Vect-Horus has a clinical-phase solution to a key drug development challenge: crossing the blood–brain barrier (BBB). By targeting receptors on the barrier, Vect-Horus is empowering partners such as Novo Nordisk and Ionis Pharmaceuticals to transport drugs into organs including the brain and improve the treatment of diseases of the central nervous system (CNS).
The BBB protects the brain from toxins and pathogens but also stops 98% of small molecules and almost 100% of large molecules from accessing targets in the CNS. Drug developers are becoming increasingly interested in crossing the barrier as they are discovering molecules that could transform the treatment of chronic neurodegenerative conditions, such as Alzheimer’s disease, providing they can enter the CNS.
Designing ligands to cross the BBB
Researchers have proposed a range of solutions, and receptor-mediated transport (RMT) is now widely regarded as “one of the most efficient and safest routes to shuttle drugs into the brain,” according to Michel Khrestchatisky, director of research at the French National Centre for Scientific Research (CNRS), who co-founded Vect-Horus with Alexandre Tokay, CEO.
Strategies that fully open the BBB allow toxins and pathogens to enter the brain. By contrast, RMT allows a drug to reach the brain while preserving the integrity of the BBB; this selective crossing of the barrier is enabled by targeting endogenous BBB receptors that transport nutrients into the brain.
For the past 20 years, Vect-Horus has built a portfolio of ligands that bind to BBB receptors using its VECTrans technology. This platform supports the discovery and design of innovative vectors that facilitate the delivery of drugs or imaging agents into organs, particularly the CNS but also diseased tissues such as tumors (Fig. 1).
Fig. 1 | The VECTrans technology. The peptide or VHH based vectors can be conjugated to various classes of therapeutic/imaging agents, including small molecules (e.g. chelating agents), peptides, oligonucleotides (e.g. siRNA, ASO), proteins, antibodies (e.g. mAb), and LNPs. ASO, antisense oligonucleotide; mAb, monoclonal antibody; LNP, lipid nanoparticle; siRNA, small interfering RNA.
Vect-Horus has used its early-mover advantage in the RMT space to create and optimize industry-leading libraries of ligands capable of carrying a wide variety of drug molecules to the brain and other organs.
The company has applied its deep expertise in medicinal chemistry-based peptide optimization to one of its peptide-based ligands. Peptides have a lower molecular weight than the antibodies that other companies use to cross the BBB. The weight difference—1 kilodalton for a peptide versus up to 150 kilodaltons for an antibody—means that ligands are cheaper to make, have lower immunogenicity and better penetrate tissues.
However, antibodies can target different BBB receptors than peptides. Vect-Horus is unlocking these opportunities by developing antibody fragments known as VHHs that are derived from heavy chain-only camelid antibodies. Using state-of-the-art molecular biology techniques, the company has built VHH libraries to engage targets such as the transferrin receptor while retaining a size advantage over conventional antibodies.
The peptide and VHH libraries reflect Vect-Horus’ commitment to looking beyond the receptors that are best known by the research community and its focus on creating more specific ligands that do not bind to tissues outside the target organ.
Partnering to validate BBB technology
Vect-Horus has established proof-of-concept in animals, showing that its ligands can deliver small molecules, peptides, oligonucleotides and large biomolecules including antibodies across the BBB. The studies have supported projects including a co-development program with the US-based biotech RadioMedix.
Working with RadioMedix, Vect-Horus is evaluating, in early clinical trials, a theranostic agent that uses VECTrans to target the low-density lipoprotein receptor (LDLR). The receptor is overexpressed in glioblastoma multiforme—a type of brain tumor—and pancreatic cancer. By using a radiotracer to detect cells that express LDLR, the collaborators could identify patients suitable for treatment with a therapeutic version of the product.
Vect-Horus’ alliance with RadioMedix is one of more than 10 collaborations between the BBB specialist and pharma and biotech companies. Novo Nordisk has an exclusive global license to use VECTrans to deliver cargo directed against specified targets. Ionis has secured an exclusive global license for delivering RNA-targeted therapies to the CNS using VECTrans. And another biotech has an option on Vect-Horus’ technology. These agreements generate revenues that implement the company’s platform and its development programs.
The agreements are part of Vect-Horus’ business model. As well as using VECTrans for in-house and co-development projects, Vect-Horus “conjugates pharma and biotech companies’ therapeutic agents to our vectors to show proof-of-concept in animal models,” according to Jamal Temsamani, CBO at Vect-Horus. The success of such studies has led to exclusive licenses for the VECTrans technology.
Vect-Horus is now in talks with other pharma and biotech companies. The interest reflects the breadth, optimization and validation of Vect-Horus’ ligand libraries. Leveraging those differentiated capabilities, the company is enabling partners to bypass the BBB and overcome a major obstacle to the development of life-changing treatments for diseases of the CNS.