Precision Targeting Technology
Protein Engineering Expertise
Navigo Proteins’ Precision Targeting unit leverages its protein engineering expertise to create proprietary Affilin® molecules, harnessed to create optimized, next generation biopharmaceutical drugs in numerous fields of use.
Navigo Proteins’ Affilin® platform benefits from the inherent engineerability, stability, safety, and ease of manufacturability. Our Precision Targeting unit comprises a versatile toolbox to custom-build selective biotherapeutic drug candidates, tailored in a flexible, modular fashion, to combine optimized selectivity, effector functions, and adjustable serum half-life.
Currently, our Affilin® molecules are being developed as protein-drug conjugates (alternatives to antibody-drug-conjugates, ADCs). Other developmental areas include Affilin® molecules as CAR-T ligands, multi-specific affinity ligands, including bispecific antibodies, radiotherapeutics, or theranostics concepts (using the same affinity ligand with different payloads for diagnostic and therapeutic purposes).
Our development projects are mainly based on collaborative efforts but can also be direct service projects. We have also developed a few of our own Affilin® pipeline candidates, mainly against solid tumors markers. For further details, please contact us.
Precision Targeting – Proprietary Affilin® Molecules for Next-Generation Biopharmaceutical Drugs
Scaffold and Advantages
Navigo’s Affilin® molecules are based on human Ubiquitin which satisfies all the pre-requisites of an ideal scaffold-protein for designing next generation biotherapeutics.
1. Ubiquitin is a natural protein of human origin (non-immunogenic).
2. It is small (76 amino acids, 8.5kDa), stable, and highly engineerable.
3. It is amenable to create large libraries of different Affilin® variants that bind the target of choice.
Read more to know the full potential of Affilin® molecules.
For decades, monoclonal antibodies (mAbs) have dominated the biotherapeutics field. Although a successful protein class in R&D and many current commercial products, mAbs come with a fair share of disadvantages including large size, complexity, inhomogeneity (glycosylation), limited engineerability, and a costly and time-consuming production process. The primary function of an antibody is to selectively bind to a specific target. This can be achieved equally well by much smaller proteins. Our Affilin® molecules are antibody-alternatives and overcome major obstacles in antibody development.
- ~1400 aa
- ~150 kDa
- Immunoglobulin fold
- 76 aa
- 8kDa
- β-Grasp fold
- ~1400 aa
- ~150 kDa
- Immunoglobulin fold
- 76 aa
- 8kDa
- β-Grasp fold
Ligand Discovery
We have implemented and over years continuously optimized, a powerful scaffold technology platform which yields high-quality Affilin® ligands against target structures of interest.Affilin® Libraries
High quality and diverse libraries are generated from the Ubiquitin-scaffold by randomization of several surface-exposed residues. Each randomized position can be substituted by any amino acids (except Cysteine) which leads to large combinatorial libraries with complexities of 1010 to 1012 different variants. Varying rationally selected Ubiquitin regions results in a range of Affilin® libraries which maximizes paratope diversity and yields varying Affilin® molecules binding to a given target structure.
Selection and Screening
During the subsequent selection process, both phage display and ribosome display technologies are employed. Our fully automated, robotics-assisted high-throughput screening (HTS) platform first identifies ligand-enriched selection pools. From the resulting ligand pools a rapid screening of more than 15,000 individual Affilin® molecules per day identifies a set of diverse Precision Targeting Affilin® candidates. Among those we select the most promising leads for further development.
Affilin® Characteristics
Human Serum Protein/Non-Immunogenic
Ubiquitin is a natural human protein, mostly known for its role in the intercellular protein degradation machinery. However, it is also a human serum protein and is evolutionarily conserved among mammalian species.
Our Affilin® therapeutics are thus expected to have no or low immunogenic potential in humans and can also be used directly in various pre-clinical animal models.
Size & Stability
Ubiquitin is a small serum protein of 76 amino acids and 8.5 kDa, roughly one twentieth of the size of an IgG1 antibody. It is a very stable, near-globular protein with a beta-grasp fold and high thermal and proteolytic stability. Affilin® molecules can be highly concentrated and remain soluble, non-aggregated over weeks even at 37°C.
Engineerability
Affilin® molecules can be easily combined to make multimers, multi-specifics or fused to monoclonal antibodies to make bi-specifics (Mabfilin™). By coupling them to other molecules like cytokines, fluorescent proteins or half-life extending moieties, the applicability of Navigo’s Affilin® toolbox is very broad. Envision these as modular protein building blocks. With this versatile toolbox, we can rapidly construct many biotherapeutic drug candidates, optimized for their task as protein-drug conjugates, radiopharmaceuticals, multi-specific affinity ligands, CAR-T ligands and more.
Selectivity
Affilin® molecules can readily be developed against a multitude of biologic targets which possess a defined 3D-structure. Typically, Affilin® ligands are designed to be extracellular molecules, but as an additional safety measure, they are also engineered such that they cannot not interfere with the cell’s internal ubiquitin machinery.
Affinity
Our selection and screening platform allows the identification of Affilin® ligands with a wide range of affinities, down to pM range, to carefully select those which are best suited for the intended application. If Affilin® ligands need higher specific binding affinity after screening, they are subjected to an additional maturation round. Another straight-forward approach is often a simple multimerization step.
Multi-Specificity
Affilin® ligands can be fused together to create modular multi-specific binders. Combined with optimized linkers, composition, and orientation, plus the optional addition of further effector modules, this yields molecules with custom-designed characteristics. They can also be easily fused to the heavy or light chains of any regular antibody to produce bispecific monoclonal antibodies.
Half-Life Adjustment
Affilin® molecules are small proteins (8.5 kDa) that are quickly eliminated from the bloodstream by renal clearance when administered intravenously. To extend and adjust the desired serum half-life and hence PK, our Affilin® toolbox contains different half-life modifying modules, which can flexibly be combined with any Affilin®.
Homogeneity
Ubiquitin contains neither cysteines nor any glycosylation sites, resulting in homogeneous products. Further, we can genetically fuse Targeted Carrier Domains (TCD) to Affilin® molecules, which contain pre-defined conjugation sites for drugs, chelators, toxins, markers, or dyes. These carrier domains can be coupled specifically with various payloads, such as drugs or chelators to yield a homogenous product with defined Affilin®-payload ratios.
Affilin® Production & Costs
Affilin® molecules, even modular or multimeric versions can routinely be produced as single chain proteins with good yields and purity, rapidly and cost-effectively in standard E. coli expression systems. If needed for other reasons, e.g., as Fc-fusions, Affilin® molecules can also readily and homogeneously be produced in mammalian, yeast, or insect cell expression systems.
IP
Navigo Proteins’ proprietary Affilin® platform and individual molecules are protected in over 100 granted patents and dozens of pending patent applications. Our assets are secured in all major markets. This provides our clients with a safe, undisputed IP protection and thus competitiveness and long-term planning security for any licensed Navigo products and technology.