TWST: Would you give us a quick overview of your technology as well as
an overview of BioDelivery Sciences International's products?Dr. Mannino: Fundamentally, BioDelivery Sciences is working on a broad
technology platform based on a lipid formulation called a cochleate. The
cochleate is a solid crystal made up of a simple natural phospholipid
made from soybeans and calcium. Therefore, cochleates are very natural,
safe products. With this cochleate delivery vehicle, BDSI has been able
to demonstrate over the years our ability to take very difficult-to-
work-with compounds, for example, water insoluble molecules many of
which can only be administered by injection, and turn them into user-
friendly formulations that can be taken as oral medications. The BDSI
cochleates can be either dry powders or can be mixed into water based
solutions. The cochleate delivery vehicles absorb the hydrophobic
compound and yet retain a hydrophilic compatible external layer.
Another benefit of cochleate delivery is increased stability. The
phospholipid structure of cochleates stabilizes the encochleated
compound against such harsh external environments as processing and
long-term storage. BDSI started out solely as a pharmaceutical company,
but we recently established a subsidiary, Bioral Nutrient Delivery,
that's working in the processed food and personal care industry. This is
possible because unlike many other delivery systems, the material used
to prepare cochleates is all-natural and very inexpensive. Therefore in
addition to providing good formulation and stability, we have a natural
product which is both effective and inexpensive.TWST: What are some of your target products? What is your lead product?
Give us an idea of your pipeline development where you are applying this
technology.Dr. Mannino: Our lead pharmaceutical product is an anti-fungal agent
called Amphotericin B. We are now working on the GMP manufacturing, and
we're on track to having our GMP material and our IND filed in the early
part of next year. In animal model studies we have shown that
Amphotericin B cochleates greatly improve Amphotericin B, which has been
around for about 50 years and is currently only available by IV
injection. Using cochleates, we've been able to formulate an orally bio-
available drug, with increased efficacy when compared to the injectable
option. We've turned this difficult, yet very important anti-fungal
treatment into a more stable and effective medication with much lower
toxicity. BDSI has a number of other anti-fungal and anti-bacterial
formulations in our pipeline. Along with the anti-microbial
formulations, we've also been able to demonstrate the benefit of
cochleates with anti-inflammatories. For example, BDSI recently
reported that we can put aspirin into our cochleate delivery vehicles,
deliver these formulations in a rat model of acute inflammation, and not
only do we make a very nice user-friendly formulation, but we protect
the stomach from the toxic effects of the aspirin. Currently one of the
major drawbacks of aspirin use is the potentially severe
gastrointestinal side effects. Aspirin cochleates, show substantially
reduced bleeding and ulceration in the rat models compared to regular
aspirin at equal dosing. In addition, we have increased the efficacy by
using cochleate delivery vehicles, so now better anti-inflammatory
action occurs at much lower dosages than with regular aspirin. This
demonstrates a common characteristic of cochleate delivery vehicles: the
ability to take compounds and along with stabilizing them, provide
manufacturers with an opportunity to have enhanced efficacy, lower side-
effects and lower toxicity and oral bioavailability. Part of our
business model for developing the cochleate delivery vehicles, is to
generate revenue early on by out-licensing. To that end BDSI already has
two signed pharmaceutical outlicenses, two evaluation projects with
major pharmaceutical companies underway, one evaluation project underway
for micronutrients in processed food with a major, multi-national
company to develop a micro-nutrient formulation that would stabilize
antioxidants, retain their viability in the food product during
processing and on the shelf, and make them more bio-available once
ingested. In addition we have reduced the cost of our raw materials by a
factor of over 100 times, developed a simple non-solvent method of
manufacturing and commercially scaled manufacturing to meet the very
large quantity needs of non-pharmaceutical applicationsTWST: What is the current market for Amphotericin B at this point? How
much, in your estimate, of the market can you garner?Dr. Mannino: The worldwide market for Amphotericin B is about $1 billion
a year. Amphotericin is a very interesting drug. Even though it's been
around for 50 years, it's still one of the leading anti-fungals.
