Provecta (rose bengal sodium) / Provectus - LARVOL DELTA

A phase 1 study to assess the safety, tolerability and effectiveness of PV-10 (Rose Bengal Sodium) in neuroendocrine tumours metastatic to the liver. (PubMed, Br J Cancer) - P1 | "IL PV-10 elicited no safety concerns. Encouraging evidence of local and systemic disease control was seen in a heavily pre-treated, progressing mNEN population."

Journal • P1 data • Cardiovascular • Endocrine Cancer • Hepatology • Hypertension • Neuroendocrine Tumor • Oncology • Solid Tumor

Cherry-red plasma: Beyond the assumption of hemolysis. (PubMed, Clin Chim Acta) - "The findings indicate that PV-10 has varying effects on different biochemical assays and test results should be examined individually. This report underlines the need for awareness of potential drug interference on laboratory tests for better result interpretation and making clinical decisions."

Journal • Hematological Disorders • Oncology

Efficacy of plant-based products and nonconventional pesticides for the management of tropical bed bug. (PubMed, J Econ Entomol) - "Here, several commercial plant-based formulations (Cedarcide, EcoRaider (also known as EcoVenger), EcoSMART, and Bio-D), a novel product, Provecta, and a pyrethroid insecticide, Pesguard FG161 were tested against pyrethroid-susceptible and resistant strains of C. hemipterus using direct spray, residual exposure, and egg dipping assays...Cedarcide and EcoRaider reduced egg hatchability by 37%-73% and 47%-70%, respectively. This study suggests that certain plant-based insecticides and an unconventional insecticide can serve as alternative direct spray treatments for managing tropical bed bugs, though their residual effects are limited."

Journal

Provectus Biopharmaceuticals Announces Notice of Allowance for U.S. Patent of Oral Administration of Rose Bengal Sodium in Hematology (Leukemia) (GlobeNewswire) - "Provectus Biopharmaceuticals, Inc...today announced that the United States Patent and Trademark Office has allowed patent application 17/232,393, titled 'Halogenated Xanthene Composition and Method for Treating Hematologic Cancers' (formerly 'Composition and Method for Oral Treatment of Leukemia'). The application covers the use of Provectus’s pharmaceutical grade rose bengal sodium ('RBS') active pharmaceutical ingredient for the single agent or combination therapy treatment of pediatric and adult leukemias."

Patent • Leukemia • Oncology

Provectus Biopharmaceuticals Announces Presentation of Cancer Immunotherapy PV-10 Poster for HNSCC at AACR 2024 Annual Meeting (GlobeNewswire) - "Provectus Biopharmaceuticals...announced that data from preclinical research by Moffitt Cancer Center ('Moffitt') on PV-10 (rose bengal sodium) for the treatments of human papillomavirus ('HPV')-positive and HPV-negative head and neck squamous cell carcinoma ('HNSCC') were presented at the annual meeting of the American Association for Cancer Research....Moffitt concluded that PV-10 demonstrated significant anti-tumor activity in HNSCC. In vitro studies illustrated that PV-10 induced potent ICD in HNSCC cells, and in vivo experiments showed that IL PV-10 led to substantial tumor regression and complete responses in some mice."

Preclinical • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Provectus Biopharmaceuticals Announces Publication of Preclinical Data of Oral Administration of Provectus Rose Bengal for Solid Tumor Cancers (GlobeNewswire) - "The Narendran Lab provided preclinical proof-of-concept data supporting the efficacy of Provectus’s rose bengal in a panel of adult solid tumors. The Lab identified that the Company’s rose bengal downregulated WNK1 and Wnt signaling. In mice, the Narendran Lab also confirmed the clinical utility of Provectus’s rose bengal by intratumoral (aka intralesional) administration and demonstrated potential utility by oral administration."

Preclinical • Oncology • Solid Tumor

PV 10 induces endoplasmic reticulum stress and autophagy, triggering immunogenic cell death and anti-tumor immunity in head and neck squamous cell carcinoma (AACR 2024) - "Our collated evidence strongly suggests that PV-10 induces ICD-associated immunogenicity in both mEER and MTE-RAS in vitro and in vivo, fostered by ROS-based ER stress and apoptosis. These findings hold promise for potential therapeutic avenues to manage HNSCC."

Immunogenic cell death • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ANXA5 • CALR • HMGB1 • HSP90AA1

Identification and In Vivo Validation of Unique Anti-Oncogenic Mechanisms Involving Protein Kinase Signaling and Autophagy Mediated by the Investigational Agent PV-10 (Multidisciplinary Digital Publishing Institute) - "In a panel of human cell lines derived from breast, colorectal, head and neck, and testicular cancers, we demonstrated that PV-10 induces cytotoxicity by apoptotic and autophagic pathways....Significant inhibition of tumor growth was also noted in tumor-bearing mice treated with PV-10 by intralesional or systemic administration. In addition to known PV-10-mediated tumor-specific cytotoxic effects, we identified the mechanisms of PV-10 and provide new insights into its effect on autophagy and metastasis."

