Agios Pharmaceuticals (AGIO) investor relations material

Strategic evolution, vision, and portfolio expansion

• Transitioning from a single-asset to a multi-asset, multi-indication platform with independent value drivers in rare hematology, including thalassemia, sickle cell disease, polycythemia vera, immune thrombocytopenia, and phenylketonuria.

• Selective and disciplined expansion into adjacent rare hematology and metabolic diseases, guided by strong biology, unmet need, and chronic treatment models, with a focus on PK activation, SYK inhibition, and siRNA TMPRSS6 inhibition.

• Pipeline includes next-generation assets such as tebapivat, cevidoplenib, AG-236, and AG-181, with AG-236 advanced to late-stage development for PV, showing durable hepcidin control and potential for extended dosing intervals.

• Commercial infrastructure and patient support built in thalassemia and PK deficiency provide a scalable foundation for future launches and growth.

• Pipeline targets over $10 billion in potential markets by 2030, with continued disciplined investment, operational efficiency, and strategic diversification.

Clinical data highlights and scientific insights

• Mitapivat demonstrated durable, clinically meaningful hemoglobin improvements in thalassemia and sickle cell disease, with nearly 60% of NTD thalassemia patients achieving ≥1.0 g/dL Hb increase and robust effects in patients with higher baseline hemoglobin.

• RISE UP phase III trial in sickle cell disease showed a 40.6% hemoglobin response rate versus 2.9% for placebo, with rapid and sustained improvements in hemolysis markers and a favorable safety profile.

• Hemoglobin responders experienced significant reductions in pain crises, hospitalizations, ER visits, fatigue, and improved patient-reported outcomes.

• Mitapivat reduced transfusion requirements by 41% in sickle cell disease, outperforming historical data for hydroxyurea and reducing iron burden in hereditary spherocytosis.

• Consistent anti-hemolytic effects observed across PK deficiency, thalassemia, and sickle cell disease, validating PK activation as a scalable therapeutic approach.

Commercial execution and market outlook

• AQVESME launch in thalassemia off to a strong start, with 242 prescriptions as of March 31, efficient REMS onboarding, and a broadening prescriber base; focus on expanding reach in non-transfusion-dependent patients.

• Mitapivat positioned as the first PK activator for sickle cell disease, targeting a U.S. population of 75,000 diagnosed patients aged 16+, with 25,000 actively treated or in need of therapy.

• Commercial strategy leverages experience, clinical differentiation, and established rare disease infrastructure to support successful market entry and expansion.

• Confirmatory REIGNITE phase III trial in sickle cell disease will expand the label to patients aged 12+, broadening the addressable population and designed to demonstrate reduction in transfusion burden.

• Ongoing engagement with the FDA for mitapivat sNDA in sickle cell disease, with confidence in regulatory and commercial readiness; AQVESME/PYRUKYND approved in U.S., EU, KSA, and UAE for thalassemia.