Newly published data in Cancer Immunology, Immunotherapy support the potential of Secarna Pharmaceuticals' LNA-modified ASOs to effectively block important immunosuppressive pathway
- Secarna's approach efficiently targets IDO1 and TDO2, key enzymes that degrade the essential amino acid tryptophan into immunosuppressive kynurenine
- Combination of IDO1-specific ASOs with small molecule inhibitors synergistically reduce production of kynurenine by cancer cells in vitro
- High unmet medical need for novel treatment options as majority of cancer patients do not respond to current immunotherapeutic approaches
MUNICH and MARTINSRIED, GERMANY / ACCESSWIRE / March 26, 2020 / 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(TM) platform, today announced that data related to one of the company's immuno-oncology programs have recently been published in the peer-reviewed journal Cancer Immunology, Immunotherapy. The article, "A highly efficient modality to block the degradation of tryptophan for cancer immunotherapy: locked nucleic acid-modified antisense oligonucleotides to inhibit human indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase expression," is available here: https://link.springer.com/article/10.1007/s00262-019-02438-1.
The in vitro data demonstrate that locked nucleic acid (LNA)-modified ASOs efficiently block the expression of TDO2* and IDO1**, which are overexpressed in a variety of tumours and have been associated with poor prognosis. Both targets are catalytic enzymes that play a key role in an important immunosuppressive pathway - the degradation of tryptophan into kynurenine. Secarna's approach also was shown to be synergistic with one of the clinically most advanced IDO1-specific small molecule inhibitors (epacadostat). In conclusion, the combination of IDO1- and TDO2-specific LNA-modified ASOs and small-molecule inhibitors should be considered as a strategy to effectively reduce the degradation of tryptophan and production of kynurenine in cancer immunotherapy.
"These in vitro data support that our novel LNAplusTM ASOs inhibit an important immunotherapy pathway - namely, the degradation of tryptophan into kynurenine - that has not been effectively blocked by other approaches," said Jonas Renz, Managing Director and Co-founder of Secarna Pharmaceuticals. "As the majority of patients do not respond to currently available immunotherapies, new options to prevent tumours from evading the immune system are urgently needed. We look forward to advancing our approach, and as a next step in development, we will investigate the efficacy of these ASOs in in vivo tumour models."
Tumours can utilize a diverse repertoire of immunosuppressive mechanisms to evade attack by the immune system. An important immunosuppressive pathway is the degradation of tryptophan into immunosuppressive kynurenine. Recent attempts to target the pathway's key enzymes IDO1 and TDO2 using small molecule inhibitors have failed to show therapeutic benefit. Despite these results there is strong support in the scientific community for both IDO1 and TDO2 as relevant targets for immunotherapy of cancer.
Secarna's approach differs from other approaches targeting this pathway: while conventional approaches such as using small molecules aim to suppress a specific function of an already expressed target, Secarna's ASO approach aims to suppress the expression of a target. The Company applied its proprietary third generation antisense drug discovery platform LNAplusTM to identify ASOs with specificity for IDO1 and TDO2. These ASOs have a phosphorothioated (PTO) backbone and various chemical modifications. This design results in an increased stability as well as target affinity and allows degradation of the target by a cellular enzyme named RNase H1. The published data show that treatment of cancer cells with LNAplusTM-modified ASOs specific for IDO1 and TDO2 lead to potent target knockdown in vitro. Accordingly, the degradation of tryptophan to immunosuppressive kynurenine by ASO-treated cancer cells is markedly decreased. With their unique pharmacokinetic properties that result in longer target exposure times, compared to current approaches, and sustained target engagement, LNAplusTM-modified IDO1- and TDO2-specific ASOs offer a novel treatment modality that could efficiently reduce the degradation of tryptophan to kynurenine in cancer patients which may overcome the shortcomings of previous small molecule approaches.
About Secarna's proprietary drug discovery platform, LNAplusTM
Secarna's proprietary third-generation antisense oligonucleotide (ASO) platform, LNAplusTM, which encompasses all aspects of drug discovery and pre-clinical development, enables the Company to discover novel antisense-based therapies for challenging or currently undruggable targets.Secarna's platform and ASOs have previously been validated by numerous in-house projects as well as in several academic and industry collaborations. With over 15 development programs focusing on targets within indications such as immuno-oncology, immunology, ophthalmology, as well as viral-, neurodegenerative- and cardiometabolic diseases, where antisense-based approaches have clear benefits compared to other therapeutic modalities, Secarna is the leading European antisense drug discovery and development company.
About Secarna Pharmaceuticals GmbH & Co. KG
Secarna Pharmaceuticals is the next generation antisense oligonucleotide (ASO) company with multiple innovative antisense therapies in various stages of pre-clinical development in the areas of immuno-oncology, immunology, ophthalmology, as well as viral-, neurodegenerative- and cardiometabolic diseases. Secarna's mission is to maximize the performance and output of its proprietary LNAplusTM antisense oligonucleotide discovery platform, to develop highly specific, safe, and efficacious best-in-class antisense therapies for challenging or currently not druggable targets. www.secarna.com
Managing Director and Co-founder
Secarna Pharmaceuticals GmbH & Co. KG
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Tel.: +49 (0)89 215 46 375
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SOURCE: Secarna Pharmaceuticals GmbH & Co. KG via EQS Newswire
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