Provectus Biopharmaceuticals, Inc. (PVCT) PETER
Post# of 23099
Posted On: 01/20/2015 9:29:42 AM
Provectus Biopharmaceuticals, Inc.
(PVCT)
PETER R. CULPEPPER, CPA, MBA
, is Chief Financial Officer and Chief Operating
Officer
of Provectus Biopharmaceuticals, Inc. Mr. Culpepper has spent 20 years in the
financial field working for a wide range of companies and industries in the U.S. and
abroad, especially high-growth startups. His experience with for-profit companies
ranges from private startups to publicly traded global conglomerates. He also has
worked with large nonprofits and a national CPA accounting firm. He led the national
operating unit of a $1 billion publicly traded telecommunications company, as well as
numerous operating units in Eastern Europe for a global telecommunications company.
He handled the capital reporting process for a $5 billion global construction project
and the formation of systems for a division that grew $150 million in revenue in two
years. Previous employers include Neptec, Inc., a privately held optical networking
component manufacturer; Metromedia Companies; and PageNet, the largest wireless
messaging company in the world. Mr. Culpepper holds a Master of Business Administration in finance from
the University of Maryland. He earned an AAS in accounting from the Northern Virginia Community College —
Annandale, Virginia. He earned a bachelor’s degree in philosophy from the College of William & Mary.
COMPANY INTERVIEW
REPRINTED FROM JANUARY 19, 2015
SECTOR — PHARMACEUTICALS
TWST: Can you give us a brief overview of Provectus’
business?
Mr. Culpepper:
I am pleased to be able to do this again
because a lot has transpired, in terms of our corporate and clinical
development, since the last interview I did with
The Wall Street
Transcript
in September 2013. To start with, we changed the corporate
name to Provectus Biopharmaceuticals, and we incorporated in
Delaware in December 2013 after approval by the shareholders. The
reason Provectus is now Biopharmaceuticals is because in our two
therapeutic areas that we are focusing on, oncology and dermatology
— we have two active INDs in both of those areas — the mechanism
of action has an effect on the immune system.
In cancer, the objective of our approach is treating solid tumors
in different indications: Melanoma, liver and breast are the three that
we’ve done the most clinical work on. When I say liver, it’s cancers
metastatic to the liver as well, not just primary liver. And in skin diseases,
it’s inflammatory dermatoses, psoriasis, atopic dermatitis, etc.
For those two therapeutic areas, the mechanism is such that
we have, through our drug product, an affinity for treating the disease
in such a way that the immune system is properly modulated. In cancer,
we upregulate the immune system, and in dermatology, we downregulate
the immune system through the mechanism of action. So that’s been our
focus: to show in the data why that is happening, that in fact it is happening
clinically and preclinically, and to the extent that we can, describe it in a
way that’s helpful to the medical community.
TWST: You mentioned that there has been a lot of clinical
development in the last year since we last spoke, so can you give us an
update on the key changes and the stages of the various trials?
Mr. Culpepper:
Let’s start with oncology and the use of our
lead agent, PV-10, which is a formulation of an active ingredient rose
bengal, a very well-known halogenated xanthene. Since the last call,
we have a new patent for the synthesis of that active pharmaceutical
ingredient, which is important, and that patent is being prosecuted
globally as well. We also have a combination patent application for
the way we are using PV-10 in combination with various co-inhibitory
blockade or systemic immunotherapy drugs. The combination of PV-
10 with several of these drugs is an important aspect of the joint
patent application with Pfizer.
For over a year, Moffitt Cancer Center has been conducting a clinical
study that uses PV-10 as a neoadjuvant to surgery in patients with disease where
it is not appropriate to remove the disease surgically alone. It turns out that
when they presented this data at ASCO earlier this year, they could show this
through the immunohistochemical-staining pathologic complete response. So
we are treating disease with PV-10, and Moffitt has shown in their clinical study
pathologic complete response of the treated lesions and also — and this gets
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PROVECTUS BIOPHARMACEUTICALS, INC. (PVCT)
to the bio part of biopharmaceuticals — the immunologic benefit of PV-10.
For the nontreated lesions, you have this enhanced tumor-specific reactivity in
circulating T cells because of PV-10.
So the most important development was to show the industry
this information; it went to the FDA and was then presented at ASCO.
Additional information was presented just earlier this month at the
Society for Immunotherapy of Cancer’s annual meeting in Washington,
D.C. In the prior year, Moffitt presented, in effect, the same information
on a preclinical basis, which was published just in the last year.
In addition, this SITC data from November is expected to be
published; the clinical data are yet to be published in a peer-reviewed
journal. I was with the Moffitt Cancer Center primary researcher, Shari
Pilon-Thomas, Ph.D., at the SITC conference on November 8, and they
are planning to publish their clinical data that they presented at ASCO.
But the main point of this for the industry, for the FDA, for Big Pharma,
is they want to see PV-10’s ability to kill disease where it is injected, and
this is a key point: The PV-10 is injected directly into the tumor. Because
of that, it’s a local treatment, good for the disease to be killed safely and
effectively; that is what the data have shown in numerous presentations.
But what Moffitt has shown is, when we do that locally, you
get systemic antitumor immunity and this pathologic complete response
in both injected and uninjected lesions, including treatment refractory
tumors. So Moffitt has been particularly helpful for the industry in
understanding that when you inject a tumor with PV-10, you get
pathologic complete response. And for tumors that you don’t directly
treat, you also get pathologic complete response because of this enhanced
tumor-specific reactivity in circulated T cells.
It can be described in two ways. PV-10 alters the T-cell
immunity, so you get the benefit when you treat locally, when you get
enough tumor destruction, and you can get a harnessing or triggering
or priming of the immune system in such a way that it can be a benefit
systemically. So with the full Phase II data, and this Moffitt initial clinical
data, which they just refer to as a feasibility study, we’re going to use
PV-10 in a Phase III study where you can treat all disease locally; this
is the Phase III design, which has been filed with the FDA. It is on
ClinicalTrials.gov and is available to be reviewed. The FDA is literally
reviewing it right now. We are working with the FDA now in a 30- to 45-
day period to review the protocol.
So for PV-10, we have a Phase III protocol that the industry
believes is appropriate with the appropriate endpoints, with the appropriate
powering and the study population. We have the active arm versus the
control arm, and there is a standard randomized controlled study for a
pivotal registration study. This is the Phase III PV-10 for melanoma. At
the same time, because of the Moffitt data, we are now designing and
have stated that we plan to start a combination study, which is a Phase Ib/
II-type study design, where we combine PV-10 with appropriate systemic
immunotherapies where you are looking at treating disease that’s already
metastasized beyond the reach of a local treatment directly.
So for instance, if a person has a brain metastasis of melanoma,
yet they still have local regional disease, which is typically the case, they
would treat PV-10 locally, where they can get the needle to easily. And
then, they would combine with PV-10, the local treatment, the appropriate
systemic treatment — let’s just say, Bristol’s Yervoy or Merck’s Keytruda —
if a patient’s refractory to systemic immunotherapies alone and local disease
still exists, some sort of combination much like what Amgen is doing right
now. We are not just implementing a new way of thinking. We are actually
doing what the industry believes is appropriate when those diseases cannot
be directly impacted as — perhaps aggressively as — you would want.
The Phase Ib/II is in process of being finalized, and we
would do the study parallel to our efforts in both the Phase III for local
melanoma. This is potentially stage 3 melanoma for our Phase III, and
then, stage 4 melanoma would be addressed in this combination study.
