The OligoPhore™ / SemaPhore™ technology has been extensively and successfully tested with various siRNA and mRNA sequences in numerous disease models in mice. For the development of our first proprietary drug product, AM-401 (OligoPhore™ siRNA targeting KRAS), we have initiated a program of IND-enabling studies.
Pancreatic and colorectal cancer
Adult T-cell Leukemia / Lymphoma (ATLL)
Rheumatoid and osteoarthritis
Metabolic syndrome / obesity
The effects of OligoPhore™ delivered siRNA in KRAS driven cancer were evaluated in vitro and in vivo in colorectal and pancreatic cancer assays and animal models (Strand et al., 2019). The KRAS gene acts as an on/off switch for cell growth. However, when the gene is mutated, KRAS may allow cells to grow uncontrollably and activate the downstream pathways. This leads to multiplication of cells and cancer growth, which in turn can cause metastases.
The study demonstrated that the nanoparticles were avidly taken up by cancer cells in vitro, could deliver KRAS-specific siRNA, inhibited KRAS expression, and reduced cell viability. Further, the study showed that OligoPhore™ can deliver siRNA to the tumor microenvironment, reduce KRAS expression, and inhibit pancreatic cancer growth in vivo. In a spontaneous model of pancreatic cancer, OligoPhore™ demonstrated its ability to effectively deliver siRNA to tumors which are difficult to reach.
Figure 1: Treatment of pancreatic tumor bearing mice with OligoPhore™ delivered KRAS siRNA leads (A) to a reduced tumor growth rate and (B) tumor volume that is reduced 4.6 fold versus controls (“scrambled siRNA”). (C) Tumor size for controls (left) and KRAS siRNA treated animals.
Figure 2: Fluorescence shows KRAS siRNA (but not controls) localized to tumor cells with relative sparing of uninvolved pancreas areas.