Provectus Info

VisiRose & Topical PV-305 • Tex’s Journey & Intralesional PV-10 • Veripure Trademark Updatem • PDAC and Intralesional PV-10 • VisiRose: Bascom Palmer ARVO 2025 abstracts

VisiRose & Topical PV-305 (eye infections)

World Cornea Congress

REAGIR data (NCT05110001) was presented at the World Cornea Congress IX on March 22, 2025 by Dr. Venkatesh Prajna, FRCOphth, Academic Director at the Aravind Eye Hospital.

We have not yet seen Dr. Prajna’s presentation or the REAGIR data, which will be published. We understand the following about RB-PDAT from an attendee at the presentation:

• Benefit for patients with Fusarium fungal keratitis (Fusarium keratitis). Among the many fungi to cause fungal keratitis, the Fusarium species are the most frequent cause¹,

• No benefit against Aspergillus keratitis. In context, epidemiological investigations of fungal keratitis in Brazil have revealed an incidence of 67% for Fusarium, 10.5% for Aspergillus, and 10% for Candida²,

• Assumed: No benefit for Acanthamoeba (parasitic) keratitis, and

• Demonstration of treatment safety.

We also understand from this attendee that Dr. Prajna concluded his presentation saying (paraphrasing), “After today, the next ulcer I see that is fusarium, I will recommend RB-PDAT.” A corneal ulcer is also known as keratitis.

It is important to note that the treatment protocol of the REAGIR study, designed by Bascom Palmer’s colleagues at the University of California San Francisco/Stanford University, comprised one cycle of RB-PDAT at a low energy level of green light irradiation. Single therapeutic interventions appear commonplace in ophthalmology.

We very much suspect that additional RB-PDAT cycles or treatments would have resulted in improved outcomes for REAGIR, particularly for patients with Aspergillus and Acanthamoeba keratitis, compared to the original single treatment protocol.

We’ve seen this story before in our intralesional PV-10 work for injectable solid tumor cancers, where limited treatment was historically given before we improved the clinical protocol to give more, nay enough PV-10: i.e., “a little PV-10 goes a long way, but enough might cure you.”

Bottom line: REAGIR may provide VisiRose with at least one indication pathway to approval (e.g., first-line Fusarium keratitis), and may significantly contribute to establishing the safety profile of RB-PDAT.

Manufacturing

Provectus successfully concluded the manufacturing of the first clinical supply of PV-305 (i.e., about 2,500 vials) with our CDMO vendor-partner.

Tex’s Journey & Intralesional PV-10 (injectable solid tumor cancers)

You may recall that we wrote about Dr. Brad (“Tex”) Evans and his experience with IL PV-10 in a combination setting (with Keytruda) for the treatment of his Stage IV cutaneous melanoma in Provectus’s April 6, 2024 Substack post titled “Stage IV Melanoma: “…the company that saved my life””

Tex is in his second season of racing Ferraris, and sent us pictures of Provectus’s logo on his car (i.e., car livery) and a video of his most recent races at Sonoma Raceway, where he finished in 5^th and 6^th places. See 11:33 to 11:49 of the video to see Tex’s Ferrari.

Veripure Trademark Update

We expect Provectus will receive a Notice of Allowance from the USPTO for its trademark application for Veripure.

mPDAC and Intralesional PV-10 (injectable solid tumor cancers)

We continue to work on our FDA Type C meeting package for our prospective Phase 1 clinical trial at Moffitt of IL PV-10 and chemotherapy for the 2^nd-line treatment of pancreatic ductal adenocarcinoma (PDAC) metastatic to the liver (mPDAC).

VisiRose: Bascom Palmer ARVO 2025 abstracts

The 2025 annual meeting of the Association for Research in Vision and Ophthalmology will take place in Salt Lake City, Utah from May 4^th to 8^th. The conference’s online planner is here.

