Product Pipeline / NOVOTARG

The CD20/CD95 bispecific antibody

Promising candidate for the treatment of B-cell malignancies.

Novotarg is Baliopharm`s lead bispecific antibody targeting CD20 and CD95. CD20 is an established target antigen for antibody-based immunotherapy in cancer (like lymphoma) and B-cell mediated autoimmune disease. CD95, also called “death receptor” induces apoptosis. However, the use of monospecific CD95 antibodies is associated with significant off-target toxicity. Therefore, CD95 mediated apoptosis should be induced only in cells expressing CD20. This can be achieved by using bispecific antibodies recognizing CD20 and inducing CD95 apoptosis only after initial interaction with the target antigen.

The bispecific antibody for the first in vitro and in vivo studies was produced by chemical hybridization of fragmental parental CD20 and CD95 antibodies. In in vitro studies, CD20xCD95 bispecific antibodies have been shown to selectively trigger the CD95 death receptor and kill CD20 positive SKW lymphoma cells. In vivo, the growth of human SKW lymphoma cells was markedly suppressed by the bispecific antibody in a nude mouse tumor model. In contrast, cell culture experiments have shown that the bispecific antibody exhibits no toxicity towards cultured CD95 sensitive cell lines, including normal human hepatocytes.

Baliopharm has developed a process for the efficient manufacturing of Novotarg and used this molecule for proof of concept studies in marmorsets, where both safety and efficacy in MS has been shown.

Moreover, Baliopharm has in-licensed a platform technology to design bispecific antibodies which will allow the generation of superior antibody therapeutics by increasing the selectivity for the respective targets with the aim to increase efficacy and safety. The bispecific concept is also applicable to a variety of different target antigens, such as CD19, CD40, tenascin and NG2 and is protected by a granted patent.

Scientific publications

1.    A Recombinant Bispecific CD20×CD95 Antibody With Superior Activity Against Normal and Malignant B-cells. Nalivaiko K, Hofmann M, Kober K, Teichweyde N, Krammer P, Rammensee HG, Grosse-Hovest L, Jung G. Mol Ther. 2016 Feb; 24(2): 298–305.
2.    Construction of optimized bispecific antibodies for selective activation of the death receptor CD95. Herrmann T, Grosse-Hovest L, Otz T, Krammer PH, Rammensee HG, Jung G. Cancer Res. 2008 Feb 15;68(4):1221-7.
3.    Target cell-restricted triggering of the CD95 (APO-1/Fas) death receptor with bispecific antibody fragments. Jung G, Grosse-Hovest L, Krammer PH, Rammensee HG. Cancer Res. 2001 Mar 1;61(5):1846-8.