What changed in this filing

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Item 1. Business

2025-03-28 compared with 2024-03-28 · 280 added, 133 removed, 141 unchanged (75% of the section changed)

Biopharmaceuticals, Inc., a Delaware corporation incorporated in 2002 (together with its subsidiaries, “Provectus” or

“the Company”), is a clinical-stage biotechnology company developing immunotherapy medicines for different diseases that

are based on a class of synthetic small molecule immuno-catalysts called halogenated xanthenes (“HXs”).

molecule is named rose bengal sodium (“RBS”).

Company’s proprietary, patented, pharmaceutical-grade RBS is the active pharmaceutical ingredient in the drug product candidates

of our current clinical development programs and the preclinical formulations of our current drug discovery programs.

Importantly, our

pharmaceutical-grade RBS displays different therapeutic effects at different concentrations and can be formulated for delivery by different

routes of administration.

Company believes that RBS targets disease in a bifunctional manner.

First, direct contact may lead to cell death or repair, depending

on the disease being treated and the concentration of the RBS utilized in the treatment.

Second, multivariate immune signaling, activation,

and response may follow that may manifest as stimulatory, inhibitory, or both.

Company believes that it is the first entity to advance an RBS formulation into clinical trials for the treatment of a disease, such

as those trials reported on the clinical trials registry at ClinicalTrials.gov.

Company believes that it is the first and only entity to date to make pharmaceutical-grade RBS successfully, reproducibly, and consistently

at a purity of nearly 100%.

Company’s small molecule HX medical science platform comprises several different drug product candidates and preclinical pharmaceutical-grade

RBS formulations using different concentrations delivered by different routes of administration specific to each disease area and/or

The Company’s HX medical science platform includes clinical development programs in oncology, dermatology, and ophthalmology;

in vivo proof-of-concept programs in oncology, hematology, wound healing, and animal health;

and in vitro drug discovery

programs in infectious diseases and tissue regeneration and repair.

hold patents covering the HX medical science platform that we have developed and are continuing to develop for drug product candidates

and drug formulations in different disease areas.

Biopharmaceuticals, Inc., a Delaware corporation (together with its subsidiaries, “Provectus” or “the Company”),

is a clinical-stage biotechnology company developing immunotherapy medicines for different diseases.

Our drug product candidates are

based on bioactive, synthetic, small molecule rose bengal sodium (“RBS”), which is a member of a class of molecules called

halogenated xanthenes (“HXs”).

Company’s proprietary, patented, pharmaceutical-grade RBS is the active pharmaceutical ingredient (“API”) in all our

clinical development and non-clinical research programs.

The Company is the first entity to advance RBS into clinical trials for the

treatment of disease.

The Company is also the first entity, and currently the only one, to date to make pharmaceutical-grade RBS API

consistently at a purity of nearly 100%.

can be delivered by different routes of administration.

RBS may concurrently display stimulatory and inhibitory effects and may target

disease in a bifunctional multi-modal manner.

Direct contact by RBS with disease may lead to cell death or repair by one or more targeting

mechanisms, depending on the disease being treated and the concentration of RBS being utilized in the formulation.

Multivariate innate

and adaptive immune activation, signaling, and response may follow.

Company’s RBS drug platform and pipeline comprise drug product candidates and non-clinical formulations that use different amounts

of RBS and are delivered by different routes of administration specific to each disease area, including:

Development programs in oncology (intratumoral administration), dermatology (topical), and ophthalmology (topical),

Proof-of-concept programs in oncology (oral), hematology (oral), wound healing (topical), and canine cancers (intratumoral),

Early discovery programs in infectious diseases and tissue regeneration and repair, and

Computer modeling of amyotrophic lateral sclerosis and other disease targets.

hold patents covering RBS and HX medical science.

All patents awarded by the U.S.

