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Barinthus Bio Presents Interim Data from Phase 2b HBV003 Trial and Phase 2a AB-729-202 Trial in Collaboration with Arbutus Biopharma in Chronic HBV Patients at AASLD

November 27, 2023 – Drug Discovery – AASLD, Arbutus Biopharma, Barinthus Biotherapeutics

Initial data from the combination of imdusiran and VTP-300 show meaningful reductions of HBsAg levels that were maintained well below baseline.
In HBV003, 31% of participants with screening HBsAg level of ≤200 IU/mL had >1 log HBsAg reductions.
VTP-300 was generally well-tolerated in both trials.

10 November 2023 — Oxford, UK — Barinthus Biotherapeutics, formerly Vaccitech, today announced the presentation of data from two HBV clinical trials at The American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting 2023. The presentations include an oral presentation of data from HBV003, an ongoing phase 2b trial designed to further evaluate the safety and efficacy of VTP-300 when combined with a low-dose anti-PD-1 antibody, and standard-of-care (SoC) nucleos(t)ide analogue (NUC) therapy. Alongside this, a late-breaking poster presentation with interim data from patients with chronic hepatitis B (CHB) from the phase 2a AB-729-202 trial combining Arbutus Biopharma Corporation’s RNAi therapeutic candidate, imdusiran (AB-729), with Barinthus Bio’s T-cell stimulating immunotherapeutic candidate, VTP-300, and SoC NUC therapy. Barinthus Bio is a clinical-stage biopharmaceutical company developing novel T-cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity and cancer.

“We believe these early data are very encouraging. In HBV003, VTP-300 in combination with nivolumab continues to show meaningful and sustained HBsAg declines across all treatment groups, with the most prominent declines occurring in patients with lower baseline HBsAg levels at screening,” said Bill Enright, CEO of Barinthus Bio.

Regarding the combination trial imdusiran with VTP300, Bill added “Although these are preliminary data, we can already see that VTP-300 appears to show a meaningful impact in sustaining low HBsAg in patients after imdusiran treatment, with clear differences shown between placebo and VTP-300. It’s very positive that we are seeing that all participants treated with imdusiran and VTP-300 have qualified to stop NUC therapy, which really highlights VTP-300’s potential as an important component of a functional cure regimen.”

Study HBV003: VTP-300 and Low-dose Nivolumab

HBV003 is designed to obtain critical information on treatment dosing regimen with patients receiving VTP-300 and low-dose nivolumab. All Groups receive ChAdOx at Day 1, Groups 1 & 2 receive MVA with nivolumab at Day 29 with Group 2 being dosed again at Day 85, Group 3 receives only MVA at Day 29, followed by nivolumab at Day 36 and a second MVA dose at Day 85 to evaluate PD-1 inhibition timing. 74 out of a planned 120 virally-suppressed CHB patients on stable NUC therapy have been enrolled in the trial and 57 have reached Day 113. VTP-300 in combination with nivolumab led to HBsAg declines in all treatment groups, particularly in participants with screening HBsAg levels ≤200 IU/mL.

>0.5 and >1 log drops have been observed in all groups at Day 113 in 23% and 9% of participants, respectively.
Participants with an HBsAg level of ≤200 IU/mL at screening were more likely to have >1 log HBsAg reductions (31%) compared to those with HBsAg levels >200 IU/mL at Day 1 (2%).
Greater mean HBsAg log reductions were observed in Group 2 (ChAdOx-HBV Day 1; MVA-HBV and nivolumab Day 29 and Day 85) but insufficient data for definitive conclusion.
Seven participants have met the criteria for NUC discontinuation; three have discontinued and two have restarted NUC therapy.
Preliminary safety data suggest VTP-300 in combination with nivolumab has been generally well tolerated, with no treatment-related SAEs observed or reported. Thyroid dysfunction reported in 7 participants attributed to nivolumab administration which has returned to normal in 4 patients.

The HBV003 trial protocol is currently being amended to include only participants with screening HBsAg ≤200 IU/mL. Participants with screening HBsAg ≤200 IU/mL have been observed to benefit the most in the preliminary data, with the trial protocol amendment being focused on improving the overall risk/benefit ratio. People with thyroid auto-antibodies, family history of auto-immune thyroiditis or abnormal thyroid levels will be excluded from trial eligibility to minimise the risk of thyroiditis.

