Clinical Trials

Date: 2016-11-14

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the AASLD (American Association for the Study of Liver Diseases) Liver Meeting 2016

Company: Transgene (France)

Product: TG1050

Action mechanism:

• immunotherapy product. TG1050 is an adenovirus-based targeted immunotherapy candidate for the treatment of chronic hepatitis B. This therapeutic vaccine is based on a recombinant non-replicative human adenovirus serotype 5, expressing multiple specific HBV antigens (Core, Envelope and Polymerase) from genotype D. The vaccine has been designed to prime de novo and/or stimulate functional T-cells expected to control the HBV replication and to elicit viral clearance.

Disease: chronic hepatitis B

Therapeutic area: Infectious diseases

Country:

Trial details:

Latest news:

• * On November 14, 2016, Transgene presented a poster on TG1050 preclinical results at the AASLD (American Association for the Study of Liver Diseases) Liver Meeting 2016, Boston (MA).The abstract has been published in Hepatology and the poster is entitled "TG1050, an HBV-targeted immunotherapeutics, efficiently decreases HBV viremia and antigenemia in a preclinical model; a meta-analysis and the determination of the involvement of CD4 and CD8 T cells". This poster shows a meta-analysis of preclinical data obtained with TG1050 in HBV persistent mice and preliminary data on the mode of action of TG1050. TG1050 has a significant treatment effect on viremia and HBsAg levels and a higher percentage of responders for viremia and HBsAg in TG1050-treated mice. Some mice treated by TG1050 displayed anti-HBsAg antibody seroconversion (clinical goal of HBV therapies). The involvement of TG1050-induced HBV-specific CD8 and CD4 T cell responses in TG1050 antiviral effects. A phase 1-1b clinical study is currrently evaluating the safety and tolerability of TG1050 in patients who are currently being treated for chronic HBV infection with standard-of-care antiviral therapy.
• • On April 23, 2015, Transgene announced that new pre-clinical data with TG1050, an immunotherapy being developed for the treatment of chronic hepatitis B, were presented at The International Liver Congress™ 2015, the 50th Congress of the European Association for the Study of the Liver (EASL) in Vienna, Austria.The TG1050 data were presented as part of a Liver Immunology session in an oral presentation entitled: TG1050, A Novel Immunotherapeutic to Treat Chronic Hepatitis B, can Control HBsAg and Provoke HBsAg Seroconversion in HBV-persistent Mouse Models (Abstract O031). The data presented  demonstrate the antiviral potential of TG1050 in a persistent hepatitis B virus (HBV) in vivo model. In this model, TG1050 was shown to significantly reduce circulating HBV DNA, to reduce the circulating HBV surface antigen (HBsAg), and to trigger seroconversion to HBsAg (i.e., to develop anti-HBsAg antibodies). The development of anti-HBsAg antibodies has been associated with HBV cure. The first-in-humans clinical trial is s expected to begin patient enrollment in mid-2015.
• • On July 1, 2014,Transgene announced that it was invited to present existing preclinical data on its proprietary program against chronic hepatitis B, TG1050 immunotherapy, at the BIT 5th Annual International Symposium of Hepatitis in Dalian, China. The presentation, entitled, “TG1050, A Novel Viral-based Immunotherapeutic Targeting Chronic Hepatitis B Infection” was given by Dr. Ren Zhu, Senior Scientist and Head of the HBV Program at TRANSGENE Biopharmaceutical Technology (Shanghai) Co., Ltd, a Transgene subsidiary located in Shanghai, China.
• The company also provided an update on activities at the company’s 50:50 equity joint venture with Tasly Pharmaceutical Group, Transgene Tasly (Tianjin) Biopharmaceutical Co. The JV was set up to develop and commercialize innovative targeted immunotherapeutic products for the Chinese market.  There are currently three projects ongoing at the joint venture: Transgene’s programs TG1050, TG3003, a monoclonal antibody to treat solid tumors and TG6002, an oncolytic viral immunotherapy to treat solid tumors. TG1050 is currently the JV’s most advanced program under development in China, with manufacturing process development ongoing and pre-clinical efficacy and toxicity studies anticipated to start later in 2014. Transgene expects to initiate a first-in-humans clinical trial outside of China in late 2014.
