth. We are well positioned to deliver on potential U.S. launches for thalassemia and sickle cell disease. Please move to the next slide. Let’s turn to thalassemia and our global commercialization strategy for PYRUKYND. Following the three-month extension of our PDUFA goal date to December 7, we remain confident in our ability to deliver a successful launch pending regulatory approval.

This confidence is further reinforced by our recent engagement with physicians, patients, and advocacy groups, which I will touch on shortly. Outside of the U.S., we have implemented a capital-efficient global commercialization strategy through partnerships with NewBridge Pharmaceuticals in the GCC and Avanzanite Bioscience in Europe. These partnerships allow us to retain full rights to PYRUKYND while preserving our capital investment for U.S. launches. In August, we announced SFDA approval of PYRUKYND for the treatment of adult thalassemia patients in Saudi Arabia, marking our first global approval for thalassemia. Launch activities are underway in Saudi Arabia. Our partner NewBridge is providing early patient access on a case-by-case basis, with the potential to expand access after securing a national procurement agreement over the next couple of years.

In Europe, we anticipate a European Commission regulatory decision in early 2026 following the positive recommendation from the CHMP, and we are actively working with our partner Avanzanite Bioscience to refine our launch strategy. Please move to the next slide. In the U.S., there are approximately 6,000 diagnosed adult thalassemia patients. It is important to remember that thalassemia is considered a spectrum of disease, not a single phenotype. Patients range from those who require regular transfusions to those who are non-transfusion dependent but still face debilitating fatigue and meaningful complications over time. The goal of treatment across the disease centers on three key to address patients, chronic anemia and hemolysis, increase their quality of life, and reduce the risk of comorbidities that can be caused by primary or secondary iron overload. Care for these patients happens in both academic centers and community hematology practices, and we’re equipped to support both.

Over the past year, we have profiled and prioritized accounts across settings. We also engaged prescribers where patients are managed and delivered disease education to them. Following the announcement of our PDUFA goal date extension, we have taken the opportunity to continue our engagement with the thalassemia community. Through these ongoing interactions, stakeholders consistently recognize the clear and compelling potential of PYRUKYND. Advocacy leaders and clinicians emphasize the magnitude of the unmet needs facing thalassemia patients and continue to stress the urgency for novel treatments like PYRUKYND. Additionally, it has become clear that providers have strong familiarity and experience with REMS across both academic and community settings and do not view a potential REMS program as a barrier to prescribing. Our established rare disease infrastructure gives us a clear advantage in launching PYRUKYND in thalassemia.

With high-touch patient services and a single specialty pharmacy model, we are well positioned to execute swiftly and compliantly within a REMS framework. The team is ready, and we look forward to potential thalassemia approval before year end. We are confident in our ability to deliver a successful launch, and with that, please move to the next slide and I will hand the call over to Sarah to cover key R&D highlights from the quarter.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Thank you, Tsveta. Next slide, please. In the third quarter, we continue to make strong progress across our pipeline. In early August, we announced PYRUKYND’s approval for adults with thalassemia in Saudi Arabia, and earlier this month, we received a positive CHMP opinion recommending PYRUKYND for marketing authorization in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha or beta thalassemia in Europe, and we look forward to a final regulatory decision by early next year. Finally, our reviews remain ongoing in the United Arab Emirates and in the U.S., where we continue to progress towards our new PDUFA goal date of December 7. Beyond PYRUKYND, we were pleased to announce enrollment completion in the Phase 2b trial of tebapivat for the treatment of low-risk MDS.

Tebapivat, our more potent PK activator, has the potential to be the first oral therapy to address anemia due to ineffective erythropoiesis in patients with low-risk MDS. I will share more on this potential opportunity shortly. Please move to the next slide. As we approach the anticipated top-line results for the Phase 3 RISE UP trial, I wanted to take a moment to highlight the significant need in this community as well as our potential to deliver a disease-modifying novel treatment with PYRUKYND. There are approximately 100,000 diagnosed adult and pediatric patients with sickle cell disease in the United States and a significantly larger number worldwide. Sickle cell disease remains profoundly underserved. The lack of suitable treatment options contributes to a high mortality rate that has in fact worsened, with U.S. life expectancy in the late 30s.

