AGIOS PHARMACEUTICALS, INC. Q1 2026 earnings call

Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' first quarter 2026 financial results and business highlights. You can access the slides for today's call by going to the investor section of our website, agios.com. Please note we'll be making certain forward-looking statements today. Actual events and results could differ materially from those expressed or implied by any forward-looking statements because of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. On the call with me today from Agios are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; Tsveta Milanova, Chief Commercial Officer; and Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development. Following prepared remarks, we will open the call for questions.

With that, I am pleased to turn the call over to Brian Goff.

Thanks, Morgan. Good morning, everyone, and thank you for joining us. Next slide, please. At the start of the year, we outlined our 2026 strategic priorities, which are designed to drive both near-term execution and long-term value creation. We are off to a strong start entering another catalyst-rich year with clear momentum across these priorities. Turning to first quarter highlights on the next slide, we delivered $20.7 million in net revenues, representing 138% growth year-over-year. The first quarter marks the U.S. commercial launch of AQVESME in thalassemia with the REMS fully operational as of the end of January, and already we have shown strong initial demand.

We continue to expect 2026 operating expenses to be approximately flat versus 2025. We ended the quarter with a strong balance sheet, including over $1 billion in cash equivalents, and marketable securities. Importantly, we've advanced two priorities that are key to our growth inflection. First, the U.S. commercial launch of AQVESME in thalassemia is off to a strong start, with 242 prescriptions written as of March 31st by REMS-certified physicians, building significantly on the 44 prescriptions we reported as of the end of January. This early progress reflects solid execution as the launch continues to broaden. Tsveta will provide additional details shortly. The early momentum highlights the strong work and rare disease capabilities of the Agios commercial team.

Second, following our pre-sNDA meeting with the FDA in the first quarter, we now plan to submit an sNDA for mitapivat in sickle cell disease in the second quarter under the U.S. Accelerated Approval pathway, marking an important step toward expanding our PK activation franchise into a significantly larger indication. I also want to underscore the caliber of our team, whose ability to respond rapidly and rigorously to FDA feedback reflects the deep regulatory and scientific expertise we've built at Agios. Next slide, please. Stepping back, our strategy is to build a sustainable rare disease company anchored by a foundation in rare hematology. In the near term, our focus is on executing the AQVESME U.S. commercial launch in thalassemia and advancing the mitapivat sNDA filing in sickle cell disease.

In parallel, we are preparing for important midterm catalysts, including phase II top-line data for tebapivat, our next generation, more potent PK activator in both lower-risk MDS and sickle cell disease this year. Over the longer term, we continue to advance our early-stage clinical programs and selectively evaluate expansion into other rare hematology diseases rather, to support our sustained growth. With that, please advance to the next slide, and I'll turn the call over to Cecilia to discuss financials. Cecilia?

Thank you, Brian. The next slide summarizes our first quarter financial results. As we have previously shared, we will report mitapivat net revenues with U.S. and ex-U.S. components. In the first quarter, we delivered $20.7 million in worldwide mitapivat net revenues, with $18.8 million from sales generated in the U.S., driven by the recent launch of AQVESME in thalassemia. Outside of the U.S., we reported $1.9 million in sales, reflecting expected quarterly fluctuations. We reported $81 million in R&D expense in the first quarter, an increase of roughly $8 million from prior year due to workforce-related expenses supporting pipeline advancement efforts as well as increased mitapivat process development expenses.

We also reported $48 million in SG&A spend, up approximately $7 million from the prior year due to an increase in activities to support the U.S. commercial launch of AQVESME in thalassemia as well as an increase in stock compensation expense. We ended the quarter with over $1 billion in cash equivalents, and marketable securities, positioning us well to remain disciplined as we invest to maximize portfolio value and build a pipeline for long-term growth. Turning to our approach to capital allocation, on the next slide, our priorities remain clear. First, we will continue to maximize the U.S. commercial launch of AQVESME in thalassemia. Second, we are managing operating expenses in a way that is aligned with our long-term value creation.