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are material to an understanding of the Company are listed in the table below.

antiperspirant and antimicrobial compositions

In 2024, we received five patent awards from the USPTO:

for the synthesis of rose bengal and related xanthenes

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of Local and Systemic Therapies for Enhanced Treatment of Dermatologic Conditions

received one patent allowance from the USPTO in 2023, U.S.

patent application number 17/488,430 titled “Halogenated Xanthenes as

Vaccine Adjuvants.” Two patent applications were also published on the USPTO’s website:

Anti-Gram-Positive Bacterial Activity of Pharmaceutical-Grade Rose Bengal (USPTO application number 18/089,011), and

Xanthene-Containing Topical Anti-Gram-Positive Bacterial Ophthalmic Composition and Method (18/089,134).

xanthenes as vaccine adjuvants

of halogenated xanthenes in oncology and virology

vitro and xenograft anti-tumor activity of a halogenated xanthene against refractory pediatric solid tumors

and method for oral treatment of leukemia

xanthene composition and method for treating hematologic cancers

2024, four patent applications were also published on the USPTO’s website:

Anti-bacterial

effect of halogenated fluorescein against colistin-resistant gram-negative bacteria (USPTO application number 18/615,444),

Xanthenes as Vaccine Adjuvants (18/581,095),

Vitro and Xenograft Anti-Tumor Activity of a Halogenated-Xanthene Against Refractory Pediatric Solid Tumors (18/642,051), and

and Method for Treating Hematologic Cancers (17/890,659).

International

2023, the Company received a patent award for Mexico for “Method of Ex Vivo Enhancement of Immune Cell Activity for Cancer

Immunotherapy With A Small Molecule Ablative Compound,” patent awards for Australia and Mexico for “Combination of Local

And Systemic Therapies for Enhanced Treatment of Dermatologic Conditions,” and patent awards for Australia, China, Europe, Hong

Kong, and Mexico for “In Vitro And Xenograft Anti-Tumor Activity Of A Halogenated-Xanthene Against Refractory Pediatric Solid Tumors.”

2024, the Company received patent awards and allowances for eight of our patent families:

of local and systemic immunomodulative therapies for enhanced treatment of cancer” in Canada,

of Local and Systemic Therapies for Enhanced Treatment of Dermatologic Conditions” in Europe,

vitro and xenograft anti-tumor activity of a halogenated xanthene against refractory pediatric solid tumors” in Canada (allowance),

and Methods for Treating Hematologic Cancers” in Japan and Australia (allowance),

Uses of halogenated xanthenes in oncology and virology” in China and Japan,

of Solid Cancerous Tumors by Oral Administration of a Halogenated Xanthene” in Japan,

Xanthene Composition and Method for Treating Hematologic Cancers” in Japan, and

xanthenes as vaccine adjuvants” in Japan.

Development and Drug Discovery

Company’s small molecule HX medical science platform includes:

Development Programs

Intratumoral (“ITU”) formulation PV-10 ® (“ITU PV-10”) has undergone and is undergoing

multiple, monotherapy and combination therapy, early- to late-stage clinical trials, expanded access programs (“EAPs”)

for groups of and individual patients, and/or quality of life (“QOL”) study at multiple clinical sites in Australia,

Europe, and the U.S.

for the treatments of Stage III and IV melanoma and different types of liver cancers.

ITU PV-10 has undergone

and is undergoing clinical monotherapy and combination therapy mechanism of action and mechanism of immune response study for melanoma,

metastatic uveal melanoma, and metastatic neuroendocrine tumors at and/or with Moffitt Cancer Center in Tampa, Florida, The Queen

Intratumoral PV-10 has undergone and is undergoing multiple, monotherapy and combination therapy, early-to-late-stage clinical

trials, expanded access programs (“EAPs”) for groups of and individual patients, and/or quality of life (“QOL”)

study at multiple clinical sites in Australia, Europe, and the U.S.

for the treatments of Stage III and IV melanoma, different types

of liver cancers, and breast cancer.

has undergone clinical monotherapy and combination therapy study of mechanisms of action and immune response for melanoma, metastatic

uveal melanoma, and metastatic neuroendocrine tumors at Moffitt Cancer Center (“Moffitt”) in Tampa, Florida, The Queen

Elizabeth Hospital in Adelaide, Australia, and MD Anderson Cancer Center in Houston, Texas.

Topical (“TOP”) formulation PH-10 ® (“TOP PH-10”)

has undergone multiple mid-stage, monotherapy clinical trials for the treatments of psoriasis

lead indication for intratumoral PV-10 is FOLRINOX-refractory pancreatic ductal adenocarcinoma (“PDAC”) metastatic to

the liver (“mPDAC”), where patients would receive the combination therapy of PV-10 and systemically administered gemcitabine

and nab-paclitaxel at a single-site early-stage clinical trial at Moffitt.

