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New BPEI preclinical data address treatment protocol, corneal biochemical environment, fungal resistance mechanism, MRSA biofilm inhibition, and enhanced cysticidal activity KNOXVILLE, Tenn., May 04, 2026 (GLOBE NEWSWIRE) -- Provectus Biopharmaceuticals, Inc. (“Provectus” or the “Company”) (OTCQB: PVCT), a clinical-stage biopharmaceutical company developing proprietary synthetic small molecule rose bengal sodium (“RBS”)-based medicines, notes that researchers from Bascom Palmer Eye Institute (“BPEI”) at the University of Miami will present four posters on rose bengal photodynamic antimicrobial therapy (“RB-PDAT”) at the 2026 Annual Meeting of the Association for Research in Vision and Ophthalmology (“ARVO”), to be held May 3–7 in Denver, Colorado. Provectus’s subsidiary VisiRose, Inc. (“VisiRose”), a private clinical-stage biotechnology company, is commercializing RB-PDAT for the treatment of infectious keratitis (“IK”) and other eye infections, such as infectious scleritis. RB-PDAT is an innovative, investigational, non-invasive treatment developed by the Ophthalmic Biophysics Center (“OBC”) at BPEI. It combines PV-305, a formulation of Provectus’s pharmaceutical-grade active pharmaceutical ingredient RBS, and OBC’s green light medical device to treat eye infections caused by bacteria, fungi, and parasites, including multidrug-resistant strains. A fifth abstract will be presented by domestic and international principal investigators and medical centers who sponsored and conducted a randomized controlled trial (“RCT”) named REAGIR. REAGIR compared one RB-PDAT treatment — an approximately 45-minute outpatient procedure — against natamycin, the standard of care (“SOC”) administered topically over multiple weeks. BPEI donated RB-PDAT devices and provided technical support. Taken together, the abstracts reflect the progression of RB-PDAT well beyond proof of concept. The questions being asked at ARVO 2026 — How many treatment cycles are needed? How does the corneal biochemical environment shape therapeutic outcome? What structural features of pathogens confer resistance? — are questions of a therapy approaching maturity of clinical understanding. Abstract A: REAGIR 12-Month Outcomes — A Signal About Protocol, Not Potential Bernard et al. “Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR): Twelve month outcomes from sham-controlled, masked, randomized trial.” Abstract 3527-0110. The REAGIR trial ( NCT05110001 ) was a 330-patient, multi-center, international, double-masked, sham-controlled RCT reporting 12-month outcomes for adjunctive RB-PDAT versus sham in fungal, Acanthamoeba , and smear/culture-negative keratitis. The protocol administered a single RB-PDAT treatment. At 12 months, no statistically significant difference was observed between arms for best-corrected visual acuity, infiltrate/scar size, or rates of corneal perforation or therapeutic penetrating keratoplasty. Abstract authors are from the University of California San Francisco (trial sponsor), Stanford University, Aravind Eye Care System (India; primary clinical sites), and Federal University of São Paulo (Brazil). Interpreting these data requires understanding the REAGIR trial design and its patient strata. Species-level results tell a differentiated story. Fungal keratitis (“FK”) comprised 91% of enrollment. Fusarium , the most prevalent cause of FK globally, was 63% of all study patients. This Fusarium subgroup showed directionally better visual acuity with RB-PDAT than with SOC alone (0.17 lines better, p=0.1), marking the first time that a therapy has demonstrated a favorable directional signal versus natamycin in an RCT. Topically applied natamycin, approved by the U.S. Food and Drug Administration in 1978, remains the only ophthalmic drug approved for FK. Aspergillus FK patients trended in the opposite direction (0.39 lines worse, p=0.07), a divergence that connects directly to the melanin-mediated resistance mechanism investigated in BPEI Abstract 2. Acanthamoeba (parasitic) keratitis accounted for 3% of patients. In this cohort, too small for statistical conclusions, RB-PDAT showed 2.5 lines better vision and smaller scar size at six months, a directional signal consistent with the literature on Acanthamoeba keratitis and treatment repetition discussed below. Scar size data further support this interpretation: RB-PDAT showed meaningfully smaller scars at three weeks and three months, converging with the sham arm only at 12 months — a temporal pattern consistent with real but not sustained biological activity from a single RB-PDAT treatment. The REAGIR trial design, first listed on ClinicalTrials.gov in 2021, administered RB-PDAT only once. Bagga et