Summary of Agios Pharmaceuticals FY Conference Call Company Overview - **Company**: Agios Pharmaceuticals (NasdaqGS:AGIO) - **Event**: FY Conference Call on March 02, 2026 - **Key Speakers**: Brian Goff (CEO), Tsveta Milanova (Chief Commercial Officer) Key Industry and Company Insights 1. Product Launch and Approval - Agios received approval for **AQVESME (mitapivat)** for treating thalassemia, with the launch currently underway [4][30] - The company is expanding its **pyruvate kinase activation franchise** with mitapivat and pursuing additional studies in sickle cell disease and myelodysplastic syndrome (MDS) [4][5] 2. Clinical Trials and Data - The **RISE UP Phase 3 study** for sickle cell disease showed a **41%** hemoglobin improvement in patients, although it did not meet statistical significance for vaso-occlusive crisis reduction [11][12] - The average hemoglobin increase was **1.6 grams per deciliter**, a significant finding as such improvements typically require transfusions [12] - Agios is preparing for a **pre-sNDA meeting** with the FDA to discuss the regulatory path for sickle cell disease [15][16] 3. Market Dynamics and Commercial Strategy - There is strong excitement among clinicians for mitapivat as an anti-hemolytic agent, focusing on hemoglobin levels and hemolytic parameters rather than vaso-occlusive crises [22][23] - The company anticipates a **$1 billion commercial opportunity** for PK deficiency and thalassemia globally, with the majority of revenue expected from the U.S. market [50][51] 4. Launch Trajectory and Patient Segmentation - The launch is expected to start with **transfusion-dependent patients**, gradually expanding to **non-transfusion-dependent patients** over time [40][42] - Approximately **two-thirds** of diagnosed thalassemia patients in the U.S. are non-transfusion-dependent, which will drive future growth [42] 5. Regulatory and Competitive Landscape - Agios is not concerned about the upcoming data from a competitor, **etavopivat**, as they believe their clinical benefits are well-established [29] - The company is also exploring pediatric trials for both thalassemia and sickle cell disease, aiming to extend treatment options to younger populations [56][58] 6. Future Pipeline Developments - Agios is developing **tebapivat** for MDS, focusing on efficacy, tolerability, and route of administration as key differentiators [64][65] - The company is also working on **AG-236**, a TMPRSS6 siRNA targeting polycythemia vera, with expectations for phase 1 data in 2026 [70][73] Additional Important Insights - Initial feedback from physicians and payers regarding AQVESME has been positive, with early prescriptions indicating a healthy start to the launch [30][31] - The company is confident in navigating payer dynamics, especially given the rarity of thalassemia, which may ease reimbursement challenges [31][32] - Agios emphasizes the importance of a broad label for AQVESME, which positions it favorably against existing treatments [36][37] This summary encapsulates the key points discussed during the Agios Pharmaceuticals FY Conference Call, highlighting the company's strategic direction, product developments, and market opportunities.

Financial Performance - Agios Pharmaceuticals reported a loss of $1.85 per share in Q4 2025, which is narrower than the Zacks Consensus Estimate of a loss of $1.97 and compared to a loss of $1.74 per share in the same quarter last year [1][10] - Total revenues for Q4 2025 were $20 million, exceeding the Zacks Consensus Estimate of $10 million [1] - For the full year 2025, total revenues reached $54 million, reflecting a 48% year-over-year increase [10] Product Performance - The lead drug, mitapivat, is marketed as Pyrukynd and Aqvesme, with Pyrukynd approved for treating hemolytic anemia in adults with pyruvate kinase deficiency and Aqvesme for anemia in adults with alpha- or beta-thalassemia [2] - Pyrukynd generated $16 million in product revenues in the U.S., marking a 49% year-over-year increase and a 24% sequential increase [5] - Aqvesme was launched in the U.S. in December 2025 and is reported to have a strong start [3] Market Developments - Outside the U.S., mitapivat continues to be marketed as Pyrukynd for both PK deficiency and thalassemia indications, with a positive opinion from the European Medicines Agency for label expansion in thalassemia [4] - Agios recorded $4 million in revenues from Pyrukynd in the ex-U.S. market, primarily due to inventory stocking as the market transitioned to commercial supply [8] Research and Development - Research and development expenses increased by approximately 6.4% year-over-year to $88.1 million in Q4 2025, driven by higher costs related to pipeline development [9] - The company is developing mitapivat for sickle cell disease (SCD) and plans to engage with the FDA in Q1 2026 before filing for approval [11][13] - Agios is also developing another candidate, tebapivat, for SCD, with patient enrollment completed and top-line results expected in the second half of 2026 [13] Stock Performance - Over the past year, Agios' stock has decreased by 15.7%, while the industry has seen an increase of 17.9% [4]