So we are moving forward with both of those, and we’ve made that very
clear publicly. We are very excited about both of those, and the industry
is excited in terms of how it sees the need for even the late-stage patients
to have a better approach from a combination-treatment perspective to
address the entire disease burden more effectively.
TWST: Is there a particular drug that you combine with
PV-10 for metastatic disease?
Mr. Culpepper:
Yes. Well, there is a particular drug at least for
melanoma. The way the industry immunologist described it is the immune
checkpoint blockade or co-inhibitory blockade. The cancer, melanoma, is
growing, is spreading throughout the body, and the immune system is not
properly aware of it or has the brakes on the T-cell response. So there is
some sort of inhibition. What these immune checkpoint blockade agents
are doing is taking the brakes off the immune cells and responding.
So you have a general priming in the immune system with
these agents, and both drugs are delivered systemically. These drugs have
certain tools, and in particular, the CTLA-4-based immune checkpoint
blockade and then the PD-1-based immune checkpoint blockade, those
agents have been approved in the last couple of years. Anti-PD-1, Merck’s
drug Keytruda, which was approved this year, but Keytruda is indicated
only when a patient is refractory to the frontline checkpoint blockade,
which is still Bristol’s Yervoy.
There is survival benefit with these drugs for late-stage
melanoma patients — that’s very important — but there is not a complete
regression of the disease burden. There still is disease burden that
needs to be addressed, and particularly, it’s locally advanced cutaneous
melanoma that needs to be addressed. This is what the industry wants
determined: What’s the optimal way to address systemic disease burden?
So the industry as a whole sees the systemic agents as very appropriate
to combine with the local drug like PV-10, which goes back to the joint
patent application we have with Pfizer.
Pfizer first approached us because they wanted us to combine
PV-10 with their initial anti-CTLA-4 immune checkpoint blockade,
which is an analog of Bristol’s. Pfizer had a parallel development effort
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PROVECTUS BIOPHARMACEUTICALS, INC.
(PVCT)
with Bristol; Bristol was successful with theirs. Pfizer just barely missed
theirs, tremelimumab. So Pfizer is interested in this field of research.
Pfizer just announced a joint partnership with Merck in this checkpoint
blockade effort with the successor compound platform or the successor
checkpoint blockade focus, anti-PD-1. So it’s a very, very intensely
focused effort, with the Big Pharma companies in particular attempting
to harness or prime the immune system, which we are ecstatic about. It
makes a lot of sense in the industry.
For PV-10, which induces this immune response or enhances this
tumor-specific reactivity in the circulated T cells, we get this expression of
the antigenic material that the T cells need to be visible. It makes sense for
the industry to combine PV-10 with the agents that are also priming the
immune system. So people have a good view on the combination.
The question is: Which is more mechanical or technical, what
is the number of patients in the study, which agent do you use, do you
use Bristol’s or Merck’s, or do you use maybe both in separate studies?
We have more of those kinds of discussions to aid in our trial designs.
Thankfully both of those initial immunotherapies are now approved, so it
makes the reimbursement cost much more straightforward.
From an industry standpoint, we are very much supported by
our investigators, the physicians, and the sites throughout the U.S. and
Europe wherever these new checkpoint blockade agents are available.
We are very well-supported by the people that we know and work with to
do both of these studies — the Phase III study and the combination study.
We are really dealing with different patient populations, so both studies
make sense for treating melanoma.
TWST: When we talked to you back in 2013, you were
talking about getting breakthrough therapy designation for PV-10.
What’s the status of that?
Mr. Culpepper:
That’s a very important question. When we
presented the full Phase II data and some of the Moffitt Cancer Center
feasibility data to the FDA in late last year, the FDA said in effect to present
the data in a formal request for action to move forward. They stated for
us to request breakthrough therapy designation — BTD — which we did,
and we announced the application sent to the FDA on March 24, 2014.
However, on May 23, 2014, in a press release, we announced that we
were denied BTD. So in the FDA filing, which we announced publicly,
which is rare, as I understand it, we announced the FDA’s decision, and
we filed the letter, the actual breakthrough denial letter, in an 8-K filing
on May 23. That was a tough Friday back in May 2014.
We made that announcement because we wanted people to
know that we tried to, in effect, accelerate the approval of PV-10. We
wanted to see if we could shorten the development process. The FDA
said, “You haven’t given us enough data to give you breakthrough therapy
designation,” but they encouraged us in the denial letter to generate more
data and try again. They also encouraged us to do certain aspects of a
study, which led from a very challenging time to a very positive outcome
in the sense that the FDA said, “Here’s what we will work with you on
to move this forward,” and that’s what led to the Phase III trial protocol.
The breakthrough effort helped in the development pathway for PV-10
and how to segment where PV-10 is appropriate.
This is a big deal in the industry because local agents have
never been approved for treating melanoma. So to have the FDA
recognize the locally advanced cutaneous melanoma — that language
actually came from the FDA, which they further stated as being a life-
threatening disease in and of itself — and then, the FDA encouraged
us to use a comparator, which of course is consistent with the National
Comprehensive Cancer Network, NCCN, guidelines. The FDA
encouraged us with those guidelines and the patient population to use,
the standard endpoints, PFS, and overall survival, etc., standard scoring
RECIST 1.1 and appropriate comparator, which NCCN guidelines states
is a systemic chemotherapy, which is dacarbazine or temozolomide.
So we have taken what the FDA gave us, and we are doing
what they want in the Phase III to provide them enough data in order
for PV-10 to presumably be approved on that basis. We don’t think we
will apply for breakthrough again even though they encouraged us to
do so because we think the Phase III does make a lot of sense; still,
they essentially gave us two options. They also told us to consider
fast-track designation, which could further expedite the Phase III
effort itself. So the FDA has helped us move forward in that discussion
of breakthrough denial on how you move PV-10 forward by itself as
a single agent and also delineate the single use of PV-10 from the
combination use. That’s been the benefit: knowing what to do to move
PV-10 forward for treating melanoma.
Now, the discussion gets a lot easier when we talk about liver
cancer. By the way, it’s a much simpler discussion for the industry
with liver cancer. The reason melanoma is so tough is melanoma is a
virulent disease once it’s unresectable. So once surgery is no longer
appropriate, melanoma moves in the body from stage 2 to stage 3 to
potentially stage 4 very quickly, unless you arrest its spread in stage 3
quickly enough. It’s a fast-moving disease; that’s why initial surgery
in stage 1 is so critically important, like all cancers of course, to get it
out as quickly as possible. If you miss a chance in melanoma, stage 3
can be really an important time to address it locally.
As the FDA said, locally advanced cutaneous melanoma is life-
threatening on its own. If you don’t deal with it enough or aggressively
enough there, you will risk metastatic disease, and so that’s been an
important distinction that’s now recognized by the industry, which is a
huge plus for PV-10 since we see its effectiveness in treating melanoma
in the recently published Phase II data in Annals of Surgical Oncology.
So we see the breakthrough denial guidance as a silver lining. It was a
way for us to have a much-enhanced dialogue with the agency to figure
out how to move PV-10 forward to treat patients.
TWST: You mentioned liver cancer is easier. So where are
you now with liver cancer?
