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Secarna Pharmaceuticals publishes new preclinical data in The Journal of Immunology demonstrating potent therapeutic activity of LNAplus™ ASO targeting NLRP3 in highly debilitating autoinflammatory diseases

  • Secarna's LNAplus™ ASOs suppress expression of NLRP3, a central component of the inflammasome pathway, which is overactive in many inflammatory diseases
  • Cryopyrin-associated periodic syndrome (CAPS) is a group of rare inherited autoinflammatory diseases driven by overactive NLRP3, resulting in systemic inflammation
  • With NLRP3-specific ASOs, inflammatory downstream effects were interrupted in immune cells and strong symptom relief and significant prolongation of survival was achieved in a CAPS disease model.
MUNICH/MARTINSRIED, GERMANY - EQS Newswire - 6 July 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, announced today the publication of compelling new preclinical data supporting the use of ASOs for the treatment of inflammatory diseases in the peer-reviewed journal, The Journal of Immunology. The article, "Antisense oligonucleotide therapy decreases IL-1β expression and prolongs survival in mutant Nlrp3 mice", addresses the joint work of the groups of Prof. Ariel Feldstein and Prof. Hal Hoffman from the University of California San Diego, world-leading specialists in the field of NLRP3-mediated inflammation and CAPS, and Secarna and can be found here.

Using its proprietary Oligofyer™ bioinformatics system, Secarna designed LNAplus™ ASOs to specifically suppress the expression of the NLR family pyrin domain containing 3 (NLRP3), the central component of the inflammasome pathway. Activation of the inflammasome results in release of proinflammatory cytokines such as IL-1β. Overactivation of this pathway has a pathological role in many diseases with an inflammatory component, such as arthritis, inflammatory bowel disease, acute and chronic kidney disease, non-alcoholic steatohepatitis, asthma and also diseases of the central nervous system, such as Parkinson's disease and Alzheimer's disease. The results of this study demonstrate that NLRP3-specific ASO treatment downregulates NLRP3 expression and IL-1β release in the CAPS disease model, suggesting ASO therapy as a potential treatment of CAPS or other NLRP3-mediated diseases.

CAPS are a spectrum of autoinflammatory diseases caused by activating mutations in the NLRP3 gene. Depending on the type of mutation, symptoms and disease severity, they are divided into neonatal onset multisystem inflammatory disease (NOMID), Muckle Wells syndrome (MWS), and familial cold autoinflammatory syndrome (FCAS). Symptoms are heterogeneous and can include fever, urticarial rash but also multiple neurological manifestations that can be debilitating and have a severe impact on quality of life. Current therapies have been designed to inhibit the IL-1β pathway and have been shown to improve clinical symptoms in patients. However, there remains an unmet clinical need for patients who do not respond adequately, emphasizing the need for improved therapies.

"With the publication of these preclinical results, we have demonstrated that NLRP3-specific ASOs can effectively target this gene across the CAPS spectrum and therefore block the overactivation of the inflammatory cascade," said Frank Jaschinski, Ph.D., Chief Scientific Officer of Secarna Pharmaceuticals. "We are excited to see that in a particularly aggressive model of CAPS clear therapeutic benefits on different readouts in relevant organs were achieved by NLRP3-ASO treatment. Furthermore, the data open the door for these ASOs to treat other diseases driven by an overactive NLRP3 inflammasome pathway, such as inflammatory bowel disease, acute and chronic kidney disease, and diseases of the central nervous system. I very much look forward to seeing the development of ASOs targeting inflammation, a field where, to date, there is no approved ASO treatment."

The groups from the University of California San Diego tested the potential of the NLRP3-ASOs for treatment of CAPS in in vitro and in vivo models. In cell culture they demonstrated that NLRP3-ASOs potently suppressed expression of the gene. Furthermore, there was a strong reduction in the secretion of the proinflammatory cytokine IL-1β in immune cell cultures derived from in vivo models from all three types of CAPS. The activity of NLRP3-ASO was tested in an in vivo NOMID disease model; NOMID is the most severe form of CAPS. After systemic ASO treatment, life expectancy was significantly increased, with weight gains and reductions in the severity of skin lesions, showing an overall reduction in systemic inflammation.

Hashtag: #SecarnaPharmaceuticals

The issuer is solely responsible for the content of this announcement.

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.The platform includes the powerful proprietary Oligofyer™ bioinformatics pipeline, 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.

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