KNOXVILLE, Tenn.--(BUSINESS WIRE)--Provectus Pharmaceuticals, Inc. (OTCQB: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, provides shareholders with an update on its corporate accomplishments, clinical progress and business development efforts during 2012, and shares well as insights on upcoming plans and milestones for 2013.
DEAR SHAREHOLDERS:
We are pleased to report on the continued advances our Company has made during 2012 in the clinical, regulatory, and commercial development of our lead drug candidates, PV-10 and PH-10. These important, incremental steps will ensure that Provectus achieves its ultimate goal of developing novel, commercially viable pharmaceuticals for the most difficult cancers and severe dermatological diseases. The progress we have made on all fronts confirms our underlying belief in the value of our products and their potential to create a new paradigm for cancer treatment as well as value for our shareholders.
PV-10, our novel oncology drug that selectively targets and destroys cancer cells without harming surrounding healthy tissue, continues to demonstrate its local and systemic benefits, excellent safety profile, and potential applicability in multiple cancer indications. Our clinical progress was well-publicized throughout the year, with non-clinical and clinical data on PV-10 presented at numerous scientific meetings including the Cancer Immunotherapy Conference, the European Post-Chicago Melanoma Meeting, the European Society for Medical Oncology (ESMO), HemOnc Today, the Society for Immunotherapy of Cancer, and the Society of Surgical Oncology. Increasingly, PV-10’s unique characteristics and safety profile are attracting the attention of clinicians at nationally recognized medical research institutions. Oncology thought leaders are taking notice that this novel therapy is not only safe and effective as a monotherapy, but also has significant potential as an adjunct to traditional chemotherapeutic agents and in combination with immunomodulatory and metabolic agents.
Provectus also reported topline data from our first Phase 2 randomized controlled study of PH-10 in Psoriasis, which showed our drug is effective on mild to moderate plaque psoriasis symptoms, with optimal effect at the lowest dosage levels. Ongoing toxicology studies are helping us understand PH-10’s uniquely low toxicity levels. We expect to have comprehensive data that elucidate this drug’s specific toxicity profile, which will be used to support an NDA filing, as well as our negotiations with potential pharma licensees.
On the commercial development front, we remained focused on our strategy to monetize our dermatological drug, PH-10, which targets abnormal or diseased cells. PH-10 is undergoing laboratory testing at a leading research facility to better understand its unique lack of toxicity and mechanism of action. This work will help define toxicity studies that are expected to support a New Drug Approval ("NDA") filing with the FDA, as well as provide important information for potential development partners. During 2012, we spent a considerable amount of time engaged in detailed discussions with many potential licensees who are interested in PH-10. This was an arduous process but it enabled us to identify the best potential licensees, based on product fit, sales and distribution infrastructure, and other important criteria. Moving forward, we can now focus our efforts on this select group of companies.
CLINICAL DEVELOPMENTS
We reported preliminary topline findings as well as final data from our Phase 2 clinical trial with PV-10 in metastatic melanoma. The final efficacy data on PV-10, presented at the ESMO meeting in Vienna, Austria, demonstrated a significant robust response rate (60% OR, and 79% disease control) in Stage III subjects. This group also achieved significantly greater mean progression free survival of at least 9.7 months, versus later stage subjects.
From the clinical perspective, one of our most noteworthy achievements this year was the independent validation of PV-10’s ability to induce a systemic immunological response. Researchers at the Moffitt Cancer Center in Tampa, Florida, conducted additional non-clinical studies that explored PV-10’s mechanism of action and ability to stimulate a systemic immunological response. Initial results of this research in murine models of melanoma were presented in March 2012, at the Society of Surgical Oncology Annual Meeting in Orlando, Florida and showed that tumor ablation using PV-10 stimulates a systemic, tumor-specific anti-tumor immune response. Additional data from multiple cancer types were presented in April 2013, at the American Association of Cancer Research (AACR) Annual Meeting in Washington, DC and confirmed that this systemic immune response occurs in multiple cancer types. Moffitt researchers continue to explore PV-10’s mechanism of action in a Phase 1 feasibility study with melanoma patients while pursuing additional avenues of research that are expected to further elucidate the systemic immunological response stimulated by PV-10.
