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DEBEER FUND MANAGEMENT LLC INFO 954-306-6545
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DE BEER FUND MANAGEMENT LLC 619 ORTON AVE, PENTHOUSE 601, FORT LAUDERDALE, FLORIDA 33304
Email:[email protected], USA TEL: 1-954-306-6545
IS PROUD TO INTRODUCE
Apogee TECHNOLOGY
H.D. De Beer
A Biotechnology Company Pioneering
Vaccine and Drug Delivery Technologies
via Intradermal and
Polyphosphazene Platforms
August 2011
Forward-Looking Statements
This presentation contains forward-looking statements as defined in
the Private Securities Litigation Reform Act of 1995. For this
purpose, any statements contained in this presentation that are not
statements of historical fact may be deemed to be forward-looking
statements. Without limiting the foregoing, the words “believes”,
“anticipates”, “plans”, “expects”, and similar expressions are
intended to identify forward-looking statements. Actual results may
differ significantly from results discussed in the forward-looking
statements. Factors that might cause such differences include those
set forth from time to time in the Company's SEC filings, including in
our annual report on Form 10-K.
• Leader in the field of polyphosphazenes for biomedical applications
• Intradermal technology licensed from Georgia Tech
• Diversified Product Pipeline:
ImmunoMer H; ImmunoMer AH; IgloPatch;
Other biomedical polyphosphazenes planned
• World class team of management, advisors and collaborators
Vision: To develop advanced and patient friendly technologies for the
prevention and treatment of infectious diseases and chronic conditions
Apogee Technology Inc.
World-Class Products, World-Class Partners
Apogee established relationships and collaborated
with leading institutions throughout the nation
- Children’s Hospital Boston
- Georgia Tech
- VIDO
- St. Jude Children’s Research Hospital
The Opportunity
Challenges in The Development of New and Improved Vaccines
• Insufficient protective immunity and memory
• High cost
• Need for cold chain distribution system
• No self-administration
Apogee’s Integrated Microneedle and
Immunoadjuvant Approach offers
a compelling solution
145 Vaccines Under Development*
Source
*Pharmaceutical Research and Manufacturers of America. 2010 Report. Medicines in
development for Infectious Diseases |
http://www.phrma.org/sites/default/files/422/infectiousdiseases2010.pdf
Unprecedented Structural Diversity – 1,000+ Derivatives
Tunable Properties – Various Potential Applications
Vaccine Adjuvants, Biodegradable Carriers, Nanoparticulates,
Microencapsulation and Modulated release, Microneedles, Biomaterials
High Throughput Discovery
Manufacturing Friendly Chemistry
P N
R
R
( )
Dial-In Biodegradability
Polyphosphazenes as Biomedical Macromolecules
• Proven In Vivo Performance: 23 Antigens in 11 Animal Models
• Enhanced Immune responses, Dose Sparing
• Demonstrated potency and safety in Clinical Trials
• CMC, DMF, Stability, Toxicology Data
• Benign Degradation Products
• 2 M Doses Available
• GMP Process Developed
• New Generation Molecules Synthesized
Polyphosphazene Immunoadjuvants – ImmunoMer Platform
PCPP
Immunoadjuvant Effect – Proof-of-Concept
Enhanced Immune Response (up to 1000x), Long Lasting, Fast Onset, Single Dose
Effective in Lethal Challenge Studies in a
Relevant Preclinical Animal Model with
Commercial Vaccine:
100% protection from mortality with reduced
dose of antigen
Demonstrated Potency in Large Animals with
Animal Health Vaccine Antigen
Clinical Trials: Reported Safe and Immunogenic Formulations, ~ 4x increase in neutralizing antibodiesSOURCE:
Bouveret Le Cam NN, et al, Research in Immunology (1998) 149: 19-23; Ison MG, et al, Antiviral research (2002) 55: 227-278
Antigen Dose Sparing Effect (up to 25x)
