VTP-300 induced sustained reductions of hepatitis B surface antigen in people with chronic hepatitis B during ongoing, fully enrolled Phase 1b/2a trial.
VTP-300 as a monotherapy and in combination with a single administration of low-dose nivolumab demonstrated no treatment-related serious adverse events and infrequent transient transaminitis, as of 28 September 2022.
A robust T cell response against all encoded antigens was observed following VTP-300 administration, notably for marked CD8+ T cell predominance.
OXFORD, United Kingdom, Nov. 07, 2022 (GLOBE NEWSWIRE) -- Vaccitech plc (NASDAQ: VACC), a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapies and vaccines for the treatment and prevention of infectious diseases, cancer, and autoimmune diseases, today announced an update to the interim analysis of safety and efficacy data from its HBV002 trial (NCT04778904). The data will be presented as a poster at the 2022 American Association for the Study of Liver Disease (AASLD) - The Liver Meeting® by Dr. Young-Suk Lim, Professor of the Department of Gastroenterology and the Liver Center, Asian Medical Center, University of Ulsan College of Medicine, Korea.
Vaccitech’s updated interim analysis includes data from the fully-enrolled trial of 55 patients with chronic hepatitis B (HBV) with at least three months of follow-up. It shows that VTP-300 induced meaningful, sustained reductions of HBV surface antigen (HBsAg) in people with chronic HBV. Declines were most prominent in patients with lower baseline HBsAg. HBsAg is a hallmark of chronic HBV infection. Fewer than 10% of patients on current standard-of-care HBV therapies achieve sustained HBsAg decrease or loss, a state associated with functional cure of the disease.
VTP-300 administered as a monotherapy or in combination with a single administration of low-dose nivolumab at the time of the booster dose was administered with no treatment-related serious adverse events and infrequent transient transaminitis as of 28 September 2022.
“The updated interim data from this Phase 1b/2a study continues to support the potential of VTP-300 as a critical component of a functional cure for people with chronic hepatitis B,” said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech. "The prominent effect we are observing in patients with lower starting HBsAg levels supports the ongoing collaborative study with Arbutus Biopharma’s siRNA, AB-729, which has shown to reduce HBsAg below 100 IU/mL in a majority of patients. In addition, we believe patients who are experiencing declines in HBsAg due to VTP-300 could benefit further from additional VTP-300 boosters, which we are evaluating in an additional ongoing study."
In the VTP-300 monotherapy Group 2 (N=18), five patients had baseline HBsAg under 100 IU/mL. Of those five patients, three showed meaningful and durable reductions of HBsAg of 0.9, 1.0 and 1.4 log10, respectively, five months after the last dose of VTP-300. Furthermore, these reductions persisted in all three patients at eight months after the last dose.
Group 3 (N=18) patients received VTP-300 in combination with a single low dose of nivolumab at the time of the booster dose, and the mean log10 reduction in HBsAg was 0.8 (n=18) at 3 months, 0.9 (n=10) at 6 months, and 1.3 (n=7) at 9 months, with more prominent declines observed in patients with baseline HBsAg lower than 1,000 IU/mL. Five patients in this group had baseline HBsAg lower than 100 IU/mL, of which four had declines over 0.6 log10. Moreover, two of those patients developed non-detectable HBsAg at 3 months, and one of the patients, who has been evaluated at 6 and 9 months, continued to maintain non-detectable HBsAg.
Patients in Groups 2 and 3 also demonstrated a robust CD8+ T cell response, against all encoded antigens; core protein, polymerase and surface antigens.
“Chronic HBV stems from the immune system’s inability to clear the virus, due to insufficient immune priming or aberrant immune tolerance due to large quantities of HBV protein expression,” said Professor Young-Suk Lim. “Many involved in the field believe it makes sense to combine an immune-stimulating agent like VTP-300 with a HBV-suppressing agent, to potentially elicit a functional cure for HBV.”
No meaningful reductions in HBsAg were observed in Group 1 in which patients received two doses of Modified Vaccinia Ankara (MVA)-HBV without ChAdOx1-HBV, or in Group 4 in which patients received low-dose nivolumab with both doses of VTP-300. These groups were discontinued after interim analysis, as previously announced in June 2022.