Mr. Culpepper:
The reason we say liver cancer, and the
industry, for that matter, says liver cancer is easier, is because it’s locally
metastatic, or in other words, it’s locally advanced and understood as an
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PROVECTUS BIOPHARMACEUTICALS, INC. (PVCT)
unmet need already. So for liver cancer, the real problem is when surgery
is no longer appropriate locally. You don’t die of melanoma when it’s on
your arm or your leg or even on your trunk area, you die when it goes
to your brain or your lung or the vital organs; that’s where you die in
melanoma. For liver cancer, you die with local disease if not surgically
removed, so it’s a different challenge.
The challenge in liver cancer is to treat the disease in the
liver where surgery is no longer appropriate. The bulk of the challenge
is in the U.S. and ex-U.S., where most liver cancer is. Over 50% is
in China alone, which is why we have an MOU — memorandum of
understanding — with Sinopharm, the largest China pharma company.
The etiology of the disease is different in China than, say, in the U.S.,
but for the industry, liver cancer is not a problem to treat locally.
Melanoma was a problem until we got this understanding from the
FDA with the segmentation or demarcation of PV-10 used locally
versus PV-10 in combination for systemic benefit.
With liver cancer, everyone says “Oh yes, treat it locally,
that’s fine. No problem at all.” Now, we just run a study to show that it
is appropriate versus standard of care alone. The liver cancer standard
of care is straightforward also; it’s sorafenib, or Nexavar. It’s a clean
regulatory path, relatively speaking.
In melanoma, it wasn’t a clear regulatory path, and a person
can see that if they go to the National Comprehensive Cancer Guidelines.
The standard of care is very challenging to determine for the different
substages of stage 3 and 4 in melanoma, whereas for liver cancer, it is
nonresectable disease. The study design is the same Ib/II study design,
where in this case, you combine PV-10 with sorafenib versus sorafenib
by itself, so it’s a straightforward comparison to standard of care. We’ve
already done necessary Phase I liver cancer work that showed that PV-10
does kill liver cancer, ablate the tumors that are injected. That’s all the
industry needs in support going forward in the Ib/II trial design.
And the reason we say it in Ib/II is we do, essentially, dose
escalation; we’ve done the necessary preclinical work combining PV-10
with sorafenib so you have no drug-drug interaction challenges. But you
have to do that in, of course, patients so that you can manage any toxicity
issues, which we don’t expect based on the extensive preclinical work,
but still, you have to make sure in humans. Therefore, we do that in the Ib
part of the Ib/II and then move immediately into the randomized portion
where you’re randomizing PV-10 in combination with sorafenib versus
sorafenib as a standalone drug. So that kind of a trial design, that kind
of clinical pathway is much easier for the industry, it’s much easier for
the FDA, it’s much more straightforward. We have been encouraged to
pursue this trial design and study immediately.
Now, the same trial design that we were talking about for the
combination PV-10, where you combine a PV-10 with immune checkpoint
blockade, it is the same type of trial design that we’re designing. I call it
a plug and play. If this combo study that could be appropriate for PV-10
with sorafenib or PV-10 with these immune checkpoint blockade agents,
or PV-10 even for breast cancer, which would be the next indication we
want to move forward. We’ve done a Phase I breast cancer study, and we
have been encouraged to move forward in breast cancer.
PV-10 does successfully treat recurrent breast cancer. We
will want to compare PV-10 to the standard of care. For breast cancer,
chemotherapy or radiation is used as neoadjuvant to surgery with this
tissue-sparing objective. You want to spare tissue, and you want to
reduce the disease burden so you can minimize the tissue removed from
a surgery standpoint. So that’s where PV-10 comes in.
We would randomize it against chemotherapy and/or radiation
because PV-10 has a much better side-effect profile based on all of our
data. We believe PV-10 is very well-tolerated versus chemotherapy and
radiation. We believe PV-10 is more effective than chemotherapy and
radiation, based on all of our data. In our various clinical studies with PV-
10, typically, we are treating patients that have been refractory to radiation
and chemotherapy. And this is why, our compassionate use protocol, we
treat patients that are refractory, and we can treat those lesions that are
refractory to chemotherapy and radiation just as easily as when the lesions
are native, or if they haven’t had radiation or chemotherapy. So we think
there is an opportunity there for PV-10 to treat multiple indications with
the aid of the same study design.
TWST: What is the time frame for those studies for liver
cancer and breast cancer; is there an order there?
Mr. Culpepper:
Yes, there is an order. The order we’ve
established is the Phase III melanoma study is filed; we’re waiting for
FDA interaction to make sure all the particulars are fine. Then, they
will submit the Phase Ib/II combination study design, which we said is
underway, and we are finalizing it. As a matter of fact, we’re meeting
with key opinion leaders on this topic next week. Then, we do the Ib/
II liver study. We’ve been meeting with individuals also for our liver
program on a regular basis. That probably will come very shortly after
the combo, and we’ve met with individuals globally.
There would probably be a Western cohort with sorafenib
as the standard of care. The Eastern cohort would have local ablative
standard of care in China, India, Singapore and Korea. Sorafenib doesn’t
work in their view, which is true from a data standpoint. They use a local
ablative agent that also doesn’t work very well. However, they use them
versus sorafenib, after surgery.
So the Ib/II for liver would follow very closely after the combo,
and then, breast unfortunately would be after that, but it would be the same
study design instead of, say, using sorafenib or the checkpoint blockade
as the combo piece. We would use chemotherapy or radiation, but breast
would definitely come after Phase III is underway and enrolling, the
Phase Ib/II combo is underway and enrolling, and Phase Ib/II liver is
underway and enrolling.
TWST: Are all of these planned for 2015?
Mr. Culpepper:
Yes. The first three are already planned. We
already have the supply chain support underway; there is the design of the
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appropriate studies underway. We’ve already interacted with the KOLs,
the different physicians, which is good. The physicians we work with
who treat melanoma are also involved, interestingly enough, in treating
the liver, so it dovetails very well.
The physicians who treat melanoma, and the institutions, are
used to treating melanoma locally. They want to treat visceral disease in
combination because they like treating locally, but they don’t want to treat
just locally if the person has brain metastasis, for example. And they also
treat the liver. The reason they treat the liver, even if they are melanoma-
focused, is because melanoma can spread to the liver; as a matter of fact,
for ocular melanoma, 40% goes to the liver. So a significant portion of the
visceral metastases for melanoma is to the liver, so it’s of concern.
The same physicians are interested in being in both studies,
so there’s a good synergy between melanoma and liver, and the same
thing with the FDA in DOP2. FDA DOP2, you work with Division of
Oncology Products 2 under Dr. Keegan and her staff. The work we’re
doing in both melanoma and liver falls within the same group. For
breast cancer, it’s DOP1, and it’s a different set of physicians, so it
would definitely be a separate effort.
So I would say, with the next three PV-10 studies, certainly
we’ll see those studies generating meaningful data in 2015. I hope the
answer will be yes in breast. We’re pushing on that. We have already
established a relationship with a breast cancer advocacy group. We
plan to be at San Antonio Breast Cancer Symposium in San Antonio in
December. We’re very focused, and of course, we’ve done clinical work
in breast, so we know PV-10 is appropriate for breast, and we’ve been
encouraged by potential partners to be treating breast cancer, particularly
in China and India where breast cancer is a top concern, but liver cancer
is of course also a cancer of very significant concern.
TWST: Given all the tasks ahead in the different
trials, what are the risks inherent in meeting the goals that you
want to achieve?