Currently Amphotericin for acute infections is only available by IV
injection. By turning Amphotericin into an oral drug, not only do we
believe that within a couple of years we can get a large share of the
acute care market, but we also believe that once Amphotericin is
available in a capsule form, we'll be able to make it available for
prophylaxis against fungal infections as well as maintenance when people
leave the hospital. In addition, unlike some other anti-fungals which
are currently on the market, Amphotericin is fungicidal, meaning it
kills the fungi. Some other anti-fungal treatments are fungistatic: they
only prevent the fungus from growing. The drawback of fungistatic
treatment is that because the fungi are not eliminated, they have the
chance to mutate and become resistant to the treatment. On the other
hand, because the Amphotericin is fungicidal, there are very few
Amphotericin resistant mutants out there, even though it's been around
for 50 years. We believe that with oral Amphotericin, BDSI has the
opportunity to get a substantial share of the acute care market. And I'm
enthusiastic about the opportunity to move into the anti-fungal market
in terms of prophylaxis and maintenance treatment. I believe the
worldwide market for anti-fungals is somewhere around $4 billion a year.TWST: What about the FDA process? Is it a shorter process for drug
delivery than filing for a new drug?Dr. Mannino: We believe it will be. Our goal is to take known drugs that
have FDA approval and make them better, more user-friendly, less toxic
and more bioavailable. In the case of a drug for which an oral delivery
formulation does not already exist, we can change the route of
administration from an injectable to an oral These drugs are already
accepted and used by clinicians, with which the FDA has experience. All
of these factors enable us to point to specific market potential and
minimize our internal costs of development. The scientific basis of our
Amphotericin B cochleate formulations is very strong. As a result, the
majority of the funds currently supporting our Amphotericin program are
coming from a grant awarded by the National Institutes of Health. By the
middle of next year, we will have received about $3 million from the NIH
to develop an oral Amphotericin B formulation using our cochleate
delivery vehicles. The NIH has been very supportive and is very
enthusiastic about cochleate drug delivery technology.TWST: When do you intend eventually to license or seek a partner for
Amphotericin B?Dr. Mannino: At this time our intentions are to take the Amphotericin
cochleates at least through Phase I clinical trials. Once Phase I is
complete, we'll evaluate our current circumstances. If we have what we
feel would be a good partner at the end of Phase I, we might partner at
that point. But we also have the capabilities to take Amphotericin
cochleates into Phase II.TWST: How much progress have you made in getting a commercial product
for the food industry?Dr. Mannino: BDSI began working with compounds for the food industry
about a year and a half ago. In the past 18 months, we've accomplished
what I believe is a stable formulation of an antioxidant called beta-
carotene. We've demonstrated our ability to process beta-carotene in a
commercially feasible way . Most recently, we produced encochleated
beta-carotene through the commercial process of spray drying and
delivered four kilograms of a stabilized beta-carotene cochleate
formulation prepared by a commercial manufacturing process to one of our
partners. Therefore BDSI in a relatively short period of time has been
able to take a difficult to work with, fragile but important micro-
nutrient molecule, and deliver it in a very stable mass-produced, low-
cost formulation using cochleate delivery vehicles.TWST: Give us a realistic picture of where you see BioDelivery Sciences
in the next three to four years?Dr. Mannino: BDSI and cochleate technology have many opportunities in
both the pharmaceutical, food and personal care industries. In the
pharmaceutical industry, we are looking to move our own internal
products forward and work with licensed partners to further their
products. We also see a relatively short-term revenue-generating stream
in the micro-nutrient area, specifically in foods and personal care
products. We provide a very broad-based opportunity to our investors
and, in the next two to three years, we believe a number of these
opportunities will be reaching major milestones and, therefore,
generating a lot of opportunity and potential both for our partners and
for our investors.TWST: What is your current burn rate and do you have the balance sheet
in place to accomplish all your goals?Dr. Mannino: BioDelivery Sciences International went public in June 2002
and in our first year we were pretty close to cash neutral because of
our licensing agreements and our revenue from the NIH. In terms of our
in-house development, we keep our burn rate low by generating funds for
the development of new products from organizations like the NIH. Our
business model is based on a system of partnering and licensing. BDSI
does the formulation development for our partners which they then test
in-house. Once we've achieved the initial milestones, our business model
is to transfer the technology to our partners and help them move
forward. Our partners underwrite the cost for the continued clinical
development. In this model BDSI will earn a licensing fee after each
milestone is achieved, for example, filing of an IND or completion of a
clinical trial, and then a royalty on sales of the final product. BDSI
has made a very conscious effort to keep the burn rate low, which allows
us the opportunity to continue developing in a number of areas.TWST: Besides the obvious risk of failure in the testing of a new drug,
what are some of your major challenges? What concerns you the most?Dr. Mannino: The milestones we see for ourselves in the next six months
to a year are focused on generating a GMP pharmaceutical, filing our
IND, getting it approved, and getting our first clinical trials done.
