Two clinical trials related to BBM-H901 are registered on ClinicalTrials.gov as follows:

• NCT04135300: Phase 1, open-label, non-randomized, uncontrolled, single-dose pilot study¹
  • A total of 10 Chinese adult patients with haemophilia B (aged >18 years) were enrolled and infused with BBM-H901²
• NCT05203679: Multi-center, Phase 1/2/3, single-arm, open-label, single-dose treatment clinical study^{3, 4}
  • The Phase 1/2 dose-escalation cohort enrolled 6 male participants³
  • The Phase 3 cohort enrolled 26 participants with haemophilia B in China⁴

The status of both clinical trials is reported on ClinicalTrials.gov as follows:

• NCT04135300: Completed¹
• NCT05203679: Active, not recruting³

• Males ≥ 18 years of age;
• Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
• Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories;
• Low titre of neutralising antibodies (≤1:4) against vector capsid

• Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer;

Details on the applied AAV capsid were extracted from the Supplementary Information in Reference #4 and are summarized below:

• Engineered liver-tropic AAV843 capsid, identified through screening of an AAV capsid gene–shuffled library constructed from AAV serotypes 1, 2, 3B, 4, 6, 7, 8, and 9
• Vector manufacturing platform: suspended HEK293 cells in a 200 L single-use bioreactor

FIX-Padua sequence in a double-stranded AAV (dsAAV) genome⁴

Expression cassette components were extracted from the information provided in Reference #4 and are summarized below:

• Codon-optimized cassette expressing FIX-Padua (R338L)
• LXP2.1 mini liver-specific promoter (188 bp) containing hepatocyte nuclear factor transcription elements, a TATA box, and specificity-protein-1 (SP1) elements
• Optimized F9 cDNA with removal of TCG and CGT codons (CpG-reducing) without altering the amino acid sequence
• Introduction of the Padua mutation (R338L) into the FIX coding sequence

Single intravenous infusion⁴

1. ClinicalTrials.gov registry — NCT04135300 (Phase 1 pilot study). Available at: Study Details | NCT04135300 | Gene Therapy for Chinese Hemophilia B | ClinicalTrials.gov
2. Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19. PMID: 35598604. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial - PubMed
3. ClinicalTrials.gov registry — NCT05203679 (Phase 1/2/3, multicenter). Available at: Study Details | NCT05203679 | Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug | ClinicalTrials.gov
4. Xue F, Ju M, Zhu T, Zhou Z, Sun J, Yang L, Yan Z, Zhou H, Du X, Zheng C, Zheng J, Wu X, Du Z, Jiang W, Yang C, Xiao X, Liu W, Yang R, Zhang L. Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials. Nat Med. 2025 Nov 20. doi: 10.1038/s41591-025-04012-y. Epub ahead of print. PMID: 41266685. Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials - PubMed

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs, adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year