Altamira Therapeutics Ltd. announced that it has filed a second 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, polyKRASmut. The nanoparticles are developed by Altamira as AM-401. The second provisional application contains in vitro data confirming the ability of polyKRASmut siRNA to knock down a broad range of KRAS mutations in cancer cell lines.

These mutations include G12C, G12V, G12D, G12R, G12A, and A146T, which account for 90.9% of KRAS mutations reported in pancreatic ductal adenocarcinoma (PDAC), 65.3% in colorectal cancer (CRC) and 80.0% in non-small cell lung cancer (NSCLC). In comparison, currently approved small molecule inhibitors target just one KRAS mutation (G12C), which represents 1.7%, 7.1% and 41.0% of total KRAS mutations in PDAC, CRC and NSCLC, respectively. Altamira expects the second provisional patent application to further strengthen its intellectual property around the AM-401 program, under which the Company is aiming to develop a treatment for KRAS-driven cancers.

Previous in vitro and in vivo work demonstrated efficient uptake of OligoPhore nanoparticles with KRAS-targeted siRNA in CRC and PDAC cells, strong inhibition of KRAS expression, reduced viability of tumor cells, and significant reduction in tumor growth and volume. 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 2025 and to partner the program upon an IND grant or following a phase 1 clinical trial.

The KRAS gene encodes one of the RAS proteins, that control - 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 progosis in several cancers, and there is a substantial body of evidence supporting the role of KRAS in the initiation and maintenance of cancer.

According to the American Cancer Society, nearly 150,000 new cases of KRAS-mutated tumors are diagnosed annually in the United States across these three tumor types alone. It is estimated that KRAS mutations account for approximately one million deaths per year worldwide. 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 previous binding sites. Only recently, the FDA approved the first two treatments for KRAS-driven cancer: motorasib and adagrasib, two small molecule inhibitors of G12C-mutated KRAS for the treatment of NSCLC.