Study AB-729-202: VTP-300 in Combination with Imdusiran (AB-729)

Clinical trial AB-729-202 enrolled 40 non-cirrhotic, virally suppressed CHB patients that were on stable NUC therapy. The patients initially received imdusiran (60mg every 8 weeks) for 24 weeks and were then randomised to receive either VTP-300 or placebo at week 26 and 30 (and conditionally at week 38 if they experienced a >0.5 log₁₀decline in HBsAg between Weeks 26 and 34), in addition to ongoing NUC therapy. The preliminary data include a subset of patients that received the two dose VTP-300 regimen (28/40 patients) and available follow-up data to Week 48 (12/40 patients) and showed the following:

Robust reductions of HBsAg were seen during the imdusiran treatment period (-1.86 log10 mean reduction from baseline after 24 weeks of treatment). This decline in HBsAg is comparable to the declines seen with imdusiran in other clinical trials conducted to date.
97% of the imdusiran treated patients (33/34) had HBsAg <100 IU/mL at the time of the first VTP-300/placebo dose.
VTP-300 treatment appeared to contribute to the maintenance of low HBsAg levels in the early post-treatment period, as the mean HBsAg levels in the placebo group begin to increase starting approximately 12 weeks after the last dose of imdusiran.
All VTP-300 treated patients have maintained HBsAg <100 IU/mL through week 48, 60% have maintained HBsAg <10 IU/mL, and all have qualified to stop NUC therapy.
Preliminary immunology data suggests HBV-specific T cell IFN-γ production was enhanced in patients receiving imdusiran plus VTP-300 compared to placebo.

The preliminary safety data from this trial demonstrate that imdusiran and VTP-300 were both generally well-tolerated. There were no serious adverse events, Grade 3 or 4 adverse events or treatment discontinuations.

Dr Karen Sims, chief medical officer of Arbutus Biopharma, commented, “Imdusiran consistently delivers compelling efficacy and safety data in multiple phase 2a populations and combinations. In this trial, all but one patient reached surface antigen levels below 100 IU/mL and one reached <LLOQ (lower limit of quantification) with 24 weeks of imdusiran plus NUC therapy alone, which is a meaningful achievement as we believe lowering surface antigen is key to promoting host HBV-specific immune reawakening. As we continue to dose and follow these patients, I look forward to seeing the potential that imdusiran, VTP-300 and NUC therapy can have on achieving a functional cure for patients with CHB.”

The presentation for HBV003 and poster for AB-729-202 can be found on the Barinthus Bio website at https://investors.barinthusbio.com/events-presentations.

About Barinthus Bio

Barinthus Bio is a clinical-stage biopharmaceutical company developing novel T-cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity and cancer. Helping people living with serious diseases and their families is the guiding principle at the heart of Barinthus Bio. With a broad pipeline, built around four proprietary platform technologies — ChAdOx, MVA, SNAP-TI and SNAP-CI — Barinthus Bio is advancing a pipeline of five product candidates across a diverse range of therapeutic areas, including: VTP-300, an immunotherapeutic candidate designed as a potential component of a functional cure for chronic HBV infection; VTP-200, a non-surgical product candidate for persistent high-risk human papillomavirus (HPV); VTP-1000, an autoimmune candidate designed to utilise the SNAP-TI platform to treat patients with celiac disease; VTP-850, a second-generation immunotherapeutic candidate designed to treat recurrent prostate cancer; and VTP-1100, a preclinical cancer candidate designed to utilise the SNAP-CI platform to treat patients with HPV-related cancer. Barinthus Bio’s proven scientific expertise, diverse portfolio and focus on pipeline development uniquely positions the company to navigate towards delivering treatments for people with infectious diseases, autoimmunity and cancers that have a significant impact on their everyday lives. For more information, visit www.barinthusbio.com.

About Arbutus

Arbutus Biopharma Corporation is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to identify and develop novel therapeutics with distinct mechanisms of action, which can be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). Arbutus believes the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen and boosting HBV-specific immune responses. Arbutus’ pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729) and an oral PD-L1 inhibitor, AB-101. Imdusiran is the only RNAi that has generated meaningful clinical data demonstrating an impact on both surface antigen reduction and reawakening of the HBV-specific immune response. Imdusiran is currently in two phase 2a combination clinical trials. AB-101 is currently being evaluated in a phase 1a/1b clinical trial. Additionally, Arbutus has identified compounds in its internal PD-L1 portfolio that could also be used in oncology indications. For more information, visit www.arbutusbio.com.