Provectus Info

VisiRose & Topical PV-305 • Published mNET paper & Intralesional PV-10 • Published RB-PDAT paper & Topical PV-305 • 2024 Form 10-K & Intellectual Property

VisiRose & Topical PV-305 (eye infections)

We discussed the REAGIR data (NCT05110001) and Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) with Bascom Palmer Eye Institute (BPEI) and its Ophthalmic Biophysics Center (OBC) on Friday.

We continue to believe the data give VisiRose — Provectus’s clinical-stage ophthalmology spinout company — a strong hand to play regulatory-wise when it comes to (i) a potential initial indication for approval for RB-PDAT and (ii) potentially gaining FDA consensus on a bridging study design.

Published mNET paper & Intralesional PV-10 (metastatic liver cancer)

A medical journal article about Provectus’s Phase 1 trial in Australia of intralesional PV-10 for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) (NCT02693067) was published in the British Journal of Cancer on March 26, 2025: “A phase 1 study to assess the safety, tolerability and effectiveness of PV-10 (Rose Bengal Sodium) in neuroendocrine tumours metastatic to the liver.”

Background: Metastatic neuroendocrine neoplasms (mNEN) require new treatment options. Intralesional (IL) PV-10 is an autolytic chemotherapy that may elicit an adaptive immune response.

Methods: This phase 1 study evaluated IL PV-10 administered percutaneously to hepatic lesions in patients with progressive mNEN. IL PV-10 was injected in a single lesion per treatment cycle. A treatment cycle could be repeated after ≥ 6 weeks if multiple targetable lesions were present. The primary endpoint was safety.

Results: Twelve patients were enrolled with a median age of 66 years (range 47-79). All patients had progressive disease at enrolment and received prior somatostatin analogues; 10 patients had peptide receptor radionuclide therapy (PRRT) treatment. One lesion was injected per cycle for all 12 patients. Reported grade 3 side effects were photosensitivity (1 patient), face oedema (1 patient), elevated transaminases (1 patient), hypertension (2 patients). Response rate was 42% of injected lesions with patient-level disease control of 84%, PFS 9.4 months and median OS 24.0 months.

Conclusions: IL PV-10 elicited no safety concerns. Encouraging evidence of local and systemic disease control was seen in a heavily pre-treated, progressing mNEN population.

Published RB-PDAT paper & Topical PV-305

BPEI and OBC have published their 19th paper about RB-PDAT since 2014: “Rose Bengal Photodynamic Antimicrobial Therapy as an Adjunct Treatment for Pseudomonas aeruginosa Infectious Necrotizing Scleritis.” The article will be published in the open-access journal Photodiagnosis and Photodynamic Therapy and, as of April 3, 2025, is available as a journal pre-proof.

As an FYI, “[n]ecrotizing scleritis is a severe inflammatory disease involving the sclera that, if untreated, can lead to permanent vision impairment or even loss of the eye. Scleritis is primarily autoimmune in origin, accounting for about 90% of cases” (Source: the article).

Purpose: To report the utility of Rose Bengal Photodynamic Antimicrobial Therapy (RBPDAT) as an adjunct treatment in rapidly progressing Infectious Necrotizing Scleritis (INS) secondary to Pseudomonas aeruginosa.

Methods: Retrospective chart review was conducted on consecutive patients with scleritis and culture-proven Pseudomonas aeruginosa who underwent RB-PDAT.

Results: Six patients with Pseudomonas aeruginosa INS were included. All patients achieved complete resolution of the infection. The mean time to resolution after RB-PDAT was 17 days (range; 6-30 days), with a total treatment course average of 36 days (range; 22-60 days). One patient with pan-resistant Pseudomonas sclerokeratitis required two RB-PDAT treatments due to persistent stromal melting. All patients received a standardized regimen of oral fluoroquinolone, topical tobramycin, and ciprofloxacin/moxifloxacin. The patient with pan-resistant Pseudomonas aeruginosa required treatment with topical imipenem as well. None of the patients required enucleation.

Conclusion: RB-PDAT is a feasible option to halt the progression of infectious necrotizing scleritis caused by Pseudomonas aeruginosa, especially in cases of impending perforation.

2024 Form 10-K & Intellectual Property

Provectus filed its Form 10-K (annual financial statements) for the period ending December 31, 2024 on March 28, 2025.

Under the Intellectual Property section on pages 2 and 3, we note that in 2024:

• the U.S. Patent and Trademark Office (USPTO) issued five patents to the Company, covering (in chronological order of award) the use of Provectus’s pharmaceutical-grade rose bengal sodium (RBS) molecule, drug substance, and active pharmaceutical ingredient for:

  • vaccine adjuvants,

  • oncology and virology,

  • pediatric solid tumors,

  • leukemia, and

  • hematology.

• the USPTO published a further four patent applications of Provectus on its website (in chronological order of publication) related to the use of RBS for:

  • colistin-resistant gram-negative bacteria (colistin is a “last-resort” antibiotic),

  • vaccine adjuvants (i.e., a further patent application of the patent awarded above),

  • pediatric solid tumors, and

  • hematology.

• the Company received patent awards and allowances for eight patent families in five countries and regions:

  • oncology combination therapy in Canada,

  • dermatology combination therapy in Europe,

  • pediatric solid tumors in Canada, Japan, and Australia,

  • oncology and virology in China and Japan,

  • oncology in Japan,

  • hematology in Japan, and

  • vaccine adjuvants in Japan.

Further, we continue to try to push out Provectus’s patent cliff for RBS into the 2040s.

Finally, thirteen (~76%) of the Company’s 17 US patents for RBS in a therapeutic setting were awarded in or after 2017. Nine (~53%; 9/17) were awarded after the start of the Covid-19 pandemic in 2020; as context, see Provectus’s April 6, 2023 Substack post 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”).

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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, 2024.