We use PASylation® — a powerful approach to design synthetic drugs with fine-tuned pharmacologic and pharmacokinetic properties to create promising disease-modifying therapies
We use PASylation® a proprietary and powerful chemistry platform to design novel long-acting peptides with fine-tuned pharmacologic and pharmacokinetic properties to create promising therapeutics for multiple chronic diseases.
The Prior Technology Hurdle: Previous attempts at using our target peptides as therapeutics for chronic diseases have failed for a multitude of reasons. In some cases, existing technology couldn't overcome the inherent limitation of their heir short plasma half-lives. In other cases, the synthetic poly ethylene gycole (PEG) polymers resulted in tissue accumulation and damage, anti-drug antibodies, or dangerous immune responses.
Our Novel Approach and Solution: Starting with native peptides that have existing pre-clinical and clinical data supporting their potential use as a therapeutic for chronic diseases, we apply our proprietary PASylation® platform to develop long-acting synthetic analogs with fine-tuned pharmacologic and pharmacokinetic properties to create promising therapeutics across multiple chronic diseases.
This approach allows us to:
1. Extend the natural half-life of selected peptide hormones from minutes to a week (or longer) without materially impacting the hormone’s pharmacological activity by maintaining the native peptide amino-acid sequence and structure.
2. Optimize the pharmacokinetics of the peptide so that a once-weekly (or longer interval) dosing schedule will provide circulating plasma levels within the optimal therapeutic range for safe and effective treatment.
3. Expand the use of the selected peptide hormones outside of the acute care setting as a potential continuous therapy for multiple chronic diseases through multiple delivery methods (e.g., subcutaneous injection, inhaled, IV infusion).
4. De-risk the pre-clinical and clinical development of the therapeutic to get our therapeutics into the clinic as quickly and as cost-effectively as possible.
PASylation is the genetic fusion with conformationally disordered polypeptide sequences composed of the amino acids Pro, Ala, and/or Ser (‘PASylation’). PASylation provides a simple way to attach a solvated random chain with large hydrodynamic volume to the protein of biopharmaceutical interest. This amino acid string adopts a bulky random coil structure, which significantly increases the size of the resulting fusion protein. By this means the typically rapid clearance of the biologically active component via kidney filtration is retarded by 1-2 orders of magnitude.
PASylation™ was designed to be a chemically-defined, non-immunogenic, non-toxic, biodegradable alternative to PEGylation with similar biophysical properties in terms of those increasing water solubility and half-life.
XL-protein’s proprietary PASylation® technology also provides for a strong patent protection. It is patented worldwide by two patent families, including patents issued in Europe, the United States, Japan as well as several other countries and territories.
XL-protein® and PASylation® are registered trademarks of XL-protein GmbH.
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