Provectus Info

VisiRose & Topical PV-305 • Oral PV-10 to treat cancer • Pre-operative Penile SCC & Intralesional PV-10 • Dermatology & Topical PH-10 • Veripure launch

VisiRose & Topical PV-305

Activity update

Our regulatory consulting firm continues to work with the Ophthalmic Biophysics Center (OBC) at Bascom Palmer Eye Institute to transfer in vitro, in vivo, and clinical data from their 10+ years of work on rose bengal photodynamic antimicrobial therapy (RB-PDAT) for the treatment of bacterial, fungal, and parasitic infectious keratitis – where PV-305 is administered topically into the eye, followed by the application of green light.

Part of this overall dataset for VisiRose’s pre-investigational new drug (IND) meeting submission package would include the dataset from the REAGIR clinical study (NCT05110001), a 330-patient, double-masked, sham-controlled trial of RB-PDAT for the treatment of fungal and parasitic keratitis.

Note: PV-305 is a formulation of PV-10, which is a formulation of only Provectus’s rose bengal sodium (RBS) in a saline solution.

World Cornea Congress

We are still led to believe that REAGIR’s data will be presented at the World Cornea Congress IX, to be held in Washington D.C. from March 20-22, 2025, and the presentation in question will be made on March 22^nd.

Oral PV-10 to treat cancer

Investor-shareholder support

A Provectus investor-shareholder – i.e., a Provectus shareholder who previously invested in Provectus’s unsecured convertible note-convertible preferred stock investment structure – approached us to invest in the Company to support our introduction of an oral formulation of PV-10 (i.e., a different route of administration that intralesional [aka intratumoral] administration of PV-10). Such financial support investment would only be via the abovementioned investment structure (i.e., there are no other terms and conditions).

They further wish to support bladder cancer in an early-stage clinical trial as a first indication for oral delivery of PV-10, a first step towards treating adult and pediatric solid tumor and blood cancers.

Oral PV-10 for cancer treatment writ large has long been in Provectus’s business and clinical strategy of the Company current leadership team since 2017. This has been especially so since Dr. Aru Narendran and the Narendran Lab of the Cumming School of Medicine at the University of Calgary (Alberta, Canada) demonstrated dose-dependent survival in in vivo studies of leukemias in 2020. A good reference for this discussion is Provectus’s Substack post of April 6, 2023 titled “The Impact of COVID-19 on Provectus’s Research & Development, Halogenated Xanthene Medical Science Platform, and Rose Bengal Sodium-based Investigational Drug & Drug Formulation Pipeline.”

The Narendran Lab’s 2020 non-clinical work builds, of course, on Ito et al. from 1986 that observed dose-dependent survival from oral administration of rose bengal in normal mice, as well as on promising non-clinical work of Provectus in the early-2000s.

Expansion of PV-10’s existing IND

Such investor-shareholder financial support could comprise paying for, via investment in Provectus, (i) the regulatory work to expand PV-10’s existing IND to include oral administration and (ii) a Phase 1 clinical trial of the lead indication for oral PV-10.

Such investor-shareholder support accelerates our business plan to potentially roll out oral PV-10.

More to come…

Oral PV-10 for…?

Establishing the regulatory groundwork for oral PV-10 can provide for more than just entry into an early-stage cancer clinical trial. This can potentially provide for an expanded access program for cancer, and the opportunity to explore diseases where systemic administration of PV-10 is more applicable, such as potentially for autoimmune diseases, neurological diseases, etc.

As an aside, while we don’t necessarily believe in labels (but do believe that some labels can help foster some conversations), one could consider PV-10 to be a gene therapy. Gene therapy involves modifying or manipulating genes within a person’s cells to treat or prevent disease. Our thinking supports the prospect of PV-10 helping the body to fix a faulty gene; however, if a gene is entirely missing, PV-10 very likely cannot help the body replace it.

Pre-operative Penile SCC & Intralesional PV-10

Turning the prior concept of a Moffitt IIT into a Provectus-sponsored study

After extended dialog with the interested Genitourinary Oncology Program team from Moffitt Cancer Center, Moffitt and Provectus agreed to undertake a sponsored-study, instead of an investigator-initiated trial (IIT). That is, the potential 18-patient Phase 1 trial of monotherapy PV-10 for the treatment of pre-operative penile squamous cell carcinoma (SCC) would be done under Provectus’s IND, rather than the Moffitt principal investigator’s IND as originally requested of Provectus.

According to Moffitt’s Penile Cancer Overview webpage, “…penile cancer is quite rare, accounting for less than 1% of cancers affecting men in developed countries. The American Cancer Society estimates that approximately 2,000 new cases are diagnosed annually in the United States, with an incidence rate of approximately 1 in 100,000 men per year. The condition is more common in certain regions of Africa, Asia and South America, where limited access to healthcare for early detection and preventive measures may contribute to its prevalence.”

Our decision to request such clinical work to be done under Provectus’s IND stems from our requirement to ensure appropriate, consistent, and comprehensive reporting of safety and tolerability of PV-10 treatment. For example, Provectus regularly makes its Development Safety Update Report (DSUR) to the FDA, a yearly exercise and report that summarizes safety information of PV-10 drug development.

In switching to Provectus’s IND, we further assessed the greater potential for Provectus to more fully fund the study, compared to funding that Moffitt’s principal investigator secured internally.

Dermatology & PH-10

Galveston helped NYC

Our research collaborators at the University of Texas Medical Branch (UTMB) in Galveston, who are currently running a pig study of a formulation of PV-10 for the treatment of full-thickness cutaneous wounds, shared PV-10-treated tissue samples (along with control samples; i.e., untreated skin) from a/the pig to our research collaborators at The Rockefeller University (TRU).

We await the results of UTMB’s non-clinical pig work…

RNA sequencing

We are waiting for the abovementioned tissue samples to be RNA sequenced (i.e., PV-10-treated and untreated mRNA skin samples). We know the TRU researchers are anxious to see the data to be definitive on their views regarding PH-10’s influence and impact on gene expression. Their views will dictate the ultimate size of PH-10’s addressable market.

Note: PH-10 is a hydrogel-based formulation of PV-10, which is a formulation of RBS.

Veripure launch

Open source research access to PV-10

We continue to prepare the groundwork for launching a Veripure website and awareness program to encourage researchers around the world to work with Provectus’s pharmaceutical-grade RBS (as PV-10), rather than purchase commercial grade rose bengal from Sigma Aldrich (now MilliporeSigma) for their research on rose bengal.

We will offer RBS (i.e., vials of PV-10) for free to any researcher of any disease or disorder.

More to come…

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.