HAMILTON, BERMUDA, Feb. 27, 2023 (GLOBE NEWSWIRE) —
- Altamira’s ability to target different KRAS mutations with a single polyvalent siRNA sequence illustrates versatility and potential of RNA therapeutics compared with conventional small molecule approaches
- Analysts project global market for KRAS inhibitors to be more than $4B by 2029
Altamira Therapeutics Ltd. (Nasdaq:CYTO), a company developing RNA-based therapeutics that address important unmet medical needs, today announced that it has filed a provisional patent application with the United States Patent and Trade Office (USPTO) to provide broad coverage of different KRAS mutations in human cancer treatment with nanoparticles comprising the Company’s OligoPhore™ platform and a single siRNA sequence.
The provisional patent describes novel nanoparticle compositions based on OligoPhore, Altamira’s peptide-based oligonucleotide delivery platform or derivatives thereof, in combination with one siRNA (small interfering ribonucleic acid) sequence designed to silence KRAS. In contrast to small molecule inhibitors, that are designed to inhibit KRAS harboring one specific mutation, Altamira’s approach, polyKRASmut, is polyvalent as it allows for silencing KRAS carrying any of the most abundant mutations described for this oncogene. The new filing is intended to expand Altamira’s intellectual property related to its AM-401 development program for the treatment of KRAS-driven cancers.
The KRAS gene encodes the RAS protein which controls – like an “on / off switch” – cell growth, maturation, migration, and death. Through mutations, the RAS proteins can be rendered persistently active, causing cancer cells to proliferate and spread in the body. Mutations of KRAS are associated with poor prognosis in several cancers, and there is a substantial body of evidence supporting the role of KRAS in the initiation and maintenance of cancer.
COO Covadonga Pañeda’s Commentary
“The ability to target different KRAS mutations with one polyvalent siRNA sequence illustrates the great versatility and potential of RNA therapeutics compared to classic small molecule approaches,” stated Covadonga Pañeda, Ph.D., Altamira Therapeutics’ Chief Operating Officer. “In addition, the use of siRNA is expected to elicit less treatment resistance than the direct inhibition exerted by small molecules, which is of particular importance in cancer treatment. However, even the most effective RNA therapeutics are useless if they cannot be delivered to their target, the cancer cell. By combining the polyKRASmut siRNA with our OligoPhore technology to form the AM-401 nanoparticles, we can get it delivered precisely where it is required. We’re excited to advance our AM-401 program to provide clinicians and patients with a treatment option that is not limited to just one particular KRAS mutation.”
The strategy behind AM-401 has already been tested in vitro and in vivo where it demonstrated efficient uptake of OligoPhore nanoparticles with KRAS-targeted siRNA in colorectal and pancreatic cancer cells, strong inhibition of KRAS expression, reduced viability of tumor cells, and significant reduction in tumor growth and volume.1 Importantly, a murine model demonstrated the capacity of the OligoPhore platform to drive targeted delivery of the nanoparticles specifically to tumor cells. Altamira intends to file for an Investigational New Drug (IND) application with the FDA in late 2023.
There exist more than a dozen different KRAS mutations, but the prevalence of mutation is exceedingly variable among different types of cancers. Mutated forms of KRAS are found in one-fifth of all human cancers, including 32% of non-small-cell lung cancers (NSCLCs), 40% of colorectal cancers (CRCs) and 85–90% of pancreatic cancers. According to the American Cancer Society, overall, almost 150,000 new cases of KRAS-mutated tumors are diagnosed in the United States alone across just these three tumors types each year. It has been estimated that mutations in KRAS alone account for approximately one million deaths per year worldwide.2 Analysts project the global market for KRAS inhibitors to grow from virtually zero in 2021 to more than $4 billion by 2029.3
Although the role of KRAS mutations in cancer has been known for decades, they have remained a challenging target for therapeutic interventions. KRAS was long considered undruggable, in part, because of the lack of obvious binding sites. Only recently, the FDA approved the first two treatments for KRAS-driven cancer: sotorasib and adagrasib, two small molecule inhibitors of G12C-mutated KRAS for the treatment of NSCLC.
OligoPhore is a versatile platform designed to enable safe and effective delivery of oligonucleotides such as siRNA (small interfering ribonucleic acid) into target cells, using systemic or local administration. It is based on a proprietary 21 amino acid peptide that can engage any type of RNA, including mRNA, 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 target tissues other than the liver. OligoPhore protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide full endosomal escape and cytoplasmic delivery. Effective delivery and positive treatment outcomes have been demonstrated in more than ten diverse murine models of disease for cancer, cardiovascular, and rheumatological targets in the NF-κB family, various members of the ETS transcription factor family, and targets in the JNK and TAM pathways.
About Altamira Therapeutics
Altamira Therapeutics (NASDAQ:CYTO) is dedicated to developing RNA-based therapeutics for extrahepatic targets (OligoPhore™ / SemaPhore™ delivery platforms). The Company currently has two flagship siRNA programs in preclinical development beyond in vivo proof of concept: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis. The versatile delivery platform is also suited for mRNA and other types of RNA therapeutics and is planned to be leveraged via out-licensing to pharma or biotech companies.
In addition, Altamira is in the process of divesting and/or out-licensing its legacy assets in allergology and viral infection with its Bentrio® OTC nasal spray (commercial stage); and with inner ear therapeutics drugs AM-125 nasal spray for vertigo (post Phase 2), and Keyzilen® and Sonsuvi® for tinnitus and hearing loss, (Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/
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