Company may pursue a secondary indication of pre-operative penile squamous cell carcinoma (“penile SCC”), where patients

would receive monotherapy PV-10 at a single-site early-stage clinical trial at Moffitt.

Topical PH-10, a formulation of PV-10, has undergone multiple mid-stage, monotherapy clinical trials for the treatments of psoriasis

and atopic dermatitis at different clinical sites in the U.S.

TOP PH-10 has undergone clinical

monotherapy mechanism of action and mechanism of immune response study for psoriasis at The

Rockefeller University in New York, New York (“TRU”).

formulations have undergone preclinical combination therapy study for psoriasis and are undergoing preclinical monotherapy study

for skin inflammation at TRU.

has undergone clinical monotherapy mechanism of action and mechanism of immune response study for psoriasis at The Rockefeller University

in New York, New York (“TRU”).

PV-10 formulations have undergone non-clinical combination therapy study for psoriasis and are undergoing non-clinical monotherapy

study for skin inflammation and skin aging at TRU.

Ophthalmology:

The Company believes that clinical monotherapy proof-of-concept (“POC”) of

TOP administration of non-pharmaceutical grade rose bengal for the treatment of infectious

keratitis has been shown by clinicians and researchers at the University of Miami’s

(“UM’s”) Bascom Palmer Eye Institute (“BPEI”) in Miami, Florida,

who are now collaborating with the Company to evaluate the potential use of our pharmaceutical-grade

PV-305 has undergone preclinical monotherapy study for diseases and disorders of the eye, such as infectious keratitis at BPEI.

Vivo Proof-of-Concept Drug Discovery Programs

ITU PV-10 has undergone preclinical monotherapy and combination therapy study for the treatment of relapsed and refractory pediatric

solid tumor cancers at the University of Calgary’s Cumming School of Medicine in Calgary, Alberta, Canada (“UCal”).

The Company believes that the UCal researchers have achieved monotherapy in vivo POC of ITU administration.

(“PO”) formulations are undergoing preclinical monotherapy study for high-risk and refractory adult solid tumor cancers

The Company believes that the UCal researchers and the Company have both achieved monotherapy in vivo POC of PO administration,

that the Company has achieved monotherapy in vivo POC of PO administration in prophylactic and therapeutic settings, and that

the Company has achieved monotherapy in vivo POC of intravenous (“IV”) administration.

PO formulations are undergoing preclinical monotherapy study for the treatment of refractory and relapsed pediatric and other

blood cancers, including leukemias, at UCal.

The Company believes that the UCal researchers have achieved in vivo POC of PO

administration.

Different formulations are undergoing preclinical monotherapy study for the healing of full-thickness cutaneous wounds.

The Company believes that monotherapy in vivo POC of TOP administration of non-pharmaceutical grade rose bengal for the treatment

of this indication has been shown by researchers at the University of Texas Medical Branch (“UTMB”) in Galveston, Texas,

who are now collaborating with the Company to use our pharmaceutical-grade RBS.

Different formulations are undergoing preclinical monotherapy study for the treatment of cutaneous canine cancers at

the University of Tennessee’s College of Veterinary Medicine in Knoxville, Tennessee.

The Company believes that clinical proof-of-concept (“POC”) of topical administration of non-pharmaceutical grade

rose bengal in combination with a light source medical device for the treatment of infectious keratitis has been shown by clinicians

and researchers at the University of Miami’s (“UM’s”) Bascom Palmer Eye Institute (“BPEI”) in

Miami, Florida, who are now collaborating with the Company to evaluate the potential use of our pharmaceutical-grade RBS.

formulation PV-305, a formulation of PV-10, has undergone non-clinical combination therapy study (i.e., drug and device) for diseases

and disorders of the eye, such as infectious keratitis, at BPEI.

Company launched a clinical-stage start-up biotechnology company named VisiRose, Inc.

(“VisiRose”), a collaboration between

the Company and UM to commercialize BPEI’s ocular research using PV-305.

