Perspective Therapeutics (CATX) 7th Annual Evercore ISI HealthCONx Healthcare Conference summary

Isotope selection and mechanism of action

• Lead isotopes are favored due to their matched elemental twin, enabling predictive scans and dosimetry before therapy.

• Lead-212 delivers a potent, short-lived alpha particle punch, minimizing prolonged immune suppression.

• Proprietary chelator ensures both lead and bismuth remain at the tumor site, enhancing safety and efficacy.

• Actinium isotopes have multiple toxic daughters, raising safety concerns compared to lead.

Melanoma program: clinical data and strategy

• MC1R is targeted, but only present in about half of melanoma patients and not in all tumors per patient.

• Lead-203 enables pre-treatment screening for MC1R expression, allowing patient selection.

• Alpha therapy induces a strong immunostimulatory response, potentially turning cold tumors hot.

• Clinical data show a bell-shaped dose-response curve; optimal benefit at 3 mCi, with higher doses harming immune response.

• Patients at 3 mCi showed prolonged PFS (up to 13 months) with minimal adverse events; lower doses (1.5 mCi) now being explored.

Dose finding and future directions

• Dose finding is ongoing, with lower doses being tested for both monotherapy and combination cohorts.

• Animal data support efficacy at even lower doses; preclinical and clinical data are aligned.

• Earlier-line patients may be included in future as combination studies with checkpoint inhibitors progress.

• Combination cohort with checkpoint inhibitors is now open for enrollment.