Mr. Culpepper:
In our case, the regulatory risk is rather
minimal, and the reason I say that is because rose bengal is a well-
known active pharmaceutical ingredient. The FDA in two diagnostic
applications has approved it. It’s an ophthalmic diagnostic agent. It has
been used in the eye for decades, and it’s been an IV hepatic function
agent, delivered intravenously throughout the body for decades. So it’s
got a lot of safety history. It’s got the important toxicity studies: LD50,
etc. There’s a lot of data in the literature in peer-reviewed publications.
There are over 3,700 peer-reviewed publications on rose bengal. And
at our own request, we got our own self-audit. We brought in a large
well-regarded CRO to do a regulatory audit.
So the regulatory risk isn’t as much of a concern; I see it as
more of an ethical and shareholder return risk. And when we’re dealing
with development-stage companies, patients are first because you don’t
get anywhere unless you are providing service and value to patients in
this industry. But the way we fund all these studies is largely through
shareholders. So the biggest risk really is: Can we be as diligent moving
it forward for the benefit of the patients and shareholders too? There
are numerous solid tumors where we want to focus on this: pancreatic
cancer, noninvasive bladder cancer, prostate cancer, etc. We’ve done the
preclinical work in numerous solid tumor indications, and so we’re being
encouraged on a regular weekly basis in our ongoing compassionate use
study to use PV-10 in numerous indications.
It’s amazing, unfortunately, how many different cancers
are going to the liver, like colorectal cancer, lung cancer, melanoma,
pancreatic cancer and even breast cancer. So I would say, the biggest
challenge we have is meeting the needs of patients as quickly as we can
and, at the same time, being responsive to our shareholders so that we can
maximize a return on their investment. It’s doable, but that’s the toughest
balance. It’s like the work-life balance in a nutshell.
Patients are clamoring. As you can see on our website, Eric
Wachter and I are company contacts for the compassionate use program,
so we see the need firsthand, along with our CEO, Craig Dees. Now, for
various reasons, we don’t get directly involved in treating the patients,
so we refer them to the different sites for treatment, but still, we get the
requests on a very regular daily basis to be in the compassionate use
program. Typically, what I do is point out the clinical trial, where they
can actually contact the study coordinators for compassionate use of
PV-10. But we see, firsthand, the needs for patients, and we also see,
firsthand, the need for funding and making sure that we can get this
done as quickly as we can for patients.
TWST: How do things stand in terms of having sufficient
funds to take you through these various trials? Will you need to raise
additional funds?
Mr. Culpepper:
We have said we have enough cash to do the
Phase III melanoma study, so that’s important. We have enough cash to
do this Ib/II combination study for the immune checkpoint blockade, and
we have enough cash to do the Ib/II liver study. We can also do certain
work in these other indications, but we can’t do a full-blown set of studies
for advancing breast cancer, pancreatic cancer, other solid tumors, and
we can’t fully advance the liver or the combination program beyond
what we have established we are doing. The only indication we can fully
advance on our own is the PV-10 melanoma trial, which is important.
That’s the indication furthest along.
Now, we have access to additional capital. What we’re trying
to do is not raise more than we need. We will need to raise what we said
we’re going to do, but because we are on the New York Stock Exchange
MKT, and we’re audited by BDO, we always want to make sure we
have enough cash to meet the regulatory requirements, so we typically
raise enough cash to offset cash burn. But at the same time, we say in
the filings, as we are required to, that we have enough cash on hand to
do what we say we’re going to do, which is the Phase III melanoma
study, the Ib/II combination study for PV-10 with the immune checkpoint
blockade agents and the PV-10 Ib/II for primary liver cancer.
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All that being said, we also say in the filings that we believe
the start of these studies or the data itself from those three studies would
be sufficient to enable a partnership of some sort where we would secure
one or more regional licenses and/or a co-development transaction,
some cash upfront, funding that’s not dilutive along with milestones and
royalties, etc., as appropriate to the transaction. So we believe we can
mitigate or reduce financing through partnerships, and that’s something
else we’re balancing as we move forward with the different activities.
TWST: Is that something that you will start looking for in
2015, or perhaps you are already doing that?
Mr. Culpepper:
Certainly, we are already doing that in
terms of the potential partnership activity, which goes to our MOU-
with-Sinopharm topic. We have MOU with Sinopharm for purposes
of a regional license in China. We’re doing the same thing we’ve said
publicly, working on partnership relationships in India, and even Russia
and elsewhere, for regional licenses. We control the supply chain, but we
utilize the partners in those respective countries and regions to enable
data generation, interface with regulatory bodies there and provide some
monetization of PV-10 to the company.
Now, we say in the filings, we want to do an overall end-
game transaction like Celgene/Abraxis or better — so an acquisition of
the company — but we want to build value first and reduce the need
for financing with nondilutive cash through those regional license
transactions and/or co-development transactions. We are discussing
potential co-development transactions on the basis of this Moffitt Cancer
Center data that was presented earlier this month of November at this
Immunotherapy Conference. So yes, we are trying to do those now.
We are trying to secure partnerships now, and we will continue
to try until we believe we’ll be successful based on the data. There’s
clearly interest as we have a number of Big Pharma executives on our
strategic advisory board that are interested for that reason. So we believe
that’s the natural course of events. It’s just a question of timing.
TWST: Is there anything that we haven’t discussed that
you’d like to add?
Mr. Culpepper:
The only thing I would like to add is about
PH-10 on the dermatology side. What we’re doing there is somewhat
similar to what we’ve already done with PV-10 on the mechanism of
action. So here you have the PV-10, its priming of the immune system
response properly to the cancer in your body; and on dermatology, there
was an improper immune response, and we have modulated this as well.
We’re starting a feasibility study like Moffitt Cancer Center did for PV-
10. We are going to do the same thing with PH-10 with a well-respected
group that we’ll announce, somewhat similar to Moffitt Cancer Center, to
do a similar feasibility study in patients to show the unique mechanism of
action for PH-10 for dermatological indications.
So the use of PH-10 because what PH-10 is doing is modulating
the immune system. It’s an anti-inflammatory nonsteroidal mechanism,
which is great for the use of PH-10, say, if you have psoriasis or atopic
dermatitis or any sort of inflammatory dermatoses. Our drug, PH-10, will
reduce the inflammation and the itching. We’ve done different clinical
studies, Phase I and Phase II studies, to show this, and the question
now is working with the FDA to go into the Phase III and showing the
mechanism for the industry just like we’ve done with PV-10.
TWST: Do you know how soon you will be announcing
whom you’ll be working with on that?
Mr. Culpepper:
Yes. It should be just after the New Year. I
can say that we are finalizing the production run of the drug product itself
for PH-10. We have the new synthesis for the active ingredient, so we
have the supply chain refined, and the production run is actually being
finished literally in December, and then, we’ll be ready to start using that
new PH-10 based on the production run and the drug product itself for
the upcoming studies. We’ll announce that as early in the New Year as we
can and also the groups that will be involved.
TWST: Thank you. (EP)
PETER R. CULPEPPER, CPA, MBA
CFO & COO
Provectus Biopharmaceuticals, Inc.
7327 Oak Ridge Highway
Knoxville, TN 37931
(866) 594-5999 — TOLL FREE
(866) 998-0005 — FAX
www.pvct.com
© 2015 The Wall Street Transcript, 622 3rd Avenue, New York, NY 10017
Tel: (212) 952-7400 • Fax: (212) 668-9842 • Website: www.twst.com
(PVCT)
PETER R. CULPEPPER, CPA, MBA
, is Chief Financial Officer and Chief Operating
Officer
of Provectus Biopharmaceuticals, Inc. Mr. Culpepper has spent 20 years in the
financial field working for a wide range of companies and industries in the U.S. and
abroad, especially high-growth startups. His experience with for-profit companies
ranges from private startups to publicly traded global conglomerates. He also has
worked with large nonprofits and a national CPA accounting firm. He led the national
operating unit of a $1 billion publicly traded telecommunications company, as well as
numerous operating units in Eastern Europe for a global telecommunications company.
