News Day: April 21, 2024
News Day: April 21, 2024
PV-10-injectable head and neck cancers; Orally administered anticancer rose bengal drug formulation; Ophthalmology & rose bengal photodynamic antimicrobial therapy
Head and Neck Cancers
On April 11, 2024, Provectus 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 (AACR), held April 5-10 in San Diego, California.
The poster presentation was titled PV-10 triggers immunogenic cell death and anti-tumor immunity in head and neck squamous cell carcinoma via endoplasmic reticulum stress and autophagy.
This work was part of research conducted by Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology and Program Leader of Head and Neck Oncology and members of the Chung laboratory at Moffitt in Tampa, Florida.
Moffitt observed that PV-10 induced reactive oxygen species-mediated apoptosis, surface expression of calreticulin, and extracellular ATP and HMGB1 release in HNSCC cells. PV-10-induced immunogenic cell death (ICD) led to surface expression of HSP-70 and HSP-90 in these cells. Intralesional (IL) injection of PV-10 promoted tumor regression in mice by inducing endoplasmic reticulum stress, triggering autophagy, and initiating apoptosis.
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. These findings, according to Moffitt, underscored the significance of PV-10-induced ICD, which may offer a novel and promising approach for managing HNSCC and potentially pave the way for improved survival rates and reduced adverse events.
Interestingly, in vivo (i.e., in mice), single-agent PV-10 (green line) was generally equivalent to PV-10 + anti-PD-1 (red line) in HPV-positive HNSCC (mEER cells; image J of Figure 5), and single-agent PV-10 was superior-to-equivalent (because of overlapping ranges) to PV-10 + anti-PD-1 in HPV-negative HNSCC (MTE-RAS cells; image K).
In other words, while there was a substantial reduction in tumor volume in both single-agent PV-10 and the combination of PV-10 and anti-PD-1 treatment groups in mEER and MTE-RAS tumors, no synergistic effect was observed with the combination therapy. So, for HNSCC, query whether monotherapy treatment with PV-10 is the way to go, depending on the line of treatment.
Oral Treatment of Cancer with Provectus’s Rose Bengal
On April 18, Provectus announced that data from preclinical research by the University of Calgary on oral administration of Provectus’s pharmaceutical-grade rose bengal for the treatments of solid tumor cancers were published in the open access journal of oncology Cancers.
The paper was titled Identification and In Vivo Validation of Unique Anti-Oncogenic Mechanisms Involving Protein Kinase Signaling and Autophagy Mediated by the Investigational Agent PV-10.
This work was part of research conducted by Aru Narendran, M.D., Ph.D., professor in the departments of Pediatrics, Oncology, and Biochemistry & Molecular Biology, and members of the Narendran Lab at the University of Calgary’s Cumming School of Medicine in Calgary, Alberta, Canada.
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 down-regulated 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.
We remain focused on initiating an FDA-cleared, lead clinical development program for intratumoral cancer immunotherapy PV-10 to treat hepatic metastatic pancreatic cancer, and pursuing a path to an initial drug approval for IL PV-10. Note that Provectus has previously demonstrated PV-10’s systemic response and systemic immune signaling and activation in clinical settings for metastatic liver cancers, such as metastatic neuroendocrine tumors and metastatic uveal melanoma (with or without extra-hepatic disease).
Building on IL PV-10’s clinical safety, efficacy, and immunotherapeutic profile, the Narendran Lab’s preclinical data suggest that Provectus’s rose bengal delivered by oral administration may have the potential to treat a larger pool of solid tumor cancers than PV-10.
Ophthalmology: Rose bengal photodynamic antimicrobial therapy
Eight abstracts of research on and clinical use of rose bengal photodynamic antimicrobial therapy (RB PDAT) for the treatment of eye infections were accepted for presentation at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), to be held May 5-9, 2024 in Seattle, Washington.
The accepted abstracts are:
Preclinical research/Poster:
Evaluating the Safety of Rose Bengal Photodynamic Therapy, Huang et al., Bascom Palmer Eye Institute (BPEI) (Poster board no. B0448, Session: Cornea),
Assessment of photosensitizer concentration with a Singlet Oxygen luminescence dosimeter for Photodynamic Antimicrobial Therapy, Carrera et al., BPEI (B0570, Cornea),
Enhanced Fungal Inhibition with High-Dose Rose Bengal Photodynamic Antimiocrobial Therapy, Merikansky et al., BPEI (B0580, Cornea),
Arginine-Mediated Enhancement of Photodynamic Antimicrobial Therapy to Target the Oxygen-Independent Pathway, Gonzalez et al., BPEI (B0005, Immunology/Microbiology), and
Exploring the Combination of Rose Bengal Photodynamic Antimicrobial Therapy and Existing Antifungals, Krishna et al., BPEI (B0010, Immunology/Microbiology).
Preclinical/Paper
Inhibition of Fungal Isolates via Singlet Oxygen Generation from Erythrosin B and Rose Bengal Photodynamic Antimicrobial Therapy, Ahmed et al., BPEI (4917, Cornea).
Clinical setting/Poster
Rose Bengal Photodynamic Antimicrobial Therapy as an Adjuvant Treatment for Infectious Keratitis, Eskenazi-Betech et al., Instituto de Oftalmologia Fundacion Conde de Valenciana IAP (Mexico) (B0338, Cornea; 13 patients treated), and
Clinical outcome in patients with infectious keratitis treated with Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) at the Federal University of Sao Paulo (UNIFESP), Tabuse et al., Universidade Federal de Sao Paulo (Brazil) (B0575, Cornea; 15 patients treated).
Bascom Palmer will provide Provectus with its presentations for a Company press release next month.
While RB PDAT is the subject of two international randomized, double masked, clinical trials (RCTs) for acanthamoeba and fungal (NCT05110001; enrollment complete) and bacterial (NCT06271772; not yet recruiting) keratitis, RB PDAT has now been used for keratitis patients in four countries:
U.S.: BPEI (treatment: 2016-2018; first clinical reporting of 18 patients treated by Naranjo et al. 2019),
India: LV Prasad Eye Institute (~2021; 7; Bagga et al. 2022) and Aravind Eye Care System (~2022-2024; ~330 patients treated ; NCT05110001 data readout potentially in Q4 2024),
Brazil: Universidade Federal de Sao Paulo (2023; 15 patients treated; ARVO 2024), and
Mexico: Instituto de Oftalmología in Mexico (2023; 13 patients treated; ARVO 2024).
Forward-Looking Statements
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