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Araris - Antibody-Drug Conjugates (ADCs) Linker Technology
Araris Biotech AG, a spin-off company from the Paul Scherrer Institute (PSI) and ETH Zurich, is pioneering the development of a novel, proprietary antibody-drug conjugate (ADC)-linker technology. Our linker platform enables payload attachment to ‘off-the-shelf’ antibodies in one step without needing to re-engineer or reduce antibodies, resulting in highly homogenous, stable and potent ADC therapies.
ADCs consist of payloads connected to antibodies through a specific linker. The molecular design enables the highly selective delivery of any payload, often a potent anti-cancer drug, to the diseased tissue, while healthy parts of the human body are spared.
Problems of current ADC technologies:
- Poor stability and high heterogeneity: Poor connection of the drug to the antibody can lead to ADC instability, allowing the drug to break apart from the antibody prior to reaching the cancerous cells. It also creates ADCs with a wide range of payloads randomly attached, or a heterogeneous ADC pool, that cannot consistently deliver the same amount of drug. Poor ADC stability ultimately increases risk of unwanted side-effects and reduces efficacy.
- Limited linker solubility: Payloads are often hydrophobic and thus tend to induce ADC aggregation, or clumping together, in water-based solutions like blood. When ADCs clump together, they cannot bind to cancerous cells efficiently and have reduced efficacy.
- Expensive and time intensive development: Current ADC technologies involve complex engineering efforts and multi-step conjugation procedures that take up significant time and require substantial resources.
We are pioneering a proprietary peptide linker technology that will give us the ability to design and develop homogenous, stable, highly soluble and high-quality ADC products in a cost- and time-effective manner.
- Superior Design: Our linker technology enables site-specific payload attachment to a privileged attachment site on a specific amino acid (Q295) within the IgG-Fc framework. When a payload is attached to this site, the antibody still maintains nearly identical performance (e.g. pharmacokinetics and effector functions) to the unconjugated, original antibody. Furthermore, the linker-payload is connected to the antibody through a very strong peptide bond resulting in exceptional stability in the blood stream and therefore, avoidance of healthy tissue damage. However, once entering a cancer cell via antibody mediated internalization, the linker can be easily broken to release the payload and kill the cancer cell. All three of these properties are key factors to enable the most efficient payload delivery and maximum ADC efficacy.
- High linker solubility: Our linkers are hydrophilic, rendering them soluble in water-based solutions like blood. Improved solubility leads to decreased clumping, allowing the ADC to properly bind to cancerous cells without the need to further edit the antibody/payload structures.
- Simple manufacturing: We can generate ADCs in one step using “off-the-shelf” antibodies that are native or engineered. The process is fast, cost-efficient and can be easily upscaled without the need for custom antibody synthesis.