He handled the capital reporting process for a $5 billion global construction project
and the formation of systems for a division that grew $150 million in revenue in two
years. Previous employers include Neptec, Inc., a privately held optical networking
component manufacturer; Metromedia Companies; and PageNet, the largest wireless
messaging company in the world. Mr. Culpepper holds a Master of Business Administration in finance from
the University of Maryland. He earned an AAS in accounting from the Northern Virginia Community College —
Annandale, Virginia. He earned a bachelor’s degree in philosophy from the College of William & Mary.
COMPANY INTERVIEW
REPRINTED FROM JANUARY 19, 2015
SECTOR — PHARMACEUTICALS
TWST: Can you give us a brief overview of Provectus’
business?
Mr. Culpepper:
I am pleased to be able to do this again
because a lot has transpired, in terms of our corporate and clinical
development, since the last interview I did with
The Wall Street
Transcript
in September 2013. To start with, we changed the corporate
name to Provectus Biopharmaceuticals, and we incorporated in
Delaware in December 2013 after approval by the shareholders. The
reason Provectus is now Biopharmaceuticals is because in our two
therapeutic areas that we are focusing on, oncology and dermatology
— we have two active INDs in both of those areas — the mechanism
of action has an effect on the immune system.
In cancer, the objective of our approach is treating solid tumors
in different indications: Melanoma, liver and breast are the three that
we’ve done the most clinical work on. When I say liver, it’s cancers
metastatic to the liver as well, not just primary liver. And in skin diseases,
it’s inflammatory dermatoses, psoriasis, atopic dermatitis, etc.
For those two therapeutic areas, the mechanism is such that
we have, through our drug product, an affinity for treating the disease
in such a way that the immune system is properly modulated. In cancer,
we upregulate the immune system, and in dermatology, we downregulate
the immune system through the mechanism of action. So that’s been our
focus: to show in the data why that is happening, that in fact it is happening
clinically and preclinically, and to the extent that we can, describe it in a
way that’s helpful to the medical community.
TWST: You mentioned that there has been a lot of clinical
development in the last year since we last spoke, so can you give us an
update on the key changes and the stages of the various trials?
Mr. Culpepper:
Let’s start with oncology and the use of our
lead agent, PV-10, which is a formulation of an active ingredient rose
bengal, a very well-known halogenated xanthene. Since the last call,
we have a new patent for the synthesis of that active pharmaceutical
ingredient, which is important, and that patent is being prosecuted
globally as well. We also have a combination patent application for
the way we are using PV-10 in combination with various co-inhibitory
blockade or systemic immunotherapy drugs. The combination of PV-
10 with several of these drugs is an important aspect of the joint
patent application with Pfizer.
For over a year, Moffitt Cancer Center has been conducting a clinical
study that uses PV-10 as a neoadjuvant to surgery in patients with disease where
it is not appropriate to remove the disease surgically alone. It turns out that
when they presented this data at ASCO earlier this year, they could show this
through the immunohistochemical-staining pathologic complete response. So
we are treating disease with PV-10, and Moffitt has shown in their clinical study
pathologic complete response of the treated lesions and also — and this gets
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PROVECTUS BIOPHARMACEUTICALS, INC. (PVCT)
to the bio part of biopharmaceuticals — the immunologic benefit of PV-10.
For the nontreated lesions, you have this enhanced tumor-specific reactivity in
circulating T cells because of PV-10.
So the most important development was to show the industry
this information; it went to the FDA and was then presented at ASCO.
Additional information was presented just earlier this month at the
Society for Immunotherapy of Cancer’s annual meeting in Washington,
D.C. In the prior year, Moffitt presented, in effect, the same information
on a preclinical basis, which was published just in the last year.
In addition, this SITC data from November is expected to be
published; the clinical data are yet to be published in a peer-reviewed
journal. I was with the Moffitt Cancer Center primary researcher, Shari
Pilon-Thomas, Ph.D., at the SITC conference on November 8, and they
are planning to publish their clinical data that they presented at ASCO.
But the main point of this for the industry, for the FDA, for Big Pharma,
is they want to see PV-10’s ability to kill disease where it is injected, and
this is a key point: The PV-10 is injected directly into the tumor. Because
of that, it’s a local treatment, good for the disease to be killed safely and
effectively; that is what the data have shown in numerous presentations.
But what Moffitt has shown is, when we do that locally, you
get systemic antitumor immunity and this pathologic complete response
in both injected and uninjected lesions, including treatment refractory
tumors. So Moffitt has been particularly helpful for the industry in
understanding that when you inject a tumor with PV-10, you get
pathologic complete response. And for tumors that you don’t directly
treat, you also get pathologic complete response because of this enhanced
tumor-specific reactivity in circulated T cells.
It can be described in two ways. PV-10 alters the T-cell
immunity, so you get the benefit when you treat locally, when you get
enough tumor destruction, and you can get a harnessing or triggering
or priming of the immune system in such a way that it can be a benefit
systemically. So with the full Phase II data, and this Moffitt initial clinical
data, which they just refer to as a feasibility study, we’re going to use
PV-10 in a Phase III study where you can treat all disease locally; this
is the Phase III design, which has been filed with the FDA. It is on
ClinicalTrials.gov and is available to be reviewed. The FDA is literally
reviewing it right now. We are working with the FDA now in a 30- to 45-
day period to review the protocol.
So for PV-10, we have a Phase III protocol that the industry
believes is appropriate with the appropriate endpoints, with the appropriate
powering and the study population. We have the active arm versus the
control arm, and there is a standard randomized controlled study for a
pivotal registration study. This is the Phase III PV-10 for melanoma. At
the same time, because of the Moffitt data, we are now designing and
have stated that we plan to start a combination study, which is a Phase Ib/
II-type study design, where we combine PV-10 with appropriate systemic
immunotherapies where you are looking at treating disease that’s already
metastasized beyond the reach of a local treatment directly.
So for instance, if a person has a brain metastasis of melanoma,
yet they still have local regional disease, which is typically the case, they
would treat PV-10 locally, where they can get the needle to easily. And
then, they would combine with PV-10, the local treatment, the appropriate
systemic treatment — let’s just say, Bristol’s Yervoy or Merck’s Keytruda —
if a patient’s refractory to systemic immunotherapies alone and local disease
still exists, some sort of combination much like what Amgen is doing right
now. We are not just implementing a new way of thinking. We are actually
doing what the industry believes is appropriate when those diseases cannot
be directly impacted as — perhaps aggressively as — you would want.
The Phase Ib/II is in process of being finalized, and we
would do the study parallel to our efforts in both the Phase III for local
melanoma. This is potentially stage 3 melanoma for our Phase III, and
then, stage 4 melanoma would be addressed in this combination study.
So we are moving forward with both of those, and we’ve made that very
clear publicly. We are very excited about both of those, and the industry
is excited in terms of how it sees the need for even the late-stage patients
to have a better approach from a combination-treatment perspective to
address the entire disease burden more effectively.
TWST: Is there a particular drug that you combine with
PV-10 for metastatic disease?
