Independent University of Lille Study Shows Rose Bengal Sodium Produces Opposing Mechanistic Effects at the Same Dose

Peer-reviewed preclinical melanoma research finds Provectus’s synthetic small molecule can both stimulate anti-tumor immunity and suppress peripheral immune cells at the same dose.

• A recently published peer-reviewed medical journal article in Molecular Therapy: Oncology by OncoThAI researchers at the University of Lille in France shows that RBS can be immunostimulatory in tumor cells and immunosuppressive in peripheral immune cells at the same dose.
  
• Low-dose RBS combined with photodynamic activation in melanoma cells avoids the immunosuppressive effect observed at high dose while achieving equivalent tumor cell kill at a fraction of the dose.
  
• The preclinical study was conducted independently of Provectus, illustrating the value of externally generated validation that the Company’s recently launched Veripure^™ open science research program is designed to produce.
  

KNOXVILLE, Tenn., July 07, 2026 (GLOBE NEWSWIRE) -- Provectus Biopharmaceuticals, Inc. (“Provectus” or the “Company”) (OTCQB: PVCT), a clinical-stage biotechnology company developing pharmaceutical-grade rose bengal sodium (“RBS”) active pharmaceutical ingredient (“API”) as a platform therapeutic across oncology, dermatology, ophthalmology, hematology, infectious disease, wound healing, tissue repair, neurodegeneration, and other diseases, today highlighted the publication of a peer-reviewed medical journal article describing a key property of RBS. The Company’s proprietary synthetic small molecule can produce opposing immune effects across distinct cell populations at the same dose. Independent, unsolicited validation of the multiple mechanisms of action of drug product candidate PV-10, formulated from RBS API, is among the most credible evidence of RBS’s platform capabilities. It reflects science robust enough to withstand investigation the Company did not commission or control.

The paper, titled “Innovative Photodynamic Therapy Using Rose Bengal for the Treatment of Human Melanoma,” was published in Molecular Therapy: Oncology (Vol. 34, June 2026), published by Elsevier on behalf of the American Society of Gene and Cell Therapy. The study was conducted by French researchers at OncoThAI – Laser Assisted Therapies and Immunotherapies for Oncology at the University of Lille (“OncoThAI”) using PV-10 supplied by Provectus. OncoThAI aims to offer photodynamic therapy (“PDT”) for cancers with no remaining treatment options.

Provectus recently announced the launch of its Veripure open science research program to make PV-10 freely available to qualified researchers worldwide. Researchers interested in studying RBS for therapeutic applications through the Veripure program are invited to contact Provectus directly at veripure@pvct.com.

Key Finding: Opposing Immune Activity at the Same Dose

Because of specific interest in using PDT to treat cancer, OncoThAI researchers investigated RBS as a photosensitizer in human metastatic melanoma. They combined low-dose RBS with green light to evaluate PDT effects in different melanoma cell lines. The authors asked whether RBS’s known photosensitizing properties could be harnessed to reduce therapeutic dose while preserving or enhancing antitumor activity.

The Company considers the central finding of the paper to be this: at the same absolute dose, RBS produced opposing mechanistic effects in two distinct cell populations. In tumor cells, high-dose RBS killed melanoma cells predominantly through necrosis. Per the broader RBS literature the authors cite, this form of cell death releases damage-associated molecular patterns (“DAMPs”) — including high mobility group box 1 (HMGB1), calreticulin, and heat shock protein 90 (HSP90) — that innate immune sensors recognize, activating dendritic cells and triggering downstream adaptive responses against tumor antigens. In peripheral immune cells, evaluated in parallel experiments, the same RBS dose significantly suppressed proliferation of peripheral blood mononuclear cells (“PBMCs”) in non-activated and PHA-activated conditions.

Put simply: High-dose RBS was immunostimulatory toward the tumor it was killing and immunosuppressive toward the peripheral immune cells positioned to respond to that killing. These are two concurrently opposing mechanistic effects by the same molecule at the same dose.

RBS’s capacity to express different, even opposing, biological activities — sometimes at once, sometimes over time — depending on dose and cellular context is the same underlying property that gives the molecule its platform breadth across its full range of indications. The OncoThAI paper demonstrates that this same context-dependence can be directed, not merely observed.