Proof-of-Concept

Intratumoral PV-10 has undergone non-clinical monotherapy and combination therapy study for the treatment of relapsed and refractory

pediatric solid tumor cancers at the University of Calgary’s Cumming School of Medicine in Calgary, Alberta, Canada (“UCal”).

The Company believes that the UCal researchers have achieved monotherapy in vivo POC of intratumoral administration for pediatric

solid tumor cancers.

(“PO”) formulations of PV-10 have undergone non-clinical monotherapy study for high-risk and refractory adult solid tumor

cancers at UCal.

The Company believes that the UCal researchers and the Company have both achieved monotherapy in vivo POC

of PO administration, that the Company has achieved monotherapy in vivo POC of PO administration in both prophylactic and

therapeutic settings, and that the Company has achieved monotherapy in vivo POC of PO administration for adult solid tumors.

PO formulations of PV-10 have undergone non-clinical monotherapy study for the treatment of refractory and relapsed pediatric

and other blood cancers, including leukemias, at UCal.

The Company believes that the UCal researchers have achieved in vivo

POC of PO administration for blood cancers.

The Company believes that monotherapy in vivo POC of topical administration of non-pharmaceutical grade rose

bengal for the treatment of this indication has been shown by researchers at the University of Texas Medical Branch (“UTMB”)

in Galveston, Texas, who are now collaborating with the Company to use our pharmaceutical-grade RBS.

formulations of PV-10 are undergoing non-clinical monotherapy study for the healing of full-thickness cutaneous wounds at UTMB.

PV-10 formulations have undergone non-clinical monotherapy study for the treatment of cutaneous canine cancers at the

University of Tennessee’s College of Veterinary Medicine in Knoxville, Tennessee.

The Company believes that it has achieved

monotherapy POC in canines of ITU administration.

Vitro Drug Discovery Programs

PO and intranasal (“IN”) formulations have undergone preclinical monotherapy study for the treatment of

SARS-CoV-2 at UCal, another Canadian academic research center, the University of Tennessee Health Science Center (“UTHSC”)

monotherapy POC of intratumoral administration for canine cancers.

Drug Discovery Programs

vaccine adjuvant:

Different formulations of PV-10 have undergone non-clinical study as a vaccine adjuvant to enhance T cell responses

for anti-viral and anti-cancer vaccines.

PO and intranasal (“IN”) formulations of PV-10 have undergone non-clinical monotherapy study for the treatment

of SARS-CoV-2 at UCal, another Canadian academic research center, the University of Tennessee Health Science Center (“UTHSC”)

in Memphis, Tennessee, and a U.S.

contract research organization.

formulations have undergone preclinical monotherapy and combination therapy study for the treatment of gram-positive and gram-negative

bacterial infections (including multi-drug resistant strains) and have undergone preclinical monotherapy study for the treatment

of oral bacterial infections at UTHSC.

formulations have undergone preclinical monotherapy study for the treatment of fungal infections at UTHSC.

Different formulations of PV-10 have undergone non-clinical monotherapy

and combination therapy study for the treatment of gram-positive and gram-negative bacterial infections (including multi-drug-resistant

strains) and have undergone non-clinical monotherapy study for the treatment of oral bacterial infections at UTHSC.

Different formulations

of PV-10 have undergone non-clinical monotherapy study for the treatment of fungal infections at UTHSC.

Regeneration and Repair :

Different formulations have undergone preclinical monotherapy study for vertebrate development, wound

healing, and tissue regrowth at the University of Nevada, Las Vegas (“UNLV”) in Las Vegas, Nevada.

April, preclinical research on the Company’s pharmaceutical-grade rose bengal sodium drug substance against colistin-resistant

gram-negative bacteria was published in The Journal of Antibiotics, a medical periodical by Nature Portfolio for the Japan Antibiotics

Research Association:

“Antibacterial effect of rose bengal against colistin-resistant gram-negative bacteria.”

June, the Company initiated a new sponsored research program with the University of Tennessee College of Veterinary Medicine to assess

the safety and preliminary efficacy of intralesional injection of a formulation of the Company’s pharmaceutical-grade RBS for canine

soft tissue sarcomas.

Company’s stockholders approved the proposals of the Board of Directors (“Board”) to seek the authority to undertake

a reverse stock split and an authorized share reduction.