These are all very important milestones and they are a primary focus for
us at this point. Another focus for BDSI, which we see as more of an
opportunity than an obstacle, is to help the drug delivery and
pharmaceutical industry understand that our technology is a truly
unique, viable and highly effective approach to the issue of drug
delivery. If one goes to the Internet and searches for 'drug delivery,'
you will find, for example, companies that work with capsules, companies
that work with little devices that pump drugs and can be implanted, and
companies that coat drugs. I believe our opportunity is to try to help
other people in the industry to understand the fundamental difference
between the opportunity that cochleate technology offers and the many
other drug delivery systems that are out there that are very useful, but
don't have the broad-based applications that cochleates do. Cochleate
technology is truly a unique technology. It provides the opportunity for
taking drugs at the molecular level and actually wrapping them up as if
with a shrink-wrap, inside a solid crystal. And this crystal then
protects the drug, delivers the drug to its target site, and then
releases the drug. So we provide formulation capability, stability
capability, reduced toxicity and better delivery. Not only are
cochleates so broad-based, they are also all natural from soy lipids and
calcium, and very inexpensive. The fact that cochleates are made of
soybean-derived material is another benefit of this technology. As it
turns out, the FDA and the USDA have already allowed nutraceutical
claims to be made for soy lipids, specifically for phosphatidylserine.
There have been more than 30 clinical trials back, starting in the
mid-19980s, and phosphatidylserine has been shown to improve mentation,
improve the functioning of the brain and increase the healing of
muscles. So between the soy lipids and the calcium, cochleates are made
from very inexpensive, natural and healthy materials.TWST: Do you have the management team in place to accomplish all your
goals?Dr. Mannino: Yes. BDSI has a very strong business and scientific
management team.Dr. Frank E. O'Donnell Jr., MD, is the Chairman and CEO of BDSI.Dr. O'Donnell is also founder and managing director of The Hopkins
Capital Group.Dr. O'Donnell has extensive experience and demonstrated achievement
developing early stage companies with disruptive technology ' technology
that can fundamentally change a field ' into successful and profitable
businesses . Our CFO, Mr. James McNulty, is the CFO for the Hopkins
Capital Group, and also very experienced and skilled in the development
of startup companies.. In addition, our Board of Directors has
tremendous experience in the industry and in successful companies, Thus,
I am very excited about the business infrastructure thatDr. O'Donnell and Hopkins Capital has put in place to move BDSI forward.
Scientifically, Dr. Susan Gould-Fogerite and I are inventors on the
critical and fundamental patents covering cochleate technology.
Together we represent almost 50 years of experience working with
cochleates, and we both hold upper level management positions at BDSI.TWST: What are your thoughts about the reaction of the financial markets
as to where you have come and where you are going?Dr. Mannino: I think that we have succeeded in making the market
receptive in a very difficult time. Remember, we went public in June
2002, in a very difficult market. But even in that environment we were
able to help the investing community understand that we do have a unique
technology. To the best of our knowledge, we are the only drug delivery
company whose technology is 'disruptive' for the marketplace in the
sense that it is a platform technology readily applicable to fragile
pharmaceuticals and micronutrients. Our technology stabilizes, protects
and delivers an extraordinary range of cargo molecules with little or no
customization required. In contrast, most drug delivery companies have
one or more 'incremental' technologies, that is, they enhance some
limited aspect of delivery. An example of this is sustained release of
injected drugs. Another important aspect of our stability as a company
is that we have a large intellectual property portfolio and a very deep
portfolio. And the investment community can understand that. At this
point, I think it is our job to demonstrate that we've been able to
reach some of the milestones we've been striving toward, in terms of
getting more licensing partners and performing our first clinical trial.
