AGIOS PHARMACEUTICALS, INC. Q2 2026 earnings call

Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' second quarter 2026 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 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.

Thanks, Morgan. Good morning, everyone, thank you for joining us. Before we review our second quarter results, I'd like to take a step back and highlight the strong position from which Agios is executing as we continue advancing toward our goal of building a multi-billion-dollar rare disease business. We are executing against multiple drivers of value creation, including the launch of AQVESME in thalassemia, the potential expansion of mitapivat into sickle cell disease, and a pipeline that continues to grow through both internal innovation and disciplined business development. During the quarter, we further strengthened our portfolio with the addition of cevidoplenib, a next-generation, highly selective oral Syk inhibitor that expands our rare hematology franchise into immune thrombocytopenia, or ITP. We also advanced AG-236 into an operationally seamless Phase II/III program in polycythemia vera, adding another potential growth driver within hematology.

Beyond hematology, AG-181 continues to progress. We expect phase I-B proof of mechanism data in phenylketonuria patients in the second half of the year. We also continue to apply a disciplined approach to portfolio management, making focused investment decisions, and directing resources toward opportunities with the greatest potential to create value for patients and shareholders. As you'll hear throughout today's call, our progress this quarter reflects the strength of that strategy, combining commercial execution, pipeline advancement, disciplined capital allocation, and strategic business development to position Agios for sustainable long-term growth. Turning to our second quarter highlights on the next slide, we delivered a quarter marked by strong commercial performance, meaningful pipeline progress, and continued portfolio discipline. First, we delivered sustained commercial momentum with $44.7 million in total net revenue, including $40.9 million in the U.S. and 442 cumulative AQVESME prescriptions from REMS-certified physicians.

Second, we further diversified our pipeline through the in-licensing of cevidoplenib, a next-generation, highly selective oral Syk inhibitor for ITP, progressing toward phase III and strengthening our rare hematology pipeline. Third, we advanced mitapivat toward a potential new indication in sickle cell disease. During the quarter, we received FDA acceptance of our sNDA with priority review and were assigned a PDUFA goal date of November 1st, bringing us one step closer to delivering a first-in-class medicine in an area of significant unmet need. Finally, we ended the quarter with approximately $1 billion in cash equivalents, and marketable securities, providing financial flexibility to support both commercial growth and pipeline progression. Overall, we entered the second half of 2026 with strong commercial delivery, a more diversified pipeline, an important near-term regulatory catalyst, and the capital position to execute on our strategy.

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

Thank you, Brian. Next slide, please. Turning to our second quarter financial results, total mitapivat net revenue was $44.7 million, including $40.9 million in the U.S. and $3.8 million outside the U.S. Cost of sales for the quarter was $3 million. Research and development expense was $100.8 million, compared to $91.9 million in the second quarter of 2025, primarily due to an increase in process research and development of $15 million, driven by the $25 million upfront payment associated with the agreement of Oscotec. Selling, general, and administrative expense was $61.5 million, compared to $45.9 million in the prior year's period, reflecting an increase in commercial-related activities as we executed a launch of AQVESME in February. Net loss for the second quarter of 2026 was $100.7 million, compared to a net loss of $112 million for the second quarter of 2025.

We ended the quarter with approximately $1 billion in cash equivalents, and marketable securities, which we believe provides financial flexibility to support commercial execution, advancement of our pipeline, and continued investment in opportunities to create long-term value. Turning to our outlook for 2026, we continue to expect approximately $45 million-$50 million from PK deficiency revenues in the U.S. Full-year operating expenses are expected to remain approximately flat versus 2025, excluding the $25 million upfront payment associated with the cevidoplenib licensing transaction recognized in the second quarter and include investment to prepare for a potential sickle cell disease launch aligned with our November 1st PDUFA date. Our priorities for the remainder of the year remain clear: driving the AQVESME launch, preparing for a potential sickle cell disease approval, advancing our pipeline, and maintaining financial discipline.