Underscoring a significant opportunity for therapeutic innovation, PYRUKYND is a potential first-in-class oral therapy for sickle cell disease targeting both hemolysis and vaso-occlusion through a unique PK activation mechanism of action, activating both PKR and PKM2 isoforms, decreasing 2,3-DPG, limiting hemoglobin S polymerization, and increasing ATP to support red blood cell health. Please move to the next slide. Guided by extensive engagement with the sickle cell community, we designed the Phase 3 RISE UP trial to align with clinical needs, positioning PYRUKYND to potentially reshape the treatment landscape for sickle cell disease. One of the two primary endpoints investigates hemoglobin increase, which addresses chronic anemia and thereby potentially reduces organ damage and improves how patients feel and function. Our other primary endpoint evaluates the reduction in analyzed rate of sickle cell pain crises, which are linked to organ dysfunction, early mortality, and a decreased quality of life for many patients.

Importantly, one of our key secondary endpoints will investigate potential improvement in fatigue, which is an overlooked symptom. In fact, chronic fatigue in sickle cell disease patients has been shown to be comparable to fatigue experienced by patients with other debilitating diseases like cancer and cystic fibrosis. In the trial, we will assess the improvement from baseline on the PROMIS Fatigue 13a scale, a validated measure of fatigue for this population. We look forward to sharing top-line results of the Phase 3 RISE UP trial by the end of this year. Please move to the next slide where we present a high-level view of the trial design and statistical plan. As a reminder, since the trial includes two primary endpoints, the trial is positive if statistical significance is achieved on either one of the endpoints.

The pre-specified statistical testing strategy allows testing of the key secondary endpoints if at least one of the primary endpoints is met, thereby preserving the opportunity to show benefit on other key features of the disease, including fatigue. We remain confident in PYRUKYND’s potential to become a transformative therapy for sickle cell patients, an underserved and underrepresented population with significant unmet needs. Next slide please. I’d like to take a moment to highlight our second, more potent pyruvate kinase activator, tebapivat, which is being investigated in ongoing Phase 2 trials for two rare diseases: lower-risk myelodysplastic syndromes and sickle cell disease. Lower-risk MDS accounts for approximately 70% of all myelodysplastic syndromes. Symptomatic anemia is the primary concern for most patients. Therefore, the primary treatment goal is to improve quality of life by managing the underlying anemia caused by ineffective erythropoiesis.

Decreased glycolytic activity has been seen in MDS patients, where they may show decreased PK activity and an abnormal pyruvate kinase hexokinase enzymatic ratio. Tebapivat is designed to correct RBC metabolism by increasing ATP production and normalizing the PKHK ratio. Today there are limited treatment options to address low-risk MDS and we believe tebapivat has the potential to be the first oral medicine to address anemia due to ineffective erythropoiesis. We completed the Phase 2 portion in November 2023 and progressed to the Phase 2b portion, which evaluates three higher doses that were evaluated in the Phase 2a portion. This trial will investigate 10 mg, 50 mg, and 20 mg doses of tebapivat daily versus placebo over 24 weeks. Today we announced that we achieved enrollment completion and we continue to expect top-line data in early 2026. We are also investigating tebapivat for the treatment of sickle cell disease.

