What are
VHHs?
The science behind VHH antibodies.
VHH Antibodies
VHHs are a lot like antibodies but smaller, simpler, and more robust.
Originally isolated from camelid species in the 1990s, these proteins represent the antigen binding region (VH domain) of a Heavy chain-only antibody.
Some VHHs were trademarked as “nanobodies” by the company Ablynx in 2003, who also launched the first FDA-approved VHH drug, caplacizumab.
These early drugs were discovered using llama immunisations, but at Isogenica we mine our Synthetic VHH Libraries for pre-humanised leads using well-characterised, pre-defined frameworks.
VHH Features
At around 10% of the size of a traditional monoclonal antibody, VHHs display the same highly sensitive and specific binding. Because all this binding is concentrated into a single protein unit, they are very simple proteins – easy to make rapidly from microbial or mammalian systems.
Unlike full-length antibodies, they do not naturally form pairs and prefer to exist in a monomeric, soluble form – ideal for therapeutics manufacture.
They are also not associated with complex immune modulatory functions which some full IgG therapies suffer from.
The big reason that Isogenica sees VHHs as special is their flexibility. Because of their simplicity, they can easily link to other biomolecules, including other VHHs, for numerous applications.
With a decade of synthetic VHH discovery campaigns under our belt, Isogenica is building on this expertise to develop internal drug assets for oncology. To explore the many different therapeutic and diagnostic uses for VHHs, including Isogenica’s multi-specifics pipeline, check out our applications pages, and for answers to FAQs on VHHs.
VHH in the Clinic
VHH single domains are one of the most accepted next generation antibody therapeutic formats.
Cablivi (caplacizumab) was the first FDA-approved single domain antibody therapeutic in 2019.
So far, VHH are being developed as:
- Monomers
- Bi-specifics
- Half-life extended
- CAR formats
| Drug | Sponsor | Domain Properties | Target | Indication | Status |
| Caplacizumab | Sanofi (Ablynx) | VHH | vWF | aTTP | Approved |
| LCAR-B38M | Legend/Janssen | Bi-paratopic VHH CAR-T | BCMA | Multiple Myeloma | Approved |
| Ozoralizumab | Taisho (Ablynx) | VHH | TNF | RA | Approved |
| Gefurulima | Alexion | VHH | C5 | Myasthenia | Phase III |
| M1095 | Moonlake Immun | VHH Bi-specific | IL-17A IL-17F | Psoriasis | Phase IIb |
| BI836880 | Boehringer Ingelheim (Ablynx) | VHH Bi-specific | VEGF, Ang2 | NSCLC | Phase II |
| HPN328 | Harpoon | VHH-scFc Tri-specific | DLL3 | SCLC | Phase II |
Isogenica ISOXTEND® half-life extension for biotherapeutics
Our VHH-based ISOXTEND® technology protects biotherapeutics from kidney clearance by ‘piggybacking’ onto the serum albumin endocytic recycling pathway, significantly extending therapeutic half-life.