Improves Vaccine Shelf-Life
IgloPatch Technology
Enhanced with
Metal
Support
PCPP - VACCINE
Microneedle Array
Band-Aid-Like Microneedle Patches To
Deliver Vaccine in The Skin
Scalable Production Process
1
2
3
4
5
Weeks
HBsAg specific IgG Titers
Single Dose
In Vivo POC studies in a relevant
animal model - pigs
IgloPatch
Adjuvanted IM
IgloPatch - In Vivo Proof-of-Concept Studies
Non-adjuvanted IM
Non-adjuvanted
Microneedles
• Improved Efficacy and Single Administration
• Improved Shelf-Life with no Reliance on Refrigeration
• Convenient Band-Aid Like Patch Administration
• Self Application Possible
• Reduced Pain or Painless Compared to Conventional
Potential Benefits of IgloPatch Technology
Microneedle Technology Licensed from Georgia Tech:
Coated Microstructures and Methods of Manufacture ThereofH.S. Gill, Harvinder Singh, M.R. PrausnitzUS 11/917705 (06.19.2006); Pub. No. US 2008/0213461 A1;
Apogee’s filings on Microneedle Technology and Adjuvanted Formulations:
Methods and Systems for Coating a Microneedle…A.K. Andrianov, A. MarinUS 12/133,505 (06.05.08); Pub. No. US 2009/0017210 A1;
Coating Formulation Including Polyphosphazene…A.K. Andrianov, A. MarinUS 12/217,437 (07.02.08); Pub. No. US/0016935 A1
Immunostimulating Polyphosphazene Compounds for Intradermal ImmunizationA.K. Andrianov, D.P. DeCollibus, H.A. Gillis, H.H. Kha, A. MarinUS 12/217,402 (07.03.08); Pub. No.2009/0041810 A1;
Apogee plans to get access to PS’s intellectual property portfolio to execute the development of product candidates in the proposedtimeframe. The portfolio relates to polyphosphazene immunoadjuvants, including “new generation” molecules, certain polyphosphazenesynthetic and production processes, microencapsulation and therapeutic protein stabilization methods, as well as some other biomedicalapplications of polyphosphazenes that Apogee believes can be complementary to its technology.
Apogee’s Intellectual Property Portfolio
Product Pipeline
•ImmunoMer H, immunopotentiating and antigen stabilizing
polyphosphazene agent for parenteral and mucosal human
vaccines
•ImmunoMer AH, immunopotentiating and antigen stabilizing
polyphosphazene agent for parenteral and mucosal animal
health vaccines
•IgloPatch, advanced immunopotentiated microneedle patch
for the application of vaccine to the skin. Potentially offers self-
applied vaccines with reduced dependence on cold chain
distribution
Product Pipeline -Timeline
Apogee plans to get access to PS’s intellectual property portfolio to execute the development of product candidates in the proposedtimeframe. The portfolio relates to polyphosphazene immunoadjuvants, including “new generation” molecules, certain polyphosphazenesynthetic and production processes, microencapsulation and therapeutic protein stabilization methods, as well as some other biomedicalapplications of polyphosphazenes that Apogee believes can be complementary to its technology.
Strategy
Partnerships with vaccine developers(ImmunoMer H)
Assumption for 3 non-exclusive arrangements for 1-2antigens, $2 million access fee, $1 million and $6 millionmilestones, royalties on sales of 5-15%.Anticipated milestone timelines:1-2013/2014/2015; 2nd-2014/2015/2016; 3rd- 2015/2016/2017
Collaboration with Global Health organizations (all product candidates)
Generate valuable preclinical and clinical data at little orno cost to company (funded R&D) retaining rights forcommercial use of developed vaccine. One fundedcollaboration is currently under way, assumption for twomore in 2011 ($1.1M) and in 2014 ($2M)
Licensing agreement with Animal Health vaccine company (ImmunoMer AH)
Target deal profile: 1.5 million upfront payment in 2012, atleast one milestone payment of $3 million in 2013, androyalties on net product sales starting in 2014.
