Agios Pharmaceuticals, Inc. (AGIO) Earnings

Management highlights

### Commercial Launch of Akvesme (mitapivat) in Thalassemia - Cumulative unique prescriptions from REMS-certified physicians reached 442 as of Q2 end, with 200 new prescriptions added in Q2 - A growing proportion of new prescriptions are for non-transfusion-dependent thalassemia (NTDT) patients, expanding beyond the initial wave of highly motivated transfusion-dependent patients - 75% of U.S. lives are now covered by payer policies, with strong conversion from prescription to treatment initiation and no major access barriers - Ex-U.S. sales included anticipated demand from Europe following recent approval, plus consistent early demand in the GCC region - Management will discontinue reporting cumulative prescription counts after Q3 2026, transitioning to revenue as the primary commercial performance metric ### Pipeline & R&D Progress - The supplemental New Drug Application (sNDA) for mitapivat in sickle cell disease was accepted by the FDA with priority review, assigned a PDUFA goal date of November 1, 2026; the first patient has been dosed in the Phase III confirmatory Reignite trial - Agios in-licensed sevadoclinib, a next-generation highly selective oral spleen tyrosine kinase inhibitor for immune thrombocytopenia (ITP), expanding the rare hematology franchise; the program is progressing toward Phase III, with upcoming regulatory alignment with the FDA - AG236 for polycythemia vera has been advanced into a seamless Phase 2-3 development program, with initiation planned for H2 2026; the program is differentiated by its potential for every-six-month dosing - AG1A1 for phenylketonuria is on track to release Phase 1b proof of mechanism data in H2 2026 - New clinical data presented at EHA reinforced mitapivat's efficacy and safety profile across thalassemia and sickle cell disease, including durable responses in NTDT patients and clinically meaningful improvements in patient outcomes ### Financial Position - Ended Q2 2026 with approximately $1 billion in cash, cash equivalents, and marketable securities, providing sufficient flexibility to support commercial execution and pipeline advancement - Q2 2026 net loss was $107 million, compared to a $112 million net loss in Q2 2025 - R&D expense was $100.8 million (up from $91.9 million in Q2 2025), driven by a $15 million increase in in-process R&D from the $25 million upfront payment for the sevadoclinib license - SG&A expense was $61.5 million (up from $45.9 million in Q2 2025), reflecting higher commercial activity tied to the Akvesme launch

Guidance

- Full-year 2026 U.S. Akvesme revenue from thalassemia is still expected to be $45-50 million - Full-year 2026 operating expenses are expected to remain approximately flat versus 2025, excluding the $25 million sevadoclinib upfront payment recognized in Q2 - Gross-to-net discount is still expected to fall within the previously guided 10-20% range, with expected quarter-to-quarter variability - Average time to treatment initiation is expected to stabilize in the guided 10-12 week range as adoption expands into the NTDT population - No material contribution to 2026 revenue from a potential sickle cell disease launch is expected, given the November PDUFA date - Management will provide updated franchise guidance after potential approval of mitapivat for sickle cell disease in November 2026

Segment performance

Agios reports only one core commercial segment for the quarter, focused on its approved rare hematology product Akvesme (mitapivat): - Total net revenue: $44.7 million (100% of total revenue) - U.S. net revenue: $40.9 million, accounting for 91.5% of total revenue - Ex-U.S. net revenue: $3.8 million, accounting for 8.5% of total revenue All pipeline programs are internal development-stage and do not contribute current revenue.

Risks & headwinds

- Quarter-to-quarter revenue variability is expected due to order timing, inventory movement, shifting patient mix (toward NTDT patients with less frequent healthcare interactions), and gross-to-net dynamics - As the first cohort of early launch patients approaches the 6-month clinical evaluation point, there is uncertainty around real-world continuation rates that could impact future revenue - Sickle cell disease has a higher Medicaid patient mix, which will result in higher mandatory rebates and lower gross-to-net performance relative to Agios' existing commercial products - Actual future results may differ materially from forward-looking statements due to regulatory, clinical, and commercial uncertainties, including potential failure to meet approval or launch expectations

Analyst Q&A

• Q: The analyst asks whether the Energize clinical trial is a good barometer for real-world time on treatment, how time to treatment initiation changed from Q1 to Q2, and if repeat prescriptions under the REMS program have started.

  A: Management confirms the Energize trial is a good proxy for expected continuation rates. Early Q1/Q2 time to initiation was faster than the 10-12 week guidance due to highly motivated early patients, but it is now moving closer to the expected range as penetration grows in the NTDT segment. Repeat prescriptions are already being processed smoothly for patients on therapy.

• Q: The analyst asks if 200 new Q2 prescriptions represents a sustainable new patient start rate, or if it still includes residual backlog from the earlier PDUFA delay and highly motivated early adopters.

  A: Management notes that prescription growth and revenue growth will become less directly correlated quarter-to-quarter as the launch matures, due to longer time to initiation and variability in treatment start timing. After the initial early adopter wave, the launch is now moving into a more steady-state expansion phase in the broader NTDT population, and management remains encouraged by adoption trends.

• Q: The analyst asks what clinical bar physicians use to continue treatment at the 6-month evaluation point, and if the 6-month mark is a strict requirement for assessment.

  A: Management explains that assessment is patient-specific, not strictly tied to the 6-month trial endpoint. For transfusion-dependent patients, physicians focus on transfusion frequency and volume reductions, not just the 50% reduction threshold used in trials. For NTDT patients, improvements in fatigue and patient quality of life are as important as hemoglobin level increases. Most providers use 6 months as a natural evaluation point aligned with clinical trial data, but decisions remain flexible.

• Q: The analyst asks if the higher Medicaid patient mix expected for sickle cell disease will change gross-to-net dynamics relative to existing products, and if competition factors into pricing planning.

  A: Management confirms that sickle cell disease does have a higher proportion of Medicaid patients, which by statute requires a 23% mandatory rebate, leading to a higher gross-to-net discount than thalassemia or PKD. The company will release specific pricing details at the time of approval, with pricing set based on the final approved label, clinical data, and the competitive environment at launch.