Enrollment remains ongoing in the Phase 2 trial and we look forward to providing updates in the coming months. Please move to the next slide. We continue to advance our early-stage rare disease pipeline with AG-181, an oral PAH stabilizer intended for the treatment of phenylketonuria, and AG-236, a siRNA selectively targeting TMPRSS6 for the treatment of polycythemia vera. Our first early-stage program is AG-181 for the treatment of PKU. There are 15,000 to 20,000 patients diagnosed with phenylketonuria in the U.S. where patients’ symptoms can range from mild to severe. Currently available treatment options have demonstrated limited efficacy or significant safety issues, leaving patients with a gap in treatment and limited to phenylalanine-restricted diets, therefore significantly impacting a patient’s quality of life. Our Phase 1 multiple ascending dose trial in healthy volunteers is currently ongoing and we look forward to providing updates on this trial in the future.

Our second early-stage program is AG-236 for the treatment of polycythemia vera, a rare hematologic disease that affects approximately 100,000 patients in the U.S. PV causes an excessive production of red blood cells, increasing blood volume and viscosity and can result in thrombosis, cardiovascular events, or death. Current treatment options are limited to phlebotomy, hydroxyurea, and other cytoreductive therapies. However, these medicines do not effectively control hematocrit for more severe patients. We believe AG-236 has the potential to address the remaining unmet need with a potentially improved safety and efficacy profile and less frequent dosing. Last quarter we received IND clearance and dosed the first subject in the Phase 1 trial in healthy volunteers and look forward to providing updates as the trial progresses. With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you, Sarah. Next slide, please. In the third quarter, we delivered meaningful progress across our 2025 R&D priorities, once again showcasing our ability to execute swiftly and effectively. Looking ahead, the fourth quarter holds exciting milestones. We are sharpening our launch planning in anticipation of the new December 7 PDUFA goal date for PYRUKYND in thalassemia, and we expect to report top line results from the Phase 3 RISE UP trial of PYRUKYND in sickle cell disease by year end. Please move to the next slide. Our fundamentals remain strong. Backed by a seasoned leadership team with a proven track record, we continue to advance our pipeline and deliver meaningful impact for the rare disease communities we serve, communities whose insights guide us and are vital to our success. We are operating from a position of strength, backed by a balance sheet that not only supports our potential U.S.

launches and advancement of existing clinical programs, but also enables us to pursue strategic business development opportunities to further expand and diversify our pipeline and ensure we can create long-term shareholder value. Before we move to Q&A, I want to take a moment to recognize the continued dedication of our employees, whose relentless focus and commitment continue to drive meaningful impact for patients with rare diseases. Their work, together with the voices of the communities we serve, is foundational to our mission. As we look ahead, we remain resolute in our pursuit of transformative medicines, advancing innovation with the aim of delivering long-term value for both patients and shareholders. 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 star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11. Again, in fairness to all, we ask that you please limit yourself to one question and one follow up. Please stand by for our first question. Our first question comes from the line of Eric Schmidt with Cantor. Your line is open.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Please go ahead.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you for the opportunity to ask a question. Maybe first, just on the thalassemia review process. It’s been almost two months now since you got the PDUFA extension. Do you have a better sense of what type of a REMS program the FDA is interested in here? I know there’s a spectrum of maybe more or less onerous REMS programs. Second follow up question. I think both Cecilia and Brian mentioned actively looking for external assets. What type of BD makes sense for the company at this stage? Would you wait until the sickle cell readout to transact? Thank you. Good morning Eric. Thanks a lot for the question. I’ll have Sarah take the first one and then I can pick up with the external pursuit question. Sarah, let me turn it over to you.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Yes, thanks Eric, for the question. In regards to REMS and label, as you know, the review is ongoing with our extended PDUFA date of December 7th. We, per process, don’t comment on the details of REMS in the label. However, indeed, to your point, there are many different forms of REMS. As you know, the REMS is requested because of hepatocellular injury. You can anticipate that it will include monitoring and some form of education.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Eric, on your second question, in terms of continuing to expand our pipeline, our pursuit really is not tied to anything in particular. I’m really proud of the work that the team does to cast the net wide and continue to look at a number of different opportunities. This goes externally, but it’s also organically, internally to see if there are other indications, for example, that we should pursue. That’s not tied to anything per se in general. I mean, our sweet spot of course is rare diseases. We look for therapies that have transformative potential for patients, early de-risking opportunities if we’re talking about earlier phase assets. I would say another opportunity would be if we find something that doesn’t have to be first in class. We always set the bar for best in class, which we feel very proud of with our current organic pipeline.

