Provectus Full-Thickness Cutaneous Wound Healing Poster Presentation at 2024 Society for Investigative Dermatology Annual Meeting
SID Poster title: "Assessing the safety and toxicity of multi-dosed topical Rose Bengal Sodium (RBS) in a murine model of full-thickness cutaneous injury"
On Thursday, February 29th, Provectus announced that data from ongoing preclinical research on the topical administration of a formulation of its proprietary, pharmaceutical-grade, immuno-catalyst small molecule, rose bengal sodium (RBS) drug substance (“pharmaceutical-grade RBS”) are going to be presented at the annual meeting of the Society for Investigative Dermatology (“SID”), which will be held May 15-18, 2024 in Dallas, Texas (the 81st meeting of the SID). As an aside, you can visit and tour the SID’s interactive skin model here.
The accepted SID abstract is titled Assessing the safety and toxicity of multi-dosed topical Rose Bengal Sodium (RBS) in a murine model of full-thickness cutaneous injury (Control ID 4074036, Final ID 813, Current Category: Translational Studies and Early Preclinical to Clinical).
The work underlying this poster presentation is part of an ongoing sponsored research program led by Amina El Ayadi, Ph.D., Assistant Professor, Division of Surgical Sciences, Department of Surgery at the University of Texas Medical Branch (“UTMB”) in Galveston to characterize the effects of pharmaceutical-grade RBS on full-thickness cutaneous wounds and during the subsequent phases of wound healing.
UTMB, Rose Bengal PDT, and Full-Thickness Wound Healing
Prior to their collaboration with Provectus, Dr. El Ayadi and her colleagues studied the combination of photodynamic therapy (“PDT”) using green light (530 nanometer [nm] wavelength) and a 0.1% concentration of 95% dye content rose bengal (“RB”) (“commercial-grade RB”) from Sigma Aldrich (also known as MilliporeSigma) (“RB PDT”).
UTMB presented preclinical data at the 2022 annual meeting of the Wound Healing Society, held April 6-10 in Phoenix, Arizona, in a poster presentation titled Rose Bengal Photodynamic Therapy Improves Cutaneous Healing Of Full-Thickness Wounds In Vivo. A copy of UTMB’s poster is shown in Figure 1 below.
Jay et al. 2022 concluded that RB PDT:
Can more naturally close full-thickness wounds with improved collagen deposition, increased vascularity, and reduced water loss over time,
Generates beneficial wound ROS [(reactive oxygen species)] without simultaneously increasing tissue oxidative stress, and
May mitigate impaired wound healing to restore tissue homeostasis.
UTMB utilized 0.1% commercial-grade RB because, among other things, this concentration level had previously been discussed in the scientific literature, such as by Bascom Palmer Eye Institute (BPEI) related to its development of RB photodynamic antimicrobial therapy (“PDAT”) (“RB PDAT”) for infectious keratitis, an eye disease. BPEI’s RB PDAT was shown in its 2019-published pilot clinical study to use either 0.1% or 0.2% commercial-grade RB; however, 0.1% appears to have since been the “standard” concentration.
Provectus reached out to UTMB in March 2022, upon learning of this wound healing work. The research program with UTMB was initiated by Provectus in September 2022.
Bascom Palmer, Rose Bengal PDAT, Keratitis, L V Prasad Eye Institute, and India
L V Prasad Eye Institute (“LVPEI”) published “Clinical Outcomes of Rose Bengal Mediated Photodynamic Antimicrobial Therapy on Fungal Keratitis with Their Microbiological and Pathological Correlation” in Current Eye Research in April 2022 that discussed the clinical outcome of RB PDAT used as an early adjuvant therapy in patients with fungal keratitis, and their microbiological and pathological correlation. A donated BPEI custom-built green light source (525 nm wavelength) was combined with 0.1% commercial-grade RB from Sigma Aldrich.
According to Wikipedia’s LVPEI entry: “The L V Prasad Eye Institute (LVPEI) is an eye-care network, established by Dr. Gullapalli Nageswara Rao, an ophthalmologist, at Hyderabad, in 1986. It is a non-profit, multi-campus, non-governmental institution. With more than 275 eye-care centres in India, it is the largest eye-care network in the world.”
