Earlier this week positive in vivo proof-of-mechanism data from the half-life extended bi-specific anti-VEGF/Ang2 Nanobody, was presented at the 8th Euro Global Summit on Cancer Therapy, taking place November 3 – 5, 2015 in Valencia, Spain.[1]

Monoclonal Antibodies or mAbs are monospecific.  As a result, they are only capable of interacting and interfering with just one, single, target. However, most complex diseases are multifactorial and involve redundant or synergistic action of disease mediators or upregulation of different receptors. This may involve crosstalk between their various signaling networks. To improve therapeutic efficacy, blockade of multiple, different pathological factors and pathways may be required. This can, in the most traditional way, be achieved by combining different drugs. However, alternatives to traditional combination therapies may involve dual targeting strategy by applying bispecific antibodies or bsAbs.[2]

Courtesy: 2015 © Ablynx.

Bispecific antibodies or bsAbs combine specificities of two unique antibodies, allowing them to  simultaneously address different antigens or epitopes.  With their ‘two-target’ functionality bsAbs are able to interfere with multiple surface receptors or ligands associated with a range of diseases, including cancer and hematological disorders. [3]

The anti-VEGF/Ang2 Nanobody was discovered and developed as part of the strategic alliance between Ablynx and Boehringer Ingelheim.

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Single-domain antibody fragments
Nanobodies® are a novel class of proprietary therapeutic proteins based on single-domain antibody fragments that contain the unique structural and functional properties of naturally-occurring heavy chain only antibodies.  The proprietary Nanobody platform technology developped by Ablynx  allows for the rapid generation and large-scale production of novel biological therapeutics that have potential in a wide range of human diseases.

The Nanobody being developed by Ablynx and Boehringer Ingelheim blocks both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2), important proteins which are involved in the formation of new blood vessels from pre-existing vessels (angiogenesis), a vital mechanism in the growth of tumors. Angiopoietin-2 (Ang2) is a vascular destabilizing factor that antagonises normalisation [3]

Bi-specific Nanobody potently inhibits VEGF and Ang2 signaling
The data was presented in a poster session by Boehringer Ingelheim on November 4, 2015. [1] The results from the pre-clinical study demonstrated that this bi-specific Nanobody potently inhibits VEGF and Ang2 signaling in multiple in vivo cancer models and strongly impairs proliferation and survival of human endothelial cells. In addition, the bi-specific Nanobody showed superior efficacy as compared to inhibition of the individual pathways by the reference monoclonal antibody drugs. The Nanobody was also found to be well tolerated in cynomolgus monkeys. 

These strong in vivo proof-of-mechanism results support the evaluation of this Nanobody in Phase I clinical studies.

 

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