That work continues ongoing and like I said, I’m really proud of the capabilities that our team has, both with internal opportunities as well as external. Thanks. Good luck with the upcoming readouts. Thank you very much. An exciting quarter.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Alex Stranahan with Bank of America. Your line is open.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Please go ahead.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Hey guys, thanks for taking our questions. Just a couple from us. It’s been interesting to see how the different geographies have approached the risk of liver injury for mitapivat and thalassemia. Maybe could you just remind us what liver monitoring requirements are so far being required in Saudi Arabia and potentially in Europe if it’s approved as well. Do you think this could change depending on the U.S. label? Maybe second as a follow up. Curious how this monitoring requirement is changing maybe your commercial approach in these different areas. Thank you. Yeah, thanks, Alec. Again, Sarah can start with the labeling so far and I’ll just preempt by saying the label we have right now, of course at this point only exists in Saudi Arabia and Sarah can comment on that.

We’re still in process with FDA and in Europe it’s a CHMP positive opinion, but we’re still awaiting the conclusion of that review in the coming couple of months and expect that by early next year. I’ll have Tsveta comment in terms of the impact of some of these scenarios. Sarah, do you want to start?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Sure.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: In regards to the label, yes, indeed. For Saudi, it’s in line with our proposal of once a month monitoring for the first six months. That label is not now available for the European Union. We indeed are very pleased that we received a positive CHMP opinion, which from their perspective confirms the benefit risk profile that we saw. Obviously, the label will only be final when you have the EC decision, so the details will become available at that point in time. Brian already mentioned it, but the U.S. review is still ongoing.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Sarah. Tsveta, comments on potential impact of REMS.

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Absolutely. As we all know, there are very few treatment options for the thalassemia patients across the board, and with regards to non-transfusion dependent and transfusion dependent patients, we remain very convicted behind the strong benefit-risk profile of PYRUKYND for these patients. That has been reiterated and confirmed by all of our stakeholders, including all the clinicians I’ve interacted with recently in the field. After the announcement of REMS for the potential U.S. label, I can tell you the team is prepared for the launch. We are taking advantage of the additional time to continue the engagement with the community and do disease education. When it comes to REMS in the U.S., we don’t anticipate that to be a barrier to prescribing or have an impact on our commercial opportunity because we know that both the academic as well as the community hematology, oncology practices have experience with REMS.

When I connected both with academics and the community prescribers, they confirmed that to me, and the team is confirming that in the field on a daily basis.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Great. Thanks for the call and looking forward to December. Yeah, same. Thank you.

Operator: Thank you. One moment for our next question. Our next question will come from the line of Emily Claudia Bodnar with H.C. Wainwright & Company. Your line is open. Please go ahead.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Hi, good morning, this is Joanne Framley. Congrats for a great quarter and start taking our questions. Shifting focus to tebapivat, how are you guys looking at what would be considered positive data in LR MDS given the data for luspatercept and imetelstat, and then a follow up. Could you also remind us of the Avanzanite strategy for the European thalassemia launch and how the cadence could look like for that? Thank you. Yeah, thanks a lot. I think we’re going to follow the same order of entry here. Sarah can get started on tebapivat and how we think about the potential in low-risk MDS, which is a very high unmet need area, as is classic across all of our diseases that we’re pursuing, very limited treatment options. Tsveta can comment on Avanzanite and also probably tuck in some comments about NewBridge too.