Financial Data and Key Metrics Changes - In Q4 2025, PYRUKYND generated $20 million in net revenue, an 86% increase year-over-year and a 55% sequential increase from $13 million in Q3 2025 [7][10] - Full-year 2025 revenue for PYRUKND reached $54 million, reflecting robust year-on-year growth [7][10] - The company ended 2025 with approximately $1.2 billion in cash, providing flexibility for future investments [8][11] Business Line Data and Key Metrics Changes - U.S. revenue for PYRUKND in Q4 was $16 million, driven by commercial focus in PK deficiency and favorable growth adjustments [10] - Ex-U.S. revenue was $4 million in Q4, primarily due to inventory stocking ahead of demand [11] - Cost of sales for Q4 was $1.9 million, while R&D expenses were $88.1 million, reflecting an increase associated with advancing the pipeline [11] Market Data and Key Metrics Changes - The U.S. launch of ACTIVASE for thalassemia is underway, with expectations for U.S. PK deficiency revenues in 2026 to be between $45-$50 million [10] - The company anticipates a sequential decline in ex-U.S. revenues into Q1 2026 [11] Company Strategy and Development Direction - The company outlined its 2026 strategic priorities, focusing on executing the launch of Pyrukynd, expanding the PK activation franchise, advancing early-stage pipeline programs, and maintaining financial discipline [5][6] - The company aims to leverage its existing commercial presence in thalassemia and PK deficiency to achieve profitability [12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the early market response to ACTIVASE, noting strong engagement from physicians and patients [16] - The company is preparing for a pre-sNDA meeting with the FDA regarding mitapivat for sickle cell disease, which is a critical step in defining the regulatory path [25][44] Other Important Information - The company has completed enrollment in the phase II sickle cell disease trial of tebapivat, with top-line results expected in the second half of 2026 [8][20] - The company is committed to financial discipline, anticipating operating expenses in 2026 to be roughly flat compared to 2025 [12] Q&A Session Summary Question: On the ACTIVASE launch and prescription updates - Management noted that early demand for ACTIVASE is encouraging, with 44 prescriptions written by REMS-certified physicians in the first five weeks of launch [31] - It is expected that prescriptions will grow ahead of revenues due to a 10-12 week conversion time from prescription to treatment initiation [31][32] Question: On sickle cell and tebapivat expectations - Management indicated that the phase II tebapivat trial is a dose-finding trial, and they are excited about the potential hemoglobin response based on previous data [35][36] Question: On payer dynamics and SG&A changes - The payer mix for thalassemia is similar to PK deficiency, with most patients under commercial payers, and initial market access is expected to occur through medical exceptions [93] - SG&A expenses will need to scale up for sickle cell, but the existing infrastructure from PK deficiency and thalassemia will be leveraged [95]