Licensing agreement with a multinational vaccine company (IgloPatch)
Target deal profile: exclusive or 3-6 antigens in a definedfield, upfront payment of $7 million (2015) and milestonesof $3 million and $7 million in 2016, royalties on sales of5-15%.
Others
Sources:
* Kalorama Information | http://www.kaloramainformation.com/about/release.asp?id=1693
** 12th annual World Vaccine Congress Lyon 2010, J. Almond, Sanofi pasteur | http://www.terrapinn.com
Vaccine Market Overview
Presence of current Top
Pharma Companies**
2005 - 3 of 10
2009 - 8 of 10
**
Global Market for preventive vaccines:
$22.1 billion in 2009*
Predicted Growth:
9.7% *compound annual rate (next five years)
• Worldwide exclusive license from Georgia Tech for coated
microneedle technology
• Know-how and world’s expert scientists in
polyphosphazene field
• Drug Master File for PCPP as an adjuvant *
• cGMP produced PCPP*
• Polyphosphazene immunoadjuvant library,
polyphosphazene drug delivery library, and biomaterial
product candidates*
* Upon closing PSI transaction after funding
Competitive Advantages
Company Products Applications Customers Finances
Celonova Bioscience(Peachtree City, GA)
PolyphosphazeneNanoparticlesEmbozeneTM
EmpolizationPP coated stent
Physicians Private
Competition
Company Products Applications Customers Finances
IntercellPatch
Vaccines/Bacterial Adjuvant
Pandemic Influenza and Traveler's
Diarrhea Vaccine Patches
Discovery- MarketPublic-$500MM
Market Cap
3MMicroneedles
(plastic)/TLR AdjuvantMultiple Clinical
Public-$61B Market Cap
Zosano PharmaMicroneedles with
PTH, EPO, GM-CSF/GMDP Adjuvant
Osteoporosis Phase IIPrivate-$90MM NEA,
Numera
Becton DickensonMicroinjection device/Alum
Soluble Vaccines On the marketPublic-$17B Market
Cap
Corium InternationalMicroCor™ Micro Delivery System
Small and large molecular weight
moleculesPrivate Private
Polyphosphazene Company
Intradermal Delivery/Adjuvant Companies
Other examples of Immunoadjuvants: AF03 (Sanofi Pasteur), ASO3 (GSK Biologicals), MF 59 (Novartis), IC31 (Intercell)
• Two additional funded contract research and development
collaborations with global health or government organizations in
Q4 2011 and in 2014
• Licensing agreement with an animal health company by year-end
2012 to develop ImmunoMer AH technology
• Three R&D partnerships with vaccine developers in the 2013-2017
time period for the development of ImmunoMer H adjuvanted
vaccines
• Licensing agreement with a multinational vaccine company for
development of IgloPatch microneedle technology
Go to Market Strategy
Business Model
• Product development partnerships with pharmaceutical and biotechnology
companies worldwide, license out application rights, maintain manufacturing
rights
• IgloPatch Technology: licensing model with multinational vaccine producers:
• Exclusive arrangement for 3-6 antigens
• Upfront payment of $5 - $20 million
• Milestone payments of $5 - $15 million per antigen
• 5 - 15% royalties on net product sales
• ImmunoMer H Technology: licensing model with smaller vaccine producers
or biotechnology companies:
• Non-exclusive arrangement for 1-2 antigens
• Upfront payment of $1 - $2 million (“Access Fee”)
• Milestone payments of $1 - $2 million per antigen
• 10 - 25% of proceeds upon acquisition of vaccine by a multinational company
• 5 - 15% royalties on net product sales
• ImmunoMer AH Technology: collaboration with Animal Health company
• Other: collaboration with Global Health or Government organizations
generating technology transfer fees
Financing Requirements
• Apogee seeks to raise $10 million in one or two rounds of funding
to develop ImmunoMer H, ImmunoMer AH, IgloPatch technologies,
as well as to purchase certain assets of Parallel Solutions
• Anticipated use of proceeds:
• Acquisition of PSI
• ImmunoMer H Preclinical
• ImmunoMer AH Preclinical
• Development of IgloPatch
• IgloPatch Preclinical
• Working Capital (inclusive of transaction costs)
PROJECTED REVENUES AND EXPENSES 2010-2016
($10,000,000)
($5,000,000)
$0
$5,000,000
$10,000,000
$15,000,000
$20,000,000
1 2 3 4 5 6 7
2010 2011 2012 2013 2014 2015 2016
Revenues
Operating Loss/Gain
Total Expenses
($10,000,000)
($5,000,000)