July, the USPTO published the Company’s patent application entitled “Photodynamic Anti-Gram-Positive Bacterial Activity of

Pharmaceutical-Grade Rose Bengal” (publication no.

August, the USPTO published the Company’s patent application entitled “Halogenated Xanthene-Containing Topical Anti-Gram-Positive

Bacterial Ophthalmic Composition and Method” (publication no.

November, preclinical data from ongoing research on the potential use of PV-10 as an adjuvant in vaccines to help them work better was

the subject of a poster presentation at the Society for Immunotherapy of Cancer (SITC) 2023 annual meeting, held in San Diego, CA from

November 1-5:

“The iodinated fluorescein derivative PV-10 enhances the antiviral activity of CD8+ T-Cells by inducing STING dimerization:

Implications for enhanced vaccine applications.”

Company provided updated data from an ongoing Phase 1 clinical trial of PV-10 for the treatment of uveal melanoma (UM) metastatic to

the liver (mUM) (NCT00986661).

Company also provided updated data from an ongoing Phase 1b/2 clinical trial of PV-10 in combination with standard of care immune checkpoint

blockade for the treatment of advanced cutaneous melanoma (NCT02557321).

December, the USPTO allowed patent application 17/488,430, titled “Halogenated Xanthenes as Vaccine Adjuvants.” The allowed

patent application covers the use of Provectus’s pharmaceutical-grade rose bengal sodium (RBS) drug substance as an adjuvant in

anticancer, antiviral, and possibly other vaccines to potentially make them work better by enhancing T-cell response.

Different formulations of PV-10 have undergone non-clinical monotherapy study for vertebrate development,

wound healing, and tissue regrowth at the University of Nevada, Las Vegas in Las Vegas, Nevada.

Different formulations of PV-10 are undergoing non-clinical study for proprietary diseases at an academic medical center.

Modeling Programs

Computer-based

molecular docking of RBS has been done and is being done for amyotrophic lateral sclerosis and other disease targets.

Company is planning to initiate new intratumoral PV-10 monotherapy and combination therapy clinical trials in mPDAC and pre-operative

penile SCC indications to generate new clinical data and appropriately utilize historical clinical data from intratumoral PV-10 trials,

EAPs, and/or QOL study of injectable solid tumor cancers.

Our goals are to pursue drug approval pathways and/or co-development relationships

with commercial pharmaceutical companies for intratumoral PV-10 based on these and other indications.

Company is developing a systemically administered formulation of PV-10 for the treatment of cancer.

Our goals, when this work is complete,

are to file and have accepted an investigational new drug application (“IND”) with the U.S.

Food and Drug Administration

(“FDA”), take an initial systemic drug product candidate into an early-stage clinic trial for an initial oncology or hematology

indication, and/or pursue a co-development collaboration or out-license arrangement for this route of administration and disease area.

Company is developing different formulations of PV-10 and different routes of administration for other disease areas by endeavoring to

show non-clinical activity and lack of toxicity.

Our goals, when each task of this work is completed, are to file and have accepted an

IND with the FDA, take an initial drug candidate into an early-stage clinic trial for an initial indication, and/or pursue a co-development

collaboration or out-license arrangement for the respective disease area and route of administration.

Company is endeavoring to fully elucidate the traits and characteristics of the RBS molecule using different academic medical centers

under sponsored research and testing agreements.

Our goal is to gain and communicate additional knowledge of the RBS molecule’s

targeting, mechanism, signaling, immune response, and other features that are common to and/or different from each disease area under

Company is doing rigorous chemical analytical comparisons of non-pharmaceutical grades of rose bengal from specialty chemical suppliers

against the Company’s pharmaceutical-grade RBS.

Our goal is to demonstrate the proprietary nature of the Company’s pharmaceutical-grade

RBS and that our pharmaceutical-grade RBS meets the necessary uniformity and purity requirements for commercial pharmaceutical use.

API and Drug Candidate Manufacturing

pharmaceutical-grade RBS resulted from:

Company’s innovation of a proprietary, patented, commercial-scale process to synthesize the RBS molecule into a viable active

pharmaceutical ingredient (“API”) for commercial pharmaceutical use,

development of unique chemistry, manufacturing, and control (“CMC”) specifications for API and drug candidate manufacturing

production and multi-year stability testing of multiple API and drug candidate lots;

the comprehensive documentation of lot composition

and reproducibility, and

review and acceptance of CMC data from these lots by seven different national drug regulatory agencies for use in a prior, multi-country,

multi-center Phase 3 randomized control trial of the Company.

