Clinical Strategy

For initial clinical development, we are focused on the treatment of triple-negative-breast cancer (TNBC) as first indication. Most preclinical data was obtained for TNBCs and GMP manufacturing for first drug candidates was initiated.

Our goal is to extend our target indications to other cancer types and viral infections.

First indication for Peptide-siRNA-Prodrug technology is triple negative breast cancer (TNBC), since there is a tremendous medical need. Especially peripheral small metastases in the liver are complicated to treat by surgery and can be difficult to target by standard-of-care treatments. Therefore, XNApharma aimes to develop a therapeutic strategy to reduce metastases growth via a gentle oligonucleotide-based treatment.

The first generation candidates (XN001) will require a lipid-nanoparticle-formulation (LND), whereas XN101 generation drug candidates will contain a molecular delivery compound. Molecular delivery will massively reduce GMP-production timelines and will increase API stability as well as bioavailability.

BianoGMP - a CDMO for oligonucleotides - and XNApharma share the same founders and are located side by side. Hence, very early in the development of drug candidates, manufacturing aspects have been included. This makes GMP development short, easy, cost effective and scalable for later clinical stages.

GMP development for the first candidates was already initiated; formulation process as well as Fill&Finish is planned. Since Lipid-Nanoparticle-Fomulation (LNP) limits stablility of the drug product and biodistribution, manufacturing of Peptide-siRNAs carrying a coupled ligand could be beneficial and is under current development.

Oligonucleotides have a high therapeutic potential for the treatment of various diseases including cancer and metabolic diseases. The major hurdle of oligonucleotide applications is their biodistribution and intracellular delivery after intravenious injection. Although using particle based delivery, for example LNPs, most of the oligonucleotide based drugs were delivered into the liver, however, only trace amounts of drug substance arrive in cancerous tissue. Overdosing in order to reach peripheral (tumor) tissue leads to liver overload and induces side effects. By using Peptide-siRNA-Prodrug, these side effects can be massively reduced. XNApharma is open for collaborations to optimize the toxicity profile of established third party siRNA drug candidates.