al. ( Journal of Ophthalmic Inflammation and Infection , 2025) (LV Prasad Eye Institute, India) treated 14 Acanthamoeba keratitis patients with two cycles of RB-PDAT in conjunction with standard anti-amoebic therapy, demonstrating clinical resolution in cases refractory to standard therapy alone (86% success). Separately, BPEI’s Naranjo et al. ( American Journal of Ophthalmology , 2019) treated 18 patients with severe, progressive bacterial, fungal, and parasitic keratitis: nine patients received one RB-PDAT treatment (67% success) and nine received two or three (78% success). The REAGIR principal investigators concluded that “there may be value in assessing alternative…treatment algorithms.” BPEI Abstract 4 below provides direct in vitro evidence for why treatment repetition may be decisive in the most challenging pathogen class. The REAGIR trial was designed and conducted by independent clinical investigators. Based on the ophthalmic RB-PDAT biomedical literature and Provectus’s experience developing RBS across multiple disease areas, the Company believes that adequate treatment is a meaningful variable in determining patient outcomes. This is a hypothesis that mechanistic data in BPEI Abstracts 1 and 4 below directly support. BPEI Abstract 1: The Corneal Biochemical Environment Actively Shapes RB-PDAT Output Paudyal et al. “Amino Acid Modulation of Reactive Oxygen Species Generation in Rose Bengal Photodynamic Antimicrobial Therapy.” Abstract 3529-0112. RB-PDAT generates reactive oxygen species (“ROS”) upon green light activation of rose bengal. This in vitro study examined how endogenous corneal amino acids modulate that ROS output. Using an optimized DCFH₂ fluorescence assay, BPEI found that aromatic amino acids (tyrosine and tryptophan) and histidine markedly increased ROS generation, while arginine strongly suppressed it, likely through guanidinium group-mediated quenching of reactive intermediates. Negatively charged and polar neutral amino acids had minimal effect. The clinical implication is significant: a patient’s individual corneal amino acid pro modulate therapeutic response to RB-PDAT in ways not captured by standard dosing protocols. The authors note that the relationship between Type 1 (ROS) and Type 2 (singlet oxygen) pathways requires further investigation to determine which dominates antimicrobial efficacy, a question with direct bearing on rational clinical protocol design. BPEI Abstract 2: Melanin as a Resistance Mechanism in Aspergillus Keratitis Sanchez Campo et al. “Impact of Melanin on Antifungal Efficacy of Rose Bengal Antimicrobial Photodynamic Therapy in Clinical Aspergillus Isolates.” Abstract 4305-0575. RB-PDAT has demonstrated consistent antifungal efficacy across multiple pathogen classes, but the Aspergillus species has remained a relative exception. This study investigated whether melanin, a known antioxidant polymer in fungal cell walls, may function as a protective shield against ROS generated by RB-PDAT. Using DHN- and DOPA-pathway melanin inhibitors across four clinical Aspergillus strains, the authors found that DHN-pathway inhibition produced the most marked depigmentation, particularly in A. fumigatus , but yielded only modest increases in RB-PDAT susceptibility and only in one of four strains ( A. glaucus ). The authors propose that melanin may act as an energy sink rather than a conventional antioxidant, a distinction with practical implications for how combination strategies targeting Aspergillus keratitis should be designed. BPEI Abstract 3: Rose Bengal Inhibits Biofilm Formation in Clinical MRSA Isolates Durkee et al. “Inhibition of Biofilm Formation of Methicillin-Resistant Staphylococcus aureus Isolates with Rose Bengal.” Abstract 4317-0587. Biofilms represent one of the primary structural mechanisms by which ocular pathogens evade both antibiotic therapy and host immune clearance. The authors exposed six clinical methicillin-resistant Staphylococcus aureus (“MRSA”) isolates from IK patients to rose bengal for 96 hours and quantified biofilm formation using an XTT metabolic activity assay. Rose bengal inhibited biofilm formation by 74% across all six strains. This finding complements and extends research published by the University of Tennessee Health Science Center and sponsored by Provectus on RBS’s antibacterial properties, Kurosu et al. ( Molecules , 2022) , which characterized RBS’s direct antibacterial activity across multiple organisms and growth conditions, including biofilms. BPEI biofilm data add an important structural dimension: rose bengal does not merely kill planktonic organisms; it may also prevent the architectural reorganization that renders infections refractory to treatment. The clinical implications are