The French researchers showed that PDT is a treatment strategy that can direct this dose-dependent biology, concentrating RBS’s tumor-killing activity locally while keeping peripheral immune cells below the concentration threshold associated with suppression. Combined with green light, PDT-RBS was far more potent than RBS alone: 121 times more effective at reducing melanoma cell viability in HBL cells and 40 times more effective in LND cells. To reach 80% cell death, this cut the required RBS dose roughly 15-fold in HBL cells (492 µM to 32 µM) and 14-fold in LND cells (1,043 µM to 74 µM). At the lower dose, RBS avoided suppressing PBMC proliferation. Conditioned media from PDT-RBS–treated melanoma cells significantly increased proliferation of activated PBMCs at 72 and 120 hours. This response was consistent with the release of immunostimulatory soluble factors and the DAMP-driven immune activation cascade, without the immunosuppressive effect observed at high dose.

Dominic Rodrigues, President and Vice Chairman of the Board of Provectus, noted, “The OncoThAI paper does something that has not been shown before in RBS literature. The data demonstrate that RBS can express multiple biological activities — some concurrent, some sequential — whose relative dominance depends on molecular quantity and cellular context. OncoThAI’s data, arrived at independently, show that dose and delivery strategy can direct which of RBS’s activities dominate in a given tissue compartment. That insight deepens our understanding of RBS’s therapeutic profile across its full indication spectrum.”

Consistent with Veripure’s Open Science Philosophy

This study was conducted in a non-sponsored setting using PV-10 supplied to OncoThAI under the practice of unconstrained academic research access that the Company has maintained for years and has since formalized under its Veripure open science program. Researchers receive PV-10 drug product candidate, formulated from pharmaceutical-grade RBS API, without restrictions on research direction, design, or findings, and without publication controls, strict data-sharing requirements, or indication limits.

Mr. Rodrigues added, “We did not commission this study, design its hypotheses, or direct its conclusions. OncoThAI asked their own question — whether photodynamic activation could optimize RBS’s dose-response profile — and arrived at a finding that meaningfully advances our understanding of the molecule’s multi-mechanistic behavior. That is precisely the kind of validation Veripure is designed to produce: independent researchers, working from their own hypotheses, generating findings of real scientific consequence using the same pharmaceutical-grade material our clinical programs depend on.”

About Provectus

Provectus Biopharmaceuticals, Inc. is a clinical-stage biotechnology company developing a pipeline of immunotherapy medicines based on rose bengal sodium, a first-in-class synthetic small molecule from the halogenated xanthene family. The Company’s clinical programs span oncology, dermatology, and ophthalmology, with additional proof-of-concept and early discovery programs in hematology, wound healing, infectious diseases, tissue repair, and neurodegeneration. For more information, visit www.provectusbio.com.

Forward Looking Statements

The information in this press release may include “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, relating to the business of Provectus and its affiliates, which are based on currently available information and current assumptions, expectations, and projections about future events and are subject to a variety of risks and uncertainties and other factors that could cause actual events or results to differ materially from those projected in the forward-looking statements. Forward-looking statements are often, but not always, identified by the use of words such as “aim,” “likely,” “outlook,” “seek,” “anticipate,” “budget,” “plan,” “continue,” “estimate,” “expect,” “forecast,” “may,” “will,” “would,” “project,” “projection,” “predict,” “potential,” “targeting,” “intend,” “can,” “could,” “might,” “should,” “believe,” and similar words suggesting future outcomes or statements regarding an outlook.

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated or that such agents as products will achieve any particular revenue levels.

Due to the risks, uncertainties, and assumptions inherent in forward-looking statements, readers should not place undue reliance on these forward-looking statements. The forward-looking statements contained in this press release are made as of the date hereof or as of the date specifically specified herein, and Provectus undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except in accordance with applicable securities laws. The forward-looking statements are expressly qualified by this cautionary statement.

Risks, uncertainties, and assumptions include those discussed in the Company’s 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 period ended December 31, 2025 and Quarterly Report on Form 10-Q for the period ended March 31, 2026.

Contacts:
Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
hraines@pvct.com
(866) 594-5999

Investor Relations & Media

Susan Xu
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(778) 323-0959

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