Agios Pharmaceuticals(AGIO) - 2023 Q4 - Earnings Call Transcript

Financial Data and Key Metrics - Full year 2023 net PYRUKYND revenue was $26.8 million, compared to$ 11.7 million in 2022 [25] - Q4 2023 net PYRUKYND revenue was $7.1 million, a 4% reduction compared to Q3 2023, driven by lower inventory levels [25] - R&D expenses for Q4 2023 were$ 77 million, and $296 million for the full year 2023, an increase of$ 16 million compared to 2022 [26] - SG&A expenses for Q4 2023 were $35 million, and$ 120 million for the full year 2023, a decrease of $2 million compared to 2022 [27] - The company ended 2023 with approximately$ 806 million in cash, cash equivalents, and marketable securities [27] Business Line Data and Key Metrics - The PK activator franchise, led by mitapivat, reported three key data readouts in the last 12 months, including positive Phase 2 data in sickle cell disease and Phase 3 data in non-transfusion-dependent thalassemia [6][7] - The Phase 3 ENERGIZE study for mitapivat in non-transfusion-dependent thalassemia showed a 42.3% hemoglobin response rate in the treatment arm compared to 1.6% in the placebo arm [15] - The company is preparing for potential U.S. launches of mitapivat in thalassemia in 2025 and sickle cell disease in 2026 [8] - AG-946, another PK activator, showed positive Phase 2a data in lower-risk MDS, with 40% of patients achieving transfusion independence [6] Market Data and Key Metrics - In the U.S., there are approximately 6,000 diagnosed adult patients with thalassemia, with 4,000 being non-transfusion-dependent and 2,000 being transfusion-dependent [19] - The company estimates approximately 13,000 thalassemia patients in the EU5 and 70,000 in the Gulf region [22] - For sickle cell disease, the U.S. patient population is estimated at 100,000, with significant unmet needs for novel oral therapies [59] Company Strategy and Industry Competition - The company aims to position mitapivat as a foundational therapy for sickle cell disease, leveraging its unique mechanism of action and oral administration [57] - The company is focused on building a multi-billion dollar PK activation franchise, with potential launches in thalassemia and sickle cell disease [8][29] - The company is preparing for a potential U.S. launch of mitapivat in thalassemia in 2025, followed by sickle cell disease in 2026 [8][22] - The company is also advancing AG-946 in lower-risk MDS and exploring its potential in sickle cell disease [69] Management Commentary on Operating Environment and Future Outlook - The company is confident in the potential of its PK activation pipeline, with multiple near-term catalysts expected to drive significant value [7] - The company expects to deliver four additional Phase 3 readouts and two potential launches in the near term [8] - The company believes its strong cash position will enable it to fund operating expenses and capital expenditures through 2026 [27] Other Important Information - The company retains rights to a potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales [27] - The company is conducting extensive market research and claims data analysis to inform its launch strategy for thalassemia [20][21] Q&A Session Summary Question: ENERGIZE-T Study Primary Endpoint - The primary endpoint for the ENERGIZE-T study is a 50% reduction in transfusions over any 12-week rolling period, which differs from Luspatercept's fixed-period endpoint [33] - The company believes this dynamic endpoint better reflects real-world patient experience [33] Question: ENERGIZE Data Transition from Phase 2 to Phase 3 - The Phase 3 ENERGIZE study incorporated a longer duration for hemoglobin response measurement, which differs from the single time point used in Phase 2 [36] - The company does not observe waning efficacy over time, with hemoglobin response maintained similarly to PKD [36] Question: Commercial Coexistence of Mitapivat and Luspatercept - Mitapivat is positioned as an oral therapy for non-transfusion-dependent thalassemia, where no current therapies exist, while Luspatercept is a subcutaneous option for transfusion-dependent patients [39] - The company emphasizes the different mechanisms of action, with mitapivat focusing on overall red blood cell health [40] Question: Powering Assumptions for ENERGIZE-T - The company has not disclosed specific powering assumptions but has studied internal programs to inform its development approach [44] - The focus is on reducing transfusions rather than increasing hemoglobin levels, reflecting the different mechanism of action [44] Question: Multibillion Dollar Opportunity in PK Activation - The company sees significant potential in moving from ultra-rare diseases like PKD to larger prevalent diseases like sickle cell and thalassemia [51] - The company is preparing for back-to-back launches in thalassemia and sickle cell disease, with a focus on pricing dynamics and commercial opportunities [52] Question: Differences Between Mitapivat and Other PK Activators - Mitapivat stimulates multiple PK isoenzymes, including PKR and PKM2, which are relevant for red blood cell health and other tissues affected by diseases like sickle cell and MDS [53] - The company is planning further clinical studies to explore the role of PKM2 in sickle cell disease, particularly in kidney health [53] Question: Sickle Cell Disease Commercial Landscape - The company believes mitapivat has the potential to be a foundational therapy for sickle cell disease, offering benefits in hemoglobin improvement and VOC reduction [57][59] - The company is preparing for a potential launch in 2026, following the thalassemia launch in 2025 [60] Question: PKD Commercial Opportunity - The company maintains its peak sales estimate for PKD at$ 200 million to $225 million in the U.S., with slow and steady growth expected [65] - The company is encouraged by patient persistency and is building capabilities for future launches [66] Question: AG-946 Development Strategy - The company is advancing AG-946 in lower-risk MDS and exploring its potential in sickle cell disease, with plans to test multiple dose levels in Phase 2b [69][74] - The company is incorporating patient voice and regulatory feedback into trial design [70] Question: ENERGIZE-T Primary Endpoint Design - The primary endpoint design for ENERGIZE-T was influenced by regulatory feedback, with the company believing the dynamic endpoint better reflects real-world patient experience [73] Question: AG-946 Phase 2b Design in MDS - The Phase 2b trial for AG-946 in MDS will test multiple dose levels, including higher doses than initially anticipated, based on Phase 2a learnings [74] - The trial will focus on patients with transfusion burden and will include a broad MDS population [74]