Based on our current plans and accounting for the mitapivat confirmatory clinical trial in sickle cell disease, we anticipate 2026 operating expenses to be approximately flat compared to 2025. We will continue to diversify our pipeline, leveraging both internal capabilities and external innovation as we continue to execute our 2026 priorities with a disciplined approach to long-term growth. Please advance to the next slide, and I'll turn it over to Tsveta to cover commercial highlights and early AQVESME used thalassemia launch dynamics.

Thank you, Cecilia. Next slide, please. Our commercial performance in the first quarter reflects exceptional execution as we transitioned the focus of our field force from PK deficiency to thalassemia. In the U.S., net revenues were $18.8 million, driven by strong early AQVESME launch demand. Outside the U.S., we reported $1.9 million in net revenue, driven mainly by thalassemia utilization in the GCC. This is in line with our expectations, given early market access dynamics ahead of securing government procurement. As in prior quarters, we expect to see continued variability quarter-to-quarter, driven by ordering patterns, inventory dynamics, and Gross-to-Net. Please move to the next slide. I'm very encouraged by what we are seeing from the AQVESME U.S. launch so far, and I want to start by acknowledging the tremendous work of our commercial, medical, and patient support teams.

Launch execution in rare diseases is complex, and the early progress we are seeing reflects both strong preparation and the depth of rare disease commercialization expertise we have built at Agios, supported by close coordination across the organization. 242 prescriptions were written in the first quarter by REMS-certified physicians, serving as an important early indicator of strong demand. Keeping in mind, the REMS became operational in late January. Here are a few points that are worth highlighting to help frame how we're thinking about these early signals. As we exited the first quarter, early adoption was concentrated among highly engaged patients, including transfusion-dependent and motivated non-transfusion-dependent patients. This is consistent with expected early launch dynamics. In the first quarter, time from prescription to initiation was shorter than expected.

This was due to early engagement by patients with stronger motivation to initiate treatment, physician readiness to prescribe, as well as effective REMS coordination. However, we continue to expect average initiation timelines of approximately 10 weeks-12 weeks in the coming quarters as we advance deeper into patient segments with less frequent clinical engagement. We are encouraged by the geographic breadth of early prescriber adoption, which has been driven by community-based hematologist-oncologists. What we're seeing so far gives us confidence in our launch readiness and the quality of demand in the early days of launch. That being said, we do not view early prescription volumes as translating into a steady run rate at this early stage of launch, particularly as demand moves more towards non-transfusion-dependent patients and adoption progresses beyond the most motivated, highly engaged patients.

The next slide captures both the strong early reception of AQVESME and how we're building towards sustainable growth. Feedback from the field has been very encouraging. Physicians and patients recognize AQVESME's meaningful clinical profile. REMS onboarding is running smoothly, and our patient support services are helping patients initiate therapy. As we look ahead, our focus is on three things. First, expanding prescriber engagement across both academic and community settings. Second, broadening adoption into non-transfusion-dependent patients who represent most adult diagnoses. Third, advancing payer access to support timely treatment initiation. Taken together, we're encouraged with how AQVESME is being received in these early days of launch, and we are focused on executing against the key levers that will drive durable adoption over time. I'm very proud of the team's execution to date.

The performance in the first quarter reinforces the team's launch readiness and deep understanding of this market.

We believe this strong foundation positions us to deliver on both the launch of AQVESME in the U.S. as well as potential future launches as we look to expand our rare disease portfolio. Please move to the next slide. With that, I will hand the call over to Sarah to cover key R&D highlights from the quarter.

Thank you, Tsveta. Next slide, please. We continue to advance a robust pipeline anchored by our PK activation franchise and complemented by differentiated early-stage clinical programs. In the first quarter, we announced plans to initiate two pediatric mitapivat trials in thalassemia, ENERGIZE Kids T in transfusion-dependent patients and ENERGIZE Kids in non-transfusion dependent patients. We look forward to the potential to expand access to this transformative medicine into pediatric populations. We are looking ahead to upcoming second quarter readouts, including phase II-B top-line data for tebapivat, our next-generation PK activator in lower risk MDS. This study evaluates 10 mg, 15 mg, and 20 mg dose levels across a broad patient population with eight consecutive weeks of transfusion independence as the primary endpoint. While this represents a higher risk opportunity, we see meaningful potential for an oral therapy in this setting. Please move to the next slide.

