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Treatment with OligoPhoreTM siRNA stops aggressive ATLL tumor growth to near zero
Significant reduction in tumor size, spleen size and peripheral blood lymphocyte counts
Results add to extensive body of evidence for effective OligoPhoreTM enabled delivery of nucleic acids to extrahepatic tissues
Hamilton, Bermuda, June 21, 2021 – Auris Medical Holding Ltd. (NASDAQ: EARS), a company dedicated to addressing unmet medical needs through RNA therapeutics, allergy and viral infection protection, and inner ear therapeutics, today announced the publication of positive results from an in vivo study demonstrating significant inhibition of tumor growth by siRNA knock-down of NF-κB employing its OligoPhoreTM technology in Adult T-cell Leukemia Lymphoma (ATLL). The article titled "Targeting NF-κB with nanotherapy in a mouse model of adult T-cell leukemia / lymphoma” was published in Nanomaterials, an international peer-reviewed open-access journal.1
The study was performed jointly by research groups at Washington University, St. Louis MO, and the University of South Florida, Tampa FL. The researchers developed and evaluated RNA nanoparticles based on Auris Medical’s OligoPhoreTM peptide carrier and siRNA targeting simultaneously two NF-κB signaling pathways. NF-κB is a protein complex that plays a key role in regulating the immune response to infection and is critical for tumor progression in ATLL. The siRNA nanoparticles were administered systemically to two groups of mice with either spontaneous ATLL tumor growth or tumor cell transplantation.
The study demonstrated rapid delivery of siRNA to the tumor and significant reduction of target mRNA and protein expression, which altered the natural history of subsequent tumor progression. Tumor size, spleen size, and peripheral blood lymphocyte counts were significantly lower in treated mice compared to controls (p<0.01), and tumor growth was reduced to near zero in the most aggressive tumors. Further, the siRNA nanoparticles sensitized late-stage ATLL tumors to conventional chemotherapy with etoposide.
ATLL is a rare and aggressive type of non-Hodgkin’s lymphoma of mature T cells caused by the Human T-cell Leukemia / Lymphotropic Virus type 1 (HTLV 1). It can be found in the blood, lymph nodes, skin or other parts of the body. There are 5-10 million people infected with HTLV 1 globally, and it is estimated that 61 out of 100,000 of carriers will develop ATLL annually. The virus is endemic to Japan, sub Saharan Africa, South America, the Caribbean, central Australia, the Middle East, and Romania. Most cases are not curable with current treatments, even when diagnosed early. The 5-year survival rate is 23.4% with a median survival of 11 months. Overall survival has remained unchanged since the disease was first described.
“We are very excited about the very encouraging results from the study in ATLL mice”, commented Samuel Wickline, MD, Auris Medical’s Chief Scientific Officer. “ATLL is a very challenging condition with high mortality rate. Although NF-κB has been known for some time as a promising target, it has remained elusive to specific and effective treatment so far. With the use of OligoPhore technology, siRNA targeting NF-κB can be delivered intravenously and track the tumor very effectively with profound suppression of aggressive tumor proliferation. Since ATLL is a highly malignant tumor with no targeted molecular therapy at present, this outcome is not only very encouraging for drug discovery and development in this therapeutic indication, but also for other tumors and inflammatory pathological conditions involving the NF-κB molecular target.”
OligoPhoreTM is a versatile platform for safe and effective delivery of oligonucleotides such as siRNA (small interfering ribonucleic acid) into target cells. It is based on a proprietary 21 amino acid peptide that can engage any type of RNA in rapid self-assembly into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach other target tissues than the liver. OligoPhoreTM protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide endosomal escape and cytoplasmic delivery. Effective delivery and positive treatment outcomes have been demonstrated in more than 10 murine models of disease for targets in the NF-κB family, various members of the ETS transcription factor family, and targets in the JNK and TAM pathways.
About Auris Medical
Auris Medical is dedicated to developing therapeutics that address important unmet medical needs. The Company is currently active in three areas: the development of RNA therapeutics for extrahepatic therapeutic targets (OligoPhoreTM / SemaPhoreTM platforms; preclinical), nasal sprays for protection against airborne viruses and allergens (BentrioTM; pre-commercial) or the treatment of vertigo (AM-125; Phase 2), and the development of therapeutics for intratympanic treatment of tinnitus or hearing loss (Keyzilen® and Sonsuvi®, Phase 3). The Company was founded in 2003 and is headquartered in Hamilton, Bermuda with its main operations in Basel, Switzerland. The shares of Auris Medical Holding Ltd. trade on the NASDAQ Capital Market under the symbol “EARS.” The Company will change its name to “Altamira Therapeutics Ltd.” and its ticker symbol to “CYTO”, subject to approval by a Special General Meeting of shareholders to be held on July 21, 2021.
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1 Rauch DA et al. Targeting NF-κB with nanotherapy in a mouse model of adult T-cell leukemia/lymphoma. Nanomaterials 2021, 11(6), 1582.