Date: 2016-04-21
Type of information: Milestone
Compound: Nanobody® therapeutics
Company: Ablynx (Belgium) Boehringer Ingelheim (Germany)
Therapeutic area: Cancer Oncology - Immune diseases - Respiratory diseases
Type agreement: R&D
development
commercialisation
Action mechanism: Nanobodies are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies. The Nanobody technology was originally developed following the discovery that camelidae (camels and llamas) possess fully functional antibodies that lack light chains. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Importantly, the cloned and isolated VHH domain is a perfectly stable polypeptide harbouring the full antigen-binding capacity of the original heavy-chain antibody. These newly discovered VHH domains with their unique structural and functional properties form the basis of a new generation of therapeutic antibodies which Ablynx has named Nanobodies.
Disease: oncology, immunology, and respiratory diseases
Details: * On March 20, 2012, Ablynx has announced a two-year extension of the initial five-year research funding by Boehringer Ingelheim of their global strategic alliance to discover, develop and commercialise up to 10 different Nanobody® therapeutics. The extension which will run until September 2014, will allow all the existing ten Nanobody programmes to advance to a stage where Boehringer Ingelheim can potentially progress each programme into development.
In September 2007, Ablynx and Boehringer Ingelheim entered into a Strategic Alliance on the discovery, development and commercialisation of Nanobody therapeutics across a range of diseases, including oncology, immunology, and respiratory diseases. The agreement allows for potential milestone payments of up to €125 million plus royalties to Ablynx for each Nanobody which reaches market. Boehringer Ingelheim is exclusively responsible for the development, manufacturing and commercialisation of any products resulting from the collaboration. Ablynx retains certain co-promotion rights in Europe.
Financial terms: Ablynx will receive a total of €6.6 million in additional research funding from Boehringer Ingelheim, some of which will be in advance. This payment is in return for work carried out by Ablynx's specialist Nanobody scientists. Ablynx has already received over €58 million from payments under the Strategic Alliance since it was signed in 2007.
Latest news: * On April 21, 2016, Ablynx and Boehringer Ingelheim announced the initiation of a Phase I study to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of an anti-CX3CR1 Nanobody®, administered intravenously. The start of the study triggers a €8 million milestone payment to Ablynx and brings the total number of Nanobodies that are currently in clinical development, both within Ablynx and in collaboration with pharmaceutical partners, to seven. The anti-CX3CR1 Nanobody was discovered and developed as part of a long-standing Strategic Alliance between both parties and Ablynx is entitled to receive further milestones and royalties if the product proceeds through development and then to commercialisation. * On January 29, 2016, Ablynx announced that Boehringer Ingelheim has administered the first dose in a Phase I dose escalation study with the half-life extended bi-specific anti-VEGF/Ang2 Nanobody® in adult patients with advanced solid tumors, triggering an €8 million milestone payment to Ablynx. The aim of the study is to evaluate the safety profile and dosing schedule for this Nanobody. The anti-VEGF/Ang2 Nanobody was discovered and developed as part of the Strategic Alliance between both parties, signed in September 2007. This Nanobody 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 tumours.
The results from the pre-clinical study have been presented by Boehringer Ingelheim at the 8th Euro Global Summit on Cancer Therapy and demonstrated that this bi-specific Nanobody potently inhibits VEGF and Ang2 signalling 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.
