• No safety concerns identified; no significant overlap of or unexpected toxicities
  • 65% overall ORR with 9% CR (RECIST 1.1) maintained
  • Preliminary PFS of 12.3 months
  • Changes in T cell populations similar to single-agent PV-10 treatment

KNOXVILLE, TN, June 03, 2019 (GLOBE NEWSWIRE) --  Provectus (OTCQB: PVCT) today announced that updated safety and response results as well as preliminary treatment durability and immune response results from the Company's ongoing Phase 1b/2 study of PV-10 in combination with KEYTRUDA (pembrolizumab), an immune checkpoint inhibitor, were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, held in Chicago, IL from May 31-June 4, 2019. Intralesional injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-5 PV-10 clinical development includes cutaneous melanoma and cancers of the liver, such as hepatocellular carcinoma, metastatic neuroendocrine tumors, and metastatic uveal melanoma, in both single-agent and combination therapy settings.

The Phase 1b portion of the study completed enrollment of 23 patients with advanced melanoma in April 2018 (NCT02557321). Patients with at least one injectable lesion and who were candidates for KEYTRUDA were eligible. Subjects received the combination treatment of PV-10 and KEYTRUDA every three weeks for up to five cycles (i.e., over a period of up to 12 weeks, with no further PV-10 administered after week 12), followed by only KEYTRUDA every three weeks for up to 24 months. The primary endpoint for the Phase 1b trial was safety and tolerability. Objective response rate (ORR) and progression-free survival (PFS) were key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter). Response follow-up of 6 patients (26%) still is ongoing.

Updated Results from the Presentation at ASCO:

  • Baseline characteristics: 83% men; median age of 70 years (range 28-90) and 70% > 65 years; 91% checkpoint naïve.
     
  • Disease characteristics: 87% Stage IV; median of 2 cutaneous/subcutaneous lesions (range 1-15)6; most subjects had substantial non-injected systemic disease burden in addition to injectable cutaneous and/or subcutaneous lesions.
     
  • Treatment summary: Median of 4 cycles (mean 3.7, range 1-5) and median of 5 injections of PV-10 (range 1-82); PV-10 was not administered after week 12.
     
  • Updated safety: Treatment-emergent adverse events were consistent with the established patterns for each drug; there were no significant overlap of or unexpected toxicities.
     
  • Updated overall efficacy (per RECIST 1.1): 9% CR and 65% ORR; 71% ORR in M1b patients and 80% ORR in M1c patients.
     
  • Updated target lesion efficacy (best overall response): 77% complete response (CR), 80% ORR, and 87% clinical benefit; 75% CR in M1b patients and 100% CR in M1c patients.
     
  • Preliminary durability: PFS of 12.3 months.
     
  • Minimal intervention: 26% of patients achieved an overall objective response after 3 or less cycles of PV-10; 30% of target lesions achieved CR after 1 injection of PV-10 and 53% achieved CR after 3 injections or less.
     
  • Preliminary changes in peripheral blood mononuclear cells: Activated T cell populations increased during the PV-10 treatment interval; NK and NKT cell populations exhibited transient increases 1 week after PV-10 injections; cytotoxic, helper, and total T cell populations were stable.

The Company is enrolling and treating patients in an expansion cohort of up to 24 subjects to assess the PV-10-KEYTRUDA combination in patients who have failed to respond to initial treatment with checkpoint inhibition. Two patients in the Phase 1b study’s main cohort were refractory to checkpoint inhibition: 1 achieved a CR after previously being on OPDIVO® for 12 months and 1 withdrew after previously being on YERVOY® for 3 years due to the onset of myasthenia gravis. Provectus plans to present preliminary data from this expansion cohort of refractory patients at a medical conference in the fourth calendar quarter of 2019.

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, “These trial results demonstrate the safety profile, treatment response, durability of response, and immune response of the PV-10-checkpoint inhibition combination after minimal PV-10 intervention.7 Successful cancer combination therapy is achieved by pairing drugs that each show single-agent activity.”

