Eric's Process

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There has been, is and probably will continue to be a contrast in the styles of Provectus' Chief Technology Officer Dr. Eric Wachter, PhD and Chief Operating Officer/Chief Financial Officer Peter Culpepper. The contrast of course derives from their roles and responsibilities at the company, past professional experiences (and the industries in which they gained them), and personalities, among other things. Having gotten to know Eric over time, and also having spent a number of years doing venture capital, technology commercialization, M&A and other corporate development in the defense and intelligence industry (where I've met similar or comparable folks), I like and feel comfortable with most (but not all) of his processes and related approaches.

One would have expected both processes and individuals (e.g., clinical development for Eric, business and corporate development for Peter) to have been much more intertwined than they historically have been. This lack of convergence (interaction, really) has been very costly to date: for management in terms of [stock] market credibility, for the company in terms of valuation along the way, and for shareholders in terms of dilution that arguably could have been mitigated to some significant extent.

Earlier this week Provectus issued a press release and made an associated 8-K filing (that included another item) regarding Brazil, Provectus Biopharmaceuticals Retains PharmaHEALTHLabs to Facilitate Investigator Advisory Board Meeting During 11Th Brazilian Melanoma Conference. See prior comments under the blog news item Kick-off (June 22, 2015). On its surface the PR appears to be nonsensical at best, and mostly irrelevant at worst. A deeper read makes it more relevant [to me], which does not however excuse its quizzical construction and opaque message.

My takeaways for this blog post are:

• The PR appears to identify the timing (mid-August) of the orientation meeting of clinical trial site investigators and coordinators (investigator advisory board meeting) for Provectus' pivotal melanoma Phase 3 trial, and

• The release also appears to name their agent or intermediary (Jeff Meehan) for a potential commercial license of PV-10 or Big Pharma relationship in Brazil and/or South America.

I'm more interested in Eric's process, and thus the first takeaway above. Within days of an orientation meeting, for example, one might expect the so-called First Patient First Visit ("FPFV") (typically a screening visit), the so-called First Patient In ("FPI") (randomized), and possibly a press release announcing the study's start. As a reference for the process of a late-stage clinical trial, see a 2010 presentation entitled Clinical Trial Timelines by Cornelia Kamp, Executive Director Strategic Initiatives, Clinical Materials Services Unit, Clinical Trials Coordination Center, University of Rochester.

Kamp, 2010

On April 15th the company issued press release Provectus Biopharmaceuticals Opens Patient Enrollment; Begins Phase 3 International FDA Comparative Clinical Trial of PV-10 for Melanoma. The Phase 3 trial protocol was updated on ClinicalTrials.gov the next day. This week (the end of June) St. Luke's University Health Network updated its website to include the trial. Interestingly the trial's St. Luke's code (SLUHN 2014-117) has a 2014 moniker, perhaps suggesting a registration of sorts last year when the protocol was first published on ClinicalTrials.gov in November 2014. I imagine St. Luke's Dr. Sanjiv Agarwala is or will be named the trial's "Lead Principal Investigator."

Click to enlarge.

While it is possible one or more patients may have been treated by Agarwala at St. Luke's (as "lead investigator" and "lead clinical site"), Kamp's presentation suggests (assuming, and I do assume, Eric followed good relevant and comparable process) it is more likely or more proper that the recruitment, enrollment and treatment of most if not all Phase 3 patients would begin after the mid-August orientation meeting that coincides with the 11th Brazilian Melanoma Conference from August 13-15 in Goiania, Brazil.

Note the illustration of the life cycle of a clinical trial, and the temporal placements of the orientation or initiation meeting, and the enrollment of patients (subjects) below (green boxes are my additions).

Click to enlarge. Kamp, 2010

Site enrollment drives recruitment. Interestingly, while the clinical trial enrollment rate (CTER, the number of patients per trial per month) grows with the number of sites added to a trial, gross site enrollment rate (GSER, the number of patients per site per month) increases at a decreasing rate. Also, larger trials have lower GSER than those of smaller trials. See Forecast Enrollment Rate in Clinical Trials by Gen Li. Kamp notes providing sites with drug supply. Peter previously discussed drug supply on the March 12th 4Q14 conference call; however, Eric has not discussed publicly whether all the sites had the requisite supply (I assume they now do). Li's research into enrollment rate also suggests it would be better for as many trial sites as possible to be activated at the same time to increase CTER and attain a more optimal GSER.

Click to enlarge. Kamp, 2010

Kamp notes activation of a single center takes an average of 100 days. If I assume activation requires the trial protocol to be finalized, and I further assume finalization is equivalent to posting the protocol on the ClinicalTrials.gov website, 100 days after April 16th (when it was first posted) is July 25th (the "average" date), or about 3 weeks before the mid-August orientation meeting. I would guess participating sites should be up on ClinicalTrials.gov by July 25th if not by mid-August.

Click to enlarge. Kamp, 2010

She reiterates the critical importance of sites having drug supply.

Click to enlarge. Kamp, 2010

Click to enlarge. Kamp, 2010

Click to enlarge. Kamp, 2010

Kamp suggests or encourages registering a trial (filing the final protocol) with ClinicalTrials.gov before FPFV.

Click to enlarge. Kamp, 2010

She discusses orientation/site initiation meetings below (the green box is my addition), noting "Timing of the mtg should be such that at least half of the sites have IRB approval and subcontracts in place" {underlined emphasis is mine} and "Sites should be ready to start screening/enrolling subjects immediately following this training." Eric previously said the company was going to employ 25 sites in the U.S. and 10 in Australia for the Phase 3 trial.

Click to enlarge. Kamp, 2010

Click to enlarge. Kamp, 2010

Finally (for this blog post), Kamp discusses the timeframe of FPFV, FPI and, potentially, study start announcement (which the company already may have made on April 15th), which could be within days of the orientation meeting (i.e., late-August).

Click to enlarge. Kamp, 2010