Clarity Adds FAP-Targeted Radiopharmaceutical to Its Pipeline

Clarity Pharmaceuticals announced the expansion of its pipeline with a novel FAP-targeted radiopharmaceutical for the diagnosis and treatment of cancer.

FAP is expressed on cancer associated fibroblasts (CAFs), a particular cell type found in the tumor microenvironment (cancer 'infrastructure' called the tumor stroma). CAFs are found in a broad range of cancers (e.g., breast, colorectal, pancreatic, lung, brain and ovarian cancers), but only minimally in normal tissue, making FAP a promising pan-cancer target for both imaging and treatment of cancers. CAFs form part of the environment surrounding the cancer cells, and they can promote cancer growth and the spread of the tumor throughout the body. Targeting the tumor stroma is an alternative way to treat cancer whereby the architecture of the tumor mass is targeted rather than the tumor cells directly.

Clarity's Targeted Copper Theranostic (TCT) targeting FAP was developed at the benchtop of Australian science, with a clear understanding of other FAP-targeted radiopharmaceuticals in development and the intent of overcoming the low uptake and retention of these agents in tumors. This was achieved by utilizing some novel chemistry, and by combining an industry leading FAP inhibitor with the proprietary SAR chelator technology. The SAR Technology enables the use of copper-64 (⁶⁴Cu) for imaging and copper-67 (⁶⁷Cu) for the targeted treatment of various cancers.

Similar to how Clarity developed its PSMA-targeted prostate cancer agent as a dimer, SAR-bisPSMA, which was designed to improve tumor uptake and retention, the Company created a novel dimer for its FAP-targeted radiopharmaceutical, SAR-bisFAP. With the benefit of comparing this novel molecule to other FAP radiopharmaceuticals in development as well as to a monomer equivalent (SAR-monoFAP), the dimer SAR-bisFAP has shown increased tumor uptake and retention over 24 hours in pre-clinical models.

In addition to comparing the mono and dimer versions of the product, Clarity compared the dimer,⁶⁴Cu-SAR-bisFAP, to an industry standard FAP-targeted monomer called⁶⁸Ga-FAPI-46. Using a FAP-expressing melanoma cell line (SK-MEL187) in this experiment, at 1-hour post-injection⁶⁴Cu-SAR-bisFAP had approximately 4 times the uptake in the cancer compared to⁶⁸Ga-FAPI-46. The improvements in uptake and retention of^64/67Cu-SAR-bisFAP compared to first-generation FAP compounds, such as FAPI-46, are key attributes for the development of next-generation radiopharmaceuticals.

Clarity is currently conducting additional investigations to enable a Phase I clinical trial, which could commence in late 2025. Research into the potential clinical use of Clarity's FAP agent has begun with several pre-clinical studies in diagnostics (utilizing⁶⁴Cu-SAR-bisFAP), which will be followed by exploring treatment opportunities of cancers based on their unmet medical needs (using⁶⁷Cu-SAR-bisFAP).

Clarity's Executive Chairperson, Dr Alan Taylor, commented, "Our commitment to always putting science first at Clarity has placed us in an enviable position in radiopharmaceuticals globally. This has allowed us, yet again, to create a novel product at the benchtop to overcome the shortcomings of competing radiopharmaceuticals by increasing the uptake and retention of the molecule over time. Coupled with the use of the perfect pairing of copper isotopes, this facilitates the use of same-day and next-day imaging, addressing the issue of low sensitivity of short half-life products using gallium-68 and fluorine-18, as well as potentially enhancing the therapeutic benefit through increasing the amount and retention of the product at the site of tumors. This is especially the case for FAP-targeted radiopharmaceuticals that offer so much hope as a pan-cancer but suffer the issue of low uptake and retention at the tumor site.