SAR-bisPSMA

^64/67Cu-SAR-bisPSMA:
A Next-Generation PSMA Theranostic

SAR-bisPSMA is a next generation theranostic radiopharmaceutical with dual PSMA-targeting agents linked to Clarity’s SAR chelator technology. It utilises the isotopes of copper for imaging (⁶⁴Cu or Cu-64) and therapy (⁶⁷Cu or Cu-67).

Prostate cancer is the second most common cancer in men and the 5^th leading cause of death in men worldwide. Patients diagnosed with prostate cancer at later stages have poor treatment outcomes, indicating a high unmet need for early detection and better treatment options for metastatic castration-resistant prostate cancer.

PSMA is a protein expressed in >87% of patients with prostate cancer and is an excellent diagnostic and therapeutic target.

Clarity is running a therapy program in metastatic castrate resistant prostate cancer (mCRPC) with ⁶⁴Cu-SAR-bisPSMA and ⁶⁷Cu-SAR-bisPSMA and multiple diagnostic trials in line with advice received from the US Food and Drug Administration (FDA) to address the two relevant patient populations for registration of diagnostic ⁶⁴Cu-SAR-bisPSMA:

• pre-prostatectomy/pre-definitive treatment of patients with confirmed prostate cancer; and
• patients with biochemical recurrence (BCR) of prostate cancer.

Pre-clinical data confirms best-in-class potential with optimised SAR-bisPSMA molecule

A comparison of the % injected activity in tumours in the same preclinical model (LNCaP) for PSMA-617 and SAR-bisPSMA demonstrates that SAR-bisPSMA is potentially the best-in-class theranostic agent for prostate cancer based on the superior uptake of SAR-bisPSMA in tumours at 1 and 24 hours compared to PSMA-617. This improvement is hypothesised to be driven by the two PSMA-targeting molecules in the optimised structure of SAR-bisPSMA.

Comparison of % Injected Activity/g in tumour of
SAR-bisPSMA to PSMA-617

SAR-bisPSMA also has the ideal product characteristics for a radiopharmaceutical: fast uptake and retention in tumours, rapid clearance from normal organs and significant anti-tumour effect in preclinical models.

⁶⁴Cu-SAR-bisPSMA

⁶⁷Cu-SAR-bisPSMA

Zia et al., 2019. Ang.Chem

Zia et al., 2019. Ang.Chem

McInnes et al., 2020. JNM

Fast uptake and retention in tumours

Biodistribution in a LNCaP xenograft model of ⁶⁴Cu SAR-bisPSMA showing high uptake and retention in tumours as well as rapid clearance from key organs over 24 hours

Rapid kidney clearance of unbound product

Positron Emission Tomography images showing ⁶⁴Cu SAR-bisPSMA targeting to tumours within 1 hour and otherwise rapid kidney clearance

Significant anti-tumour effect

Xenograft mice with LNCaP tumours were injected with a single or repeat dose of up to 30 MBq of ⁶⁷Cu SAR-bisPSMA.

Multiple clinical trials are generating robust data on SAR-bisPSMA

⁶⁷Cu-SAR-bisPSMA therapy

⁶⁴Cu-SAR-bisPSMA diagnostics