Preclinical • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Testicular Cancer

Enhance the physicochemical properties of the citronella oil -SLNPs to improve the insecticidal activity against Spodoptera littoralis (Boisd) (Lep. Nactuidae). (PubMed, Nat Prod Res) - "The Nano-formulation of citronella essential oil (Cymbopogon nardus (L.) and their mixtures of three adjuvants (Provecta®, Top film®, and PEG600-dioleate) were studied to enhance physico-chemical properties of the Nano-formulation and improve the insecticidal effect against Spodoptera littoralis (Boisd)...Before storage the acidity, alkalinity (pH), and viscosity exhibited an acidic pH value in the range (4.11-5.34), whereas after three months of storage was recorded high pH, a shift in the pH on storage can indicate the instability of active substances or product under semi field-laboratory conditions. Nano-formulation of the citronella oil mixed with the three adjuvants increased the mortality percentage of S. littoralis larvae."

Journal

Provectus Biopharmaceuticals Announces Acceptance of Cancer Immunotherapy PV-10 Abstract for HNSCC at AACR 2024 Annual Meeting (GlobeNewswire) - "Provectus Biopharmaceuticals...announced that data from preclinical research on PV-10 (rose bengal sodium) for the treatments of human papillomavirus ('HPV')-positive and HPV-negative head and neck squamous cell carcinoma ('HNSCC') will be presented at the upcoming annual meeting of the American Association for Cancer Research ('AACR')....Moffitt’s preclinical findings strongly suggest PV-10 induces immunogenic cell death-associated immunogenicity in HPV-positive and HPV-negative HNSCC in vitro and in vivo."

Preclinical • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Provectus Biopharmaceuticals Announces Acceptance of Pharmaceutical-Grade Rose Bengal Sodium Abstract for Poster Presentation at 2024 Society for Investigative Dermatology (SID) Annual Meeting (GlobeNewswire) - "Provectus Biopharmaceuticals, Inc...today announced that data from ongoing preclinical research on the topical administration of a formulation of Provectus’s proprietary, pharmaceutical-grade, small molecule, rose bengal sodium ('RBS') drug substance are being presented at the annual meeting of the Society for Investigative Dermatology (“SID”), to be held May 15-18, 2024 in Dallas, Texas."

Preclinical • Dermatology

PV-10-MM-1201: PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=50 | Active, not recruiting | Sponsor: Provectus Biopharmaceuticals, Inc.

Checkpoint inhibition • Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Provectus Biopharmaceuticals Announces Notice of Allowance of First U.S. Patent of Rose Bengal Sodium for Use as Anticancer and Antiviral Vaccine Adjuvant (GlobeNewswire) - "Provectus...today announced that the United States Patent and Trademark Office (USPTO) has allowed patent application 17/488,430...The allowed patent application covers the use of Provectus’s pharmaceutical-grade rose bengal sodium (RBS) drug substance as an adjuvant in anticancer, antiviral, and possibly other vaccines to potentially make them work better by enhancing T-cell response...The allowed application would be Provectus’s first patent award in the field of vaccines from the USPTO."

Patent • Oncology

PV-10-MM-1201: PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=50 | Active, not recruiting | Sponsor: Provectus Biopharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2 | N=192 ➔ 50

Checkpoint inhibition • Combination therapy • Enrollment change • Enrollment closed • Metastases • Phase classification • Melanoma • Oncology • Solid Tumor

Provectus Biopharmaceuticals Provides Updated Data on Cancer Immunotherapy PV-10 for Advanced Cutaneous Melanoma (GlobeNewswire) - P1b/2 | N=192 | NCT02557321 | Sponsor: Provectus Biopharmaceuticals, Inc. | "Provectus...provided updated data from an ongoing Phase 1b/2 clinical trial of investigational cancer immunotherapy PV-10 (rose bengal sodium) in combination with standard of care immune checkpoint blockade (CB) for the treatment of advanced cutaneous melanoma....For all CB-naïve patients: ORR was 72%; 20% complete response (CR) and 52% partial response (PR), Median PFS (mPFS) was 12.5 months for all patients, Median overall survival (mOS) was 37.6 months (3.1 years), and Median disease-specific survival (mDSS) was 64.4 months (5.4 years). For CB-naïve Stage III patients: ORR was 83%; 50% CR and 33% PR, CRs were rapid and durable, having been reached within 15 weeks by 2 patients and within 27 weeks by the third, and are ongoing after 24-44 months of follow-up,...mOS is estimated to be 36.3 months (3.0 years), mDSS is estimated to be 42.5 months (3.5 years)..."

P1/2 data • Cutaneous Melanoma

Provectus Biopharmaceuticals Provides Updated Data on Cancer Immunotherapy PV-10 for Metastatic Uveal Melanoma (GlobeNewswire) - P1 | N=78 | NCT00986661 | Sponsor: Provectus Biopharmaceuticals, Inc. | "Objective response of PV-10-injected hepatic lesions was assessed using 2D-EASL imaging measurement, which accounts for changes in viable and necrotic tumor: patient achieved complete response (4%); 7 patients achieved partial response (28%); 32% objective response rate, and 8 patients achieved stable disease (32%); 64% disease control rate....Median overall survival (mOS) of all patients was 11.0 months via Kaplan-Meier: mOS of all M1a patients was 30.6 months (2.6 years), and mOS of M1a patients receiving PV-10 + IN was 50.0 months (4.2 years)."

