Since our last letter, Provectus has gone through significant changes on multiple levels. The past several months have placed us in a much different, and stronger position than we had been previously. This is true for our regulatory path, our scientific situation, our corporate structure, our financial strength and our commercial prospects. This is an ideal time to review where we have been and to discuss where we are going in a continuing effort to be as transparent as possible.
The most prominent development recently was the information obtained from our application for Breakthrough Therapy Designation (BTD) to the
PHASE 2 RESULTS
Our development plans for PV-10 stem from the results of our phase 2 study. In that trial, tumors were no longer detectable in 50% of patients with locally advanced cutaneous melanoma who had all of their existing lesions injected. Results from these patients support the potential of PV-10 as a single agent, and provide rationale for a phase 3 randomized controlled trial in patients with unresectable, locally advanced cutaneous melanoma.
Top-line results from the phase 2 trial have been posted on clinicaltrials.gov, for the study entitled “Phase 2 study of Intralesional PV-10 for Metastatic Melanoma,” [NCT00521053]. http://clinicaltrials.gov/ct2/show/NCT00521053?term=NCT00521053&rank=1
When we completed data collection two years ago, we knew we had a promising oncolytic agent with consistent response in injected tumors, but we also had intriguing data on the bystander effect that implicated a secondary immunologic mechanism of action. At that time, we had no agreement with
The gap between completion of the data collection and the outlining of our plans in the conference call of
After presenting data from our phase 2 study in a Type C meeting last December and in our BTD application submitted this spring, the
PHASE 3 OUTLINE FOR MELANOMA
The planned phase 3 study will assess response to intralesional PV-10 vs. that of systemic chemotherapy in patients with disease confined to cutaneous and subcutaneous sites. These patients will have failed or be ineligible for systemic immunotherapy. Patients who would be eligible have extremely limited options, consisting principally of systemic chemotherapy (such as DTIC or temozolomide) or a clinical trial.
The primary endpoint of the study is progression-free survival (PFS) assessed using standard RECIST 1.1 criteria. Secondary endpoints are complete response rate and overall survival. Progression-free survival and overall survival are standard endpoints for oncology approvals. With these assessment methods and endpoints we’re following what the
Based on estimated effect size derived from the phase 2 data and literature data for the comparator drugs, we project that approximately 210 patients will be needed for the study, with 2 to 1 randomization. Meetings with scientific advisors, investigators and advocates in the field have led us to expect a starting date for the phase 3 study sometime in the second half of 2014. Based on our experience enrolling similar patients in the mechanism of action study we’re sponsoring at
We have recently signed agreements with two manufacturers to supply us with clinical-quality PV-10, and we now have sufficient quantities of PV-10 available to commence this phase 3 trial and undertake our other development activities. To assure smooth execution of the study we’ve lined up specialty contract research organizations (CROs) and other service providers with expertise in clinical operations and integrated data management. As is standard in our industry, this includes a full-service, international CRO who will coordinate the global efforts of this team of specialists.
We’ll work with this team to establish an independent Clinical Trial Data Monitoring Committee (DMC). The
THE INTRALESIONAL APPROACH TO TREATMENT
Provectus is not alone in advocating for an intralesional approach in the treatment of cancer. For melanoma patients with recurrent or in-transit disease confined to their skin this approach has been used to treat patients for many years, as evidenced by guidelines published by the National Comprehensive Cancer Network (NCCN Guidelines®) defining the standard of care for cancer treatment in
And for those patients who do not have all disease accessible to injection, medical oncologists have stated that using an agent like PV-10 to prime the immune system could be synergistic in combination with a systemic agent. Our patent application on this strategy was published in 2012 and we’ve been vigorously pursuing this approach. The nonclinical research we first presented at the
LIVER AND METASTATIC CANCERS
We have recently expanded our exploratory phase 1 study of cancers of the liver to 3 centers (St. Luke’s
The current phase 1 study, initially designed solely to establish safety of percutaneous injection of PV-10 into liver tumors (that is, injection through the skin), is providing valuable data crucial for planning such phase 2 development. This trial is open to patients with hepatocellular carcinoma or other cancers metastatic to the liver who have at least one tumor that has either originated in or spread to the liver and are not candidates for surgery or transplant. All patients enrolled in this open-label study receive the same treatment: an interventional radiologist injects PV-10 percutaneously into a single liver tumor. Patients with multiple injectable tumors may later receive further PV-10 to their other tumors. We have received numerous inquiries about this study from researchers as well as patients and their doctors, and refer these to our investigators through the contact information available on the clinicaltrials.gov website.
