Targeted Copper Theranostics: The Perfect Pairing of copper-64 and copper-67

Targeted Copper Theranostics

Clarity’s SAR Technology platform is leading the way in the development of copper-based theranostics. Targeted Copper Theranostics (TCTs) are the next-generation disruptive platform in radiopharmaceuticals that employ the “perfect pairing” of copper-64 (Cu-64 or ⁶⁴Cu) and copper-67 (Cu-67 or ⁶⁷Cu) for diagnosis and therapy, respectively. TCTs deliver a compelling combination of high accuracy and high precision in the treatment of a range of cancers, as well as providing supply and logistical advantages over current theranostics. TCTs present a highly efficacious, scalable, and cost-effective way to expand radiopharmaceuticals into the global oncology market.

The Perfect Pairing

The “perfect pairing” of copper-64 and copper-67 isotopes for diagnosis and therapy has been discussed in scientific literature for over . The pairing is well suited for precision medicine due to the unique physical characteristics of these isotopes of copper as well as having the “ideal theranostic pair”, meaning the same product and same element are used for both diagnosis and therapy.

The physical characteristics of copper-64 and copper-67 position this pairing to compete head-to-head with gallium-68 (Ga-68 or ⁶⁸Ga), fluorine-18 (F-18 or ¹⁸F) and lutetium-177 (Lu-177 or ¹⁷⁷Lu) and other currently used isotopes.

Advantages of the copper pairing

Copper-64

Ideal half-life and shelf-life

Copper-64 differentiates itself from other diagnostic imaging isotopes with an ideal half-life of 12.7 hours, which facilitates a significantly longer product shelf-life (up to 48 hours) compared to most commonly used radio-diagnostics on the market. This enables operational flexibility with imaging timepoints up to 72 hours and helps to overcome the acute supply restraints of current-generation radio-diagnostics based on gallium-68 with a half-life of ~1 hour and fluorine-18 with a half-life of ~2 hours.

Central manufacture and mass production

The longer shelf-life of copper-64 based diagnostics enables centralised manufacture, as opposed to almost all current-generation PET diagnostics which require an expensive and extensive network of cyclotrons, radioisotope generators and radiopharmacies next to imaging sites due to the shorter half-life and shelf-life of gallium-68 and fluorine-18. Copper-64 can be mass produced (>1000 Ci per day) in the US by existing cyclotrons and accelerator infrastructure.

On-demand distribution to every zip-code in the US

Copper-64 can be widely distributed as a ready-to-use cGMP product, which can improve patient access to this important diagnostic tool. This has the potential to reduce disparities in prostate cancer care and ensure that all patients, regardless of geographic location, can benefit from the latest advances in diagnostic imaging.

Commercial-scale supply and manufacturing network

Clarity has developed a large-scale and robust manufacturing capacity for the copper-64 isotope from multiple suppliers and continues to strengthen its network to support its clinical programs as well as a successful commercial roll-out of TCTs globally.

In the US, a commercial-scale agreement for copper-64 with Nusano ensures high-volume, cost-effective mass production of this isotope. Nusano is capable of producing enough copper-64 to supply more than 18,000 patient doses per day at 200 MBq per dose, with a 48 hour shelf-life. Combined with Clarity’s existing copper-64 supply network in the US, this is well in excess of commercial-scale demands across multiple large oncology indications, ensuring supply to any zip-code in the US, on demand, 24/7.

Diagnostic radionuclides

Copper-67

No reliance on nuclear reactors

Copper-67 does not require nuclear reactors to manufacture, meaning the supply of the radioisotope is not constrained by the handful of reactors available globally. A significant portion of the world supply of therapeutic radionuclides, such as lutetium-177, is produced directly or indirectly on nuclear reactors. Supply issues are frequent and can be caused by a single reactor shutting down.

Scalable electron accelerator production

Copper-67 is a therapeutic isotope produced on electron accelerators, which are relatively inexpensive and readily scalable in all geographies of the world, including the US, Europe and Asia.

Environmentally preferrable

The only inputs for copper-67 production are electricity and zinc, with no long-lived impurities from the production process. In contrast, lutetium-177 production requires rare earth elements and leads to the production of high-level radioactive waste.

Commercial-scale supply and manufacturing network

Clarity’s strategy is to develop reliable, scalable and environmentally preferable solutions to radionuclide sourcing with purpose-built supply in the​ markets of focus, including ​a US domestic supply.

Clarity currently has an exclusive supply agreement with NorthStar Medical Isotopes for high-volume supply of copper-67 as well as supply agreements with other copper-67 producers.

Therapeutic radionuclides

High accuracy/ high precision theranostic pairing

By utilising chemically identical products for diagnosis and therapy, something unique to TCTs, Clarity is aiming to achieve highly precise and highly accurate targeting of therapeutics.

High accuracy is achieved by only selecting those patients for therapy who show product uptake in the tumours when imaging with a PET scan during the diagnostic stage (using copper-64). This is an indicator that the product targets the cancer and not healthy tissues, thereby maximising the probability of treatment success.

High precision is achieved by using the same targeting molecule with the same chemical element inside the chelator (using copper-67), ensuring both the diagnostic and therapeutic products have identical targeting in vivo.