Secarna Pharmaceuticals publishes new data in Nucleic Acid Therapeutics showcasing strategies to detect and prevent immunostimulatory potential of LNA-modified ASOs

• Antisense oligonucleotides (ASOs) possess the potential to cause considerable immune stimulation via toll-like receptor 9 (TLR9)
• Specific chemical modifications of ASOs, such as LNA or methylation, may mitigate – but in certain cases also enhance – immune reactions triggered by ASOs
• New published data will help in selecting optimal ASOs for further development in distinct disease indications such as inflammatory diseases or cancer

Munich/Martinsried, July 22, 2024 – Secarna Pharmaceuticals GmbH & Co. KG (Secarna), the leading independent European antisense drug discovery and development company, announced today the publication of compelling new data on the toll-like receptor 9- (TLR9-) mediated immunostimulatory potential of therapeutic, LNA-modified ASOs in the peer-reviewed journal, Nucleic Acid Therapeutics. The article, entitled Characterization of the TLR9-Activating Potential of LNA-Modified Antisense Oligonucleotides, addresses the intricacies of the effects of chemical modifications of ASOs on their immunoregulatory profile and can be found here.

TLR9 is expressed by different cell types of the innate immune system and has been shown to trigger a pro-inflammatory cytokine response upon activation. While there is ample data on the TLR9-stimulatory potential of older-generation ASOs, there is limited publicly available data for current state-of-the-art ASOs, such as LNA-modified ones.

Early identification and characterization of an ASO’s immunostimulatory potential is crucial in the drug development process to ensure that oligonucleotides with potential unwanted side effects are eliminated early in development. For this purpose, Secarna performed a comprehensive, systematic analysis of the TLR9-activating potential of LNA-modified oligonucleotides using different mouse and human cell culture systems. Concomitantly, mitigation of immune stimulation by chemical modifications, such as methylation, was tested. Results indicated that TLR9-dependent immunostimulatory potential is an individual feature of an ASO and thus needs to be investigated on a case-by-case basis.

“Our data shine light on the immunostimulatory potential of LNA-modified ASOs. While this characteristic can be beneficial in cancer therapies, it may be a factor in undesired side effects for treating other indications, such as inflammatory and fibrotic diseases. The published data further substantiate the importance of elucidating and identifying potential triggers of immunomodulatory effects of ASOs early on to support the development of safer, yet highly potent drugs,” said Frank Jaschinski, Ph.D., Chief Scientific Officer of Secarna Pharmaceuticals.
 

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 antisense oligonucleotide discovery and development platform to generate 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

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