The Use of Provectus’s Rose Bengal Sodium as a Vaccine Adjuvant
On Monday, December 18, 2023, Provectus announced that the United States Patent and Trademark Office (USPTO) allowed the Company’s patent application 17/488,430 titled “Halogenated Xanthenes as Vaccine Adjuvants” (allowed patent application) that covers, among other things, the use of Provectus’s rose bengal sodium (RBS) drug substance as an adjuvant in anticancer, antiviral, and potentially other vaccines. The allowed patent application would be the Company’s first patent award from the USPTO in the field of vaccines.
As a matter of business course, Provectus files patent applications in major countries in Asia, Europe, and North America, using its initial USPTO application for the germane intellectual property (IP) to guide the process of protecting fundamental and incremental IP worldwide. Increasing IP protection for the Company’s halogenated xanthene (HX) medical science platform further into the 2030s, and potentially into the 2040s, is important for, among other things, potentially increasing intrinsic company valuation based on established financial and pharmaceutical industry valuation techniques (i.e., including but not limited to risk-adjusted net present value [rNPV] and discounted cash flow utilizing peak annual sales revenues).
Provectus’s foray into vaccines, which resulted from the Narendran Lab’s novel discovery, demonstrates that RBS’s underlying vaccine adjuvant mechanisms are consistent with the mechanisms in RBS’s potential systemic effectiveness in injectable solid tumor cancers.
A stronger immune response. The overall medical scientific premise of RBS as an ingredient and adjuvant in a vaccine is that RBS may potentially help create a stronger immune response in the person receiving the vaccine, compared to using another adjuvant. See Provectus’s November 8, 2023 Substack titled “Provectus’s PV-10 (rose bengal sodium) as a vaccine adjuvant.”
A stronger, better immune response. The specific premise for RBS, however, is that this stronger immune response may also be made potentially better (i.e., a response is good; a stronger response is better; a stronger, better response is best), when compared to the response from a vaccine that uses a different adjuvant. Given the demonstrated and emerging mechanisms of immune actions of RBS and, as we alluded to in the November 8th Substack, RBS may be a vaccine itself1, rather than merely a vaccine adjuvant.
Vaccine adjuvant allowed patent application.
Aru Narendran, MD, PhD, Professor of Pediatrics, Oncology, Biochemistry and Molecular Biology and Physiology and Pharmacology at the University’s Cumming School of Medicine is a co-inventor on the allowed patent application. The research underlying the allowed application was led by Dr. Narendran and his lab team (Narendran Lab).
Preclinical data from ongoing research on the potential use of investigational cancer immunotherapy PV-10 (rose bengal sodium) as a vaccine adjuvant was the subject of a poster presentation by the Narendran Lab at the Society for Immunotherapy of Cancer (SITC) 2023 annual meeting, titled “The iodinated fluorescein derivative PV-10 enhances the antiviral activity of CD8+ T-Cells by inducing STING dimerization: Implications for enhanced vaccine applications.”
The Narendran Lab previously discovered that PV-10 activated stimulator of interferon (IFN) genes (STING), demonstrating its potential as a vaccine adjuvant in PV-10-mediated systemic anti-tumor immune responses. This work, titled “Association of Heat Shock Proteins as Chaperone for STING: A potential link in a key immune activation mechanism revealed by a novel anticancer agent PV-10” was the subject of a poster presentation at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting II.
In its SITC 2023 work, the Narendran Lab showed that PV-10 treatment induced STING activation, up-regulated cytokines and chemokines, and increased IFN-γ secretion by CD8+ T-cells. Dr. Narendran and his colleagues demonstrated PV-10’s ability to function as an effective adjuvant to enhance T-cell responses and concluded that PV-10’s unique modulation of the STING pathway was a potential mechanism of this activity. This work also portends the potential benefit of PV-10 in combination with targeted immunotherapies and antibody-drug conjugates for cancer treatment.
Situational awareness.
From the start2:
Our mission has been to make the Company’s drugs, if and when approved, globally affordable and accessible,
Our business strategy has been to become a commercial-stage company by, among other things, (a) pursuing a drug approval pathway for PV-10, one that is driven down the middle of the regulatory fairway, and (b) expanding Provectus’s medical science platform. Developing new medical science, such as RBS as a vaccine adjuvant and/or a vaccine itself, and thus new IP, such as the allowed patent application, and subsequently protecting the new IP, is one element of this business strategy,
Our drug discovery strategy has been to learn what RBS, and later all HXs, are truly capable of, biologically molecularly speaking, and to demonstrate the expansiveness of the HX medical science platform. The vaccine adjuvant discovery and showing that the vaccine adjuvant mechanisms of RBS are consistent with the mechanisms of RBS in a cancer setting (and in other disease areas) are a couple of elements of this drug discovery strategy, and
Our clinical development strategy has been to better position PV-10’s clinical development program, while leveraging our drug discovery approaches to pursue other disease areas for which RBS, and later all HXs, can be utilized to treat (i.e., as a vaccine) or help to treat (i.e., as a vaccine adjuvant). Eventually showing that RBS can make an anticancer or antiviral or other vaccine work better, or eventually showing that RBS can itself be vaccine-like will be a couple of elements of this clinical development strategy.
Market opportunity(ies) for vaccine adjuvants.
The market opportunity for RBS as a vaccine adjuvant that may be added to, say, an anticancer vaccine or an antiviral vaccine is possibly very large because RBS is so multifaceted, targeting many things, enabling many immune signals and immune system elements, “playing well” (in an additive or synergistic manner from safety and efficacy perspectives) with other components and agents, etc.
It is obviously not financially realistic or prudent at this time for Provectus and its shareholders to pursue the capital-intensive path of becoming a vaccine maker. Companies like Moderna, BioNTech, etc., however, may be utilized as so-called “comps” to value this line of work (i.e., a sum-of-the-parts analysis underscoring an rNPV approach to the intrinsic valuation of the Company).
Provectus may also take several pages out of Cisco Systems’s early-Internet days’ picks-and-shovels playbook by having the Company work towards partnering with established and emerging vaccine makers now that Provectus has proof-of-concept preclinical data of RBS as a vaccine adjuvant in a range of disease areas.
Forward-Looking Statements
The information in Provectus’ Substack post may include “forward-looking statements,” within the meaning of U.S. securities legislation, relating to the business of Provectus and its affiliates, which are based on the opinions and estimates of Company management 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 “seek,” “anticipate,” “budget,” “plan,” “continue,” “estimate,” “expect,” “forecast,” “may,” “will,” “project,” “predict,” “potential,” “targeting,” “intend,” “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 Provectus’ Substack 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 (SEC), including those described in Item 1A of:
the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, and
Provectus’ Quarterly Report on Form 10-Q for the period ended September 30, 2023.
The initial mechanism of action of a drug formulation of RBS, such as PV-10, is that it needs to come in contact with the unit of disease abnormality, such as cancer cells that comprise a cancer tumor, for RBS’s mechanisms of immune action to unfold. The initial action creates the very antigens of which some are loaded onto a vaccine.
For historical context, a “group” of stockholders (i.e., PRH) entered into a Definitive Financing with the Company in 2017. PRH, then and now, specifically disclaims that it was or is a “group” as defined in U.S. federal securities laws.