Mr. Culpepper:
Yes. Well, there is a particular drug at least for
melanoma. The way the industry immunologist described it is the immune
checkpoint blockade or co-inhibitory blockade. The cancer, melanoma, is
growing, is spreading throughout the body, and the immune system is not
properly aware of it or has the brakes on the T-cell response. So there is
some sort of inhibition. What these immune checkpoint blockade agents
are doing is taking the brakes off the immune cells and responding.
So you have a general priming in the immune system with
these agents, and both drugs are delivered systemically. These drugs have
certain tools, and in particular, the CTLA-4-based immune checkpoint
blockade and then the PD-1-based immune checkpoint blockade, those
agents have been approved in the last couple of years. Anti-PD-1, Merck’s
drug Keytruda, which was approved this year, but Keytruda is indicated
only when a patient is refractory to the frontline checkpoint blockade,
which is still Bristol’s Yervoy.
There is survival benefit with these drugs for late-stage
melanoma patients — that’s very important — but there is not a complete
regression of the disease burden. There still is disease burden that
needs to be addressed, and particularly, it’s locally advanced cutaneous
melanoma that needs to be addressed. This is what the industry wants
determined: What’s the optimal way to address systemic disease burden?
So the industry as a whole sees the systemic agents as very appropriate
to combine with the local drug like PV-10, which goes back to the joint
patent application we have with Pfizer.
Pfizer first approached us because they wanted us to combine
PV-10 with their initial anti-CTLA-4 immune checkpoint blockade,
which is an analog of Bristol’s. Pfizer had a parallel development effort
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PROVECTUS BIOPHARMACEUTICALS, INC.
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with Bristol; Bristol was successful with theirs. Pfizer just barely missed
theirs, tremelimumab. So Pfizer is interested in this field of research.
Pfizer just announced a joint partnership with Merck in this checkpoint
blockade effort with the successor compound platform or the successor
checkpoint blockade focus, anti-PD-1. So it’s a very, very intensely
focused effort, with the Big Pharma companies in particular attempting
to harness or prime the immune system, which we are ecstatic about. It
makes a lot of sense in the industry.
For PV-10, which induces this immune response or enhances this
tumor-specific reactivity in the circulated T cells, we get this expression of
the antigenic material that the T cells need to be visible. It makes sense for
the industry to combine PV-10 with the agents that are also priming the
immune system. So people have a good view on the combination.
The question is: Which is more mechanical or technical, what
is the number of patients in the study, which agent do you use, do you
use Bristol’s or Merck’s, or do you use maybe both in separate studies?
We have more of those kinds of discussions to aid in our trial designs.
Thankfully both of those initial immunotherapies are now approved, so it
makes the reimbursement cost much more straightforward.
From an industry standpoint, we are very much supported by
our investigators, the physicians, and the sites throughout the U.S. and
Europe wherever these new checkpoint blockade agents are available.
We are very well-supported by the people that we know and work with to
do both of these studies — the Phase III study and the combination study.
We are really dealing with different patient populations, so both studies
make sense for treating melanoma.
TWST: When we talked to you back in 2013, you were
talking about getting breakthrough therapy designation for PV-10.
What’s the status of that?
Mr. Culpepper:
That’s a very important question. When we
presented the full Phase II data and some of the Moffitt Cancer Center
feasibility data to the FDA in late last year, the FDA said in effect to present
the data in a formal request for action to move forward. They stated for
us to request breakthrough therapy designation — BTD — which we did,
and we announced the application sent to the FDA on March 24, 2014.
However, on May 23, 2014, in a press release, we announced that we
were denied BTD. So in the FDA filing, which we announced publicly,
which is rare, as I understand it, we announced the FDA’s decision, and
we filed the letter, the actual breakthrough denial letter, in an 8-K filing
on May 23. That was a tough Friday back in May 2014.
We made that announcement because we wanted people to
know that we tried to, in effect, accelerate the approval of PV-10. We
wanted to see if we could shorten the development process. The FDA
said, “You haven’t given us enough data to give you breakthrough therapy
designation,” but they encouraged us in the denial letter to generate more
data and try again. They also encouraged us to do certain aspects of a
study, which led from a very challenging time to a very positive outcome
in the sense that the FDA said, “Here’s what we will work with you on
to move this forward,” and that’s what led to the Phase III trial protocol.
The breakthrough effort helped in the development pathway for PV-10
and how to segment where PV-10 is appropriate.
This is a big deal in the industry because local agents have
never been approved for treating melanoma. So to have the FDA
recognize the locally advanced cutaneous melanoma — that language
actually came from the FDA, which they further stated as being a life-
threatening disease in and of itself — and then, the FDA encouraged
us to use a comparator, which of course is consistent with the National
Comprehensive Cancer Network, NCCN, guidelines. The FDA
encouraged us with those guidelines and the patient population to use,
the standard endpoints, PFS, and overall survival, etc., standard scoring
RECIST 1.1 and appropriate comparator, which NCCN guidelines states
is a systemic chemotherapy, which is dacarbazine or temozolomide.
So we have taken what the FDA gave us, and we are doing
what they want in the Phase III to provide them enough data in order
for PV-10 to presumably be approved on that basis. We don’t think we
will apply for breakthrough again even though they encouraged us to
do so because we think the Phase III does make a lot of sense; still,
they essentially gave us two options. They also told us to consider
fast-track designation, which could further expedite the Phase III
effort itself. So the FDA has helped us move forward in that discussion
of breakthrough denial on how you move PV-10 forward by itself as
a single agent and also delineate the single use of PV-10 from the
combination use. That’s been the benefit: knowing what to do to move
PV-10 forward for treating melanoma.
Now, the discussion gets a lot easier when we talk about liver
cancer. By the way, it’s a much simpler discussion for the industry
with liver cancer. The reason melanoma is so tough is melanoma is a
virulent disease once it’s unresectable. So once surgery is no longer
appropriate, melanoma moves in the body from stage 2 to stage 3 to
potentially stage 4 very quickly, unless you arrest its spread in stage 3
quickly enough. It’s a fast-moving disease; that’s why initial surgery
in stage 1 is so critically important, like all cancers of course, to get it
out as quickly as possible. If you miss a chance in melanoma, stage 3
can be really an important time to address it locally.
As the FDA said, locally advanced cutaneous melanoma is life-
threatening on its own. If you don’t deal with it enough or aggressively
enough there, you will risk metastatic disease, and so that’s been an
important distinction that’s now recognized by the industry, which is a
huge plus for PV-10 since we see its effectiveness in treating melanoma
in the recently published Phase II data in Annals of Surgical Oncology.
So we see the breakthrough denial guidance as a silver lining. It was a
way for us to have a much-enhanced dialogue with the agency to figure
out how to move PV-10 forward to treat patients.
TWST: You mentioned liver cancer is easier. So where are
you now with liver cancer?
Mr. Culpepper:
The reason we say liver cancer, and the
industry, for that matter, says liver cancer is easier, is because it’s locally
metastatic, or in other words, it’s locally advanced and understood as an
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PROVECTUS BIOPHARMACEUTICALS, INC. (PVCT)
unmet need already. So for liver cancer, the real problem is when surgery
is no longer appropriate locally. You don’t die of melanoma when it’s on
your arm or your leg or even on your trunk area, you die when it goes
to your brain or your lung or the vital organs; that’s where you die in
melanoma. For liver cancer, you die with local disease if not surgically
removed, so it’s a different challenge.
