Israeli firm Prolor Biotech has negotiated an exclusive license to a technology known as Reversible PEGylation, developed at the Weizmann Institute of Science. The agreement, brokered through Weizmann’s technology transfer and commercialization arm Yeda Research and Development, builds on an existing deal through which Prolor has been developing a preclinical-stage long-acting oxyntomodulin anti- obesity candidate that uses the Reversible PEGylation platform, under a limited option-to-license agreement.
The firm’s decision to exercise its license option means it can now also use the Reversible PEGylation technology for all therapeutic indications, except for applications in hemophila and the development of insulin products.
Reversible PEGylation has been developed to boost the half-life and biological activity of small molecule candidates as well as peptides and proteins. According to the Weizmann Institute, the technology addresses one of the drawbacks of PEGylating drugs, which is the tendency for the PEG polymers to block the active sites of the therapeutic molecule. In contrast, Reversible PEGylation attaches the PEG polymers to a protein drug using chain-like structures held in place by reversible chemical bonds that dissolve in the bloodstream, so the PEG molecules can detach from the therapeutic. Critically, these chains do not all dissolve at once, so the active protein is released in a slow, continuous, and predictable manner, which the scientists claim is an ideal way to provide a steady supply of the drug for optimal effect.
Prolor claims the Reversible PEGylation platform will complement its own core CTP technology, which is designed to extend the half-life of therapeutic proteins and peptides. The CTP approach uses a short, naturally occurring peptide derived from the human pregnancy hormone hCG, to slow the removal of therapeutic proteins from the body without increasing toxicity or altering the overall biological activity, Prolor claims.
Its CTP-based pipeline of long-acting therapeutics is headed by the early clinical-stage human growth hormone candidate hGH-CTP (MOD-4023). Phase II studies with hGH-CTP are ongoing in Europe, and during August 2010 FDA granted the firm clearance for a Phase II trial in the U.S. At that time Prolor stated that it was not planning to include U.S. sites in its Phase II study, but said the FDA clearance would help ensure it remained fully in sync with regulatory requirements in key territories, and would in addition allow it to utilize data from the European Phase II program with hGH-CTP as the basis for anticipated submission of applications to conduct Phase III trials in both the U.S. and Europe.
Prolor’s pipeline includes additional CTP-formulated products in preclinical development. These include: an interferon candidate IFN-β-CTP (MOD-9013); Factor VIIa-CTP (MOD-5023); an erythropoietin candidate EPO-CTP (MOD-7023); GLP-1-CTP (MOD-1001); and an obesity candidate OBES-CTP (MOD-1002).
Prolor and Merck & Co are both licensees of the CTP technology, which was developed at Washington University in St. Louis. Merck’s license covers use of the technology with FSH and three other fertility hormones. Prolor has exclusive rights to the CTP platform for all other therapeutic proteins and peptides.
During early 2010 the European regulatory authorities cleared Merck’s CTP-based drug ELONVA® (corifollitropin alfa injection), which is indicated for use in combination with a GnRH antagonist, to trigger controlled ovarian stimulation in women undergoing an assisted reproductive technology.