Financial Data and Key Metrics Changes - Research and development expenses for Q3 2025 were $14.3 million, a decrease from $14.6 million in Q3 2024, primarily due to reduced employee compensation costs and decreased costs associated with a discontinued program [10] - General administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, mainly due to lower professional services costs [10] - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024 [11] - Cash, cash equivalents, and marketable securities at the end of Q3 2025 totaled $200.6 million, down from $241 million at the end of 2024, primarily due to cash used for operating activities [11] - The company expects its existing cash resources to fund operations into 2028, allowing for substantial progress in clinical development [11] Business Line Data and Key Metrics Changes - The lead program, FTX-6058, for sickle cell disease showed promising results, including a dose-dependent increase in fetal hemoglobin and a reduction in vaso-occlusive crises [5][8] - Enrollment in the 20-milligram dose cohort was completed with 12 evaluable patients, and data will be presented at the upcoming ASH conference [6][7] - The company is also advancing programs for bone marrow failure syndromes and plans to submit an IND for these conditions in Q4 2025 [9] Market Data and Key Metrics Changes - Approximately 100,000 people in the U.S. and 7.7 million worldwide suffer from sickle cell disease, indicating a significant market need for effective treatments [4] - The company estimates that about 20% of the U.S. sickle cell disease population meets the inclusion-exclusion criteria for the Phase 1B Pioneer trial [35] Company Strategy and Development Direction - The company aims to position FTX-6058 as a best-in-class once-daily oral therapy for sickle cell disease, with plans for an open-label extension trial to evaluate long-term safety and efficacy [6][8] - The strategy includes engaging with the FDA for an end-of-Phase 1 meeting in Q1 2026 to discuss the next stages of clinical development [8] - The company is focused on expediting the drug's market entry to address the unmet needs of sickle cell disease patients globally [36] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the encouraging results from the 12-milligram cohort and the upcoming data readout at the ASH conference [12][13] - The management team highlighted the importance of generating additional safety data through the open-label extension study, which is expected to inform future discussions with the FDA [24][75] Other Important Information - The company has seen a high adherence rate of over 90% among patients in the study, indicating strong patient engagement with the treatment regimen [7] - The management team emphasized the need for a comprehensive approach to evaluating the drug's efficacy, considering multiple parameters such as fetal hemoglobin levels and reduction in vaso-occlusive crises [52] Q&A Session Summary Question: How does the company define a win in the context of the trial results? - Management believes they have already achieved a win with the 12-milligram cohort, showing robust increases in fetal hemoglobin and a favorable safety profile [16] Question: What are the expectations for the 20 mg dose cohort? - Management anticipates that the 20 mg cohort will outperform the 12 mg cohort based on previous healthy volunteer data [18] Question: What is the addressable market following the withdrawal of a competitor's product? - The company estimates that about 20% of the 100,000 U.S. patients with sickle cell disease currently meet the trial criteria, with plans to discuss potential market expansion with the FDA [35] Question: What metrics will be important for defining the activity of FTX-6058? - Management indicated that the totality of data, including fetal hemoglobin levels, pan-cellularity, and reduction in markers of hemolysis, will be crucial for evaluating the drug's efficacy [52] Question: What is the timeline for the final Pioneer data set? - The full data set is expected to be available in the first quarter of the following year [56]

Financial Data and Key Metrics Changes - Research and development expenses for Q3 2025 were $14.3 million, a slight decrease from $14.6 million in Q3 2024, primarily due to reduced employee compensation costs and discontinued programs [10] - General administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, mainly due to lower professional services costs [10] - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024 [11] - Cash, cash equivalents, and marketable securities at the end of Q3 2025 totaled $200.6 million, down from $241 million at the end of 2024, primarily due to cash used for operating activities [11] Business Line Data and Key Metrics Changes - The pociredir program for sickle cell disease showed promising results, with a dose-dependent increase in fetal hemoglobin and a reduction in vaso-occlusive crises [5][8] - Enrollment in the 20-milligram dose cohort was completed, with 12 evaluable patients, and data will be presented at the ASH conference [6][9] Market Data and Key Metrics Changes - Approximately 100,000 people in the U.S. and 7.7 million worldwide suffer from sickle cell disease, indicating a significant market need for effective treatments [4] - The company estimates that about 20% of the 100,000 U.S. patients meet the inclusion-exclusion criteria defined in the PIONEER trial [34] Company Strategy and Development Direction - The company aims to position pociredir as a best-in-class once-daily oral therapy for sickle cell disease, with plans to engage the FDA for an end-of-Phase I meeting in Q1 2026 [8][9] - The company is also