particularly relevant for contact lens-associated keratitis, which was the most common risk factor in BPEI’s Naranjo et al. noted above. BPEI Abstract 4: Repeat and High-Fluence RB-PDAT Substantially Enhance Cysticidal Activity Navia JC, et al. “RB-PDAT Enhances Cysticidal Efficacy Without Altering the Stability of Standard Antiamoebic Agents.” Abstract 3530-0113. This abstract may carry the most direct implications for clinical protocol development. The study evaluated Standard (1×), Repeat (2×), and High-Fluence (3×) RB-PDAT in combination with standard anti-amoebic agents (PHMB and chlorhexidine) against four Acanthamoeba isolates induced to encyst. Standard RB-PDAT alone was insufficient to achieve sustained cyst inhibition, with trophozoite regrowth observed at 24 hours. Repeat and High-Fluence RB-PDAT, in combination with either PHMB or chlorhexidine, achieved 100% inhibition at 24 hours and maintained 50% cysticidal activity at 21 days. Anti-amoebic monotherapy produced only transient suppression, with regrowth by 21 days. Critically, PHMB and chlorhexidine retained full chemical stability under all RB-PDAT exposure conditions, confirming their compatibility for concurrent use. Dominic Rodrigues, Provectus’s President and Vice Chairman of its Board of Directors and Acting Chief Executive Officer of VisiRose, said, “The body of science presented at ARVO 2026 tells us what Provectus has come to understand deeply from years of work with this molecule in different diseases: rose bengal sodium is a potent, biologically active, versatile agent whose full therapeutic potential is realized when adequate treatment is given.” He added, “In the REAGIR trial, a single RB-PDAT treatment cycle was a starting point. This independently conducted international study has advanced the ophthalmology field’s clinical understanding of RB-PDAT considerably, including the first directionally favorable signal versus natamycin, the standard of care in fungal keratitis, in nearly 50 years.” Mr. Rodrigues concluded, “The REAGIR trial identified the next important question for advancing this investigational ophthalmic treatment for infectious keratitis: what can RB-PDAT achieve when clinical protocol matches biology? We intend to begin answering that question with a proposed Phase 2b/3 clinical trial following VisiRose’s pre-Investigational New Drug Application meeting with the U.S. Food and Drug Administration.” About VisiRose VisiRose is a clinical-stage biotechnology company focused on commercializing Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT), an innovative ocular therapy developed at the Bascom Palmer Eye Institute's Ophthalmic Biophysics Center at the University of Miami Miller School of Medicine, which ranked No. 1 in ophthalmology in the United States 24 times ( U.S. News & World Report , 2025-2026 Best Hospitals rankings ). RB-PDAT leverages the inherent anti-pathogenic properties of RBS, combined with light activation, with the potential to deliver safe, effective, broad-spectrum, and non-invasive treatment for infectious keratitis and other serious eye infections. RB-PDAT has been clinically validated across hundreds of patients at leading medical centers in the United States, India, Brazil, and Mexico. For more information, visit . About Provectus Provectus Biopharmaceuticals, Inc. is a clinical-stage biotechnology company developing a pipeline of immunotherapy medicines based on rose bengal sodium, a synthetic small molecule from the halogenated xanthene family. The Company’s clinical programs span oncology, dermatology, and ophthalmology, with additional proof-of-concept programs in hematology, wound healing, infectious diseases, and tissue repair. For more information, visit . 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 . Contacts: Provectus Biopharmaceuticals, Inc. Heather Raines, CPA Chief Financial Officer hraines@pvct.com (866) 594-5999 Investor Relations & Media Susan Xu sxu@allianceadvisors.com (778) 323-0959

Scientists have developed a new way to fight gum disease without wiping out the mouth’s helpful bacteria—a major shift from traditional treatments. Instead of killing everything, this targeted approach blocks only the harmful microbes that drive periodontitis, allowing beneficial bacteria to thrive and restore balance naturally.Periodontitis is a common condition that can affect much more than just oral health. Scientists at Fraunhofer have discovered a compound that specifically blocks the bacteria responsible for this disease while leaving the rest of the oral microbiome intact. This innovation has since been developed into a range of oral care products by the spin-off company PerioTrap. The human mouth contains more than 700 types of bacteria, but only