$0
$5,000,000
$10,000,000
$15,000,000
$20,000,000
1 2 3 4 5 6 7
PROJECTED CONSLIDATED BALANCES 2010-2016
Assets
Liabilities
Financial Assumptions 2010-2016
1. $10 Million Private Placement
2. Restructuring of bridge loans (all but $156K) has been effected in the Financials.
3. Legal fees of $1.5 MM being settled for $600k.
2010 2011 2012 2013 2014 2015 2016
Investment Rationale
• A strong balance sheet will strengthen Apogee’s negotiating
position with potential strategic partners
• Acquisition of certain assets of Parallel Solutions, Inc. (PSI)
for 700,000 shares of Apogee stock and 25% of future joint
venture payments will provide Apogee with access to
• PSI’s intellectual property portfolio
• Drug Master File
• cGMP produced material
• Polyphosphazene libraries (new adjuvants, drug delivery) and
other polyphosphazenes for potential biomedical and industrial
applications
Apogee Technology
Management Team
• Herbert Stein, CEO and Chairman:
Mr. Stein brings over fifty years of management experience to Apogee and has served on the boards
and in executive management positions at several life sciences companies, including as Chairman
and CEO of Organogenesis.
• Paul J Murphy, Chief Financial Officer and Vice President of Finance:
Mr. Murphy has 25 years of experience as Chief Financial Officer of public and private companies.
Prior to joining Apogee, Mr. Murphy was an independent contractor with JH Cohn, LLP, where he
worked with public companies to design, assess and test controls for compliance with Section 404 of
the Sarbanes-Oxley Act of 2002.
• Alexander K. Andrianov, Ph.D., Vice President of Research and Development:
Dr. Andrianov, as the inventor of the polyphosphazene immunoadjuvant technology, has unique
expertise in polyphosphazene chemistry. He is an author of more than 60 scientific papers and book
chapters, an inventor on 41 issued and pending patents, and an editor of the book “Biomedical
Applications of Polyphosphazenes”. He has ~20 years of experience in the biotechnology industry
having served as Chief Scientific Officer of Parallel Solutions, Inc., and in various management
positions at Avant Immunotherapeutics and Virus Research Institute Inc (VRI). Dr. Andrianov also has
extensive academic experience as a faculty member in Moscow State University (MSU) and visiting
scientist at Massachusetts Institute of Technology (MIT) with Professor Robert Langer.
Summary
• Apogee Technology is a biotechnology company pioneering advanced
vaccine and drug delivery systems via its proprietary technology platform
• Core expertise: biomedical polyphosphazenes and their integration into
value added products
• Vaccine antigens stabilized and adjuvanted by polyphosphazenes and
delivered via Apogee’s microneedle technology have demonstrated to
confer a more potent immune response using reduced amounts of antigen
and provide an extended shelf life
• Potential self-administration and reduced dependence on cold chain
distribution open up developing countries as attractive target markets
• Licensing agreements with vaccine developers, an animal health company
and Global Health or Government organizations are expected to generate
significant revenue from upfront, milestone, and royalty payments, as well
as funded collaborations
• In addition to vaccine and drug delivery applications, potential uses of
polyphosphazenes extend to biomaterials
Apogee Technology Inc. Confidential
1
Apogee Technology, Inc.