Enrollment in the HBV002 trial is complete, with a final update expected early in the second quarter of 2023. A trial to evaluate timing of low dose nivolumab and additional doses of the MVA boost component of VTP-300 (HBV003; NCT05343481) has been initiated in multiple countries within the Asia-Pacific region.
Phase 1b/2a Study of Heterologous ChAdOx1-HBV/MVA-HBV Therapeutic Vaccination (VTP-300) Combined With Low-Dose Nivolumab (LDN) in Virally-Suppressed Patients with CHB on Nucleos(t)ide Analogues
Final Poster Number:
Dr. Young-Suk Lim, Professor of Gastroenterology in the Liver Center at University of Ulsan College of Medicine and clinical trial investigator for Vaccitech
1 – 2 p.m. EST on Monday, November 7, 2022
HBV002 is an open-label trial designed to evaluate the safety, immunogenicity and preliminary efficacy of ChAdOx1-HBV and MVA-HBV (VTP-300), with or without low-dose nivolumab, in patients with chronic HBV with suppressed HBV DNA on nucleos(t)ide therapy.
As of November 4th, 2022, the study was fully enrolled at 55 patients, with no reported safety signals of concern or vaccine-related serious adverse events.
VTP-300 is a novel immunotherapy, dosed in a prime-boost regimen, whereby the immune system is primed with an adenovirus (ChAdOx1) and boosted with a pox virus (MVA). Both vectors have been modified to improve safety, enhance the immune response they induce and include HBV-specific antigens including core, polymerase and surface antigen. Clinical data generated to date have demonstrated that this regimen has been generally well-tolerated, that antigen-specific T cell responses are stimulated to each antigen and there were meaningful reductions in hepatitis B surface antigen when this regimen is given alone or when given in combination with a low dose of nivolumab at the boost.
About Vaccitech plc.
Vaccitech is a clinical-stage biopharmaceutical company engaged in the discovery and development primarily of novel immunotherapies for the treatment of chronic infectious diseases, cancer, autoimmunity and diseases where the T cell arm of the immune system is believed to play an important role. The company’s proprietary platforms include modified simian adenoviral vectors (ChAdOx1 and ChAdOx2), other viral vectors including the well-validated Modified Vaccinia Ankara (MVA) and synthetic nano-particle technologies (SNAPvax™ and Syntholytic™). The combination of different technologies in a mix and match approach (heterologous prime-boost) consistently generates significantly higher magnitudes of T cells compared with other technologies and approaches. The company has a broad pipeline of both clinical and preclinical stage therapeutic programs to treat solid tumors, chronic viral infections, as well as prophylactic viral vaccine programs. Vaccitech co-invented a COVID-19 vaccine with the University of Oxford, now approved for use in many territories and exclusively licensed worldwide to AstraZeneca through Oxford University Innovation (OUI). Vaccitech is entitled to receive a share of all milestones and royalty income received by OUI from AstraZeneca.
Forward Looking Statement
This press release contains forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, which can generally be identified as such by use of the words “will,” “could,” “expect,” “believe,” “potential,” “initiate,” “continue,” and similar expressions, although not all forward-looking statements contain these identifying words. These forward looking statements include express or implied statements regarding the Company’s future expectations, plans and prospects, and include, without limitation, statements regarding the timing of the Company’s ongoing Phase 1b/2a clinical trial of VTP-300 and statements regarding the initiation of a future clinical trial of VTP-300. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to numerous risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to: the success, cost and timing of the Company’s product development activities and planned and ongoing clinical trials, the Company’s ability to execute on its strategy, regulatory developments, the Company’s ability to fund its operations, global economic uncertainty and the impact that the current ongoing COVID-19 pandemic will have on the Company’s clinical trials, preclinical studies and access to capital and other risks identified in the Company’s filings with the Securities and Exchange Commission (the “SEC”), including its Annual Report on Form 10-K for the year ended December 31, 2021, its Quarterly Report on Form 10-Q for the second quarter of 2022 and subsequent filings with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company expressly disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.
Christopher M. Calabrese