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

• Pilot study (Phase 1 | NCT04135300): 5 × 10¹² vg/kg — 10 participants²
• Phase 1/2 dose-escalation cohort (NCT05203679): 5 × 10¹² vg/kg — 6 participants⁴
• Phase 3 cohort (NCT05203679): 5 × 10¹² vg/kg — 26 participants⁴

Follow-up times were extracted from various publications and are summarized as follows:

• Pilot study (Phase 1, NCT04135300):
  • median follow-up 58 weeks (IQR 51.5 – 99.5 weeks)²
  • median (range) of 210 (159–270) weeks postgene therapy at the data cutoff date of 22 July 2024.
• Phase 3 study (NCT05203679): primary 52-week follow-up post-infusion for bleeding rate (ABR), FIX:C, safety endpoints⁴
• Registry / post-marketing / extension follow-up: According to sponsor/dissemination report, follow-up continues up to 5 years post-infusion in some participants⁵

Information on the clotting assays used in this trial was extracted from Reference #4 and is summarized below:

• OS clotting assay was used to measure FIX activity
• Two commercial OS methods were employed to ensure assay reliability and consistency across measurements: OS SynthASil and OS Actin FSL
• Chromogenic (CH) assay was not reported for this trial.

Long-term follow-up FIX activity level ranges for the Phase 1 Pilot Study (n = 10), assessed using the OS Actin-FSL method, are summarized in the table below based on the categorical data provided in Reference #4:

Mean, median and individual FIX activity levels for the Phase 1/2 Trial were extracted from Reference #4 and are summarized in the table below:

* IST: Participants on additional immune suppressive treatment in phase 1/2 study

FIX activity (IU/dL) levels for the Phase 3 Trial were extracted from Reference #4 and are summarized in the table below:

    Overall Table Annotations:

• All mean FIX activity levels shown here were assessed using the OS Actin-FSL assay, except at Week 52 where both OS Actin-FSL and OS SynthASil assays were applied
• The reported mean SynthASil : Actin-FSL activity ratio was 1.35 (SD 0.54)

Information on the early kinetics of FIX activity following BBM-H901 infusion was extracted from Reference #4. Based on the available time-course data, the mean time to peak FIX activity can be summarized as follows:

• Phase 3 cohort:
  • Mean time to peak FIX activity: ~6 days post-infusion, corresponding to the reported mean peak FIX:C level of 59.3 IU/dL on Day 6.
• Phase 1/2 cohort:
  • Not reported in Reference #4
• Phase 1 pilot cohort: 
  • Not reported in Reference #4 (long-term follow-up data do not include early peak kinetics) and in Reference #2.

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
5. Unpublished sponsor report / web source — Dalnacogene Ponparvovec (BBM-H901) long-term follow-up data. DHG. Available at: https://www.dhg.de/fileadmin/dokumente/EHC/NTR-August-2025.pdf (accessed 26 November 2025).

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