From cells to therapeuticsvivalis. Humalex Fully human antibody discovery platform An integrated therapeutic development offering

Transcription

1 From cells to therapeuticsvivalis Humalex Fully human antibody discovery platform An integrated therapeutic development offering

2 Humalex from bench-top to clinical development The Humalex platform enables the discovery of naturally occurring, fully human therapeutic antibodies The platform has its foundations on the principle that humans spontaneously and naturally develop humoral immune responses, particularly antibody expression, against exogenous or selfantigens. Based on a well known technology, the Humalex platform has been optimized to immortalize human B-lymphocytes producing these antibodies from the peripheral blood of a person producing antibodies against a target of interest. This process can now be effectively used to develop new therapeutic antibodies.

3 EBV immortalization: Humalex technology Classical methodology It is well known that mammals produce antibodies against invading or non-self agents. The isolation of antibodies from a person exposed to or recovering from a disease, either self (eg. inflamatory diseases) or infectious, has been well established. These individuals have developed a humoral immune response (B-lymphocytes secreting antibodies) against their specific condition. For over 30 years, the Epstein-Barr Virus (EBV) has been used to immortalize human B-cells in hopes of accelerating antibody production, yet convincing results in developing a therapeutic using this method has been limited. The likelihood of finding monoclonal antibodies of interest using this method is very low. Using the classical method requires more than 10 immortalization experiments to obtain one monoclonal antibody. Compounded by the fact that one experiment requires six months to perform, a full-scale development program could take several years. Hence, this method has all but been abandoned as a useful tool for monoclonal antibody discovery. Humalex breakthrough Despite the inefficiencies of using EBV, multiple experts agree that the EBV immortalization approach could lead to high quality, human monoclonal antibodies since they have been isolated from those exposed to disease itself. The Humalex platform solves the challenge of scalability of using EBV. This has been achieved through targeting the CD40 receptor found on B-lymphocytes. CD40, a cell surface receptor and member of the tumor necrosis factor (TNF) family of receptors, when activated, enhances the level of B-lymphocyte antibody expression. Resulting antibody yields using the Humalex platform are significantly increased up to 400 times over the classical method. Using only 50 ml of blood from an exposed patient, the Humalex platform is able to immortalize a high number of human B-lymphocytes of interest makink the EBV methodology suitable for industry level discovery research. Humalex antibody discovery Blood collection B-cell isolation CD40-mediated activation EBV immortalization Screening and cloning The Humalex platform generates antibodies similar to native antibodies from individuals exposed to or recovering from a disease. This allows: Minimizing the risk of side effects and loss of efficacy linked to immune responses directed toward non-human sequences contained by therapeutic antibodies generated by other methods, such as the human anti-mouse antibody (HAMA) response associated with murine species Reduction in cross reactivity Obtaining highly active antibodies against infectious disease targets, particularly when the antibodies are generated from an individual who has recovered from a related pathology.

4 A fully integrated offering Vivalis offers the Humalex human antibody discovery platform for interested partners engaged in antibody drug development. Along with the Humalex platform, Vivalis provides a full portfolio of technologies for antibody drug development. From discovery, clone generation, and up through Phase II production, Vivalis provides a full portfolio of antibody discovery and production capabilities in the human antibody therapeutic field. The EB66 cell line, which naturally enhances the ADCC activity of monoclonal antibodies, is a complementary platform for oncology and anti-infective based antibodies. Derived from avian embryonic stem cells, the EB66 cell line was isolated and characterized under highly stringent conditions to assure industrial robustness, stability, and safety. Clone development, cell banking and GMP production in EB66 -based clones is provided by Vivalis under a variety of contractual and partnering arrangements. Now in use by over 25 commercial partners, the EB66 cell line continues to grow in world-wide industrial acceptance. In addition to the EB66 platform, clone generation and GMP production services using the CHO cell line are also available. Using classical methodologies that have been established by the industry for over 20 years, Vivalis offers CHO-based services under standard contract manufacturing agreements.

5 Humalex technology advantages Through the establishment of close collaborations with the French Blood Institute, Vivalis has the capability to identify healthy donors or patients with many different diseases whose blood contains antibodies directed toward a targeted antigen. The Humalex platform enables natural antigen processing by the human immune system. Humalex antibody generation results in a large number of human monoclonal antibodies directed against the selected antigen(s), highly improving on traditional EBV based technologies. In contrast to competitive technologies, Humalex antibody generation does not require any molecular changes to the antibody structure, such as isotype switching or somatic hypermutations. Using the Humalex platform significantly reduces preclinical costs and timelines while increasing the likelihood of success through selecting from a large panel of antibodies, in their final configuration, best suited for therapeutic applications. The Humalex platform can be applied to multiple therapeutic areas, such as inflammation, hematological disorders, infectious disease, and other conditions where B-lymphocyte antibody production is stimulated and active monoclonal antibodies result. Antibodies produced using Humalex technology can be from the entire human repertoire, derived from naive and memory B-lymphocytes, and isolated from both blood and tissue. Humalex monoclonal antibodies are not restricted to any one class or sub-class. IgM s, IgA s, IgG s, and IgE s are all produced, thus allowing the development of antibody therapeutics where a particular isotype might be preferred.

6 From cells to therapeuticsvivalis Campus Bio-ouest 6, rue Alain-Bombard Saint-Herblain cedex Nantes France Tel +33 (0) Fax +33 (0) About us Vivalis is combining two of its proprietary biopharmaceutical platforms with in-house cgmp manufacturing into a fully integrated, monoclonal antibody discovery and development offering. Pending client requirements, Vivalis is able to provide: New fully human monoclonal antibodies directed toward specific targets using the Humalex antibody discovery platform, Characterization of these newly discovered antibodies, Establishment of stable producer cell lines in either Vivalis EB66 ADCC enhancing avian cell line or CHO, Process development services, Manufacture under cgmp both preclinical or clinical materials (up to Phase II) in an inspected cgmp facility. Financial terms for licensing Vivalis technologies model best practices used in industry, which include upfront and milestone payments, royalties on net-sales, and fees for work performed under contractual service agreements. Contact Europe Philippe Guillot-Chêne guillotchene@humalys.com Asia Pierre Miniou pierreminiou@vivalis.com North America Frederic Legros fredericlegros@vivalis.com