Company’s API and drug candidate manufacturing processes employ Quality-by-Design principles, current good manufacturing practice

(“cGMP”) regulations, and the guidelines of The International Council for Harmonization (ICH) of Technical Requirements for

Pharmaceuticals for Human Use.

These processes utilize controls that eliminate the formation of historical impurities and avoid the introduction

of potentially hazardous impurities that the Company believes may have been and could be present in uncontrolled and unreported amounts

in non-pharmaceutical grades of rose bengal.

Company’s processes of synthesizing the RBS molecule into pharmaceutical-grade RBS and manufacturing RBS API and PV-10 drug candidate,

the processes’ CMC specifications, and the CMC data from the production of stability lots of API and drug candidate have been reviewed

by multiple national drug regulatory agencies prior to granting clinical trial authorizations for the Company to commence a historical

Phase 3 study of intratumoral PV-10 for the treatment of the Company’s former lead indication of locally advanced cutaneous melanoma

(LACM), including the U.S.

FDA, Germany’s Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Australia’s Therapeutic

Goods Administration (TGA) under a clinical trial notification, France’s Agence Nationale de Sécurité du Médicament

et des Produits de Santé (ANSM), Italy’s Agenzia Italiana del Farmaco (AIFA), Mexico’s Comisión Federal para

la Protección contra Riesgos Sanitarios (COFEPRIS), and Argentina’s Administración Nacional de Medicamentos, Alimentos

y Tecnología Médica (ANMAT).

Non-proprietary Name

RBS name for the Company’s pharmaceutical-grade API was selected by and passed the review of the World Health Organization (“WHO”)

Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations after the Company applied for a non-proprietary

name in 2020 and reached the status of recommended International Non-proprietary Names (“INN”).

INN Recommended List 88,

which includes the RBS name, was published with the No.

3 issue of the WHO Drug Information, Volume 36 in 2022.

Non-Pharmaceutical

Grades of Rose Bengal

grade rose bengal can be purchased from specialty chemical suppliers in the U.S.

and other parts of the world that manufacture it under

non-cGMP conditions.

Commercial grade rose bengal appears to have reported purities that may vary between 80% and 95%, which we believe

may not be wholly accurate, and may contain substantial amounts of unreported related impurities and/or gross contaminants.

grade rose bengal is typically used by researchers unaffiliated with the Company for non-clinical study of the rose bengal molecule for

potential biomedical therapeutic applications.

The Company provides PV-10 to researchers affiliated with the Company for their non-clinical

study of RBS for potential biomedical therapeutic applications.

believe that commercial grade rose bengal is still manufactured using the original historical process, or a variant thereof, developed

by the molecule’s original Swiss creator Rudolph Gnehm in 1881.

Some chemical manufacturers may, however, apply purification techniques

that the Company believes still result in commercial grade rose bengal possessing questionable purity and contaminants and substantial

lot-to-lot manufacturing variability.

grade rose bengal describes non-approved rose bengal that is used as an ingredient in historical or current ophthalmic solutions, strips,

and devices, has been historically or is presently compounded by pharmacists for ophthalmic use, and has been or is in other non-ophthalmic

diagnostic tests such as the rose bengal test for human brucellosis.

presume, but have not yet confirmed, that diagnostic grade rose bengal is derived from commercial grade rose bengal that may have undergone

a form of purification under cGMP regulations and/or may have been compounded by a pharmacist, academic medical researcher, or commercial

entity under cGMP regulations.

Here too, the Company believes that purification may not sufficiently improve the amounts and accuracy

of diagnostic grade rose bengal purity and lot contents and may not adequately reduce or eliminate lot-to-lot manufacturing variability.

Analytical Comparison

2022, the Company began work with a U.S.

contract development and manufacturing organization to assess rigorously and methodically three

lots of commercial grade rose bengal, one each from three different specialty chemical suppliers, and compare these non-pharmaceutical

grade materials with the Company’s pharmaceutical-grade RBS.

