Bluejay Therapeutics Reports Best-in-Class Monoclonal Antibody Achieved 100% Virologic Response & Up To 78% Combined Virologic Response, & ALT Normalization as Monotherapy in Participants With Chronic Hepatitis D

Bluejay Therapeutics recently announced new data from its Phase 2 study of BJT-778, a best-in-class investigational, fully human, high-affinity monoclonal antibody (mAb) that targets hepatitis B virus surface antigen (anti-HBsAg). The Phase 2 study is investigating BJT-778 as a potential monotherapy for adults with chronic hepatitis D (CHD). CHD is the most aggressive form of viral hepatitis.

These data will be presented in detail in an oral presentation on Nov. 18 at The Liver Meeting 2024 of the American Association for the Study of Liver Diseases (AASLD). The company will also present data from its chronic hepatitis B (CHB) functional cure development program, including preclinical studies on uptake and T cell stimulation by BJT-778 and the preclinical characterization of cavrotolimod, a spherical TLR9 agonist and potential combination partner for BJT-778.

“For the more than 12 million patients globally with chronic hepatitis D, the most severe and aggressive form of viral hepatitis, there are limited treatment options,” said presenting author Kosh Agarwal, MD, Consultant Hepatologist and Transplant Physician of the Institute of Liver Studies at King’s College Hospital in London, United Kingdom. “We need to do better for patients. These BJT-778 Phase 2 data show that this monotherapy regimen has the potential to be an important treatment advance in CHD.”

In this Phase 2 study, participants with quantifiable hepatitis D virus (HDV) RNA and hepatitis B virus (HBV) suppressed on nucleos(t)ides were assigned to one of three doses of BJT-778: 300 mg weekly (QW) (n=18); 600 mg every week for 12 weeks, then every two weeks (Q2W) (n=11); and 900 mg every four weeks after a loading dose administered at week two (Q4W) (n=18). Patients with compensated cirrhosis and those with well-controlled HIV were allowed.

Key endpoints of the study include safety and tolerability; virologic response (defined as ≥2 log10 HDV RNA IU/mL reduction from baseline or HDV RNA target not detected [TND]; ALT normalization in those participants with abnormal ALT at baseline; and the combined response of virologic response plus ALT normalization. According to FDA guidance, this combined endpoint is a reliable predictor of clinical benefit and directly supports approval of new drugs in CHD.

BJT-778 achieved 100% virologic response across all dose arms and up to 78% of participants reached the combined endpoint of virologic response and ALT normalization. These parallel declines in HDV viral load and ALT were observed across all doses, indicating a beneficial effect on liver inflammation as the result of viral load reduction.

By the last timepoint available for each dose, the results were as follows:

• 300 mg QW (n=10): By Week 44, this group had 100% virologic response, including 60% with HDV RNA below the Lower Limit of Quantification (<LLOQ [HDV RNA 10 IU/mL]) and 50% with undetectable HDV RNA (<LLOQ, TND);
• 600 mg Q2W (n=10): By Week 36, had 100% virologic response, including 50% <LLOQ and 40% <LLOQ, TND; and
• 900 mg Q4W (n=8): By Week 24, had 100% virologic response, including 75% <LLOQ and 50% <LLOQ, TND.

A favorable safety profile of BJT-778 was observed with all doses being safe and well tolerated. There were no ≥ grade 3 AEs, no severe AEs and no treatment discontinuations due to AEs.

“BJT-778 has the potential to be both practice-changing for physicians and life-changing for patients,” said Nancy Shulman, MD, Chief Medical Officer of Bluejay Therapeutics. “A monotherapy for HDV with 100% virologic response, high rates of ALT normalization, a strong safety profile and convenient dosing regimens is now achievable. These results support advancing BJT-778 into larger, randomized controlled studies and we plan to commence these studies as soon as possible.”

Longer-term, 48-week data across all dose arms are expected to be shared in the second half of 2025.

As part of its program investigating combination therapy approaches to achieve functional cure of CHB, Bluejay Therapeutics announced data showing that in a preclinical study, BJT-778 significantly increased uptake of hepatitis B surface antigen (HBsAg) compared to control Ab or HBsAg alone. Enhanced uptake of HBsAg resulted in increased HBV-specific CD4 T cell activation, supporting a dual mechanism of action through removal of circulating HBsAg and stimulation of HBV-specific T cell immunity.

The company also announced preclinical characterization data on cavrotolimod (CAVRO), a spherical TLR9 agonist. These data show that CAVRO selectively activates TLR9 and induces the production of key cytokines in human peripheral blood mononuclear cells, as well as T cells, NK cells and myeloid dendritic cells, indicating a strong cellular immune response which may result in sustained control of hepatitis B infection. In addition, cytokine responses to repeated dosing in non-human primates remained stable over time with no significant fluctuations in pharmacodynamic response. A Phase 1b study has been initiated to evaluate CAVRO in participants with CHB.

Oral presentation details are as follows:

Title: BJT-778, Anti-HBsAg Monoclonal Antibody, Achieved 100% Virologic Response in Subjects with Chronic Hepatitis D (CHD): Phase 2 Study Results
Presentation number: 239
Session: Hepatitis D: Natural History and Treatment
Date: Monday, Nov. 18
Time: 6-6:15p.m. PT
Presenter: Kosh Agarwal, MD, Institute of Liver Studies, King’s College Hospital, London, UK

Poster presentation details are as follows:

Title: Pre-clinical Characterization of Cavrotolimod, a TLR9 Agonist for the Treatment of Chronic Hepatitis B 
Presentation number: 1414
Session: Hepatitis B
Date: Friday, Nov. 15
Time: 1-2p.m. PT
Presenter: Hilario J. Ramos, PhD, Bluejay Therapeutics

Title: Uptake and T Cell Stimulation by BJT-778-HBsAg Immune Complexes: Insights into Anti-HBs Monoclonal Antibody Function
Presentation number: 1406
Session: Hepatitis B
Date: Friday, Nov. 15
Time: 1-2p.m. PT
Presenter: Loghman Salimzadeh, PhD, Schwartz-Reisman Liver Research Centre, University Health Network, Toronto, Ontario, Canada

BJT-778 is a high potency, fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets the surface antigen (anti-HBsAg) of the hepatitis B virus. BJT-778 neutralizes and removes hepatitis B and hepatitis D virions and depletes HBsAg-containing subviral particles, which makes BJT-778 a potentially safe and highly efficacious treatment for CHD, a condition with urgent unmet medical need. In addition, BJT-778 has also shown immunomodulatory functions in CHB patients, which may help to reconstitute antiviral immunity and contribute to functional cure for CHB when combined with other agents. BJT-778 has received Orphan and PRIME designation from the European Medicines Agency based on early results from a Phase 1/2 study in CHD.

Cavrotolimod (CAVRO) is a proprietary spherical toll-like receptor 9 (TLR9) agonist oligonucleotide designed to activate both innate and adaptive immune responses. It is being investigated for its potential to enhance antiviral immunity in patients with CHB and improve the functional cure rate as a part of combination regimens.

Bluejay Therapeutics is a clinical-stage biopharmaceutical company focused on the development of potentially life-changing treatments for viral hepatitis and liver diseases. The company is currently investigating BJT-778 for the treatment of CHD and CHB. Additionally, Bluejay is advancing several innovative programs with the goal of finding a combination regimen to achieve functional cure for CHB, including a proprietary TLR9 agonist (cavrotolimod) and a liver-targeted HBV transcript inhibitor (BJT-628). For more information, visit www.bluejaytx.com.