Provectus Biopharmaceuticals Establishes Research Collaboration with University of Tennessee Health Science Center to Investigate Small Molecule Rose Bengal Disodium for Antibiotic Resistance

Wednesday September 9, 2020

 

KNOXVILLE, TN, September 9, 2020 (GLOBE NEWSWIRE) - Provectus (OTCQB: PVCT) today announced that the Company has initiated a new sponsored research program with Michio Kurosu, PhD, Professor, Department of Pharmaceutical Sciences at the College of Pharmacy of the University of Tennessee Health Science Center (UTHSC) in Memphis, Tennessee to investigate rose bengal disodium (RBD) targeting of multi-drug resistant (MDR) bacteria. RBD is Provectus' proprietary lead molecule, and a member of a class of small molecules called halogenated xanthenes that is entirely and wholly owned by the Company.

Dr. Kurosu's team will undertake in vitro studies on:

  • The spectrum of RBD activity against drug-susceptible and drug-resistant bacterial strains,
  • Synergistic activity of combinations of RBD and US Food and Drug Administration-approved antibiotics for Gram-negative bacteria,
  • The mutation frequency of RBD against bacterial strains, measuring spontaneous bacterial mutations for RBD and these combinations, and
  • Gene analyses of mutant bacterial strains to understand resistance mechanisms.

Each year, according to the Centers for Disease Control and Prevention, drug-resistant bacteria and fungi kill more than 35,000 Americans, while more than 2.8 million Americans are infected with antibiotic-resistant bacteria.1

Provectus' current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company's quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus' RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

Dominic Rodrigues, Vice Chair of the Company's Board of Directors said, "The initiation of this antibiotic resistance research is another aspect of our ongoing work to investigate and demonstrate rose bengal disodium's unique mechanistic properties and behavior across different disease areas and disease indications. Such work is fundamental to the continued expansion of Provectus' drug product platform, where disease-specific formulations of rose bengal disodium can be delivered by oral, intralesional, topical, and potentially other routes of administration."

 

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein disodium, a halogenated xanthene and Provectus' proprietary lead molecule. The Company manufactures cGMP RBD using a patented process designed to meet stringent modern global quality requirements for pharmaceuticals and pharmaceutical ingredients.

An intralesional (IL) formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10®, is being developed as a clinical-stage autolytic immunotherapy drug product for solid tumor cancers. By targeting tumor cell lysosomes, RBD treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells and a T cell mediated immune response against treatment refractory and immunologically cold tumors.2-4 Adaptive immunity can be enhanced by combining immune checkpoint blockade (CB) with RBD.5 IL PV-10 is undergoing clinical study for relapsed and refractory adult solid tumor cancers, such skin and liver cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma6,7.

A topical formulation of cGMP RBD drug substance, PH-10®, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers8.

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia9,10.

Oral formulations of cGMP RBD are undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Intellectual Property (IP)

Provectus' IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which GMP RB and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

About Provectus

Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing immunotherapy medicines for different disease areas based on an entirely- and wholly-owned family of small molecules called halogenated xanthenes. Information about the Company's clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.

References

  1. Greg Frank OC. Secretary Azar can't wait to address antibiotic resistance. TheHill. Published August 20, 2020.
  2. Wachter et al. Functional Imaging of Photosensitizers using Multiphoton Microscopy. Proceedings of SPIE 4620, 143, 2002.
  3. Liu et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7, 37893, 2016.
  4. Qin et al. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death and Disease 8, e2584, 2017.
  5. Liu et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One 13, e0196033, 2018.
  6. Swift et al. Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma. OncoTargets and Therapy 12, 1293, 2019.
  7. Swift et al. In vitro and xenograft anti-tumor activity, target modulation and drug synergy studies of PV-10 against refractory pediatric solid tumors. 2018 ASCO Annual Meeting, J Clin Oncol 36, 2018 (suppl; abstr 10557).
  8. Krueger et al. Immune Modulation by Topical PH-10 Aqueous Hydrogel (Rose Bengal Disodium) in Psoriasis Lesions. Psoriasis Gene to Clinic, 8th International Congress, British Journal of Dermatology 177. /li>
  9. Swift et al. In Vitro Activity and Target Modulation of PV-10 Against Relapsed and Refractory Pediatric Leukemia 2018 ASH Annual Meeting, Blood 132 2018 (suppl; abstr 5207).
  10. Thakur et al. Association of heat shock proteins as chaperone for STING: A potential link in a key immune activation mechanism revealed by the novel anti-cancer agent PV-10. 2020 AACR VAM II, pending (abstr 5393).

Trademark

PV-10® and PH-10® are registered trademarks of Provectus, Knoxville, Tennessee, U.S.A.

FORWARD-LOOKING STATEMENTS: This release contains forward-looking statements as defined under U.S. federal securities laws. These statements reflect management's current knowledge, assumptions, beliefs, estimates, and expectations and express management's current views of future performance, results, and trends and may be identified by their use of terms such as "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "plan," "predict," "project," "will," and other similar terms. Forward-looking statements are subject to a number of risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements. Readers should not place undue reliance on forward-looking statements. Such statements are made as of the date hereof, and we undertake no obligation to update such statements after this date. No claims with respect to PV-10, Provectus' investigational drug for oncology, or PH-10, the Company's investigational drug for dermatology, are intended regarding safety or efficacy in the context of any forward-looking statements made in this press release.

Risks and uncertainties that could cause our actual results to materially differ from those described in forward-looking statements include those discussed in our filings with the Securities and Exchange Commission (including those described in Item 1A of the Company's Annual Report on Form 10-K for the year ended December 31, 2019 and Provectus' Quarterly Report on Form 10-Q for the quarter ended June 30, 2020.

Contact:

Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
Phone: 866-594-5999

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