Positive Findings Reported for SECuRE Copper-67 Clinical Trial

Clarity Pharmaceuticals shared several updates on the 67Cu-SAR-bisPSMA program. Cohort 4 is anticipated to be the final cohort in the dose escalation phase of the SECuRE study (pending final safety assessment by the Safety Review Committee [SRC]), with participants receiving a minimum of 2 and a maximum of 4 doses of 67Cu-SAR-bisPSMA at 12GBq.

The SRC has completed the review of the safety data of the third participant in cohort 4 who received 2 doses of 67Cu-SAR-bisPSMA. The safety profile of multiple doses of 12GBq of 67Cu-SAR-bisPSMA remains favorable, confirming the preliminary safety findings of previous cohorts (single-dose cohorts, 1, 2 and 3). Almost all AEs in the 3 participants in cohort 4 were mild to moderate, with the majority having resolved or improved at the last assessment. No DLTs have been observed in any participants across all cohorts in the SECuRE trial to date.

The third participant, who recently completed his DLT period, is a 93-year-old patient with a long history of prostate cancer (diagnosed over 26 years ago, stage IIIB). He had failed several lines of therapy (e.g. androgen deprivation therapy [ADT] and 2 androgen pathway receptor inhibitors [ARPIs]) prior to entering the SECuRE trial. The participant only experienced 1 AE (Grade 2 nausea) during the trial, which followed the first cycle of 67Cu-SAR-bisPSMA (12GBq). This nausea resolved in just over a week from the time it was first reported.

Early preliminary efficacy assessment showed a reduction in PSA levels following 2 treatment cycles in all 3 participants in cohort 4, with 2 patients already showing PSA reductions >50% vs. baseline. The last patient's PSA peaked at 32.7 ng/mL and has so far dropped to 20.2 ng/mL. The largest drop in PSA in cohort 4 to date is a decline of 95.7% (from a baseline of 157.4 ng/mL), and it remains in a downward trend based on the latest assessment. This participant, who had failed multiple lines of therapy prior to receiving 67Cu-SAR-bisPSMA (e.g. ADT, ARPI and an investigational agent), has already had a radiographic partial response based on Response Evaluation Criteria in Solid Tumours v1.1 (RECIST) assessment, with a reduction of 60.6% in tumor volume thus far, evaluated by prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging with 64Cu-SAR-bisPSMA.

The 3 remaining slots in cohort 4 have been allocated. Two participants have been enrolled and have received their first cycle of 67Cu-SAR-bisPSMA. Both patients continue in follow-up. The final participant is being planned for his first therapy cycle in the coming weeks, pending the outcome of ongoing screening assessments. Cohort 4 will be followed by a cohort expansion phase of the trial (Phase II) in 14 participants, pending safety evaluation.

The first patient to receive 2 doses of 67Cu-SAR-bisPSMA at 8GBq (first dose through the SECuRE trial and second dose under FDA EAP) had been heavily pre-treated (e.g. chemotherapy, ADT, 2 ARPIs and an investigational agent). 67Cu-SAR-bisPSMA treatment led to a complete anatomical, molecular and biochemical response (assessed by RECIST criteria, PET and PSA, respectively). The patient's latest follow up on showed that he remains with undetectable PSA for almost 13 months, having received his first dose of 67Cu-SAR-bisPSMA over 17 months ago (June 2023). Most AEs related to 67Cu-SAR-bisPSMA were mild to moderate, with the majority having either improved or resolved over time.

One of the participants from cohort 1 who initially received the lowest dose in the SECuRE trial of 67Cu-SAR-bisPSMA (4GBq) in October 2022, went on to receive 3 additional cycles under the EAP (4GBq each). The patient had failed several lines of treatment prior to receiving 67Cu-SAR-bisPSMA (i.e. ADT and 2 ARPIs). A reduction greater than 50% in PSA levels was observed in this patient following the first administration of 67Cu-SAR-bisPSMA and a drop of 94% in PSA was observed after the fourth cycle4.

A recent 64Cu-SAR-bisPSMA PET scan performed in July 2024 showed a reduction in tumor volume vs. baseline (41.6%), despite the patient not having received any 67Cu-SAR-bisPSMA for approximately 14 months since his last dose in June 2023 (Figure 1).

Most recently, this patient's clinician requested an additional dose of 8GBq of 67Cu-SAR-bisPSMA under the EAP following rising PSA levels. In the weeks following the administration of the fifth dose, a reduction in PSA of 47.5% was observed (vs. the most recent PSA peak value of 10.1 ng/mL), with the PSA continuing to decline at the last assessment (Figure 2). This patient continues to derive clinical benefit approximately 25 months after receiving his first dose of 67Cu-SAR-bisPSMA. The only reported AE in this patient related to the fifth dose of 8GBq of 67Cu-SAR-bisPSMA was mild thrombocytopenia (Grade 1), which is improving. No other related AEs were reported for this patient following the first 4 doses at 4GBq.

Clarity's Executive Chairperson, Dr Alan Taylor, commented, "We continue to be very impressed by the data generated with our proprietary molecule, SAR-bisPSMA. Recently we announced that we have received the U.S. FDA Fast-Track Designation (FTD) for the use of this molecule in the pre-prostatectomy setting, coupled with copper-64 for imaging. This week we provided our shareholders with feedback from the FDA in relation to our second Phase III clinical trial in BCR of prostate cancer with the same molecule for imaging. We plan to commence recruitment into this trial, AMPLIFY, early next year given the data demonstrating that we are able to pick up lesions far earlier and far smaller than other PSMA imaging agents. And now we are continuing to share very compelling safety and efficacy data with the use of the same molecule, coupled with copper-67 for therapy, even in patients in their 90s who have had cancer for over a quarter of a century. This means that every patient through the entirety of the prostate cancer journey may benefit from this extraordinary molecule when it is coupled with the perfect pairing of copper isotopes. All of these individual indications, being imaging in pre-prostatectomy and BCR patients, as well as therapy, are blockbuster markets individually for PSMA-targeted products...”