Business Plan
August 2011
Apogee Technology Inc. Confidential
2
Certain statements made herein that use the words "anticipate," "may," "hope," "estimate," "project,"
"will," "intend," "plan," "expect," "believe" and similar expressions are intended to identify forward-
looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These
forward-looking statements involve those related to the use of proceeds from the private placement,
the design, development and production efforts of our PyraDerm™ and Sensilica® technologies, known
and unknown risks and uncertainties, which could cause the actual results, performance or
achievements of the Company to be materially different from those that may be expressed or implied.
Please refer to the Company's risk factors as set forth in the Company's filings with the Securities and
Exchange Commission, including its report on Form 10-KSB, as amended, for the year ended December
31, 2008, as updated in its quarterly reports on Form 10-Q. The information contained in this press
release is believed to be current as of the date of original issue. The Company does not intend to update
any of the forward-looking statements after the date of this document to conform these statements to
actual results or to changes in the Company’s expectations, except as required by law.
Apogee Technology Inc. Confidential
3
This business plan does not constitute an offer to sell or a solicitation of any offer to buy the securities to which it relates in any jurisdiction in which, or to any person whom, it is unlawful to make such an offer or solicitation. Neither the delivery of this business plan nor any offer of sale made hereunder shall, under any circumstances, create any implication that there has been no change in the information set forth herein or in the affairs of Apogee Technology since the date hereof. This business plan contains confidential and proprietary information of Apogee Technology, which is for the sole use of its intended recipient. Any unauthorized review, use, disclosure or distribution is prohibited. The financial projections in this business plan were developed by the management of Apogee Technology and are based on a number of assumptions, some of which are listed here. These assumptions include the timing and success of our future development efforts, acceptance of our products, our ability to successfully implement our hiring goals, our average sales price, the size of the market, our market share, general industry conditions and other matters. Although Apogee Technology believes that these assumptions are reasonable, they may be incomplete or incorrect, and unanticipated events and circumstances are likely to occur. The assumptions involve significant elements of subjective judgment and analysis, and no representation can be made as to their attainability. The projected financial information has not been examined, reviewed or compiled by independent accountants. The projections were not prepared with a view to public disclosure and do not comply with the published guidelines of the SEC or any state securities commission or the guidelines established by the American Institute of Certified Public Accountants. Actual results achieved during any future period may vary from the projections, and the variations may be material and adverse. We do not intend to update or otherwise revise these projections to reflect circumstances existing after the date hereof or to reflect the occurrence of future events, even if the assumptions or estimates underlying the projections are shown to be in error. Prospective investors should not rely on, and will be deemed not to have relied on, the projections in making an investment decision.
Apogee Technology Inc. Confidential
4
Company
Apogee Technology, Inc. is a (ATCS.OB) is a publicly traded development stage company,
developing vaccine and drug delivery technologies and immunomodulating systems for the prevention
and treatment of infectious diseases and chronic conditions. To address the unmet needs of the field,
the Company advances a unique approach based on polyphosphazene macromolecules, which are
designed to enhance biological activity of vaccines or drugs, and display synergistic effect when
integrated with non-conventional administration routes, such as topical (intradermal) delivery using
microneedle enhanced patches. The technology has the potential to enhance protective immunity
induced by vaccines, simplify and decrease the cost of drug or vaccine administration, improve the
efficacy of the treatment, and increase the product shelf-life. Apogee has established a strong
intellectual property position through licensing and filing of several patent applications in the field and
plans to extend it through the acquisition of Parallel Solutions, Inc. The Polyphosphazene approach can
be applied across a range of other disease areas and biomedical applications providing a broad and
flexible platform for the discovery and development of novel drug delivery systems and biomaterials.
Apogee is initially focused on the development of and for the prevention and treatment of infectious
diseases, cancer, and allergies using advanced immunopotentiating and microneedle delivery
technologies - ImmunoMer H, ImmunoMer AH, and IgloPatch.