The challenge in liver cancer is to treat the disease in the
liver where surgery is no longer appropriate. The bulk of the challenge
is in the U.S. and ex-U.S., where most liver cancer is. Over 50% is
in China alone, which is why we have an MOU — memorandum of
understanding — with Sinopharm, the largest China pharma company.
The etiology of the disease is different in China than, say, in the U.S.,
but for the industry, liver cancer is not a problem to treat locally.
Melanoma was a problem until we got this understanding from the
FDA with the segmentation or demarcation of PV-10 used locally
versus PV-10 in combination for systemic benefit.
With liver cancer, everyone says “Oh yes, treat it locally,
that’s fine. No problem at all.” Now, we just run a study to show that it
is appropriate versus standard of care alone. The liver cancer standard
of care is straightforward also; it’s sorafenib, or Nexavar. It’s a clean
regulatory path, relatively speaking.
In melanoma, it wasn’t a clear regulatory path, and a person
can see that if they go to the National Comprehensive Cancer Guidelines.
The standard of care is very challenging to determine for the different
substages of stage 3 and 4 in melanoma, whereas for liver cancer, it is
nonresectable disease. The study design is the same Ib/II study design,
where in this case, you combine PV-10 with sorafenib versus sorafenib
by itself, so it’s a straightforward comparison to standard of care. We’ve
already done necessary Phase I liver cancer work that showed that PV-10
does kill liver cancer, ablate the tumors that are injected. That’s all the
industry needs in support going forward in the Ib/II trial design.
And the reason we say it in Ib/II is we do, essentially, dose
escalation; we’ve done the necessary preclinical work combining PV-10
with sorafenib so you have no drug-drug interaction challenges. But you
have to do that in, of course, patients so that you can manage any toxicity
issues, which we don’t expect based on the extensive preclinical work,
but still, you have to make sure in humans. Therefore, we do that in the Ib
part of the Ib/II and then move immediately into the randomized portion
where you’re randomizing PV-10 in combination with sorafenib versus
sorafenib as a standalone drug. So that kind of a trial design, that kind
of clinical pathway is much easier for the industry, it’s much easier for
the FDA, it’s much more straightforward. We have been encouraged to
pursue this trial design and study immediately.
Now, the same trial design that we were talking about for the
combination PV-10, where you combine a PV-10 with immune checkpoint
blockade, it is the same type of trial design that we’re designing. I call it
a plug and play. If this combo study that could be appropriate for PV-10
with sorafenib or PV-10 with these immune checkpoint blockade agents,
or PV-10 even for breast cancer, which would be the next indication we
want to move forward. We’ve done a Phase I breast cancer study, and we
have been encouraged to move forward in breast cancer.
PV-10 does successfully treat recurrent breast cancer. We
will want to compare PV-10 to the standard of care. For breast cancer,
chemotherapy or radiation is used as neoadjuvant to surgery with this
tissue-sparing objective. You want to spare tissue, and you want to
reduce the disease burden so you can minimize the tissue removed from
a surgery standpoint. So that’s where PV-10 comes in.
We would randomize it against chemotherapy and/or radiation
because PV-10 has a much better side-effect profile based on all of our
data. We believe PV-10 is very well-tolerated versus chemotherapy and
radiation. We believe PV-10 is more effective than chemotherapy and
radiation, based on all of our data. In our various clinical studies with PV-
10, typically, we are treating patients that have been refractory to radiation
and chemotherapy. And this is why, our compassionate use protocol, we
treat patients that are refractory, and we can treat those lesions that are
refractory to chemotherapy and radiation just as easily as when the lesions
are native, or if they haven’t had radiation or chemotherapy. So we think
there is an opportunity there for PV-10 to treat multiple indications with
the aid of the same study design.
TWST: What is the time frame for those studies for liver
cancer and breast cancer; is there an order there?
Mr. Culpepper:
Yes, there is an order. The order we’ve
established is the Phase III melanoma study is filed; we’re waiting for
FDA interaction to make sure all the particulars are fine. Then, they
will submit the Phase Ib/II combination study design, which we said is
underway, and we are finalizing it. As a matter of fact, we’re meeting
with key opinion leaders on this topic next week. Then, we do the Ib/
II liver study. We’ve been meeting with individuals also for our liver
program on a regular basis. That probably will come very shortly after
the combo, and we’ve met with individuals globally.
There would probably be a Western cohort with sorafenib
as the standard of care. The Eastern cohort would have local ablative
standard of care in China, India, Singapore and Korea. Sorafenib doesn’t
work in their view, which is true from a data standpoint. They use a local
ablative agent that also doesn’t work very well. However, they use them
versus sorafenib, after surgery.
So the Ib/II for liver would follow very closely after the combo,
and then, breast unfortunately would be after that, but it would be the same
study design instead of, say, using sorafenib or the checkpoint blockade
as the combo piece. We would use chemotherapy or radiation, but breast
would definitely come after Phase III is underway and enrolling, the
Phase Ib/II combo is underway and enrolling, and Phase Ib/II liver is
underway and enrolling.
TWST: Are all of these planned for 2015?
Mr. Culpepper:
Yes. The first three are already planned. We
already have the supply chain support underway; there is the design of the
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PROVECTUS BIOPHARMACEUTICALS, INC.
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appropriate studies underway. We’ve already interacted with the KOLs,
the different physicians, which is good. The physicians we work with
who treat melanoma are also involved, interestingly enough, in treating
the liver, so it dovetails very well.
The physicians who treat melanoma, and the institutions, are
used to treating melanoma locally. They want to treat visceral disease in
combination because they like treating locally, but they don’t want to treat
just locally if the person has brain metastasis, for example. And they also
treat the liver. The reason they treat the liver, even if they are melanoma-
focused, is because melanoma can spread to the liver; as a matter of fact,
for ocular melanoma, 40% goes to the liver. So a significant portion of the
visceral metastases for melanoma is to the liver, so it’s of concern.
The same physicians are interested in being in both studies,
so there’s a good synergy between melanoma and liver, and the same
thing with the FDA in DOP2. FDA DOP2, you work with Division of
Oncology Products 2 under Dr. Keegan and her staff. The work we’re
doing in both melanoma and liver falls within the same group. For
breast cancer, it’s DOP1, and it’s a different set of physicians, so it
would definitely be a separate effort.
So I would say, with the next three PV-10 studies, certainly
we’ll see those studies generating meaningful data in 2015. I hope the
answer will be yes in breast. We’re pushing on that. We have already
established a relationship with a breast cancer advocacy group. We
plan to be at San Antonio Breast Cancer Symposium in San Antonio in
December. We’re very focused, and of course, we’ve done clinical work
in breast, so we know PV-10 is appropriate for breast, and we’ve been
encouraged by potential partners to be treating breast cancer, particularly
in China and India where breast cancer is a top concern, but liver cancer
is of course also a cancer of very significant concern.
TWST: Given all the tasks ahead in the different
trials, what are the risks inherent in meeting the goals that you
want to achieve?
Mr. Culpepper:
In our case, the regulatory risk is rather
minimal, and the reason I say that is because rose bengal is a well-
known active pharmaceutical ingredient. The FDA in two diagnostic
applications has approved it. It’s an ophthalmic diagnostic agent. It has
been used in the eye for decades, and it’s been an IV hepatic function
agent, delivered intravenously throughout the body for decades. So it’s
got a lot of safety history. It’s got the important toxicity studies: LD50,
etc. There’s a lot of data in the literature in peer-reviewed publications.
