- Neuropilin-1 (NRP1), implicated in various pro-tumorigenic processes, is a promising therapeutic target for cancer treatment
- Secarna designed LNA-modified NRP1 specific antisense oligonucleotides (ASOs) that effectively knockdown target gene expression, resulting in increased survival and reduced tumor size in animal tumor models
- Further improvement was achieved in combination with immune checkpoint inhibitors
Munich/Martinsried, Germany, November 3, 2023 – Secarna Pharmaceuticals GmbH & Co. KG (“Secarna”), a biopharmaceutical company focusing on the discovery and development of next-generation antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets via its LNAplus platform, presented data demonstrating the potential of Secarna’s third-generation ASOs to target Neuropilin-1 (NRP1), a promising therapeutic target for the treatment of cancer. The data were presented at The Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting & Pre-Conference Programs (SITC 2023) in San Diegowhich took place November 1 – 5, 2023.
“NRP1 is a promising new target with multiple pro-tumorigenic roles mediated by separate domains. As our LNA-modified ASOs potently reduce the expression of NRP1, all of these functions will be suppressed simultaneously. The compelling results presented at SITC demonstrate that ASOs are a promising therapeutic modality that may overcome the limitations faced by alternative approaches that can only block an individual domain,” said Frank Jaschinski, PhD, Chief Scientific Officer of Secarna Pharmaceuticals. “Given in combination, these ASOs further enhance the effect of immune checkpoint inhibitors, which are considered to be a breakthrough in cancer therapy.”
The poster: Knockdown of Neuropilin-1 by third generation antisense oligonucleotides has strong antitumor activity that can be further increased by combination with immune checkpoint inhibitors, was presented by Frank Jaschinski, PhD. Using the Company’s in-house Oligofyer™ system, Secarna designed locked nucleic acid (LNA) modified ASOs specifically targeting NRP1. NRP1 is a membrane bound multi-domain protein, which has been implicated in various pro-tumorigenic processes, including stability of regulatory T-cells, exhaustion of CD8+ T-cells, macrophage migration and polarization, as well as neovascularization. The most potent candidates were selected through cellular screens and then administered in immune-competent cancer mouse models (syngeneic mouse models) by systemic administration. A strong reduction of NRP1 levels was observed in relevant cell types within the tumor microenvironment and in plasma. Furthermore, a striking suppression of tumor growth rates was achieved, concomitantly with an increased survival rate. Additionally, in many animals, complete and durable tumor eradication and was seen in combination with an antibody targeting the the immune checkpoint inhibitor PD-L1. Re-challenge experiments with mice that were tumor-free after treatment indicated the establishment of anti-tumor immunity in treated mice.
Secarna is currently planning studies to further delineate the proposed antitumor mechanisms of the NRP1 ASOs by spatial analysis of the tumor microenvironment.
About Secarna’s proprietary drug discovery and development platform, LNAplus
Secarna’s proprietary, customized LNAplus platform is being applied to the discovery, testing and selection of antisense oligonucleotides (ASOs) for pre-clinical and clinical development. LNAplus encompasses all aspects of drug discovery and pre-clinical development and has proven to be fast, reliable, scalable and efficient, enabling the discovery of novel antisense-based therapies for challenging or currently undruggable targets. This platform includes the powerful proprietary Oligofyer™ bioinformatics system, a streamlined, high efficiency screening process, including Secarna’s proprietary LNA-Vit(r)ox™ safety test system, as well as target-specific functional assays. Secarna’s platform and ASOs have been validated by numerous in-house projects as well as in several academic and industry collaborations.
About Secarna Pharmaceuticals GmbH & Co. KG
Secarna Pharmaceuticals is the leading independent European next-generation antisense drug discovery and development company addressing high unmet medical needs in immuno-oncology and immunology, as well as viral, neurodegenerative and cardiometabolic diseases. Secarna’s mission is to maximize the performance and output of its proprietary LNAplus antisense oligonucleotide discovery platform, as well as to develop highly specific, safe, and efficacious best-in-class antisense therapies. With over 20 discovery and development programs, including both proprietary pipeline projects and partnered programs, Secarna focuses on targets in indications where antisense-based approaches have clear potential benefits over other therapeutic modalities. www.secarna.com