Technology
Polyphosphazenes
Polyphosphazenes, macromolecules with a phosphorus and nitrogen backbone and organic side groups
(Scheme 1), possess a number of features that make them highly attractive for life sciences applications
and also distinguish them from other classes of biomedical polymers. Firstly, the inorganic backbone is
capable of hydrolytical degradation, which can be modulated through the selection of the appropriate
side group. Secondly, the unique synthetic pathway to these polymers, the so-called macromolecular
substitution, allows a huge selection of substituents to be introduced by common organic chemistry
methods, free of many ambiguities and restrictions associated with polymerization processes. Thirdly,
such methods lend themselves to high throughput synthesis, which accelerates the discovery process.
Fourthly, the unique flexibility of the backbone and its ability to participate in non-covalent bonding and
supramolecular assemblies create new opportunities for the interface with biological systems.
Apogee Technology Inc. Confidential
5
Scheme 1. Polyphosphazenes
Polyphosphazene Immunoadjuvants
The search for potent, well characterized, and safe vaccine adjuvants and delivery vehicles has been
widely recognized as a key strategic factor in the development of new and improved vaccines [1]. In this
regard, an emerging class of well defined macromolecules, based on a polyphosphazene backbone
(Scheme 2), offers a number of important advantages, both from immunostimulation and delivery
standpoints. Impressive immunopotentiation activity and dose sparing effects of these water-soluble
molecules [2-11] are augmented with the ease of their assembly into supramolecular microparticulate
structures to achieve optimal delivery performance [12-17]. The synthetic origin of polyphosphazene
adjuvants and their well characterized molecular structures assure a high level of reproducibility and
ease of quality control [18-20]. Adequate stability, the “mix and fix” aqueous formulation approach,
which does not involve covalent conjugation with antigen [3], long lasting immune responses, and a
good safety profile, which includes the results of clinical trials in humans, are among other advantages
of this adjuvant system. The polyphosphazene backbone of these molecules allows their biodegradation,
which can be modulated through the choice of the side group and results in the release of
physiologically benign compounds [4, 21-23]. The commercial development of the lead compound is
sustained by the existence of a robust GMP manufacturing process and the availability of a drug master
file to support regulatory applications. A substantial research effort has already been invested in the
field, including work in multiple animal models and with various antigens, both synthetic and
mechanistic studies [2-10]. It becomes evident that the polyphosphazene adjuvant technology evolves
through the discovery of new, more potent derivatives [24-26], development of microparticulate
delivery systems, and the investigation of alternative delivery routes, such as mucosal and intradermal.
The mechanism of action of ionic polyphosphazene immunoadjuvants, which are highly superior to their
non-polyphosphazene counterparts [3, 9], is still largely under discussion. It has been established that
adjuvant activity of PCPP is not associated with a depot formation, as the excision of the injection site
had no detectable effect on the kinetics of antibody induction [7]. The adjuvant activity of PCPP appears
to be linked to its ability to form water-soluble non-covalent complexes with the antigen, a process
which may enhance their interaction with antigen presenting cells [3]. This can be an important factor
DIVERSITY
BIODEGRADABILITY
HT COMPATIBLE
INTERACTIVE
DIVERSITY
BIODEGRADABILITY
HT COMPATIBLE
INTERACTIVE
Apogee Technology Inc. Confidential
6
taking into account a unique antigen presenting function of dermal dendritic cells mentioned above
[27]. More recent evidence suggests that PCPP activates innate immune cells to secrete IL-4 and IL-12
[28]. Since these cytokines are known to influence adaptive immune responses, activation of innate
immunity may be important in mediating the adjuvant activity of PCPP. Regardless of the mechanism,
PCPP appears to display immunoadjuvant activity with a broad spectrum of viral and bacterial antigens,
which are of interest in combating such important infectious diseases as influenza, hepatitis B, herpes,
tetanus, and HIV [11].
