Pociredir

Pociredir is a once daily oral HbF inducer. Results from the 12-week treatment period of the 20 mg dose cohort of the Phase 1b PIONEER trial (n=12) were announced:

• Mean absolute HbF increased by 12.2% at 12 weeks (vs. 8.6% at Week 12 in the 12 mg cohort)
• All patients demonstrated a clinically relevant HbF increase.
• Based on treating physician-documented medical records from the 6-12 months before enrollment, approximately 16 VOCs would have been expected during the 12-week treatment period. During the 12-week treatment period, six VOCs were reported. Seven of 12 patients (58%) reported no VOCs during the treatment period.

Sources: https://ir.fulcrumtx.com/news-releases/news-release-details/fulcrum-therapeutics-announces-positive-12-week-results-20-mghttps://ir.fulcrumtx.com/static-files/ad8b1e95-b4be-4100-9815-4a90e0b93327
Corporate Presentation, March 2026

Update: 22 December 2025

Results from the Phase 1b study were presented at the 67^th ASH Annual Congress (6 – 9 December 2025) in Orlando (USA). The data showed that:

• Cohort 3b was created following a protocol amendment to allow patients with ≥ 4 VOCs per year, ≥ 2 VOCs over 6 months, or documented SCD-related organ damage and not receiving hydroxyurea to enroll.
• Sixteen patients were enrolled in Cohort 3b and administered a dose of 12mg, completing the 12-week treatment period.
• At week 12, all participants had an increase of HbF, with 44% of patients achieving levels of more than 20% – a threshold associated with reduced VOCs
• Markers of haemolysis showed improvements.

Sources: Pociredir, a novel oral once-daily fetal hemoglobin inducer: Results from the Phase 1b pioneer study in adult participants with severe sickle cell disease and hydroxyurea intolerance or unresponsiveness
https://www.fulcrumtx.com/wp-content/uploads/251206-PIONEER-PHASE-1B-ASH-POSTER-vF.pdf

Update: 30 September 2025

• Data to be shared from the 20mg dose cohort by year’s end.
• Interim results from 16 patients who completed a 12-week treatment period with 12mg pociredir showed:
  • A mean increase of 8.6% of fetal haemoglobin (HbF)
  • 7/16 (44%) participants saw HbF rise over 20% – a threshold associated with reduced VOCs
  • Mean total haemoglobin increased by 0.9 g/dL

Sources: https://www.rttnews.com/3577462/pociredir-trial-and-dba-ind-filing-put-fulcrum-therapeutics-on-watchlist.aspx
https://sicklecellanemianews.com/news/pociredir-well-tolerated-shows-promising-activity-scd-trial/

Update: 30 June 2025

Enrolment is complete for the groups receiving 2mg, 6mg, and 12mg. Begun enrolment for the 20mg dose group.

Source: https://sicklecellanemianews.com/news/sickle-cell-disease-patients-being-recruited-pioneer-trial-pociredir/

Update: 31 March 2025

No update available.

Update: 19 December 2024

No update available.

Update: 30 September 2024

No update available.

Update: 30 June 2024

Data presented at the 29^th EHA Annual Congress (13 – 16 June 2024) in Madrid (Spain) from 3 dose-finding cohorts (6mg, 2mg, and 12mg) to induce fetal haemoglobin (HbF) enrolled 10, 2 and 4 patients respectively, showed that:

• • All patients adherent to the once daily oral administration of pociredir had HbF induction with increases of 9.8% and 10% in the 6mg and 12mg cohorts, respectively.
  • Dose-dependent increases were not affected by hydroxyurea use.

Source: Interim Results of a Phase 1b Study (Pioneer) of an Oral HbF Inducer, Pociredir, in Sickle Cell Disease