We have two very valued partners outside the U.S. Sarah, you want to start?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Sure.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Thank you for the question. In regards to the positive data for lower-risk MDS, we are very pleased that we were able to announce enrollment of our Phase 2b trial today. More data will come at the beginning of next year for our program. Obviously, we are going to take the ecosystem around us into account when we look at the data that this program will generate. What is important, I think, is what Brian just mentioned. There is a huge unmet need for this patient population, specifically as the goal for this population tends to be really also now more and more focused on quality of life. As you know, for PK activators, quality of life has been an important component of their benefit profile. That is something that we were definitely hoping to deliver to.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Great. Thanks, Sarah and Tsveta. Pivoting then to Avanzanite, and since you’ve also spent some time outside the U.S. recently in Saudi Arabia, maybe you can comment on NewBridge as well in the preparation of our partners.

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Absolutely. Starting with Avanzanite, first of all, we are very excited about the potential EC decision and approval of PYRUKYND for thalassemia in Europe coming early next year. We’re working very closely with the Avanzanite team to refine our strategy for Europe. It’s important to remember that in Europe, after a regulatory decision and approval, each of the countries needs to undergo a pricing and reimbursement process. At the moment, we are going with Avanzanite, assessing the market opportunities, prioritizing markets where to submit for pricing and reimbursement. The pricing and reimbursement process in the European countries can take 12 to 18 months. Keep in mind that we wouldn’t see the immediate impact of an approval on the commercial opportunity in Europe after the EC decision is announced.

We prioritize Avanzanite as our selected partner because they have very strong rare disease capabilities and expertise as well as pricing and market access capabilities. We look forward to continuing to work with them to provide access to patients in Europe. As Brian mentioned, I actually had the opportunity to spend some time with the team in Saudi for the SFDA approval in August. Again, very similar team here in Saudi Arabia. We consistently hear the high unmet need for thalassemia patients, strong excitement about the benefit-risk profile of PYRUKYND and the value it can bring to that community. As a reminder, in Saudi Arabia, the process after approval starts with one-on-one requests from physicians for individual patients for PYRUKYND early in patient access and market access.

It’s going to take about a couple of years until we get to the stage of a national procurement agreement, which will open access more broadly and see the commercial opportunity there.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Good. Thank you. That makes sense. Thank you for answering our questions. You’re welcome.

Operator: Thank you. One moment for our next question. Our next question will come from the line of Marc Alan Frahm with TD Cowen. Your line is open. Please go ahead.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks for taking my questions. Just back on the liver events, maybe just as you’ve continued to dose people and follow them for longer and longer, just kind of comment on if any additional events have been observed across the PKR trials and to the extent any have, have they continued to conform to the kind of description before of occurring within six months and, you know, importantly the patient returning to baseline whenever they do stop MIT as a result. Maybe on the commercial side, I recognize it’ll take quite a while to work through case-by-case access and actually get to revenue for any of those patients, let alone the reimbursement negotiations. Maybe can you comment on just any level of demand you’re already seeing in the Gulf to kind of start that process? Sure. Thanks, Mark.

Sarah, maybe you could just start then with the question Mark has around the hepatocellular injury and have there been additional cases that have met the pattern that we observed in thalassemia? Then Tsveta again can talk about the green shoots, I could say, of the demand so far.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Sure. In regards to the observations that we had in the thalassemia program that allowed us to determine the hepatocellular injury risk for thalassemia specifically, nothing has changed the way we have assessed the risk. The safety profile remains exactly the same as when we declared this hepatocellular injury risk. We have not observed anything across the program that warrants us to update the safety profile the way we currently understand it.

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Good.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Sarah. Tsveta.