Please advance to the next slide, I'll turn it over to Tsveta to cover commercial highlights and AQVESME U.S. thalassemia launch progress.

Thanks, Cecilia. Next slide, please. With six months of launch experience now behind us, we're encouraged by the underlying drivers of performance. What we have seen so far continues to reinforce our confidence in the long-term PYRUKYND opportunity in thalassemia. Importantly, the strong execution across our commercial and patient-focused organization further strengthens our confidence in future launch opportunities. In the U.S., performance reflected continued growth in thalassemia demand and solid commercial execution. Net revenue in the quarter reflected approximately $5 million of one-time benefits related to stocking in thalassemia, along with modest gross-to-net favorability. We continue to expect gross to net within our previously guided 10%-20% range, with quarter-over-quarter variability. Outside the U.S., we delivered $3.8 million in net sales, reflecting anticipated demand for thalassemia in Europe following approval and continued consistent early demand for thalassemia in the GCC.

As we have seen consistently across rare disease launches, the shape of new patient starts naturally moderates as adoption broadens beyond the earliest wave of highly motivated patients and prescribers. We continue to expect quarter-over-quarter revenue variability reflecting order timing, inventory movement, and gross-to-net dynamics. Next slide, please. I'm very pleased with the continued U.S. launch performance of PYRUKYND. During the second quarter, we generated an additional 200 prescriptions from REMS-certified physicians, bringing cumulative prescriptions to 442 as of June 30th. As a reminder, this metric captures unique prescriptions for patients with completed START forms from REMS-certified physicians and serves as an early indicator of underlying demand. Importantly, the underlying launch dynamics remain healthy. While demand continues to come from highly motivated patients.

We saw a growing proportion of non-transfusion-dependent patients in the second quarter, a profile consistent with the therapy moving beyond the earliest, most motivated cohort of transfusion-dependent patients. We continue to see strong conversion from prescription to treatment initiation. Time to START is naturally trending towards our anticipated 10-12 -week range as adoption broadens across the NTDT population, where treatment decisions often involve more deliberate clinical discussions and patients may have less frequent interactions with the healthcare system. Access continues to strengthen. We now have approximately 75% of thalassemia lives covered under payer policies. Additionally, physician REMS certification continues to progress in step with prescribing activity. It's not a barrier to patient access. As the launch matures, prescriptions with completed START forms become a less informative measure of performance. Whereas revenue increasingly reflects both new patient starts and persistence on therapy.

For that reason, in anticipation of a potential FDA approval for mitapivat in sickle cell disease, we plan to discontinue reporting prescriptions from REMS-certified physicians after the third quarter and transition to revenue as our primary measure of commercial performance. Upon a potential sickle cell disease approval, we will assess the most meaningful metrics to communicate the progress and outlook of the broader mitapivat franchise. Next slide, please. I wanted to take a few moments to highlight thalassemia launch considerations in the second half of this year. The first half reflected a distinct initial phase of the launch. The first quarter benefited from a strong pre-launch anticipation and momentum built in the period leading to approval following the more than three-month PDUFA delay.

Second quarter demand continues to reflect adoption from highly motivated patients and prescribers, with time to treatment initiation beginning to approach our anticipated 10-12-week average at launch maturity. Looking ahead, we expect the shape of the launch to naturally evolve. Adoption is expanding into a broader non-transfusion-dependent population, where patients are typically seen less frequently and treatment decisions may take more time. As the patient mix continues to shift towards non-transfusion-dependent patients, we expect time to treatment initiation to move well within the 10-12-week range we consistently discuss. We are also mindful that the first cohort of patients who initiated therapy in the earliest month of launch is approaching six months of treatment, a natural point at which physicians assess clinical response.

