Agios Pharmaceuticals, Inc. Q4 FY2025 earnings call

Strategic Priorities - Focused on executing a high-impact launch of Afesmi for thalassemia in the U.S. - Expanding PK activation franchise into sickle cell disease and lower-risk myelodysplastic syndrome (MDS) with catalysts in 2026. - Advancing early-stage pipeline with AG-236 and AG-181 for future value in hematologic and other rare diseases. - Committed to long-term sustainability via disciplined capital allocation and operational efficiency. ### Pipeline Catalysts 2026 - Afesmi launch in thalassemia U.S. underway; potential to expand PK activation franchise into sickle cell disease and lower-risk MDS. - Early-stage pipeline progress with AG-236 and AG-181. ### Commercial Performance - Pyrukynd had Q4 2025 net revenue of $20M, full-year $54M with robust growth. - Afesmi received FDA approval in December 2025, with 44 prescriptions written by REMS-certified physicians by January 30. - Enrollment completed in Phase II sickle cell disease trial of tebipivat, with top-line results expected in second half of 2026; Phase IIb trial in lower-risk MDS expected top-line data in first half of 2026.

Pyrukynd delivered $20 million in net revenue in the fourth quarter of 2025, bringing full year 2025 revenue to $54 million. In the U.S. fourth quarter, Pyrukynd revenues were $16 million, driven by commercial focus in PK deficiency. Outside the U.S., fourth quarter revenue was $4 million, primarily reflecting inventory stocking ahead of demand for PK deficiency patients transitioning to commercial supply. Afesmi, recently approved by the FDA for thalassemia, has started its U.S. launch with 44 prescriptions written by REMS-certified physicians by January 30.

2026 Outlook - Operating expenses expected to be roughly flat with 2025, assuming investment in Afesmi launch, gated investment for sickle cell disease, and operating model refinement. - Anticipates a clear path to profitability through existing commercial presence in thalassemia and PK deficiency. - 2026 strategic priorities include executing Afesmi U.S. launch, pre-sNDA meeting for sickle cell disease in Q1 2026, Phase II top-line data for tebipivat in sickle cell disease later in 2026, and Phase IIb top-line data for tebipivat in lower-risk MDS in first half of 2026.

Q: On Afesmi launch, how does prescription translation to treatment initiation and revenue recognition?

A: Cecilia Jones mentioned early demand with 44 prescriptions, expecting prescriptions to grow ahead of revenues as it takes 10-12 weeks to convert prescriptions to treatment initiation. Sarah Gheuens compared to Truseltiq launch as an analog.

Q: On sickle cell disease pre-sNDA meeting, potential outcomes?

A: Sarah Gheuens stated the goal is to gain insights on regulatory pathways for mitapivat, going in with data package for full approval based on RISE UP data with strong anti-hemolytic profile.

Q: On type of physicians prescribing Afesmi initially?

A: Tsveta Milanova said initial prescriptions are from community heme-oncs, primarily physicians engaged with previously, with healthy breadth of prescribing across the country.

Q: On dosing rationale for tebipivat in lower-risk MDS vs sickle cell disease?

A: Sarah Gheuens explained that in lower-risk MDS, higher doses are tested because MDS patients metabolize the drug faster than in healthy volunteers, whereas sickle cell disease patients metabolize similarly to healthy volunteers.