A flexible, cost-effective,
targeted protein degradation platform.
Aptadegrad enables the rapid discovery of novel degraders tailored for the degradation of targeted proteins.
Rapid development of new degraders
Flexible and compatible with different molecules
A new way of treating diseases
Aptadegrad is a flexible, cost-effective platform developed for the discovery of novel compounds (protein degraders), based on the combination of an aptamer (as a warhead against the protein of interest) and a degrader, that harnesses protein degradation pathways within the cells.
A platform for the discovery of novel compounds
Rapid development of new degraders
The in vitro aptamers selection allows the rapid development of warheads, paving the way to address various types of diseases that currently are highly unmet clinical needs.
Flexible and compatible with different molecules
Our compounds can be tailored by a) changing the warhead to target intra-, extracellular or membrane proteins or b) by shifting the degrader tail to trigger the lysosomal or the proteasomal degradation pathway.
Reduce costs and logistic constraints
Non-biological manufacturing of both the chemical degraders and the warheads avoids high costs and greatly reduces logistics constraints.
Advantages of Targeted Protein Degradation
- The compound does not need to reach functional regions of a given target; it just needs to reach it to unleash the cell machinery to degrade the whole protein.
- Degradation induces slower kinetics, thus enabling a moderate, dose-dependent and reversible effect.
- Absence of hypersensitivity reactions (such as cytokine-release reactions).
- Low immunogenicity avoiding issues from anti-drug antibodies (ADAs) formation after repeated mAbs administration.
- Avoid undesired effects of other blocking approaches with mAbs.
Mechanism of Action
1. TPD System for specific Recognition of POI
2. Mechanisms
of internalization
3. Mechanisms
of Degradation
Platform building-blocks
In vitro selection of highly specific warheads against proteins in the intracellular, extracellular space or membrane proteins.
Chemical techniques for the development of small molecule protein degraders and their conjugation with the aptamers.
Cutting-edge in-vitro assays to assess the internalization, induced degradation, safety and mechanism of action of the compounds.
Advanced in-silico methodology for compound optimization.
Pipeline
| Type of degradation | Program/ indication | Targeted protein | Discovery | Lead optimization | Preclinical development | Phase 1 |
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| Extracellular | Ophthalmologic/ Dry Eye | MMP-9 |
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| Intracellular | Infection | SARS-CoV-2 Spike |
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| Membrane protein | Infection/ Oncology | CD47 |
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| Membrane protein | Oncology | CD44 |
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Aptamer
SELEX
Identification of single-stranded DNA aptamers. We perform in vitro followed by in vivo cell-SELEX to select cell-targeting DNA, highly specificity aptamers against a given target.
Aptamer
optimization
Using in vitro and in silico techniques we enhance the functionally and the bioavailability of the aptamers by including modifications at the 3’ and 5’
Linker
conjugation
We use chemical techniques for the optimal linker development and click chemistry techniques to conjugate the degraders, the linker and the ssDNA aptamers, ensuring the optimal performance of the candidates.
Custom
developments
we can help academia researchers, non-profit research centres and biopharma companies to develop their degraders candidate from the discovery and lead optimization phases to the in vivo preclinical studies.
Binding assays
Degraders-protein equilibrium-binding affinity (Kd) with the target is assessed by cell-based binding assays with flow cytometry. Moreover, the quantitative evaluation of the interactions between the degraders and the targets is evaluated through SPR.
Internalisation studies
The binding and intracellular fate of the warheads/degraders against the target is monitored by confocal microscopy to evaluate degradation pathway. The cellular distribution of the compound is be determined by colocalization experiments.
Degradation assays
The degradation is evaluated by quantitative immuno-PCR on formaldehyde-fixed non-permeabilized cells, western blot and luminescence. Parameters such as degradation rate, maximum degradation, DC50 and/or protein recovery are assessed.
