Clarity Pharmaceuticals begins Phase II SECuRE trial with first patient dosed using 67Cu-SAR-bisPSMA and enzalutamide

How is Clarity Pharmaceuticals advancing prostate cancer treatment with the SECuRE trial?

Clarity Pharmaceuticals has commenced a pivotal new chapter in its clinical development program with the Phase II Cohort Expansion of its SECuRE trial, marking the treatment of the first patient using its investigational copper-based therapy, 67Cu-SAR-bisPSMA. The therapy, aimed at addressing metastatic castration-resistant prostate cancer (mCRPC), is now being administered in combination with enzalutamide, a leading androgen receptor pathway inhibitor (ARPI), following a protocol amendment that reflects evolving therapeutic strategies in prostate oncology.

The SECuRE trial (NCT04868604) is a multi-site, Phase I/IIa study investigating the safety and efficacy of Clarity’s dual-purpose SAR-bisPSMA molecule. Designed as a Targeted Copper Theranostic (TCT), the molecule uses the copper-64 isotope for imaging and copper-67 for treatment. With a total of 24 patients planned for the expansion cohort, this phase builds upon promising safety and efficacy data from the earlier dose escalation stage and introduces longer treatment durations of up to six cycles at an 8 GBq dose level.

This development comes amid broader shifts in prostate cancer treatment that increasingly emphasize molecularly targeted and minimally invasive therapies. The SECuRE trial positions Clarity’s candidate as a potential frontline radiopharmaceutical alternative for patients who have yet to receive chemotherapy.

Why is this Phase II trial expansion significant in the context of current oncology trends?

The significance of the Cohort Expansion Phase lies not only in the increased dosing duration but also in the strategic decision to incorporate combination therapy with enzalutamide. This amendment is grounded in the positive findings from the Enza-p trial, which demonstrated the enhanced potential of radiopharmaceutical and ARPI combinations. Clarity’s Clinical Advisory Board, including experts such as Prof Louise Emmett and Prof Oliver Sartor, endorsed this approach in consultation with the Safety Review Committee (SRC), aligning the trial design with the latest clinical thinking in mCRPC management.

Preliminary results from the earlier phase of SECuRE support this trajectory. Among pre-chemotherapy participants, 92% (12 of 13 patients) experienced PSA declines greater than 35%, with more than 60% achieving reductions above 50%. Impressively, 46.2% of participants recorded PSA drops of 80% or more. These outcomes were observed despite most patients receiving only a single dose, reinforcing the potential efficacy of 67Cu-SAR-bisPSMA even in heavily pre-treated populations.

By focusing on patients earlier in their treatment course—before chemotherapy is initiated—Clarity aims to deliver improved quality of life and delay the onset of more aggressive interventions. This approach could set a new clinical benchmark if validated in later-stage trials.

What enhancements have been made to Clarity’s 67Cu-SAR-bisPSMA therapy?

As Clarity transitions into Phase II, it has also launched an improved formulation of 67Cu-SAR-bisPSMA, engineered to remain stable at room temperature. This innovation addresses a long-standing issue in radiopharmaceutical logistics: temperature-sensitive products often experience manufacturing or distribution delays due to cold chain dependency.

The new formulation enables greater supply chain resilience, reducing the risk of batch failures and making commercial-scale production more feasible. According to Dr Alan Taylor, Clarity’s Executive Chairperson, these enhancements prepare the company for a potential Phase III trial and eventual commercialisation. He also highlighted that consistent product delivery is critical to ensure that no patient experiences treatment delays due to manufacturing shortcomings.

The room temperature-stable formulation represents a strategic advantage as Clarity scales up, facilitating broader adoption in clinical settings that may lack the infrastructure for highly temperature-sensitive compounds.

What makes SAR-bisPSMA different from other radiopharmaceuticals?

SAR-bisPSMA is built on Clarity’s proprietary sarcophagine (SAR) chelator technology, which securely encapsulates copper isotopes to prevent them from leaking into the body. The “bis” in SAR-bisPSMA denotes the molecule’s two PSMA-targeting components, enhancing its ability to localize to cancerous lesions.

This dual-action mechanism—imaging with 64Cu and treatment with 67Cu—positions SAR-bisPSMA as a versatile theranostic tool. Unlike conventional radiopharmaceuticals that may use less stable chelators, Clarity’s SAR platform maintains isotope integrity, improving safety and precision in targeting.

The use of copper isotopes also offers several advantages over lutetium-based compounds, such as longer half-lives for imaging and potentially improved pharmacokinetics. These factors could translate into better tumour localization and treatment efficacy, particularly in metastatic disease.

How is Clarity Pharmaceuticals performing in the stock market, and what is the current investor sentiment?

Clarity Pharmaceuticals Ltd (ASX: CU6) is a publicly traded company on the Australian Securities Exchange. As of mid-April 2025, the company’s stock is trading at approximately AUD 1.83, well below its 52-week high of AUD 8.98. This represents a year-over-year decline of more than 32%, reflecting investor caution amid broader sector volatility.

However, the sentiment has shown signs of reversal. Following the announcement of the Phase II SECuRE trial expansion and the first patient dosing, Clarity’s stock rose by 14.9% over the past week. The renewed investor interest reflects optimism around the company’s product pipeline, particularly its advancements in copper-based radiopharmaceuticals for prostate cancer.

Analyst projections for Clarity’s stock are mixed. While some models suggest the stock could fall further, others forecast a rebound with a five-year price target of AUD 14.22. The average one-year price target of AUD 7.59 implies significant upside potential—over 300% from current levels—if clinical milestones continue to be met.

Technical indicators also reflect near-term volatility. Short-term moving averages point to a potential buying opportunity, whereas long-term trends remain bearish. Investors should weigh these signals alongside Clarity’s clinical progress and regulatory strategy.

Investment Outlook:

For risk-tolerant investors, Clarity presents a speculative but potentially high-reward opportunity. The company’s proprietary technology platform, expanding clinical pipeline, and FDA Fast Track designations for SAR-bisPSMA products enhance its long-term prospects. Existing shareholders may consider holding their positions, while risk-averse investors might adopt a wait-and-see stance as further trial data emerges.

What’s next for Clarity and the future of prostate cancer radiopharmaceuticals?

With the SECuRE trial entering its Cohort Expansion Phase, Clarity is on track to generate key data that could underpin a Phase III registrational study. The integration of enzalutamide, enhanced formulation readiness, and a targeted pre-chemotherapy focus all underscore the company’s commitment to precision oncology and regulatory advancement.

Beyond the SECuRE trial, Clarity’s SAR platform has broader applicability in other cancers expressing specific molecular targets. The ability to seamlessly pair imaging and therapeutic agents within the same molecular framework could prove transformational for oncology treatment paradigms.

For now, all eyes are on the upcoming results from the ongoing Phase II expansion. If Clarity continues to demonstrate robust safety and efficacy, especially in combination therapy settings, it may secure a leadership position in the next generation of radiopharmaceutical companies.