Scheme 2. A Representative Structure of a Polyphosphazene Vaccine Adjuvant
Intradermal Immunization
Skin is an attractive organ for administration of vaccines since it constitutes an anatomic barrier,
defending the body against external pathogens. Targeting of vaccine compounds to skin and/ or skin-
draining lymph node dendritic cells (DCs) is a valuable strategy to induce robust cellular responses that
protect against infectious and chronic diseases caused by intra-cellular pathogens. The unique antigen
presenting function of skin draining lymph node DCs has been the focus of intense studies for the
purpose of vaccine development [27]. Intradermal vaccination approaches have a potential to facilitate
induction of more potent immune responses and provide the basis for a significant antigen sparing
effect [29-34]. The latter can be highly desirable during times of vaccine shortages, such as epidemic
emergencies, and can also reduce the cost of vaccine manufacturing, which is especially important for
expanding vaccine use in less developed areas of the world [33, 35]. This could increase the possibility of
mass intradermal vaccination programs and result in major global health benefits, particularly in areas
where access to healthcare personnel is an issue.
Microneedle Technology for Intradermal Administration of Vaccines
Although the intradermal immunization approach appears to be promising, its technical realization faces
significant challenges, such as special training of personnel who would be needed to administer
vaccinations through the intradermal route effectively [36]. Microneedles and micro-injection devices
Apogee Technology Inc. Confidential
7
can provide a convenient alternative potentially offering ease of application and distribution, possibility
of self-administration and pain-free delivery [37].
Apogee Technology, Inc. is engaged in the development of microneedle systems (Fig. 1), which utilize
sub-millimeter structures to pierce the stratum corneum and deliver vaccines in the epidermis or dermis
compartments [37-40]. Microneedles are designed to combine vaccine formulation as a solid coating,
and metal, as a supporting material to provide the required mechanical strength. Once applied to the
skin, these formulations dissolve to release vaccine antigen in the skin compartment. Solid vaccine
formulations used in such systems are especially attractive since they also potentially offer improved
shelf life and reduced dependence on temperature-controlled supply chains [41, 42]. These
microneedles can also potentially be self-
administered and safely disposed of. Thus the
technology can significantly reduce biohazard
risks and drastically lowers the cost of
disposal as compared to contaminated
needles and syringes.
Polyphosphazene Immunoadjuvants for
Intradermal Immunization
A significant barrier on the way to a successful
development of microneedle vaccines is a
reliance of modern vaccine technologies on
immune-enhancing additives, i.e.,
immunoadjuvants, to engender the desirable
protective immune responses [1].
Unfortunately, many of the currently
employed vaccine adjuvants may not be
compatible with intradermal delivery
approaches. For example, alum, which is the
most common adjuvant used in the vaccine
market globally [1] and one of only two
adjuvants currently approved in the United
States, was shown to induce serious adverse
effects, such as formation of granulomas, when administered intradermally [43]. Other advanced
adjuvants, which contain biphasic systems, such as oil emulsions or liposomes, may not be sufficiently
stable to withstand the microneedle coating and drying processes. Although there are clear indications
that intradermal immunization can potentially offer significant improvements over intramuscular
Apogee Technology Inc. Confidential
8
vaccination [37], it appears that the majority of studies have been conducted using non-adjuvanted
vaccine formulations.
Apogee Technology develops microneedle systems, which utilize polyphosphazene adjuvants, both as
immunostimulant and microfabrication material. Polyphosphazene polyelectrolytes are one of the most
remarkable classes of vaccine adjuvants due to their macromolecular nature, well-defined structure, and
synthetic origin and have demonstrated excellent immunomodulating potential when tested in multiple
animal models with both viral and bacterial antigens [2, 5, 7, 11, 44]. The lead compound,
poly[di(carboxylatophenoxy)phosphazene] (PCPP) has been advanced into clinical trials [45-47] and
PCPP formulated vaccines were reported to be safe and immunogenic in humans [45, 46]. Most
importantly, the macromolecular nature of PCPP ensures excellent film forming and microencapsulating
properties [12, 13]. It has been also demonstrated that PCPP can protect and stabilize vaccine antigens
Apogee Technology Inc. Confidential
9
during the microfabrication process [48, 49]. PCPP is a water-soluble molecule, which can be formulated
with proteins in aqueous solutions under mild conditions [3] and has the potential to be dissolved easily
in a highly hydrated environment, such as skin. Finally, dual functionality of such a molecule, as an
immunoadjuvant and film forming/microfabrication material, eliminates the need for the use of
additional macromolecular excipients and thus can potentially result in a higher vaccine loading
capacity.