This chemical analytical work was substantially completed in 2022.

The Company believes that the preliminary results of these analyses indicate that all three lots of commercial grade rose bengal had

rose bengal purity that was drastically different from what was represented on their respective certificates of analysis (“CofAs”),

and that one of the three lots contained gross contaminants that were not represented on its CofA.

Barriers to Entry

Company believes that the Company’s proprietary, patented, pharmaceutical-grade RBS possesses several competitive advantages over

non-pharmaceutical-grade rose bengal (i.e., commercial and diagnostic grades) that researchers, clinicians, and academic, business, and/or

governmental competitors have used, are using, and/or may attempt to use for potential biomedical applications.

The Company believes

that non-pharmaceutical-grade rose bengal may suffer from the uncontrolled presence of substance-related impurities and/or gross contaminants,

substantial lot-to-lot manufacturing variability, inaccurately reported and/or misrepresented purity and contents, and the lack of reproducible,

consistent, and fulsome CMC specifications and documentation.

The Company believes that historical and potentially hazardous impurities

and other manufacturing and handling issues facing non-pharmaceutical grade rose bengal may pose significant scientific, technological,

and economic challenges to overcome and validate for compliance with modern drug regulatory standards.

February, the Company engaged IR Labs, Inc.

(“irlabs”) to develop a comprehensive investor relations and corporate communications

program for the Company.

irlabs was acquired in July 2024 by shareholder engagement and advisory company Alliance Advisors LLC and is

now known as Alliance Advisors Investor Relations.

Company also held an investor conference call in February.

March, the USPTO allowed patent application 17/212,723, titled “Novel Uses of Halogenated Xanthenes in Oncology and Virology.”

The application covers the use of Provectus’ s pharmaceutical grade rose bengal sodium (“RBS”) drug substance for the

treatment of infectious diseases, such as coronaviruses.

USPTO also allowed patent application 17/344,418, titled “In Vitro and Xenograft Anti-Tumor Activity of a Halogenated-Xanthene

Against Refractory Pediatric Solid Tumors” in March.

This prospective award covers the use of RBS in combination with one or more

immune checkpoint inhibitors and is a continuation of U.S.

patent 11,058,664 (2021), Provectus’ s first for pediatric oncology.

Company’s previously allowed patent application 17/488,430 in December 2023, titled “Halogenated Xanthenes as Vaccine Adjuvants”

and covering RBS’s use as an adjuvant in vaccines to potentially make them work better, was also awarded in March as U.S.

Company entered into an agreement with the University of Miami (the “University”) in March for the exclusive worldwide license

of the University’s intellectual property related to rose bengal photodynamic antimicrobial therapy (“RB-PDAT”) for

treating bacterial, fungal, and parasitic (acanthamoeba) infections of the eye.

The agreement contemplated the Company forming a majority-owned

start-up company in which the University would be a minority equity shareholder, aimed at developing and commercializing the University’s

RB-PDAT medical device in combination with a formulation of RBS.

Provectus would contribute the license to the new entity and have an

exclusive RBS supply arrangement with it.

In December, the Company launched VisiRose, Inc.

(“VisiRose”), the Company’s first Founded Entity and a new clinical-stage

biotechnology company focused on commercializing RB-PDAT for the treatment of infectious keratitis and other serious eye infections using

a formulation of PV-10, with Provectus having 95% ownership and the University having 5%.

April, data from non-clinical research by Moffitt on intratumoral PV-10 for the treatments of human papillomavirus -positive and -negative

head and neck squamous cell carcinoma were presented at the annual meeting of the American Association for Cancer Research held in San

Diego, California from April 5-10.

Company’s Board of Directors appointed Ed Pershing as Chief Executive Officer and Dominic Rodrigues as President in April.

from non-clinical research by the University of Calgary on oral administration of PV-10 for the treatments of solid tumor cancers were

published in April in the open access journal of oncology Cancers, “Identification and In Vivo Validation of Unique Anti-Oncogenic

Mechanisms Involving Protein Kinase Signaling and Autophagy Mediated by the Investigational Agent PV-10.”