Financial Data and Key Metrics Changes - In Q4 2025, Agios Pharmaceuticals reported net revenue of $20 million from PYRUKYND, an increase of 86% year-over-year and a sequential increase of 55% compared to $13 million in Q3 2025 [10][11] - Full-year 2025 revenue for PYRUKYND reached $54 million, reflecting robust year-on-year growth [7][10] - The company ended Q4 2025 with approximately $1.2 billion in cash, cash equivalents, and marketable securities, providing flexibility for future investments [8][11] Business Line Data and Key Metrics Changes - U.S. revenue for PYRUKYND in Q4 was $16 million, driven by commercial focus in PK deficiency and favorable growth adjustments [10][11] - Ex-U.S. revenue was $4 million in Q4, primarily reflecting inventory stocking ahead of demand from PK deficiency patients in Europe [11] - The company anticipates U.S. PK deficiency revenues to be in the range of $45-$50 million in 2026 [10] Market Data and Key Metrics Changes - The ACTIVASE launch for thalassemia in the U.S. is underway, with strong early demand and 44 prescriptions written by REMS-certified physicians as of January 30 [15][41] - The company has received approval for mitapivat for thalassemia in two regions, with plans for commercialization in Europe and the GCC [18][19] Company Strategy and Development Direction - Agios has outlined its 2026 strategic priorities, focusing on executing the ACTIVASE launch, expanding the PK activation franchise, advancing early-stage pipeline programs, and maintaining financial discipline [5][6] - The company aims to leverage its existing commercial presence in thalassemia and PK deficiency to achieve profitability [12][72] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the early market response to ACTIVASE, noting that physicians view its profile as addressing significant gaps in current treatment options for thalassemia [16][18] - The company anticipates a pivotal year ahead with multiple catalysts, including the pre-sNDA meeting for mitapivat and phase 2 data for tebapivat [25][26] Other Important Information - The company is committed to financial discipline, with operating expenses in 2026 expected to be roughly flat compared to 2025 [12] - Agios is focused on maximizing the launch of ACTIVASE while continuing to advance its pipeline programs [8][25] Q&A Session Summary Question: Can you provide insights on the ACTIVASE launch and prescription updates? - Management noted that early demand is encouraging, with 44 prescriptions written in the first five weeks of launch, and expects prescriptions to grow ahead of revenues due to a 10-12 week conversion time to treatment initiation [31][41] Question: What are the expectations for the phase 2 data in sickle cell disease? - Management indicated that the phase 2 tebapivat trial is a dose-finding study, and they are excited about the potential hemoglobin response based on previous data [35][36] Question: Can you discuss the payer dynamics for ACTIVASE? - The payer mix is similar to PK deficiency, with most patients under commercial payers, and initial access will occur through medical exceptions [93] Question: What is the rationale for higher dosing in lower-risk MDS? - Higher doses are being tested in MDS due to faster metabolism in patients compared to sickle cell disease, which is modeled after healthy volunteers [101] Question: How does the REMS program for thalassemia impact sickle cell disease? - Management believes that the experience gained from the thalassemia REMS program will provide a solid foundation for executing a similar program if needed for sickle cell disease [104]

Financial Data and Key Metrics Changes - In Q4 2025, Agios Pharmaceuticals reported worldwide PYRUKYND revenue of $20 million, an increase of 86% compared to Q4 2024, and a sequential increase of 55% from $13 million in Q3 2025 [9][10] - Full-year 2025 revenue for PYRUKYND reached $54 million, reflecting robust year-on-year growth [5][9] - The company ended Q4 2025 with approximately $1.2 billion in cash, cash equivalents, and marketable securities, providing flexibility for future investments [6][10] Business Line Data and Key Metrics Changes - U.S. fourth quarter revenues for PYRUKYND were $16 million, driven by commercial focus in PK deficiency and favorable growth adjustments [9] - Ex-U.S. revenue was $4 million in Q4, primarily reflecting inventory stocking ahead of demand [10] - Cost of sales for Q4 was $1.9 million, R&D expenses were $88.1 million, and SG&A expenses were $51.6 million, roughly flat year-on-year [10] Market Data and Key Metrics Changes - The ACTIVASE launch for thalassemia in the U.S. is underway, with expectations for U.S. PK deficiency revenues in 2026 to be in the range of $45-$50 million [9][10] - The company anticipates a sequential decline in ex-U.S. revenues into Q1 2026 due to inventory adjustments [10] Company Strategy and Development Direction - The company outlined its 2026 strategic priorities, focusing on executing the ACTIVASE launch, expanding the PK activation franchise, advancing early-stage pipeline programs, and maintaining financial discipline [4][5] - Agios aims to leverage its capital-efficient global commercial model to focus investments on the U.S. market, which presents the most significant revenue opportunity [16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the early demand for ACTIVASE, noting strong engagement from physicians and a healthy breadth of early prescribers [14][40] - The company sees a clear path to profitability through its existing commercial presence in thalassemia and PK deficiency, with operating expenses expected to remain flat in 2026 [11][68] Other Important Information - The company received FDA approval for ACTIVASE on December 23, 2025, and the U.S. launch is underway with positive early feedback from physicians [18][19] - Enrollment in the phase II sickle cell disease trial of tebapivat is complete, with top-line results expected in the second half of 2026 [6][20] Q&A Session Summary Question: How does the ACTIVASE launch translate to treatment initiation and revenue recognition? - Management indicated that prescriptions are expected to grow ahead of revenues due to a 10-12 week conversion time from prescription to treatment initiation [29][30] Question: What are the expectations for the phase II data in sickle cell disease? - Management expressed excitement about the trial, noting that it is a dose-finding study aimed at exploring hemoglobin response [34][35] Question: What is the payer mix for ACTIVASE and how does it affect revenue? - The payer mix is similar to PK deficiency, with most patients under commercial payers, and initial market access will occur through medical exceptions [90] Question: What is the rationale for higher dosing in lower-risk MDS compared to sickle cell disease? - Higher doses in MDS are due to faster metabolism in MDS patients, while sickle cell patients metabolize the drug similarly to healthy volunteers [98] Question: What is the expected timeline for profitability? - Management has not provided specific timing but indicated that thalassemia presents a meaningful opportunity for profitability [68][70]