In addition, researchers from Provectus presented non-clinical data at AACR that demonstrate PV-10's ability to reduce untreated tumor burden via this tumor-specific immunologic stimulation. Our research suggests that PV-10 could be a logical potential complement to anti-CTLA-4 agents such as ipilimumab, and we are evaluating conducting a Phase 1/2 trial with “ipi” to validate this effect.
Another key clinical achievement was the commencement of patient enrollment in the Company's Phase 1 protocol expansion study of PV-10 for liver metastasis, which includes two additional study cohorts to evaluate the safety and efficacy of PV-10 as a mono and combination therapy for patients with hepatocellular carcinoma ("HCC"). The combination therapy will assess PV-10 in patients with HCC who are on a stable dose of sorafenib, a standard treatment for HCC. In addition to the protocol expansion, we recently announced the addition of a second clinical site to this trial. At the Southeastern Center for Digestive Disorders & Pancreatic Cancer at Florida Tampa Hospital, Tampa, Florida, Dr. Alexander S. Rosemurgy, M.D., a widely-respected leading pancreatic cancer surgeon, will serve as principal investigator, which is slated for completion by December 2013.
REGULATORY PROGRESS
Provectus is finalizing details for submission of a pivotal Phase 3 randomized controlled trial ("RCT") of PV-10 for metastatic melanoma, suitable for Special Protocol Assessment ("SPA"), to the Food and Drug Administration ("FDA"). While preparation for submission of our SPA has taken longer than expected, it is crucial to remember that oncology presents a moving playing field. Fine tuning of the study design is expected to mitigate clinical efficacy risk, optimize patient accrual, and increase FDA’s confidence that the study design and protocol will ensure the best possible outcome for our pivotal trial. We have every reason to believe this key milestone will be achieved in 2013.
Provectus is also considering applying for the new Breakthrough Therapy Designation for PV-10 to treat melanoma. This new regulatory pathway was announced with the passage of The Food and Drug Administration Safety and Innovation Act (FDASIA) in July 2012. Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A breakthrough therapy designation conveys all of the fast track program features as well as more intensive FDA guidance on an efficient drug development program. However, because this program is relatively new, the potential impact of receiving such designation is still unclear, but could be pivotal in achieving an accelerated path for approval of PV-10.
COMPASSIONATE USE PROGRAM
PV-10's Compassionate Use Program continues to progress with 78 subjects at five centers in the U.S. and Australia enrolled in the study as of the end of 2012. This Compassionate Use protocol provides expanded access for investigational use of PV-10 in cancer patients who are not eligible for an existing PV-10 clinical trial, for whom there is no comparable or satisfactory approved alternative therapy and for those who, in the opinion of the investigator, may benefit from PV-10 administration. One of the investigators participating in this program has initiated a study whose protocol includes PV-10 chemoablation followed by radiotherapy that has enrolled ten subjects as of the end of 2012.
ADDITIONAL INDICATIONS
Based upon our research into PV-10's multi-indication potential, we continued our nonclinical work on PV-10 for several indications, including pancreatic, bladder and other solid tumors. Here again, we look forward to demonstrating PV-10's potential for treating these cancers. In the nonclinical research studies conducted at the Moffitt Cancer Center by Dr. Shari Pilon-Thomas, PV-10 showed efficacy in murine models of breast and lung cancer as well as melanoma, providing several avenues for additional indications. Studies are in progress at Provectus to investigate the potential treatment of bladder cancer, which has the fourth highest incidence rate in the U.S.
FINANCIAL CONDITION
The Company’s financial condition remains sound. The financing completed during 2012 and additional transactions to date ensure our ability to operate through 2014. Our cash position of $1,221,701 at December 31, 2012 was supplemented by the approximately $5.2 million in cash we received in the first three months of 2013 due to private placements of equity at a substantial premium to the fair market value of our common stock at the time of the sale. We continue to manage our variable cash expenses prudently and control our fixed costs. We believe these efforts, combined with our current cash position should be sufficient to meet our current and planned operating needs until well into 2014 without consideration being given to additional cash inflows.