PH-10 FOR DERMATOLOGICAL TREATMENTS
So far over 220 patients have participated in phase 1 and 2 trials of PH-10. We anticipate posting results from these studies on the clinicaltrials.gov website in the coming months and are encouraged by what has been observed to date. Following the model we’ve used successfully with PV-10, we’re planning a translational clinical study to better understand the possible immunologic mechanism of PH-10 in the skin in relation to psoriasis, eczema and other inflammatory dermatoses. Our investigators are currently evaluating the results of our studies. When their assessments are complete, we will move forward with the necessary further trials and regulatory requirements to bring this compound to patients who need it.
Provectus has built a solid portfolio of patents to protect our shareholders’ value. Among recent additions to this portfolio are: US Patent 8,557,298, “Medicaments for Chemotherapeutic Treatment of Disease,” which provides detailed protection of PV-10; US Patent 8,530,675, “Process for the Synthesis of 4,5,6,7-tetrachloro-3’,6’-dyhydroxy-2’,4’,5’,7’-tetraiodo-3H-spiro[isobenzofuran-1,9’-xanthen]-3-one (Rose Bengal) and Related Xanthenes,” which details our new process for the manufacture of Rose Bengal and related iodinated xanthenes in high purity; and US Patent Application 2012/0263677, “Combination of Local and Systemic Immunomodulative Therapies for Enhanced Treatment of Cancer,” which covers methods for treating cancer through combination use of intralesional agents (such as PV-10) with systematic anticancer agents (such as checkpoint protein inhibitors).
During the past several months, researchers have presented data on PV-10 in multiple major international conferences. These include annual meetings of the
INTERNATIONAL LICENSING OPPORTUNITIES
Provectus has provided data on a confidential basis to both potential global and geographic partners for both PV-10 for oncology and PH-10 for dermatology via a secure electronic data room. We are encouraged by the number of companies doing due diligence on our technologies. For instance, we recently had a team in
Whenever we obtain a Memorandum of Understanding (MOU), definitive agreement or similar indication of interest from a potential partner, we will issue a press release and Form 8-K filing to notify the market. Furthermore, the strategy of the company for the benefit of shareholders is a series of partnerships followed by an acquisition of the company along the lines of Celgene/Abraxis.
We have already signed an advisory agreement with
MONETIZING PV-10 AND PH-10
The primary financial objective of the Company is to strategically monetize the core value of PV-10 and PH-10 through the various transactions discussed elsewhere in this letter. Ultimately, the Company wants to leverage value creation through the sale of the business or a merger that may include upfront cash, acquirer stock, and/or a contingency value right (CVR) as part of the total consideration. A CVR represents the right for its holder to receive certain defined payments upon the achievement of a specified milestone and would be designed to facilitate potential upside for the Company’s shareholders on a post-transaction basis. A CVR could trade on an exchange. The Company is not in discussions regarding the sale of its business and there can be no assurance, however, that the Company will be able to monetize PV-10 or PH-10 in the manner described herein.
SUFFICIENT CAPITAL ON HAND
Our financial position and corporate governance are such that we expect to continue to meet the relevant listing requirements of NYSE MKT. We believe our efforts to obtain regulatory clarity will be helpful to facilitate such transactions with potential partners. Additionally, the existing and forthcoming clinical and nonclinical mechanism of action data for both PV-10 and PH-10 are expected to further aid in both regulatory clarity and transactions with potential partners. The Company’s current cash position is sufficient to meet our obligations. In addition, management is returning
We have changed our Company’s name to
In addition, we have “up-listed” our stock onto the NYSE MKT. Moreover, we have added several important individuals to our
Further, we have retained Roberti+White to assist in developing a commercialization strategy for PV-10 by implementing a plan to expand our congressional outreach to key Members of
We are grateful for the long-term support of our shareholders and their faith in our Company’s future. The next several months hold great promise for Provectus, and we look forward to sharing the latest developments with you.
FORWARD-LOOKING STATEMENTS: This letter 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
our determination, based on guidance from the |
|•||our determination whether to license PV-10, our melanoma drug product candidate, and other solid tumors such as liver cancer, if such licensure is appropriate considering the timing and structure of such a license, or to commercialize PV-10 on our own to treat melanoma and other solid tumors such as liver cancer;|
|•||our ability to license our dermatology drug product candidate, PH-10, on the basis of our phase 2 atopic dermatitis and psoriasis results, which are in the process of being further developed in conjunction with mechanism of action studies; and|
|•||our ability to raise additional capital if we determine to commercialize PV-10 and/or PH-10 on our own, although our expectation is to be acquired by a prospective pharmaceutical or biotech concern prior to commercialization.|