Financial Data and Key Metrics Changes - In Q1 2025, net PyroKine revenue was $8.7 million, a 6% increase compared to $8.2 million in Q1 2024 [30] - Revenue decreased by 19% compared to Q4 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [33] - Cost of sales for the quarter was $1.1 million, R&D expenses were $72.7 million, an increase of $4.1 million compared to Q1 2024, and SG&A expenses were $41.5 million, an increase of $10.5 million compared to the prior year [36] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in Q1 2025, translating to 136 net patients on therapy, also a 5% increase versus the prior quarter [31] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [34] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with approximately 6,000 adults diagnosed in the U.S., and the company estimates that PyroKine's initial launch focus will address about 65% of the adult thalassemia patient population [27][28] - The sickle cell disease community is estimated to include 120,000 to 135,000 individuals in the U.S. and EU5, with a global prevalence exceeding 3 million [13] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [7] - The company is preparing for a potential U.S. approval and launch of PyroKine for thalassemia in September 2025, followed by sickle cell disease in 2026 [6][16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming PDUFA date and the potential to serve patients with unmet needs in thalassemia and sickle cell disease [46][66] - The company is confident in its strong balance sheet, which provides financial independence to support potential launches and advance existing programs [37][39] Other Important Information - The company has a robust early and mid-stage pipeline, with plans to file an investigational new drug application for AG-236 targeting polycythemia vera in mid-2025 [9][20] - The company has engaged in disease state education campaigns to prepare for the launch of PyroKine, focusing on both patients and healthcare providers [24] Q&A Session Summary Question: Has the mid-cycle review happened, and what are the next steps? - Management confirmed that no advisory committee meeting is planned and that the regulatory review is ongoing, with strong engagement with the FDA [45][46] Question: How has the withdrawal of Oxbreda impacted trial recruitment? - Management noted that while the withdrawal was disappointing, it has not affected their clinical trial conduct, and they see a significant opportunity in the sickle cell market [48][49] Question: What are the plans for launching mitapivat ex-U.S.? - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [54][57] Question: Any changes in communication frequency with the FDA? - Management stated that communication with the FDA remains consistent, with no changes due to recent agency reshuffling [65][66] Question: Rationale for starting the Phase II tebapivat study in sickle cell? - Management expressed confidence in the unmet need for therapies in sickle cell disease and the potential to grow the patient population with multiple products [72][73] Question: Plans for marketing to non-transfusion dependent patients? - The company plans to focus on both transfusion-dependent and non-transfusion-dependent patients, emphasizing the value proposition of PyroKine for both groups [78] Question: Anticipated evolution of PyroKine's pricing? - Pricing decisions will be based on the value proposition of the label received, with positive feedback from payers regarding the product profile [98]

Financial Data and Key Metrics Changes - In the first quarter of 2025, net PyroKine revenue was $8,700,000, a 6% increase compared to $8,200,000 in the first quarter of 2024 [32] - Revenue decreased by 19% compared to the fourth quarter of 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [32] - Cost of sales for the quarter was $1,100,000, R&D expenses were $72,700,000, an increase of $4,100,000 compared to the first quarter of 2024, and SG&A expenses were $41,500,000, an increase of $10,500,000 compared to the prior year quarter [34] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in the first quarter since the January label update, translating into 136 net patients on therapy, also a 5% increase versus the prior quarter [30] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [33] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with 67% of diagnosed patients in the U.S. having no approved therapies [12] - The company estimates that its initial launch focus will address approximately 65% of the adult thalassemia patient population [26] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [6] - The company is preparing for a potential approval and launch in thalassemia in the U.S. by September 7, 2025, followed by sickle cell disease in 2026 [5][6] - The company is focused on disease state education campaigns to prepare for the launch, emphasizing the importance of monitoring and management of thalassemia [23] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential approval and launch of PyroKine for thalassemia and the Phase III readout for sickle cell disease, viewing 2025 as a breakout year [38] - The company maintains a strong balance sheet with approximately $1,400,000,000 in cash, providing financial independence to support product launches and pipeline advancement [5][36] Other Important Information - The company has a robust early and mid-stage pipeline poised for clinical advancement, with significant expected events for 2025 [8] - The company has welcomed Krishnan Viswanathan as Chief Corporate Development and Strategy Officer to enhance corporate strategy and capital allocation [10] Q&A Session Summary Question: Confirmation about no advisory committee for the September PDUFA - Management confirmed that there is no advisory committee planned and that the regulatory review is ongoing, with strong engagement with the FDA [42][43] Question: Impact of Oxbreda withdrawal on sickle cell trial recruitment - Management noted that they have not observed changes in clinical trial conduct and emphasized the need for multiple therapeutic options for sickle cell disease [46][47] Question: Plans for launching mitapivat ex-U.S. - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [50][53] Question: Changes in communication frequency with the FDA - Management stated that communication with the FDA remains consistent and normal, with no changes due to recent agency reshuffling [63] Question: Rationale for starting Phase II tebapivat study in sickle cell - Management highlighted the large unmet medical need in sickle cell disease and the importance of having multiple therapy options for patients [66][69] Question: Anticipated evolution of PyroKine's pricing - Management indicated that pricing decisions will be based on the value proposition of the label received and expressed confidence in navigating pricing opportunities [94][95]