a small number are linked to periodontitis. These harmful microbes collect in dental plaque, especially along the gum line, where they can trigger inflammation (gingivitis). If left untreated, this inflammation can progress into chronic periodontitis, leading to gum recession and tooth loss. The risks extend beyond the mouth. When disease-causing bacteria enter the bloodstream, they may play a role in serious conditions such as diabetes, rheumatic disease, arthritis, cardiovascular disease, chronic inflammatory bowel disease, and even Alzheimer's disease. Why Conventional Treatments Fall Short Traditional oral care products like alcohol-based mouthwashes and chlorhexidine solutions kill harmful bacteria, but they also wipe out beneficial microbes. After treatment, the oral microbiome has to rebuild itself from scratch. In this process, harmful bacteria such as Porphyromonas gingivalis often regain dominance quickly because they thrive in inflamed gum tissue. Beneficial bacteria grow more slowly, which can lead to an imbalance known as dysbiosis and allow the disease to return. A New Way to Block Harmful Bacteria Researchers at the Fraunhofer Institute for Cell Therapy and Immunology IZI in Halle identified a substance that targets harmful pathogens without affecting the rest of the microbial community. This compound, called guanidinoethylbenzylamino imidazopyridine acetate, works by preventing the growth of bacteria like Porphyromonas gingivalis rather than killing them outright. Stephan Schilling, Head of the Fraunhofer IZI branch Molecular Drug Biochemistry and Therapy Development, explains: "Rather than simply killing gingivitis pathogens, it inhibits their growth. They are unable to exert their toxic effects, so beneficial bacteria can occupy niches that would otherwise be inaccessible to them. In this way, the substance works in harmony with healthy bacteria to gently rebuild and stabilize the microbial balance in the mouth," says Schilling. From Research Project to Toothpaste The underlying technology was first developed through an EU-funded research project involving international partners. In 2018, Periotrap Pharmaceuticals GmbH was established in Halle to turn this discovery into practical oral care solutions. Working closely with Fraunhofer IZI and the Fraunhofer Institute for Microstructure of Materials and Systems IMWS, the team created a toothpaste designed to support the oral microbiome. "The product is designed to prevent periodontitis. Like conventional toothpaste, it also contains abrasives and fluoride to prevent tooth decay," explains Mirko Buchholz, one of the company's founders. Overcoming Development Challenges Transforming the compound into a usable ingredient required extensive testing. The final product needed to block harmful bacteria effectively while remaining safe for everyday use. It could not be toxic, enter the bloodstream, or cause discoloration of teeth. To achieve this, Fraunhofer IZI researchers carried out biochemical and structural studies to better understand how the substance works and to fine-tune the formulation. "This allows us to gain a better understanding of how the substances work and determine the optimum composition of the toothpaste's active ingredients," Schilling explains. Testing Toothpaste Safety and Effectiveness Fraunhofer IMWS contributed by evaluating how different formulations interact with teeth and gums. Using advanced tools such as scanning electron microscopy and chemical analysis, researchers examined compatibility and performance in detail. As Andreas Kiesow, Group Manager Characterization of Medical and Cosmetic Care Products, explains: "Scanning electron microscopy, chemical characterization and quantitative measurements enable us to draw detailed conclusions about a substance's compatibility and function. To put it simply: We ultimately find out whether the toothpaste works or not." Quality Standards and Future Products All testing followed Good Laboratory Practice (GLP) standards, ensuring that results meet strict national and international requirements. "Compliance with GLP guidelines was a key element of the project. We didn't just develop a good toothpaste with a new ingredient: we developed a high-quality oral care product of medical-grade standard," says Schilling. Work on the technology is continuing. In addition to toothpaste, researchers and the PerioTrap team have developed a gel used after professional dental cleanings to block harmful bacteria, support a healthy microbiome, and maintain gum health. More products are in development, including a mouthwash and other oral care solutions. There is also potential for use in veterinary care, since gum disease in dogs and cats has similar underlying causes.