advancing programs for bone marrow failure syndromes and plans to submit an IND for these conditions in Q4 2025 [9] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming data readout at the ASH conference and the potential for pociredir to provide a differentiated therapeutic option for sickle cell disease [8][13] - The company is focused on getting pociredir to market quickly to address the unmet needs of patients following the withdrawal of other treatment options [35][36] Other Important Information - The company has completed enrollment in the 20-milligram dose cohort and expects to present data from this cohort at the ASH conference [6][9] - The open-label extension study for pociredir was initiated to allow patients to continue treatment after the PIONEER trial [22][24] Q&A Session Summary Question: How are you internally thinking about what is a win here and whether ways to measure if there's a dose response? - Management believes they have already achieved a win with the 12-milligram cohort, showing robust increases in fetal hemoglobin and a trend toward reduced vaso-occlusive crises [16] Question: Can you provide insight into the baseline level of HbF for the patients in the first half of the 20 mg cohort? - The initial patients enrolled in the 20 mg cohort trended lower than the overall mean, but the exact numbers will be revealed at the data disclosure [29][32] Question: What do you need to see from the 20 mg dose cohort for it to be the go-forward Phase III dose? - Management will look for efficacy endpoints indicating improvement, favorable tolerability, and adherence to the study drug [44] Question: What is the FDA's expectation regarding safety data? - The FDA has not provided specific numerical criteria but expects ongoing favorable safety and tolerability data to be contextualized with the potential benefits of the therapy [75] Question: When will the final PIONEER data set be available? - The full data set is expected to be shared in the first quarter of next year [56]

Financial Data and Key Metrics Changes - Research and development expenses for Q3 2025 were $14.3 million, a slight decrease from $14.6 million in Q3 2024, primarily due to reduced employee compensation costs and discontinued programs [10] - General administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, mainly due to lower professional services costs [10] - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024 [11] - Cash, cash equivalents, and marketable securities at the end of Q3 2025 totaled $200.6 million, down from $241 million at the end of 2024, primarily due to cash used for operating activities [11] - The company expects its existing cash resources to fund operations into 2028, allowing for substantial progress in clinical development [11] Business Line Data and Key Metrics Changes - The lead program, FTX-6058, for sickle cell disease showed promising results, with a dose-dependent increase in fetal hemoglobin and a reduction in vaso-occlusive crises [4][8] - Enrollment in the 20-milligram dose cohort was completed, with data to be presented at the upcoming ASH conference [5][6] - The company is also advancing programs for bone marrow failure syndromes and plans to submit an IND for these conditions in Q4 2025 [9] Market Data and Key Metrics Changes - Approximately 100,000 people in the U.S. and 7.7 million worldwide suffer from sickle cell disease, indicating a significant market need for effective treatments [3] - The company estimates that about 20% of the U.S. sickle cell population meets the inclusion-exclusion criteria for the Phase 1B Pioneer trial [30] Company Strategy and Development Direction - The company aims to position FTX-6058 as a best-in-class once-daily oral therapy for sickle cell disease, with plans for an open-label extension trial to evaluate long-term safety and efficacy [5][21] - The strategy includes engaging with the FDA for an end-of-Phase 1 meeting in Q1 2026 to discuss the next stages of clinical development [8] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the encouraging results from the FTX-6058 program and the potential to provide differentiated therapeutic options for sickle cell disease patients [8][12] - The company is focused on expediting the drug's market entry to address the unmet needs of patients, especially following the withdrawal of other treatment options [31] Other Important Information - The company presented preclinical data for FTX-6274, an oral EED inhibitor, showing efficacy in prostate cancer models, indicating potential expansion beyond hematology programs [9] Q&A Session Summary Question: Insights on baseline characteristics of the 20 mg cohort - Management noted that the baseline characteristics of the 20 mg cohort are similar to previous cohorts, and they are analyzing the data to determine the dose response [14][15] Question: Interest in the open-label extension study - The decision to initiate the open-label extension study was influenced by patient and investigator feedback, allowing continued treatment for patients post-trial [20][21] Question: Addressable market assumptions - The company estimates that about 20% of the 100,000 U.S. patients with sickle cell disease meet the trial criteria, and they aim to expand treatment access [30][31] Question: Safety follow-up requirements from the FDA - The FDA has not specified numerical criteria for safety follow-up, but ongoing favorable safety profiles will be crucial for future discussions [64] Question: Future clinical plans beyond Phase 1B - The next study design will depend on discussions with regulators and may include a registrational trial focused on VOC reduction as a primary endpoint [65][66]