Abstract 477: The Nanoprimer: Overcoming the liver challenge to increase the efficacy of IV-administered biologic therapies

Abstract Despite progress in the design of therapies administered by intravenous (IV) route, the liver remains one of the main challenges for treatment delivery. The hepatic clearance is responsible for the low delivery of treatment to the target site and the limited efficacy outcome. Moreover, the unintended liver distribution could cause harmful side effects. Curadigm’s innovative Nanoprimer technology aims to shift the balance of therapeutic agents’ bioavailability and toxicity. The platform is designed to decrease therapeutic agents’ liver trapping, to increase their systemic bioavailability for optimal accumulation in target tissues. This technology has the potential to redefine the benefit/risk ratio of drugs, improving their clinical outcomes and treatment value. The Nanoprimer is an engineered, biocompatible liposome that transiently and specifically occupies the liver clearance pathways responsible for sub-optimal therapeutic bioavailability. The Nanoprimer is administered just before the treatment. By interacting specifically with the receptors of the mononuclear phagocytic system cells, the Nanoprimer enables a temporary reduction of the drug clearance. Multiple proofs of concept were realized, showing the ability of the Nanoprimer to improve the efficacy of different natures of treatments including nanomedicines such as irinotecan-loaded liposomes and nucleic acid-loaded lipid nanoparticles in various therapeutic areas. Evaluation of the Nanoprimer has now been extended to biologic therapies: - Protein-based therapy: E. Coli asparaginase is used to treat Acute Lymphoblastic Leukemia (ALL). This protein depletes asparagine from the blood leading to tumor cell death since they are not able to synthetize this amino acid contrary to healthy cells. Bioavailability evaluation performed on a mouse model showed that the Nanoprimer increases by 3-fold the systemic bioavailability of the asparaginase. Adding the Nanoprimer in ALL treatments could allow a decrease of the number of asparaginase injections, potentially reducing the related toxicity for the same efficacy. - Oncolytic viruses: The use of oncolytic viruses by IV route is highly limited by the liver that removes up to 90% of the administered dose. In a collaborative study, we evaluated the impact of the Nanoprimer on the biodistribution of a herpes simplex virus-1 in a mouse model xenografted with a B-16 tumor model. The addition of the Nanoprimer led to a 10-fold increase in the viral copy number in the tumor, opening perspectives for cancer treatment by IV route administered oncolytic viruses. Altogether these data demonstrate that the ubiquitous mode of action of the Nanoprimer allows its application to a broad spectrum of drugs ranging from nanomedicine to biologic therapies. Citation Format: matthieu Germain, Julie Devalliere, Laurence Poul, Maxime Bergere, Francis Mpambani, Andromeda Savari. The Nanoprimer: Overcoming the liver challenge to increase the efficacy of IV-administered biologic therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 477.