Bascom Palmer had at least eight RB-PDAT abstracts accepted:

• Acanthamoeba Keratitis: In vitro Cysticidal Effect of High-Fluence Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) and Antiamoebic Drugs (Abstract Number: 620 - A0359),

• Combined Inhibition of Photodynamic Antimicrobial Therapy with Amphotericin B and Natamycin: In Vitro Analysis (6267),

• Evaluating Corneal Stiffness Changes Following Rose Bengal Cross-Linking with Green Light Irradiation using Atomic Force Microscopy (1931),

• Hyaluronic Acid Conjugation for Enhanced Corneal Penetration of Rose Bengal (622 - A0361),

• Inhibition of Community- and Healthcare-Associated Methicillin-resistant Staphylococcus aureus Isolates with Photodynamic Antimicrobial Therapy (623 - A0362),

• Release Profile and Suitability of Rose Bengal Strips for Photodynamic Antimicrobial Therapy (617 - A0356),

• Singlet Oxygen Generation and Antifungal Efficacy of Rose Bengal Photodynamic Antimicrobial Therapy with Amino Acids (619 - A0358), and

• Singlet Oxygen Production of Photodynamic Antimicrobial Therapy (PDAT) in Ex Vivo Corneas (618 - A0357).

Other RB-PDAT abstracts accepted at ARVO include Adjuvant Topical 0.1% Losartan for Corneal Opacity: A Pilot Study After Rose Bengal Photodynamic Antimicrobial Therapy in Severe Infectious Keratitis (Instituto de Oftalmologia Fundacion Conde de Valenciana IAP, Mexico City, CDMX, Mexico, 621 - A0360).

Interestingly, the abstract titled “Release Profile and Suitability of Rose Bengal Strips for Photodynamic Antimicrobial Therapy” concluded that:

The rapid initial release of RB followed by a slower, gradual increase into a plateau suggests a logarithmic or exponential release model, consistent with diffusion-controlled release kinetics. The maximum concentration achieved was 0.01529%, significantly less than the intended 0.1% concentration. This indicates that the RB strips are not a good source of RB for RB-PDAT because they do not release from the strips in a way to deliver the therapeutic concentration.

These RB strips are akin to (but not actually) GloStrips Rose Bengal Ophthalmic Strips (Amcon), which Bascom Palmer first used to introduce RB-PDAT in a clinical setting in their paper titled “Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) for Patients with Progressive Infectious Keratitis: A Pilot Clinical Study” (Naranjo et al. 2019).

Bottom line: We believe there is a valid, tangible, keratitis indication pathway to approval for RB-PDAT. Key to this potential approval pathway, aside from potentially utilizing a bridging study design that would employ one or more RB-PDAT treatment cycles, is Provectus’s pharmaceutical-grade rose bengal sodium formulated at a predictable, consistent, and potentially regulatory-approvable 0.1% concentration — i.e., PV-305.

Forward-Looking Statements

The information provided in this Provectus Substack Post 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. Such statements are made in reliance on the safe harbor provisions of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. 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 Provectus’s drug agents and/or their 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 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 Provectus Substack Post are made as of the date hereof or as of the date specifically specified herein, and the Company undertakes no obligation to update or revise any forward-looking statements, whether because 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 U.S. Securities and Exchange Commission, including those described in Item 1A of Provectus’ Annual Report on Form 10-K for the period ended December 31, 2023 and on Form 10-Q for the period ended September 30, 2024.

1. Oliveira Dos Santos C, Kolwijck E, van Rooij J, Stoutenbeek R, Visser N, Cheng YY, Santana NTY, Verweij PE, Eggink CA. Epidemiology and Clinical Management of Fusarium keratitis in the Netherlands, 2005-2016. Front Cell Infect Microbiol. 2020 Apr 3;10:133. doi: 10.3389/fcimb.2020.00133. PMID: 32318355; PMCID: PMC7146074.

2. Castano G, Elnahry AG, Mada PK. Fungal Keratitis. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493192/