P1 data • Oncology • Solid Tumor • Uveal Melanoma

Provectus Biopharmaceuticals Announces Presentation of Preclinical PV-10 Vaccine Adjuvant Data at Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting (GlobeNewswire) - "In its SITC work, the Narendran lab showed that PV-10 treatment induced STING activation, upregulated cytokines and chemokines, and increased IFN-γ secretion by CD8+ T-cells. Dr. Narendran and his colleagues demonstrated PV-10’s ability to function as an effective adjuvant to enhance T-cell responses and concluded that PV-10’s unique modulation of the STING pathway was a potential mechanism of this activity."

Preclinical • Solid Tumor

The iodinated fluorescein derivative PV-10 enhances the antiviral activity of CD8+ T-Cells by inducing STING dimerization: implications for enhanced vaccine applications (SITC 2023) - "Our studies show its unique modulation of the STING pathway as a potential mechanism for this activity. We discuss, in detail, the experimental findings and the development of PV-10 for future clinical studies."

Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Liver Cancer • Melanoma • Oncology • Solid Tumor • CD8 • CSF2 • CXCL8 • IFNG • IL18 • IL6 • STING • TNFA

Provectus Biopharmaceuticals Announces Acceptance of PV-10 Poster Presentation at Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting (GlobeNewswire) - "Provectus...announced that preclinical data from ongoing research on investigational cancer immunotherapy PV-10 (rose bengal sodium) as an immune vaccine adjuvant will be presented on a poster presentation at the Society for Immunotherapy of Cancer (SITC) 2023 annual meeting to be held in San Diego, CA from November 1-5. This PV-10 research has been led by Aru Narendran, MD, PhD and his team of researchers at the Cumming School of Medicine at the University of Calgary in Alberta, Canada."

Preclinical • Oncology

Provectus Biopharmaceuticals Announces Acceptance of PV-10 Poster Presentations at Society for Melanoma Research (SMR) 2023 Congress (GlobeNewswire) - "Provectus...announced that data from ongoing clinical trials of investigational cancer immunotherapy PV-10 (rose bengal sodium) for the combination therapy treatments of uveal melanoma metastatic to the liver (NCT00986661) and Stage III-IV cutaneous melanoma (NCT02557321) will be presented on two poster presentations at the Society for Melanoma Research (SMR) 2023 Congress (the SMR annual meeting) to be held in Philadelphia, PA from November 6-9."

P1 data • P1/2 data • Cutaneous Melanoma • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Metabolic complete responses (mCR) in patients with metastatic uveal melanoma (mUM) treated with image-guided injection (IGI) of PV-10. (ASCO 2022) - P1 | "FDG-PET-CT shows that PV-10 is capable of inducing mCR in injected (adscopal) and non-injected (abscopal) lesions. This pattern of response is suggestive of immunogenic cell death in mUM patients with liver metastases."

Clinical • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immune Modulation • Immunology • Inflammation • Liver Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

[VIRTUAL] Pre-clinical evaluation of PV-10 for in vitro anti-tumor activity in refractory and high-risk adult solid tumors. (ASCO 2021) - P1, P1b/2 | "This study provides the first pre-clinical results of PV-10 as a novel systemically-delivered therapeutic agent for a range of high-risk and refractory adult solid tumors . Data obtained from our in vitro experiments using a broad repertoire of cell lines that represent diverse molecular and phenotypic subtypes of solid tumors in adults can serve as prerequisite pre-clinical data to establish clinical testing in these populations."

Preclinical • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Melanoma • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • Uveal Melanoma • CASP3

PV-10-NET-01: A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Provectus Biopharmaceuticals, Inc. | Trial completion date: May 2021 ➔ Sep 2023

Metastases • Trial completion date • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

"Preciosa tu chica. Yo no quiero tanta máquina, que tengo una edad ya provecta y poco adecuada para morder el asfalto." (@Baricorcho)

Provectus Biopharmaceuticals Announces New Data from Combination Therapy Trial of Small Molecule Cancer Immunotherapy PV-10 and Keytruda for First-Line Stage III Melanoma at Melanoma Bridge 2022 (GlobeNewswire) - P1/2 | N=192 | NCT02557321 | Sponsor: Provectus | "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...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....Single-agent PV-10 achieved 56% CR (and 63% ORR) of injected lesions in Stage III patients4, but only 23% CR (and 54% ORR) of non-injected lesions, and a median PFS of 8.9 to 9.8 months ...'To prove the synergistic clinical benefit of combining PV-10 and checkpoint blockade for the first-line treatment of Stage III melanoma, we plan to initiate a Phase 2/3 randomized control trial of PV-10 and standard of care checkpoint blockade versus standard of care checkpoint blockade in 2023.'"

New P2/3 trial • P1/2 data • Melanoma • Oncology • Solid Tumor