This is an important part of the treatment journey. It is the period during which we will begin to build a broader real-world understanding of how physicians and patients evaluate response and integrate mitapivat into long-term care. Taken together, these dynamics reinforce that AQVESME is delivering a healthy launch that is successfully progressing beyond the initial wave of adoption and into a broader expansion phase. As we move through the second half of the first launch year, our focus remains on expanding reach across the thalassemia community, expanding adoption in the non-transfusion-dependent segment while continuing to add new prescribers. We remain highly confident in the long-term opportunity for AQVESME and in our ability to build a durable, growing thalassemia franchise over time. Please move to the next slide.

We are actively preparing for a potential sickle cell disease launch in the U.S. and are encouraged by both the commercial opportunity and the unmet need we see in this community. Our initial launch focus is on approximately 25,000 patients who are actively treated or in need of therapy today. We believe the population alone represents a meaningful opportunity for mitapivat, with potential to expand beyond the initial segment over time. Importantly, we are leveraging the capabilities, relationships, and insights we have developed through the thalassemia launch while continuing to invest in market access, education, and community engagement activities ahead of the PDUFA goal date. Pending FDA approval, we believe these efforts position us well to support a successful launch and to deliver mitapivat to patients in need of innovative treatment options. 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. Turning to our pipeline on the next slide. Following recent portfolio prioritization decisions, we remain focused on advancing a diversified rare hematology portfolio with opportunities across multiple stages of development. Mitapivat continues to anchor the portfolio with approved indications in pyruvate kinase deficiency and thalassemia, and a potential accelerated approval in sickle cell disease later this year. During the first half of this year, we achieved an important milestone with thalassemia approval in Europe and the UAE, completing regulatory approvals across all four priority launch geographies following prior approvals in the U.S. and KSA. Since first quarter results, we filed and received acceptance in the U.S. for the mitapivat sNDA in sickle cell disease, with priority review and a PDUFA goal date of November 1st.

We remain committed to bringing mitapivat to patients with sickle cell disease and recently dosed the first patient in reignite, our phase III confirmatory trial, an important milestone in advancing the program. We also strengthened the pipeline during the quarter through the in-licensing of cevidoplenib, a next-generation Syk inhibitor that expands our reach within rare hematology and adds a compelling opportunity in immune thrombocytopenia. Beyond mitapivat and cevidoplenib, we continue to invest in future growth drivers, including AG-236 in polycythemia vera and AG-181 in phenylketonuria. Taken together, we believe the pipeline reflects a focused allocation of capital and resources towards programs where we see the greatest potential to create long-term value for patients and shareholders. Please move to the next slide.

As we discussed when we announced the in-licensing of cevidoplenib, our interest in the program is grounded in its potential to address some of the limitations that have historically constrained the Syk inhibitor class. Cevidoplenib was designed to optimize both selectivity and pharmacokinetics, support a sustained target inhibition while maintaining a tolerability profile suitable for chronic use. The clinical data generated to date are encouraging and support this design rationale, demonstrating dose-dependent activity, no dose-limiting toxicity through phase II, and evidence of durable platelet responses. Taken together, these data support the rationale for advancing cevidoplenib as a next-generation highly selective Syk inhibitor. We're looking forward to engaging with the FDA in the coming months to align on progression to phase III. Next slide, please.

At EHA in June, we were pleased to share a broad body of data across both thalassemia and sickle cell disease that continues to strengthen our confidence in mitapivat. Across the portfolio, we have 10 abstracts accepted, including the RISE UP phase III study, which was selected for the EHA oral plenary session. In sickle cell disease, RISE UP demonstrated hemoglobin responses consistent with the mechanism of PK activation, with hemoglobin responders experiencing clinically meaningful improvement in sickle cell pain crisis-related endpoints and fatigue. At EHA, we presented new data showing clinically meaningful reductions in transfusion burden and red blood cell units transfused across the total trial population, exceeding historical experience with hydroxyurea. Importantly, outcomes from the subgroup of patients with at least one transfusion in the 52 weeks prior to enrollment directly informed the treatment effect and powering assumptions for the ongoing REIGNITE confirmatory trial, supporting accelerated approval.