It's our job to continue educating the market and the industry to our
uniqueness and to our earnings potential.TWST: What sort of investor relations program do you have to get your
message out to shareholders?Mr. Zangani (PR): At this point, we are not pushing too heavy because
there are a lot of things that are happening. We don't want anybody to
buy the stock now if they don't fully understand the potential of the
company and the times. Here you have a situation where the company can
be making money by year-end or possibly waiting six months or one year.
So, from an investor relations point of view, we are keeping everybody
posted on what is going on with the company, but we are not actually
very aggressive because we are waiting for something to happen. And we
are confident that it will happen. That is the point when we will come
out and tell you that we did what we said we were going to do. You see,
I am not in a situation where I need to overexpose the stock because the
company needs to raise money. The company is very comfortable with the
existing financial position and rate of growth.Dr. Mannino: We're actually not trying to raise money over the next 12
months. We really believe that we'll be able to bring in revenue through
licensing opportunities both in the pharmaceutical and the processed
food industries. And because we have a relatively low burn rate, we're
comfortable that we can continue to move forward. We're very, very
pleased with the progress that we've been making in all of these areas,
and we believe that reaching more of these milestones will speak for
itself in terms of our potential.Mr. Zangani: We are extremely comfortable because two major entities
participated in a substantial way to our IPO. PPDI underwrote 35% of the
IPO. And, the third largest Italian pharmaceutical company, Sigma-Tau,
underwrote 9.9%. They understood the potential of the company, and that
is when they took their position. This is the kind of shareholders that
we have and are able to attract. That is why I don't want to overexpose
the stock and get the Street excited only to come down because the
quarter is not exactly as they wanted. We are not going quarter-to-
quarter. We know what we have and what we are building. That is why we
are attractive to these kinds of investors.TWST: What are some of the key investment messages that you would like
to give to your shareholders or potential shareholders?Dr. Mannino: BDSI is aggressively developing an extraordinary delivery
technology which represents a long list of advantages that can be
summarized as product enabling-stability of fragile compounds, oral
delivery of parenterals, targeted delivery to specific cell types in the
body. Cochleates are a low-cost, all natural delivery vehicle with
proven ability to commercially scale manufacturing. Using cochleate
technology, BDSI has balanced and diversified business opportunities:
out licensing for applications to pharmaceuticals and micronutrients;
applications to generic injectables. BDSI is adhering to its financial
model by keeping our burn rate low, generating income through grants and
licensing. BDSI has already achieved two licenses in the pharmaceutical
industry and we are working with two other major pharmaceutical
companies. We continually apply for and receive NIH funds to support new
research and development. In addition, BDSI opened a new area of
potential revenue in the processed food, beverage and personal care
industries, which could be generating revenues in the near term. During
the last year we've streamlined our manufacturing program, and reduced
our cost of raw materials. By converting from synthetic phospholipids to
soybean derived lipids we've reduced our cost of raw materials by about
100-fold. Over the last couple of months, we've been able to demonstrate
scaled-up manufacturing protocols for our products in the processed
food, beverage and personal care industries, which make the cochleate
delivery vehicles a very viable technology in this area. BDSI is moving
very aggressively in the pharmaceutical area to do the same.TWST: Thank you. (WT)RAPHAEL J. MANNINO
Executive VP & CSO
LEONARDO ZANGANI
Public Relations
BioDelivery Sciences International, Inc.
185 South Orange Avenue
Newark, NJ 07103
(973) 972-0015
(973) 972-0323 - FAX
www.biodeliverysciences.comCopyright 2003 The Wall Street Transcript Corporation
All Rights Reserved
Drug Delivery >> CEO Interview >> November 24, 2003
RAPHAEL MANNINO
RAPHAEL J. MANNINO is Executive Vice President, Chief Scientific Officer
and a Founder of BioDelivery Sciences International, Inc. and has served
as a member of the Board of Directors since the incorporation of BDS in
1995. Dr. Mannino is a world leader in cochleate technology and an
internationally recognized expert in applying artificial lipid-based
delivery systems to problems in biotechnology, including drug delivery,
vaccine design and gene therapy applications... More










