Radiopharmaceuticals selectively deliver radiation to cancer cells, thereby reducing damage to other cells in the body. Our scaffolds comprise four components: a binder, a linker, a chelator, and a radioisotope. Alpha-9 designs each component for optimal selectivity, radiation delivery, and stability.
The binder targets cell surface proteins on cancer cells. There are many classes of binders – for example antibodies, small molecules, or peptides. Alpha-9’s initial focus is on peptides and peptide derivatives.
The linker connects the binder to the chelator. The linker can be optimized to improve tumor uptake, distribution, and pharmacokinetics.
The chelator holds the radioisotope. Chelators vary in isotope compatibility and radiolabeling efficiency. Some radioisotopes require specialized chemical structures to ensure effective chelation. Alpha-9 uses both conventional and proprietary structures to bind radioisotopes to our peptide scaffolds.
The radioisotope mediates the therapeutic or diagnostics properties of a molecule. Lutetium or actinium can cause DNA damage and kill cancer cells, while gallium or fluorine can be used for tumor imaging.
Source: Human Protein Atlas
Target selection is a critical activity in radiopharmaceutical development. The key is ensuring differentiated expression and sufficient radioactive payload delivery to the tumor cell while minimizing exposure to healthy organs. We evaluate targets across multiple parameters including tumor overexpression, tumor selectivity, and tractability for therapeutic drug development.
Alpha-9 has deep expertise in the optimization of peptides, peptidomimetics, and small molecules for radiotherapeutic development. Our systemic approach is fueled by a rich toolkit that includes proprietary fluorine-labeling technology, novel chelators, and various binder and linker modifications (e.g., unnatural amino acids, structural modifications, and novel geometries).
For each target we develop molecules optimized for imaging, dosimetry and therapy. Imaging and dosimetry studies – cost effective, first-in-human studies with the target patient population – demonstrate proof-of-concept for the target while also providing valuable feedback on molecule design.
Imaging studies show whether a molecule demonstrates tumor specific uptake while identifying off-target sites of accumulation. These studies are done with an imaging radioisotope, such as gallium or fluorine. The molecule “lights up” tumor tissue, which can be visualized through PET/SPECT scans.
Dosimetry studies quantitatively show how much radioactivity a molecule delivers to tumor tissue. These studies are often done with lutetium. Based on the dosimetry calculations, it is possible to determine whether the radiation dose delivered is high enough to kill tumor tissue without significantly harming non-target tissues.
Therapy studies are similar to Phase I/II trials in other modalities. Therapy studies are done with lutetium, actinium, or other high-energy isotopes. The study design is guided by human data from imaging and dosimetry studies. Often, the molecule used in the imaging study is used for patient selection in the therapy study.
Alpha-9’s purpose-built research facilities reside in Vancouver and house its chemistry, biology, translational research and radiochemistry R&D teams. Our dedicated labs and vivarium support and accelerate our expanded pipeline.
Alpha-9 Oncology, Inc.
27 E7th Ave, Suite 300
Vancouver, V5T 1M4
185 Dartmouth St, 6th Floor
Boston, MA 02116