In the first quarter, we completed a pre-sNDA meeting with the FDA and aligned on a path towards U.S. Accelerated Approval for mitapivat in sickle cell disease. Since that meeting, we've had a series of informal and formal engagements to gain official alignment on the confirmatory clinical trial required under this pathway. We are pleased with the progression of these discussions and now expect we will file an sNDA in the second quarter. We look forward to sharing additional data from the RISE UP phase III trial at an upcoming medical congress, including analyses that informed our selection of the confirmatory clinical trial's primary endpoint.

Taking a step back, as we consider development of the confirmatory trial design, we emphasized operational feasibility, including enrollment timelines and time to completion while looking to maximize probability of success and the potential to further enhance the mitapivat label should U.S. full approval be granted upon results of confirmatory trial. Next slide, please. In parallel, we are advancing tebapivat, our next-generation PK activator in phase II studies across low-risk MDS and sickle cell disease. Tebapivat was intentionally designed to go beyond first generation PK activators. It is structurally differentiated with potent dual activation of PKR and PKM2 and PK and PD properties that support once daily dosing without the need for a taper. Importantly, the early clinical data reflect these design features. In sickle cell disease, tebapivat demonstrated a long half-life of approximately 87 hours-93 hours.

Those dependent reductions in 2,3-DPG and increases in ATP and pharmacodynamic effects that remain durable for up to 4 weeks after the last dose. We also observed a mean hemoglobin increase of 1.9 grams per deciliter at the 5 mg once daily dose. Beyond red blood cell metabolism, tebapivat shows broader biological activity driven by PKM2 activation. In preclinical models, this translated into anti-fibrotic effects, including reduced glomerular injury and myofibroblast signaling, supporting the potential for disease-relevant activity beyond mature red blood cells. In low-risk MDS, we observed early clinical signals, including transfusion independence in the low transfusion burden cohort. However, we observed 50% lower drug exposure relative to healthy volunteers, which prompted investigation at higher doses.

The ongoing phase II-B study, which is evaluating higher doses in a broader lower risk MDS population, will test the hypothesis that deeper PKR and PKM2 activation may extend biological activity into erythroid maturation in the bone marrow. In sickle cell disease, our phase II study is designed to rapidly assess hemoglobin response and key markers of hemolysis to confirm whether this deeper biology translates into broader clinical benefit. We look forward to reporting top-line phase II-B data in lower risk MDS in the first half of this year, followed by top-line phase II data in sickle cell disease in the second half of 2026. Please move to the next slide, and I will hand the call back to Brian for closing remarks.

Thank you, Sarah. Next slide, please. As you've heard today, 2026 is shaping up to be a growth inflection and catalyst-rich year for Agios, with meaningful progress across our commercial business and our pipeline. In the first half of the year, we advanced the regulatory path for mitapivat in sickle cell disease. We expect phase II-B top-line data for tebapivat in lower risk MDS, along with phase I healthy volunteer top-line data for AG-236. In the second half of the year, we anticipate phase II top-line data for tebapivat in sickle cell disease, as well as phase I-B proof of mechanism data for AG-181 in phenylketonuria. Throughout the year, we remain focused on executing the U.S. commercial launch of AQVESME in thalassemia with the goal of building a strong and sustainable commercial foundation. Next slide, please.

Stepping back, we believe Agios is differentiated by the combination of a growing commercial base and a pipeline increasingly weighted towards later-stage high-value opportunities. As shown here, our current pipeline represents greater than $10 billion in potential market opportunity in 2030. Most importantly, everything you've heard today is grounded in our commitment to the patients we serve, patients living with serious and often underserved rare diseases who are still waiting for better treatment options. I also want to recognize and thank our employees. Their focus, expertise, and dedication are what make this progress possible. From advancing critical clinical and regulatory milestones to executing a complex commercial launch with care and discipline. With that, we appreciate your continued interest in Agios, and I'd now like to open the call for questions. Operator, please open the line.