There are over 3,700 peer-reviewed publications on rose bengal. And
at our own request, we got our own self-audit. We brought in a large
well-regarded CRO to do a regulatory audit.
So the regulatory risk isn’t as much of a concern; I see it as
more of an ethical and shareholder return risk. And when we’re dealing
with development-stage companies, patients are first because you don’t
get anywhere unless you are providing service and value to patients in
this industry. But the way we fund all these studies is largely through
shareholders. So the biggest risk really is: Can we be as diligent moving
it forward for the benefit of the patients and shareholders too? There
are numerous solid tumors where we want to focus on this: pancreatic
cancer, noninvasive bladder cancer, prostate cancer, etc. We’ve done the
preclinical work in numerous solid tumor indications, and so we’re being
encouraged on a regular weekly basis in our ongoing compassionate use
study to use PV-10 in numerous indications.
It’s amazing, unfortunately, how many different cancers
are going to the liver, like colorectal cancer, lung cancer, melanoma,
pancreatic cancer and even breast cancer. So I would say, the biggest
challenge we have is meeting the needs of patients as quickly as we can
and, at the same time, being responsive to our shareholders so that we can
maximize a return on their investment. It’s doable, but that’s the toughest
balance. It’s like the work-life balance in a nutshell.
Patients are clamoring. As you can see on our website, Eric
Wachter and I are company contacts for the compassionate use program,
so we see the need firsthand, along with our CEO, Craig Dees. Now, for
various reasons, we don’t get directly involved in treating the patients,
so we refer them to the different sites for treatment, but still, we get the
requests on a very regular daily basis to be in the compassionate use
program. Typically, what I do is point out the clinical trial, where they
can actually contact the study coordinators for compassionate use of
PV-10. But we see, firsthand, the needs for patients, and we also see,
firsthand, the need for funding and making sure that we can get this
done as quickly as we can for patients.
TWST: How do things stand in terms of having sufficient
funds to take you through these various trials? Will you need to raise
additional funds?
Mr. Culpepper:
We have said we have enough cash to do the
Phase III melanoma study, so that’s important. We have enough cash to
do this Ib/II combination study for the immune checkpoint blockade, and
we have enough cash to do the Ib/II liver study. We can also do certain
work in these other indications, but we can’t do a full-blown set of studies
for advancing breast cancer, pancreatic cancer, other solid tumors, and
we can’t fully advance the liver or the combination program beyond
what we have established we are doing. The only indication we can fully
advance on our own is the PV-10 melanoma trial, which is important.
That’s the indication furthest along.
Now, we have access to additional capital. What we’re trying
to do is not raise more than we need. We will need to raise what we said
we’re going to do, but because we are on the New York Stock Exchange
MKT, and we’re audited by BDO, we always want to make sure we
have enough cash to meet the regulatory requirements, so we typically
raise enough cash to offset cash burn. But at the same time, we say in
the filings, as we are required to, that we have enough cash on hand to
do what we say we’re going to do, which is the Phase III melanoma
study, the Ib/II combination study for PV-10 with the immune checkpoint
blockade agents and the PV-10 Ib/II for primary liver cancer.
COMPANY INTERVIEW
——
PROVECTUS BIOPHARMACEUTICALS, INC. (PVCT)
All that being said, we also say in the filings that we believe
the start of these studies or the data itself from those three studies would
be sufficient to enable a partnership of some sort where we would secure
one or more regional licenses and/or a co-development transaction,
some cash upfront, funding that’s not dilutive along with milestones and
royalties, etc., as appropriate to the transaction. So we believe we can
mitigate or reduce financing through partnerships, and that’s something
else we’re balancing as we move forward with the different activities.
TWST: Is that something that you will start looking for in
2015, or perhaps you are already doing that?
Mr. Culpepper:
Certainly, we are already doing that in
terms of the potential partnership activity, which goes to our MOU-
with-Sinopharm topic. We have MOU with Sinopharm for purposes
of a regional license in China. We’re doing the same thing we’ve said
publicly, working on partnership relationships in India, and even Russia
and elsewhere, for regional licenses. We control the supply chain, but we
utilize the partners in those respective countries and regions to enable
data generation, interface with regulatory bodies there and provide some
monetization of PV-10 to the company.
Now, we say in the filings, we want to do an overall end-
game transaction like Celgene/Abraxis or better — so an acquisition of
the company — but we want to build value first and reduce the need
for financing with nondilutive cash through those regional license
transactions and/or co-development transactions. We are discussing
potential co-development transactions on the basis of this Moffitt Cancer
Center data that was presented earlier this month of November at this
Immunotherapy Conference. So yes, we are trying to do those now.
We are trying to secure partnerships now, and we will continue
to try until we believe we’ll be successful based on the data. There’s
clearly interest as we have a number of Big Pharma executives on our
strategic advisory board that are interested for that reason. So we believe
that’s the natural course of events. It’s just a question of timing.
TWST: Is there anything that we haven’t discussed that
you’d like to add?
Mr. Culpepper:
The only thing I would like to add is about
PH-10 on the dermatology side. What we’re doing there is somewhat
similar to what we’ve already done with PV-10 on the mechanism of
action. So here you have the PV-10, its priming of the immune system
response properly to the cancer in your body; and on dermatology, there
was an improper immune response, and we have modulated this as well.
We’re starting a feasibility study like Moffitt Cancer Center did for PV-
10. We are going to do the same thing with PH-10 with a well-respected
group that we’ll announce, somewhat similar to Moffitt Cancer Center, to
do a similar feasibility study in patients to show the unique mechanism of
action for PH-10 for dermatological indications.
So the use of PH-10 because what PH-10 is doing is modulating
the immune system. It’s an anti-inflammatory nonsteroidal mechanism,
which is great for the use of PH-10, say, if you have psoriasis or atopic
dermatitis or any sort of inflammatory dermatoses. Our drug, PH-10, will
reduce the inflammation and the itching. We’ve done different clinical
studies, Phase I and Phase II studies, to show this, and the question
now is working with the FDA to go into the Phase III and showing the
mechanism for the industry just like we’ve done with PV-10.
TWST: Do you know how soon you will be announcing
whom you’ll be working with on that?
Mr. Culpepper:
Yes. It should be just after the New Year. I
can say that we are finalizing the production run of the drug product itself
for PH-10. We have the new synthesis for the active ingredient, so we
have the supply chain refined, and the production run is actually being
finished literally in December, and then, we’ll be ready to start using that
new PH-10 based on the production run and the drug product itself for
the upcoming studies. We’ll announce that as early in the New Year as we
can and also the groups that will be involved.
TWST: Thank you. (EP)
PETER R. CULPEPPER, CPA, MBA
CFO & COO
Provectus Biopharmaceuticals, Inc.
7327 Oak Ridge Highway
Knoxville, TN 37931
(866) 594-5999 — TOLL FREE
(866) 998-0005 — FAX
www.pvct.com
© 2015 The Wall Street Transcript, 622 3rd Avenue, New York, NY 10017
Tel: (212) 952-7400 • Fax: (212) 668-9842 • Website: www.twst.com
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I'm in it to win it!
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Intuitive;
means having the ability to understand or know something without any direct evidence or reasoning process.
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Alway's searching for winners'
NASDAQ DIP and RIP
Here is the best word that describes what i do here.
Intuitive;
means having the ability to understand or know something without any direct evidence or reasoning process.
I was born with it, I'm truly blessed!
Alway's searching for winners'