Brii Biosciences Limited shared three posters at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in Boston, MA, two of which were accepted as late-breakers providing new data from two Phase 2 assets, BRII-179 (VBI-2601) and BRII-835 (VIR-2218), within the chronic hepatitis B (CHB) clinical program. In a late-breaking poster presentation, Brii Bio announced additional interim data that were unblinded at the cohort level from a randomized, placebo-controlled and double-blinded Phase 2 study of BRII-179, in combination with pegylated interferon-alpha (PEG-IFNa) in patients with CHB infection. Findings from this presentation include: BRII-179 add-on therapy to existing PEG-IFNa treatment was generally safe and tolerated, with adverse events similar to those associated with PEG-IFNa treatment and BRII-179 as previously reported.

At Week 36 (12 weeks after end-of-treatment [EOT]), BRII-179 + PEG-IFNa combination group achieved higher HBsAg loss rate compared to Placebo + PEG-IFNa group (Full Analysis Set (FAS): 24.6% vs.14.0%, Per Protocol Set (PPS): 31.8% vs.14.9%). The difference in HBsAg loss rate was observed at Week 24 (EOT) and maintained through Week 36. The clinical study also found that the combination group had significantly higher HBsAg seroconversion rates than Placebo + PEG-IFNa group (FAS: 15.8% vs.

1.8%, p=0.016; PPS: 19.6% vs. 2.0%, p=0.0058) at Week 24 (EOT). The addition of BRII-179 induced robust and functional HBsAg antibody responses, participants in BRII-179 + PEG-IFNa combination group achieved significantly higher hepatitis B surface antibody (HBsAb) response rate than those in Placebo + PEG-IFNa group both at Week 24 (FAS: 38.6% vs.

14.0%, p=0.0052; PPS: 39.1% vs. 13.7%, p=0.0054) and Week 36 (FAS: 33.3% vs. 12.3%, p=0.0131; PPS: 34.1% vs.

10.6%, p=0.0105). The HBsAb titer was significantly associated with HBsAg loss at Week 24 and 36. 4 out 5 patients who rebounded had no detectable antibody responses.

The data from this proof-of-concept study demonstrated that the addition of BRII-179 induced functional immune responses that could improve the rate and duration of HBsAg loss in CHB patients who receive PEG-IFNa treatment, thereby increasing the CHB functional cure rate. In a second late-breaking poster presentation, Brii Bio presented translational research data from BRII-179-001 and BRII-179-835-001 studies, indicating the distinct HBsAg antibody responses induced by BRII-179 observed only in a subset of CHB subjects, suggesting that intrinsic immune responses against HBV in some patients may be more profoundly impaired. Additionally, researchers found: BRII-179 in combination with BRII-835 (VIR-2218) was generally well tolerated when administered up to 9 monthly doses, with no treatment related adverse events > Grade 2. In CHB participants on nuceos(t)ide reverse transcriptase inhibitors (NrtI) therapy, BRII-179, alone or in combination with BRII-835, induced substantial HBV specific T cell responses, while significant HBsAg antibody responses were elicited in some but not all chronic HBV participants even after 9 doses of vaccination in combination with BRII-835, an HBV-targeting siRNA lowering immunosuppressive viral antigens such as HBsAg.

Immunological analysis suggests that BRII-179 may offer a unique opportunity to enrich CHB patients who are able to elicit the necessary HBsAg antibody response in achieving higher functional cure rate in some patients while sparing others from unnecessary treatments. In a poster presentation, Brii Bio highlighted the multiple dose pharmacokinetics (PK) of BRII-835 (VIR-2218) in patients with chronic HBV infection from Phase 1b/2 and Phase 2 clinical trials, and the impact of regional or ethnic background may have on the PK of the drug. Highlights include: The PK characteristics of BRII-835 in patients with chronic HBV infection are generally similar to those in healthy volunteers.

At doses of 50 and 100 mg, dose dependent increases in systemic exposures were observed. There was no apparent accumulation in plasma after a second dose given four weeks later. Similar PK profiles between patients enrolled in the Asia-Pacific region and mainland China demonstrate that Chinese ethnic background from mainland China has no apparent impact, which could serve as a bridge to support mainland China's participation in future global trials for further evaluation of BRII-835.

As part of Brii Bio's unique approach to develop a functional cure for HBV, the Company and its partners are progressing multiple ongoing phase 2 studies, including BRII-835 and BRII-179 combination, BRII-179 and PEG-IFN? combination, BRII-835, BRII-877 (VIR-3434) with or without PEG-IFN?. In addition, Vir Biotechnology Inc. ("Vir") is also investigating VIR-2218 and/or VIR-3434 for the treatment of HBV/HDV co-infection.