Provectus’s Immuno-Dermatology Drug PH-10 and Ambient Light
In developing PH-10, which has varied in concentration from 0.0001% to 0.1% pharmaceutical-grade RBS, the Company’s investigational immuno-dermatology clinical-stage asset, Provectus started out by conducting Phase 1 and 2 trials of PH-10 in combination with 532-544 nm light activation for inflammatory dermatoses (i.e., psoriasis, actinic keratosis), well before the work of BPEI and others. Active light activation was later replaced by ambient light.
During Provectus’s First Quarter 2024 Conference Call, the Company said that one of the two prongs of its strategic plan was to prove RBS’s applicability to other diseases:
“We began this at the outset of our tenure at the Company by greenlighting mechanisms of action and immune action research on Provectus’s immuno-dermatology drug PH-10, a clinical-stage asset that people at the Company wanted to discard. This research revealed PH-10’s potential curative properties for psoriasis, identified its multi-immune signaling possibilities that were later confirmed by research on PV-10 for cancer, and deeply influenced subsequent research on rose bengal sodium as a possible multi-disease, broad-spectrum immunotherapeutic.”
Given this PH-10 clinical research by James Krueger, MD, PhD, head of the Laboratory for Investigative Dermatology at The Rockefeller University in New York City as well as PH-10 clinical work by other investigators and PH-10 research by Provectus, we asked UTMB to consider 0.01% pharmaceutical-grade RBS, multi-dosing, and ambient light to treat full-thickness cutaneous wounds.
We asked UTMB to change the design of treating and potentially healing wounds from 0.1% RB + green light to 0.01% RBS + ambient light, because we wanted to align our knowledge of, among other things:
PH-10 (RBS) in dermatology with emerging knowledge of RBS in wound healing and knowledge of RB in ophthalmology,
The optional contribution of light to RBS’s (RB’s) mechanisms of action in dermatology and wound healing, and, eventually, in ophthalmology, and
Lower concentrations and/or multi-dosing of RBS in dermatology and wound healing, and, eventually, in ophthalmology.
The ultimate goals of the UTMB team, and our goals too, are for the topical application of pharmaceutical-grade RBS for full-thickness cutaneous wounds (e.g., surgical, burn, etc.) to potentially achieve rapid wound closure, infection prevention, scar elimination, and return of function.
Ophthalmology: How many people in India are blind?
LVPEI has a long-standing relationship with BPEI. Further, Aravind Eye Care System (AECS) has a long-standing relationship with the University of California, San Francisco (UCSF). UCSF is the sponsor of both Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction (REAGIR) clinical trials (i.e., REAGIR I for acanthamoeba and fungal keratitis, and REAGIR II for bacterial keratitis).
The incidence of infectious keratitis in South India, with a potential approximate population of more than 250 million people (India’s total population is approximately 1.4 billion), based on a rate of 113 per 100,000 population-year (see Gonzales et al. 1996; there are limited studies in the literature of the rate of infectious keratitis), could be 300,000 people per year.
According to Wikipedia’s AECS entry: “Aravind Eye Hospitals…was founded by Dr. Govindappa Venkataswamy (popularly known as Dr.V) at Madurai, Tamil Nadu in 1976. It has grown into a network of eye hospitals and has had a major impact in eradicating cataract related blindness in India. As of 2012, Aravind has treated nearly 32 million patients and performed 4 million surgeries.”
AECS and LVPEI are the two largest visions centers (“VCs”) in India, seeing nearly one million patients in 2017-2018, as shown in Figure 2 below.
According to Rohan Bir Singh’s May 2023 Newslaundry article titled Progress, but not enough: Why blindness remains a public health challenge in India:
“Most news reports estimate India has around 12 million blind people, but this data is from a national survey conducted in 1986-89. Over 30 years later, a study estimated that the prevalence of blindness over the age of 45 is as high as 2.30 percent of the age group population in the country,” and
“According to the World Health Organisation, India accounts for one-fifth of the global burden of blindness in 2010,” and approximately 27% of the global burdens of low vision and visual impairment, as shown in Figure 3 below.
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