Establishing GMP manufacturing of a complex drug such as Atu027 is a major step forward in the product's development and potential out-licensing.
Atu027 is a siRNA based anti-cancer drug that is on track to enter initial clinical trials in the first half of 2007.
SR Pharma's drugs are based on RNA interference (RNAi), a natural selective process for turning off genes, which holds great potential in its ability to treat disease at the genetic level.
In contrast to other classes of therapeutics such as proteins, antibodies and small molecules, RNAi requires neither "drugable" domains on the molecular target (e.g. kinase domains) nor specific locations at the cell membrane or extra-cellular.
RNAi is triggered by siRNA (short interfering RNA) molecules that engage a group of cellular proteins, known as RISC (RNA induced silencing complex).
RISC guides the siRNA to its target mRNA (messenger RNA) by complementary base pairing and breaks it up in a selective fashion, thus halting protein expression or viral replication.
To achieve systemic delivery of siRNA, SR Pharma has developed a liposomal delivery system, called AtuPLEX, which consists of a cationic lipid, that introduces the therapeutic siRNA molecule into mammalian cells, and a fusiogenic lipid that allows the escape of the siRNA from the endosomal/lysomal compartment inside the cytoplasm of the cells.
Genzyme Pharmaceuticals, a US manufacturer of liposomal products, has successfully completed the GMP production of the two main components of the delivery system for Atu027, namely the cationic lipid AtuFECT and the fusiogenic lipid.
German based oligonucleotide manufacturer BioSpring is conducting the GMP standard manufacturing of the proprietary siRNA molecules that are the main active ingredients of Atu027.
Formulation specialist OctoPlus will scale up the GMP formulation of the component ingredients within Atu027.
In combination, these suppliers will provide product for the forthcoming pharmacokinetic and toxicology studies as well as the planned clinical studies.
"Atugen is rapidly moving forward towards testing the clinical applications of Atu027 and towards delivering some potential commercial out-licensing applications for its drug delivery system AtuPLEX," said Iain Ross, SR Pharma executive chairman.
"Consultation with the German regulatory agency for drug approval (BfArM) will be held shortly to define the final steps before entering the clinic with Atu027."
Completion of the pre-clinical trials of Atu027 later this year will provide the basis for the company to progress third party out-licensing deals for the general RNAi delivery system used in Atu027 as well as permitting SR Pharma to start the first phase I clinical trial of Atu027 during the first half of 2007.