We also presented additional patient-reported outcomes data showing clinically meaningful improvements in how hemoglobin responders feel and function, including reductions in physical pain. In addition, 56-week follow-up data from the SATISFY phase II investigator-sponsored trial in related hemoglobinopathies show robust hemoglobin response rates and mean hemoglobin improvement, as well as suggesting decreased iron burden. In non-transfusion-dependent thalassemia, we shared open-label extension data showing that 60% of patients continuing on mitapivat met criteria for hemoglobin response, and 60% of patients who switched onto mitapivat in the open-label extension achieved hemoglobin response. Additionally, subgroup analyses indicate high hemoglobin response rates for non-transfusion-dependent patients with high baseline hemoglobin levels, indicating that less severely anemic NTDT patients achieve improvements in hemoglobin levels and fatigue.

These data were received very favorably by the thalassemia community and reinforce the value of mitapivat in non-transfusion-dependent patients, which comprise the majority of the eligible adult patients in the U.S. Taken together, these data reinforce the consistency of mitapivat's profile across indications and further strengthen our confidence in the long-term potential of mitapivat in hemolytic anemia. While we continue to advance and expand the mitapivat opportunity, we're also focused on building the next generation of potential growth drivers within rare hematology. AG-236 is an important example of that strategy. Next slide, please. Following encouraging phase I data, we're advancing AG-236 into an operationally seamless phase II/III development program in polycythemia vera. What continues to differentiate AG-236 is its potential profile within an evolving treatment landscape.

The molecule demonstrated hepcidin induction through day 57 and favorable effects on iron parameters in extended follow-up, supporting the potential for an every six-month dosing regimen without saturation. The phase II portion of the study is designed to identify the optimal therapeutic window across multiple dose levels while enabling efficient progression into the registrational portion of the program. More broadly, the seamless phase II/III strategy reflects our commitment to disciplined execution while advancing development as efficiently as possible, with phase II initiation planned for the second half of 2026. We believe AG-236 has the potential to further diversify our rare hematology leadership and contribute to our long-term growth beyond mitapivat. With that, please move to the next slide, I will hand the call back to Brian for closing remarks.

Thank you, Sarah. Next slide, please. As we look across the business, we continue to make meaningful progress against the strategic priorities we established for 2026. We're building commercial momentum with AQVESME and thalassemia, reaching 442 cumulative prescriptions as of June 30th. We're advancing mitapivat toward a potential approval in sickle cell disease, which represents an important opportunity to expand our PK activation franchise and a potential next growth driver for the company. We're also advancing AG-236, our siRNA TMPRSS6 inhibitor for polycythemia vera, into an operationally seamless phase II/III program expected to begin in the second half of this year. During the quarter, we further diversified our portfolio through the addition of cevidoplenib, a next-generation, highly selective Syk inhibitor in ITP progressing toward phase III. Importantly, our progress this year reflects both execution and discipline.

We're investing behind the opportunities where we believe Agios can have the greatest impact for patients and create the strongest long-term value for shareholders. Next slide. Taken together, we enter the second half of the year with a growing commercial foundation, a meaningful near-term regulatory catalyst, and an increasingly diversified pipeline and the financial strength to execute on our strategy. Next slide, please. Today, Agios is anchored by a growing commercial business and supported by a pipeline spanning multiple development stages and disease areas. Across the portfolio, we are pursuing opportunities where differentiated biology, meaningful patient unmet need, and disciplined execution can support durable long-term growth. Collectively, these opportunities represent rare disease markets estimated at more than $10 billion in 2030.

Before we open the call for questions, I'd like to thank the entire Agios team for their unwavering commitment to patients and their continued dedication to executing on our strategy. Their passion, resilience, and focus have been instrumental in the progress we've made this year. With that, thank you all for joining us today. Operator, we're ready to begin the question and answer session.