Q4 and FY 2025 Financial Results and Business Highlights Conference call for investors and analysts 12 February 2026 4 2026 strategic priorities – driving long-term value creation | Execute high-impact launch for AQVESME | | --- | | (mitapivat) in thalassemia | | Potential to expand PK activation franchise into | | sickle cell disease and LR-MDS | | Unlock future value in hematology and other rare | | disease by advancing early-stage pipeline | | Ensure long-term sustainability through disciplined | | capit ...

Core Insights - Agios Pharmaceuticals reported strong execution in 2025, highlighted by the U.S. approval and launch of AQVESME, the first treatment for anemia in adults with thalassemia, which has received positive feedback from the community [2][5] - The company aims to expand its product portfolio and pipeline, focusing on high-value indications such as sickle cell disease and myelodysplastic syndromes, while maintaining disciplined capital allocation [2] Financial Performance - For Q4 2025, Agios reported net revenues of $20.0 million from PYRUKYND, with a full-year total of $54.0 million, marking a 49% increase from Q4 2024 [5][12] - The net loss for Q4 2025 was $108.0 million, compared to a net loss of $96.5 million in Q4 2024 [8] - Total revenues for the year 2025 reached $54.0 million, up from $36.5 million in 2024 [15] Research and Development Highlights - AQVESME received FDA approval in December 2025 and is now available in the U.S. [6][12] - A pre-sNDA meeting with the FDA for mitapivat in sickle cell disease is scheduled for Q1 2026, with plans to submit a marketing application thereafter [5][6] - The Phase 2 trial of tebapivat in sickle cell disease has been fully enrolled, with topline results expected in the second half of 2026 [7] Cash Position - As of December 31, 2025, Agios had $1.2 billion in cash, cash equivalents, and marketable securities, down from $1.5 billion a year earlier [12][14] - The company anticipates that its financial resources will support the U.S. launch of AQVESME and the advancement of its clinical programs [12]