We are seeking to improve our cash flow through both the licensure of PH-10 based on our Phase 2 atopic dermatitis and psoriasis results, and primarily the geographic licensure of PV-10 based on our Phase 2 metastatic melanoma and Phase 1 liver results in certain areas of the world, as well as pursuing a strategic investment strategy, including equity sales to potential pharmaceutical and/or biotech partners. In addition, the PV-10 mechanism of action data now available from Moffitt Cancer Center has been particularly helpful in supporting our development plans with both the FDA and prospective partners. The geographic areas of interest for PV-10 principally include China, India, Japan and Middle East and North Africa (MENA). We are also considering the global licensure of PV-10 as well since it has come to our attention that this is of interest to potential partners. We also expect to continue with the majority stake asset sale and licensure of our non-core assets. However, the primary objective of ours is to strategically monetize the core value of PV-10 and PH-10 through various transactions, leveraging value creation up to and including an appropriate Merger and Acquisition transaction.
CORPORATE DEVELOPMENTS
In May 2012, the Company appointed Doug Ulman, President and CEO of LIVESTRONG, to its Corporate Advisory Board. A cancer survivor and survivorship advocate, Doug joined LIVESTRONG in 2001 as its director of survivorship, and was appointed President and CEO in 2007. He has received numerous awards for his leadership in the fight against cancer and his contributions to community service. Doug’s personal experience with melanoma and his high visibility in the national media make him a wonderful advocate who is helping to raise awareness and visibility of Provectus among the oncology community as well as the general public.
Provectus is also implementing measures that will assure we meet the standards and best practices required for a national exchange listing, such as NASDAQ. To strengthen our corporate governance, the Company formed an independent board to meet NASDAQ regulations, which require a majority of independent Board Members. To accomplish this, Jan E. Koe was appointed to its Board of Directors, replacing Eric Wachter, Ph.D., who resigned from the Board and was named Chief Technology Officer, a new position. With the appointment of Mr. Koe, Provectus now has three independent directors on its five member Board, including independent directors Dr. Kelly M. McMasters, M.D., Ph.D. and Alfred E. Smith IV. The Company intends to apply for a listing on NASDAQ when appropriate.
LOOKING AHEAD
The Company made excellent progress in 2012 that has served to validate our clinical efforts, broaden our visibility in the oncology community, and strengthen our ability to attract viable commercial partners for our lead products. We look forward to achieving several milestones in the upcoming year which include:
- Receiving consensus for Phase 3 in melanoma from the FDA and Australia's Therapeutic Goods Administration ("TGA")
- Completing additional immunology studies at Moffitt Cancer Center regarding PV-10's mechanism of action
- Expanding the PV-10 Compassionate Use Program
- Meeting with the FDA and beginning Phase 2/3 clinical trials of PV-10 for liver carcinoma
- Investigating new oncology indications for PV-10, such as pancreatic cancer
- Scheduling an End-of-Phase 2 meeting with FDA to review PH-10 for psoriasis and atopic dermatitis and plan transition to Phase 3 testing
- Complete additional research into the unique properties of PH-10 regarding its mechanism and lack of toxicity
- Complete our discussions with potential licensees, hire a financial advisor and sign a licensing agreement that covers dermatological indications for PH-10
- Complete our discussions with potential partners interested in licensing PV-10, whether on a geographic or global basis, followed by appropriate licensing agreement(s)
Provectus is a small company focused on developing treatments for some of the most serious and devastating cancers. This is not an easy mission, but all of us are dedicated to fulfilling it. We remain confident that we can achieve our ambitious goals, and we look forward to 2013 with great anticipation. Thank you for your continued support.
Respectfully,
Craig Dees, Ph.D., CEO
Provectus Pharmaceuticals, Inc.
About Provectus Pharmaceuticals, Inc.
Provectus Pharmaceuticals specializes in developing oncology and dermatology therapies. Its novel oncology drug PV-10 is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects. Its oncology focus is on melanoma, breast cancer and cancers of the liver. The Company has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications. Its dermatological drug PH-10 also targets abnormal or diseased cells, with the current focus on psoriasis and atopic dermatitis. Provectus has recently completed Phase 2 trials of PV-10 as a therapy for metastatic melanoma, and of PH-10 as a topical treatment for atopic dermatitis and psoriasis. Information about these and the Company's other 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.pvct.com or contact Porter, LeVay & Rose, Inc.
FORWARD-LOOKING STATEMENTS: The forward-looking statements contained herein are subject to certain risks and uncertainties that could cause actual results to differ materially from those reflected in the forward-looking statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which reflect management's analysis only as of the date hereof. The company undertakes no obligation to publicly revise these forward-looking statements to reflect events or circumstances that arise after the date thereof.