• • On November 5, 2013, Transgene has announced that pre-clinical data on TG1050, an immunotherapy candidate for the treatment of chronic Hepatitis B (CHB), were presented recently at two major scientific and medical meetings. An oral presentation entitled, “TG1050, a viral-vector based immunotherapeutic designed to treat chronic Hepatitis B induces immune responses with properties similar to those displayed by HBV resolving patients and has an early antiviral effect in a HBV tolerant model,” was given by Geneviève Inchauspé, Ph.D., Department Head, Infectious Diseases at Transgene on November 3, 2013 at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington. The presentation featured a summary of pre-clinical data regarding the potential of TG1050 to treat patients with CHB.  The data included new results from an in vivo model that demonstrated the proper functioning of T cells following treatment with TG1050. An oral presentation entitled “Cross-reactivity studies of an immunogenic fusion sequence show potential for the development of a novel pan genotypic immunotherapeutic to treat chronic Hepatitis B,” was given recently at the 2013 International Meeting on Molecular Biology of Hepatitis B Viruses in Shanghai, China.  This presentation was given by Ren Zhu, Ph.D., Senior Scientist, Head of the HBV Program at Transgene's China subsidiary, Transgene Biopharmaceutical Technology (Shanghai). Dr. Zhu presented detailed pre-clinical data supporting the potential utility of TG1050 across a number of genotypes of HBV.  TG1050 expresses a gene sequence from genotype D, common in Europe.  The data presented showed that this sequence can induce immune responses capable of recognizing antigenic sequences from genotypes B and C, the most prevalent in China.  Equivalent data has also been generated with respect to genotypes A and E.  These findings support the potential for TG1050 to be developed to treat CHB patients irrespective of genotype, which may facilitate the development of TG1050 for a number of markets. Pharmaceutical development and preparation for toxicity studies are currently ongoing.  Transgene expects to initiate a first-in-humans clinical trial in late 2014.
• • On April 29, 2013, Transgene has announced pre-clinical data obtained with its novel immunotherapeutic, TG1050, to treat chronic hepatitis B infection (CHB). These results were presented in an oral session (Hepatitis B and D Experimental) at this year’s European Association for the Study of the Liver Conference (Amsterdam, Netherlands, April 24-28, 2013). Transgene expects to start a first-in-human clinical trial in 2014. The selection process from 32 promising product candidates of TG1050 was endorsed and approved by different panels of key opinion leaders in the viral hepatitis field. TG1050 is based on a non-replicative Adenovirus 5 vector that encodes three HBV (Hepatitis B Virus) antigens or related domains. The clinical candidate has demonstrated potent immunogenicity in pre-clinical mouse models as well as genetic stability. Immunogenic properties include induction of potent, multi-specific, functional and cross-reactive T cell responses, including both cytokines production and in vivo cytolysis; all important characteristics that have been associated with viral clearance during natural infection.
• This presentation provided updated and more recent data that demonstrated the capacity of TG1050 to induce long-lasting HBV-specific memory T cells. Experiments in two murine models based on hepatic expression of the full length HBV genome, a HBV transgenic mouse model (University of Ulm) and a model using a recombinant adenovirus associated virus encoding HBV (AAV-HBV, Institute Pasteur) showed that a single injection of TG1050 had the capacity to educate HBV-specific functional T cells within a tolerant environment without inducing liver inflammation, whilst displaying antiviral activities, which were particularly shown in the AAV model.
• • On April 19, 2012, Transgene has announced that it has achieved pre-clinical proof of concept with a new therapeutic vaccine candidate, TG1050, aiming at treating chronic infection by the hepatitis B virus. Positive pre-clinical data supports further development of the product. These data include A Robust and broad immune (T cell) response in pre-clinical models after one or more injections; potent in vivo cytolysis against several epitopes; and genetic stability of the vaccine.  The product is expected to enter clinical development in 2014.

Is general: Yes