Core Thesis - Agios Pharmaceuticals, Inc. is positioned as a compelling investment opportunity due to its innovative therapies and strong financial standing, particularly with the recent FDA approval of its lead product, mitapivat, for thalassemia [1][4][5] Company Overview - Agios Pharmaceuticals is a clinical-stage biotech company focused on cellular metabolism through oral, small-molecule allosteric activators of the pyruvate kinase (PK) enzyme [2] - The lead product, mitapivat, is marketed as PYRUKYND for PK deficiency and received FDA approval in December 2025 under the brand name AQVESME for alpha- and beta-thalassemia [2] Clinical Trials and Efficacy - Phase 3 trials in thalassemia demonstrated strong efficacy, with ENERGIZE showing a 42.3% hemoglobin response in non-transfusion-dependent patients and ENERGIZE-T achieving a 30.4% transfusion reduction in dependent patients [3] - In sickle cell disease, the RISE UP trial met hemoglobin endpoints but showed only favorable trends in pain crisis reduction [3] - Agios is advancing tebapivat, which achieved proof-of-concept in lower-risk myelodysplastic syndromes, with 40% of patients reaching transfusion independence [3] Financial Position - As of Q3 2025, Agios holds approximately $1.3 billion in cash and marketable securities, sufficient to fund launches and clinical programs without dilutive financing [4] - PYRUKYND revenues grew 44% year-over-year, although net losses persist due to high R&D and SG&A expenses [4] Market Position and Competitive Advantage - The thalassemia approval provides a first-mover advantage in a larger patient population, while the upcoming sickle cell opportunity could further expand its market [4] - Agios differentiates from competitors like Reblozyl and gene therapies by offering a twice-daily pill with broad accessibility [4] Future Catalysts - Led by CEO Brian Goff, the company is positioned to scale globally, with upcoming catalysts in early 2026 including the AQVESME U.S. launch, FDA discussions for sickle cell indications, and Phase 2b tebapivat data [5] - Multiple approved indications and a strong balance sheet enhance Agios's potential for successful commercial execution and global expansion [5]

Core Insights - Agios Pharmaceuticals has outlined its strategic priorities and key milestones for 2026, focusing on the launch of AQVESME™ and expansion into additional indications for its PK activation franchise [1][3] Company Performance - In 2025, Agios achieved significant progress, highlighted by the U.S. approval of AQVESME™, the first medicine approved for treating anemia in adults with alpha- or beta-thalassemia [2][9] - The company aims to become a sustainable and diversified rare disease company, leveraging its existing commercial presence [2][3] 2026 Strategic Priorities - The company plans a high-impact U.S. launch of AQVESME in thalassemia and seeks to expand its PK activation franchise into sickle cell disease and lower-risk myelodysplastic syndromes [3][8] - Agios is committed to disciplined capital allocation and operational efficiency to support long-term sustainability [3] Anticipated Milestones - AQVESME's U.S. commercial launch is set for late January 2026, following FDA approval in December 2025 [9] - A pre-sNDA meeting with the FDA for mitapivat in sickle cell disease is anticipated in Q1 2026, with a regulatory submission to follow [8][9] - Topline results from the Phase 2b trial of tebapivat in lower-risk myelodysplastic syndromes are expected in the first half of 2026 [6][8] - Enrollment in the Phase 2 sickle cell disease trial of tebapivat was initiated in 2025, with topline results expected in the second half of 2026 [9] Pipeline Development - Agios is advancing its early- and mid-stage pipeline across multiple high-value indications, including a Phase 1 trial of AG-236 for polycythemia vera and a Phase 1b trial of AG-181 for phenylketonuria [10][11]

RISE UP Phase 3 Trial Results - Mitapivat met the primary endpoint with a 40.6% hemoglobin response rate, defined as ≥1.0 g/dL increase in average Hb from Week 24 through Week 52 compared to baseline, significantly higher than the 2.9% in the placebo arm[38] - There was a trend favoring mitapivat with a 14% reduction in the annualized rate of sickle cell pain crises (SCPCs) compared to placebo, although this did not reach statistical significance[39] - Mitapivat showed a statistically significant improvement in average change from baseline in hemoglobin concentration, with a 7.43 g/L difference compared to placebo[41] - Mitapivat significantly reduced the average change from baseline in indirect bilirubin compared to placebo, with a difference of -16.91 µmol/L[46] - The trial showed a trend in favor of mitapivat with a 14% reduction in the annualized rate of hospitalizations for SCPC compared to placebo[50] - Percent reticulocytes substantially decreased from baseline in the mitapivat arm vs placebo[52] Safety and Discontinuation - The safety profile observed in the RISE UP Phase 3 trial was consistent with previous mitapivat sickle cell disease trials, with no new safety signals identified[57] - The discontinuation rate in the double-blind treatment period was low, with 13% in the mitapivat arm and 18.8% in the placebo arm[34] Next Steps - The company intends to submit a marketing application for mitapivat in the U S for sickle cell disease after a pre-sNDA meeting with the FDA in Q1 2026[61, 68]