D-VITylation® Technology

Significance

Many potent and specific peptides are not viable therapies for patients due to their inherently short half-lives. To overcome this, a peptide must be injected several times per day, or delivered intravenously to see a therapeutic effect. Neither of these are feasible options for patients with a chronic disease. The poor pharmacokinetic properties of peptides are mainly due to rapid proteolysis upon injection or removal of the peptide from circulation by the kidney because of the small size of the peptide. Longer-acting versions of peptide-based drugs are clearly needed, and if developed, have the potential to be life-changing therapeutics for patients.

Approach

Extend Biosciences has a platform technology that harnesses the biology of vitamin D to prolong the half-life and enhance the absorption and bioavailability of peptides and proteins when delivered subcutaneously. Using our D-VITylation® technology, a derivative of vitamin D is covalently attached to the peptide or protein, and this can be done site-specifically. When the peptide-vitamin D conjugate is injected subcutaneously, it is recognized by the Vitamin D Binding Protein (VDBP), which naturally waits in the skin for sunlight to activate vitamin D. VDBP then actively transports the conjugate into circulation and carries it around for an extended period of time. This results in an extended half-life and improved absorption and bioavailability of the peptide.

Results

Proof-of-concept studies showed that attachment of this proprietary modification extends the half-life of peptides from minutes to hours in rats, which can translate to once weekly dosing in humans. D-VITylation has also been shown to improve the absorption and bioavailability of small, labile proteins when administered subcutaneously.

Research services using our D-VITylation technology are available for your peptide or protein. Contact us for more details.

Competitive Advantage

Typically, a large protein or PEG molecule is attached to a peptide or small protein to extend its half-life. However, with a small peptide, this large modification can significantly reduce the functional activity of the peptide. Improvement in pharmacokinetic properties can also be seen when peptides are modified such that they bind albumin or other stable albumin-like molecules. These types of conjugates can also suffer from reduced efficacy, or from sub-optimal pharmacokinetic characteristics. Notably, none of these modifications address the low subcutaneous bioavailability of peptides. Extend Biosciences’ modification is small and does not interfere with the activity of the peptide, and improves both half-life and bioavailability.

Use of this technology would reduce the amount of drug needed for injections, as well as the frequency of injections, and would allow for efficient subcutaneous administration. For patients, these attributes translate to an enhanced quality of life and a more patient-friendly drug that can be self-administered via an injector pen, improving compliance. For pharmaceutical companies, this broadly applicable technology can transform a lead peptide into a viable therapeutic drug, or can enable life cycle management via the creation of a novel composition of matter.