Provectus announced that new data from the Company’s ongoing, multi-cohort, Phase 1b/2 study of the combination of small molecule cancer immunotherapy PV-10, an intratumoral formulation of Provectus’ rose bengal sodium (RBS) active pharmaceutical ingredient, and anti-PD-1 therapy Keytruda (pembrolizumab) for the treatment of immune checkpoint blockade (CB)-naïve Stage III cutaneous melanoma (NCT01223415) are being presented at Melanoma Bridge 2022 in Naples, Italy and online from December 1-3, 2022. Key Highlights of the Melanoma Bridge 2022 Presentation: Efficacy: (6 patients; investigator-assessed RECIST v1.1); 50% complete response (CR) (3/6) and 83% overall response rate (ORR) (5/6): Rapid CRs – 2 within 15 weeks and 1 within 27 weeks. Durability: Median progression-free survival (PFS) not reached during 2-year treatment interval 83% PFS rate; All CRs ongoing after 18 to 36 months of study follow-up.

Survival: Median overall survival (OS) not reached; 100% OS rate for CRs; ongoing after 18 to 36 months of study follow-up. Safety Consistent: with established patterns of PV-10 and Keytruda single-agent use. Consistent with prior PV-10 and Keytruda combination therapy cohorts of CB-naïve and CB-refractory advanced melanoma patients.

Mechanism of immune action Precise, increased, PV-10-induced T-cell activity preceded CR. Similar immune upregulation observed in (a) monotherapy PV-10 treatment of Stage III melanoma patients and (b) PV-10 and Keytruda combination treatment of CB-refractory advanced melanoma patients. Successfully combining PV-10 and CB in Stage III melanoma patients (50% CR and 83% ORR) is predicated on achieving rapid response of PV-10-injected lesions that may lead to rapid, durable CR of patients and ultimately to improved PFS and OS: Single-agent PV-10 achieved 56% CR (and 63% ORR) of injected lesions in Stage III patients, but only 23% CR (and 54% ORR) of non-injected lesions, and a median PFS of 8.9 to 9.8 months; Single-agent CB may exhibit a similar response rate in Stage III (M0) patients (27% CR and 54% ORR) to PV-10’s response rate in non-injected lesions, with a median PFS of 11.7 months, and The combination of PV-10 and CB in CB-naïve Stage IV patients has shown the potential for significant combinational interaction and durability, while also presenting a non-overlapping safety profile.