May, the USPTO allowed patent application 17/232,393, titled “Halogenated Xanthene Composition and Method for Treating Hematologic

The application covers the use of Provectus’s pharmaceutical grade rose bengal sodium (“RBS”) active

pharmaceutical ingredient for the single agent or combination therapy treatment of pediatric and adult leukemias.

and non-clinical data on RB-PDAT were presented at the annual meeting of the Association for Research in Vision and Ophthalmology in

Seattle, Washington from May 5-9.

data on PV-10 for the topical treatment of full-thickness cutaneous wounds were presented by the University of Texas Medical Branch at

Galveston at the annual meeting of the Society for Investigative Dermatology in Dallas, Texas from May 15-18.

June, the Company held its annual stockholder meeting where stockholders approved the proposals of the Board of Directors (“Board”)

to seek the authority to undertake a reverse stock split and an authorized share reduction.

Meeting activities and the company update

were made accessible by Zoom Webinar.

October, the Company held an investor conference call accessible by Zoom Webinar.

August, the USPTO awarded patent 12,064,507, titled “Composition and method for oral treatment of leukemia.”

general, the pharmaceutical and biotechnology industries are competitive, characterized by steady and sometimes disruptive advances in

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and may be further along in their respective product cycles.

2023, we undertook extensive validation testing of our supply of prescription drug candidate PV-10.

2024, we began manufacturing new clinical supplies of PV-10 and PV-305.

Regulation of Therapeutic Products

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basis, if at all.

Success in preclinical or early-stage clinical trials does not assure success in later-stage clinical trials.

or research institution conducting the trials may suspend clinical trials or may not permit trials to advance from one phase to another

at any time for various reasons, including a finding that the subjects or patients are being exposed to an unacceptable health risk.

Success in non-clinical or early-stage clinical trials does not assure success in later-stage clinical trials.

FDA or research institutions conducting the trials may suspend clinical trials or may not permit trials to advance from one phase to

another at any time for various reasons, including a finding that the subjects or patients are being exposed to an unacceptable health

Once issued, the FDA may withdraw a prescription drug approval if we do not comply with pertinent regulatory requirements and standards

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Capital Resources

have four full-time employees who currently serve as CFO, CTO, senior scientist, and controller.

We also engage independent contractors,

who currently serve as chief operations consultant, director of clinical operations, clinical research associates, and information technology manager.

have six full-time employees who currently serve as CEO, CFO, CTO, president, senior scientist, and controller.

We also engage an independent

contractor, who currently serves as an information technology manager.

believe the Company’s success depends on its ability to attract, develop, and retain key personnel.

12 unchanged sentences

The website is http://www.sec.gov .

The Company also intends to use press releases, the Company’s website and certain social media accounts as

a means of disclosing information and observations about the Company and its business, and for complying with the Company’s disclosure

obligations under Regulation FD:

the Provectus Substack account (provectus.substack.com), the @ProvectusBio X account (twitter.com/provectusbio),

and the Company’s LinkedIn account (linkedin.com/company/provectus-biopharmaceuticals).

The information and observations that the

Company posts through these social media channels may be deemed material.

Accordingly, investors should monitor these social media channels

in addition to following the Company’s press releases, SEC filings, and website.

The social media channels that the Company intends

to use as a means of disclosing the information described above may be updated from time to time.

The contents of the websites provided above are not intended to be incorporated by reference into this Annual Report

on Form 10-K or in any other report or document we file with the SEC.

Further, our references to the URLs for these websites are intended

to be inactive textual references only.

Company also intends to use press releases, the Company’s website and certain social media accounts as a means of disclosing information

and observations about the Company and its business, and for complying with the Company’s disclosure obligations under Regulation

the Provectus Substack account (provectus.substack.com), the @ProvectusBio X account (twitter.com/provectusbio), and the Company’s

LinkedIn account (linkedin.com/company/provectus-biopharmaceuticals).

The information and observations that the Company posts through

these social media channels may be deemed material.

Accordingly, investors should monitor these social media channels in addition to

following the Company’s press releases, SEC filings, and website.

The social media channels that the Company intends to use as

a means of disclosing the information described above may be updated from time to time.

contents of the websites provided above are not intended to be incorporated by reference into this Annual Report on Form 10-K or in any

other report or document we file with the SEC.

Further, our references to the URLs for these websites are intended to be inactive textual

references only.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business