Mr. Rodrigues added, “Together with safety, response, biomarker, and quality of life data of single-agent PV-10 for the treatment of metastatic neuroendocrine tumors presented earlier today at ASCO, these advanced melanoma combination therapy data add to the abundance of drug activity information of PV-10 in both high and low mutation tumor types, and in both T cell and non-T cell inflamed tumor types.”

A copy of the ASCO poster presentation is currently available on Provectus’ website at https://www.provectusbio.com/media/docs/publications/PV-10-MM-1201_ASCO2019.pdf.

About PV-10

PV-10 causes acute oncolytic destruction of injected tumors, releasing damage associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. T cell function can be further augmented by combining PV-10 with immune checkpoint inhibition.

PV-10 is undergoing clinical study for adult solid tumor cancers like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma) and preclinical study for pediatric cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.

Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

PV-10’s active pharmaceutical ingredient is rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), a small molecule halogenated xanthene. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.

Provectus’ intellectual property includes a family of US and international patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to identify and control these substances is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of active pharmaceutical ingredient that is suitable for clinical trial and commercial pharmaceutical use. US patent numbers are 8,530,675, 9,273,022, and 9,422,260; patent expirations range from 2030 to 2031.

About Provectus

Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing a new class of drugs based on an entirely- and wholly-owned family of chemical small molecules called halogenated xanthenes. Information about the Company’s clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.

References

1.    Wachter et al. Functional Imaging of Photosensitizers using Multiphoton Microscopy. Proceedings of SPIE 4620, 143, 2002.

2.    Liu et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7, 37893, 2016.

3.    Qin et al. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death and Disease 8, e2584, 2017.

4.    Liu et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One 13, e0196033, 2018.

5.    Swift et al. Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma. Onco Targets Ther 12:1293-1307, 2019.

6.    Two patients with baseline burden too numerous to count (TNC) were excluded from this calculation.

7.    To date, clinical trial and expanded access patients have received the combination of PV-10 and checkpoint inhibition for advanced melanoma (+KEYTRUDA), mucosal melanoma of the vagina (+KEYTRUDA), Merkel cell carcinoma (+BAVENCIO®), breast cancer (+OPDIVO), Basal cell carcinoma (+ KEYTRUDA and ERIVEDGE®), and uveal melanoma metastatic to the liver (+OPDIVO and YERVOY).

Preliminary results from this combination study were presented at the Society for Melanoma Research (SMR) 2017 Congress, held in Brisbane, Australia from October 18-21.

Interim results from the study were presented at the SMR 2018 Congress, held in Manchester, England from October 24-27.

Lesion-level response data from the study were presented at Melanoma Bridge 2018, held in Naples, Italy from November 30-December 1.

Trademarks

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, New Jersey, U.S.A.

BAVENCIO® is a trademark of Merck KGaA, Darmstadt, Germany.

OPDIVO® and YERVOY® are registered trademarks of Bristol-Myers Squibb, New York, New York, U.S.A.

ERIVEDGE® is a registered trademark of Genentech, Inc., San Francisco, California, U.S.A.

FORWARD-LOOKING STATEMENTS: This release contains “forward-looking statements” as defined under U.S. federal securities laws. These statements reflect management's current knowledge, assumptions, beliefs, estimates, and expectations and express management's current views of future performance, results, and trends and may be identified by their use of terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “will,” and other similar terms. Forward-looking statements are subject to a number of risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements. Readers should not place undue reliance on forward-looking statements. Such statements are made as of the date hereof, and we undertake no obligation to update such statements after this date.

Risks and uncertainties that could cause our actual results to materially differ from those described in forward-looking statements include those discussed in our filings with the Securities and Exchange Commission (including those described in Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2018).

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Contact:

Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
Phone: (866) 594-5999

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