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Publications of Secarna Pharmaceuticals' immuno-oncology data in peer-reviewed scientific journals support potential of LNAplusTM antisense oligonucleotide platform for discovering novel cancer therapies

DGAP-News: Secarna Pharmaceuticals GmbH & Co. KG / Key word(s): Scientific publication

06.05.2019 / 14:00
The issuer is solely responsible for the content of this announcement.

Publications of Secarna Pharmaceuticals' immuno-oncology data in peer-reviewed scientific journals support potential of LNAplusTM antisense oligonucleotide platform for discovering novel cancer therapies

  • New strategies urgently needed to prevent tumors from evading the immune system and to make them more susceptible to attack by immune cells
  • Secarna's anti-CD39 ASO is a novel approach that improves anti-tumor immune responses in in vivo models of cancer; significant reduction in tumor growth in combination with PD-1 blocking antibodies
  • Proof of principle established that application of ASOs ex vivo prevent expression of T cell immunosuppressive factors and are thus a promising new strategy to enhance efficacy of T cell-based therapies

Munich/Martinsried, Germany, May 06, 2019 - Secarna Pharmaceuticals ("Secarna"), a new breed of biopharmaceutical company focusing on the discovery and development of antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets, today announced that data related to two of its immuno-oncology programs have been published in peer-reviewed scientific journals.

"These published data support the ability of our platform to design novel antisense compounds that have the potential to enhance the efficacy of existing therapies, including PD-1 inhibitors, or overcome the limitations of cell-based therapies such as T cell therapies," said Jonas Renz, Managing Director and Co-founder of Secarna Pharmaceuticals. "We look forward to advancing these programs in development, including initiating IND-enabling studies with our ASOs against CD-39."

Promising pre-clinical data with ASO against CD39

The first article, "Antisense oligonucleotide targeting CD39 improves anti-tumor T cell immunity," was published in the Journal for ImmunoTherapy of Cancer. The article is available here.

To advance the progress made in recent years in treating cancer with immunotherapy, more efficient strategies are needed to prevent tumors from evading the immune system and to make them more susceptible to attack by immune cells. CD39 is expressed in different immune cells, as well as certain types of tumor cells, and supports the tumor in escaping immune recognition and destruction.

Secarna's ASO approach differs from other approaches in development targeting this pathway (CD39/CD73). While antibodies and small molecules in development may modulate the activity of already expressed targets, ASOs are designed to prevent the formation of the target protein by degrading its mRNA. Further attributes of Secarna's ASO approach compared to conventional approaches include enhanced stability and half-life, which could result in longer-lasting effects; high target specificity, which could reduce side effects; and - in comparison to antibodies - low molecular weight, resulting in better tumor penetration.

Using its proprietary third-generation antisense drug discovery platform LNAplusTM, Secarna identified ASOs against CD39. In the recently published data, anti-CD39 ASOs were shown to potently suppress CD39 in various cell types in both in vitro and in vivo models of cancer and revert immunosuppressive functions of CD39.

Of particular relevance, there was a very pronounced suppression of CD39 expression in intra-tumoral regulatory T cells (Treg), an immunosuppressive cell population that can potently suppress the anti-tumor activity of effector T cells. This was accompanied by a strong reduction of intra-tumoral Treg levels, resulting in decreased immunosuppression.

Additionally, it was found that expression of the protein PD-1 was increased in intra-tumoral T cells of animals treated with anti-CD39 ASO. PD-1 is induced as a feedback mechanism after an initial immune response and its expression dampens further immune responses. It thus was hypothesized that there could be potential synergy between PD-1 blocking antibodies and the anti-CD39 ASO, and in vivo testing provided proof of principle for this combination approach, showing a significant reduction in tumor growth.

The Company plans to further characterize the anti-CD39 ASOs to determine which ones to bring forward for further development.

Proof of principle established of ability of Secarna's ASOs to enhance efficacy of T cell-based therapies

There is excitement in the medical and scientific communities about T cell therapies and their ability to treat and even cure certain cancers. Such therapies isolate a patient's own immune cells from blood, modify the cells outside the body (ex vivo) and then re-administer them to the patient; these modified cells then recognize and attack the patient's tumor cells. While these treatments are marking a paradigm shift in treating certain hematological (blood) cancers, they have been far less effective in treating solid tumors.

Paulo Rodriguez, Ph.D., associate member of the Department of Immunology and his team at the H. Lee Moffitt Cancer Center & Research Institute (Tampa, FL, USA) investigated how the immune system becomes dysfunctional in cancer patients, with the hope that a better understanding of these mechanisms may lead to improved treatment strategies. In particular, this work further elucidated the role of the protein, Chop (C/EBP homologous protein) in cancer.

As part of this research, Secarna designed ASOs against Chop, and they were applied to T cells ex vivo to determine the effect of silencing Chop expression in CD8+ T cells, an important type of immune cell. In an in vivo model for T cell therapies, ex vivo treatment of T cells with Chop-specific ASOs markedly enhanced tumor control.

The results established proof of principle that the treatment of T cells ex vivo with an ASO could increase the efficacy of T cell-based therapies by overcoming T cell dysfunction.

These data were recently published in the article, "ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression," in Nature Communications. The article can be found here.

More research on the potential of ASOs to improve the efficacy of cell-based therapies such as T cell therapies is planned.

About Secarna's Proprietary Drug Discovery Platform, LNAplusTM

Secarna's proprietary third-generation drug discovery platform, LNAplusTM, which encompasses all aspects of drug discovery and pre-clinical development, enables the Company to discover novel antisense therapies for challenging or currently undruggable targets. Secarna's LNAplusTM platform and LNAplusTM based ASOs have previously been validated by in-house projects as well as in academic and industry collaborations. With over 15 development programs focusing on targets and indications such as immuno-oncology, immunology, antiviral, fibrotic diseases, ophthalmology, neurodegenerative diseases and cardiometabolic diseases, where antisense-based approaches have clear benefits compared to other therapeutic modalities, Secarna is a leading 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, ophthalmology, immunology, fibrotic diseases (airways, liver, kidney), and anti-viral applications. 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 antisense therapies for challenging or currently not druggable targets.



Jonas Renz
Managing Director and Co-founder

Secarna Pharmaceuticals GmbH & Co. KG
Am Klopferspitz 19
82152 Planegg/Martinsried
Tel.: +49 (0)89 215 46 375

For media enquiries:

Anne Hennecke
MC Services AG
Tel.: +49 (0)211.52 92 52 22

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Last Updated: 06-May-2019