Tsveta Milanova, Chief Commercial Officer, Agios Pharmaceuticals: Yes, ma’am. Actually, I had the opportunity to meet with some key customers in Saudi Arabia this week in some of the biggest hospitals. As I said, we definitely hear the interest in PYRUKYND’s profile, the desire to try it in individual patients and gain experience with the product at the very beginning in the country. It’s a very burdensome process, which actually takes months from an individual patient prescription and request until approval at the hospital level and securing the budget. We expect that to be a slow process, slow and steady. As the individual patient requests get approved, the experience gets stronger and stronger. Definitely, the interest from the community is there and it’s high. It’s just the process in the country takes time.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Mark, what I would add is what’s unique about Saudi Arabia is, of course, the prevalence is quite different from what we see in the U.S. On a per capita basis, about eight to nine times more common. On the less rare side, for sure, most people, most clinicians certainly have a good working knowledge of thalassemia. However, the common denominator that we see across all geographies really is a function of the limited treatment options available and the need for us to continue to educate, particularly the burden that non-transfusion dependent thalassemia patients face on a daily basis because they’re subjected to chronic hemolysis and all the downstream consequences that come from that. We’re doing our part to make sure that clinicians have that top of mind as they think about the potential that tebapivat and PYRUKYND could offer. That’s one thing that’s not unique to geography.

It’s across all markets in the world. Okay, thank you. You’re welcome.

Operator: Thank you. As a reminder to ask a question, please press star one one on your telephone. One moment for our next question. Our next question comes from the line of Tessa Thomas Romero with JP Morgan. Your line is open.

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Please go ahead.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Hi Brian and team, thanks so much for taking our question. For the Phase 3 portion of RISE UP, has the last patient exited the trial yet, and what are any considerations in terms of the steps and timing to get to your top line? I have a follow-up.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Okay, I will allow Sarah to comment. I will just remind that we will not be more refined on our timely guidance for the Rise Up data that we’re all so eagerly awaiting. We won’t be more refined by saying that we’re on track for that data by year end. Sarah, I’m not sure if you want to say anything additional about where we are in that process.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: No, I think you summarized it, Brian. We are not commenting on individual patient status, but we are indeed on track to deliver the top line data by year end. We have delivered several Phase 3 clinical trials per our milestone. We are a well-oiled machine at this point in time to get from database lock to top line results.

Operator: Okay.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: I mean, Tess, if I can just add, I am really pleased with the continued excellence in operations from the team because of course we have a lot of moving parts underway. Simultaneously we have launch preparation. You’ve heard from Tsveta, we’ve got Sarah, the team working on labeling for our PDUFA date that’s approaching for thalassemia December 7th, and then of course getting ready for a data readout for RISE UP. This team is really delivering and I’m really pleased with the operational activity.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Okay, so you can’t tell us if your top line will be before or after your PDUFA date.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: What an excellent follow-up question. I’m going to stick to it’s by year end.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Okay, thanks so much, guys.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: You’re welcome.

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

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Hi, good morning team. This is Lydia on for Salveen. Thanks so much for taking the question. Maybe just another one. On the REMS program, do you anticipate the requirements to apply kind of across the label to PKD and sickle cell as well? Have you received any physician feedback on how this might impact uptake, particularly with sickle cell, where some of these treatment centers might not see PKD and thalassemia patients as well? Thanks so much.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: I think, Lydia, I might just start on this one to say first of all, the REMS request has been specific to thalassemia. That’s an important point. With respect to any potential outcome or impact, rather in sickle cell disease, the most important step is what we literally just discussed, which is getting to the point of the RISE UP Phase 3 data. That’s the most important next step. From there we’ll be better guided around the benefit risk profile.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Helpful. Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: You’re welcome.

Operator: Thank you. I’m showing no further questions at this time. I would like to hand the conference back over to Brian Goff for closing remarks.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you very much everyone for joining us on this morning’s call. As you’ve seen, and as I just mentioned, we’ve delivered on many of our milestones this year. We have two of our most anticipated inflection points approaching by year end. As you can imagine, this is a very exciting time at Agios Pharmaceuticals. We truly believe that we are poised to deliver transformative new therapies for patients and create significant long term value for shareholders. Thank you 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.

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