Synergy between Polyphosphazene Immunoadjuvant and Microneedle Technology Creates New
Approach to Intradermal Immunization
Recent studies conducted by Apogee have demonstrated that a macromolecular adjuvant, PCPP,
exhibits potent immunoadjuvant activity when delivered intradermally and also enables efficient
incorporation of vaccine antigens into microfabricated delivery devices.
In vivo proof-of-concept studies in pigs using recombinant Hepatitis B surface Antigen (HBsAg)
demonstrated that Apogee’s intradermal delivery systems dramatically increase antibody responses
compared to intramuscular administration of non-
adjuvanted and adjuvanted formulations after a single
dose immunization (Fig. 2a). They also provide significant
antigen sparing ability (Fig. 2b). These results appear
especially significant as the anatomy of pig skin presents a
reasonable model for human skin [50]. In fact, a powerful
synergistic effect between microneedle system and
polyphosphazene adjuvants observed in these
immunization studies requires further mechanistic studies
focusing on the specifics of immunological pathways
associated with delivery to skin and the role of PCPP.
PCPP is not only compatible with solid state microneedle
technology, but can potentially eliminate the need for
inert “engineering” polymers, such as CMC, whose sole
role is to serve as a microfabrication material. Since both
immunostimulating and “engineering” functionalities can
now be integrated in a single compound - PCPP - the
approach creates opportunities for maximizing antigen
doses or achieving faster dissolution profiles using the same amount of the formulation. The results also
suggest that PCPP can potentially provide surfactant-free or low surfactant coating solutions allowing
more flexibility in formulation development, which is especially important when high contents of
surfactant are undesirable [42, 51].
The micro-dip coating process utilized by Apogee is anticipated to be scaleable and inexpensive. A
number of proprietary methodologies have been developed to assure accurate and reproducible dosing
of the vaccine formulation [52]. The results of recent studies also showed no loss of activity in the
0
20
40
60
80
100
0 5 10 15 20
Time, days
Residual activity, %
1
2
Fig. 3. Residual enzymatic activity of
HRP encapsulated on microneedles (1)
and in aqueous solution (2) during
accelerated thermal stability studies as
a function of time (80° C).
Apogee Technology Inc. Confidential
10
coating process utilizing model protein compounds, which indicated high efficiency of encapsulation in
the process of microneedle fabrication [52].
One of the most significant potential advantages of solid state microneedle technology, being developed
by Apogee, is an expected improved shelf life of solid state formulations as compared to their solution
counterparts. Stability of microneedles containing model biological, Horse-Radish Peroxidase (HRP) was
compared to the same enzyme in aqueous formulation at 80 °C (Fig.3). The accelerated degradation
profiles show a dramatic improvement in the stability of a solid state formulation as compared to HRP in
solution [52]. As mentioned above, the stability and better shelf-life of the microneedle formulations
can be a critical parameter in decreasing the reliance of vaccine distribution on cold chain supply,
resulting in a major global health benefit.
Business Strategy
Apogee’s business strategy is to develop high value vaccine and drug enabling systems based on
unique polyphosphazene technology synergized with advanced delivery approaches. Our core expertise
is the development of novel biomedical, immunopotentiating and protein stabilizing polyphosphazenes
and their integration into value added products. Due to high costs of vaccine development and
regulatory approval, we intend to develop products thru partnerships, further licensing out application
rights while maintaining manufacturing rights.
Apogee will pursue partnerships with pharmaceutical and biotechnology companies worldwide,
which conduct preclinical and clinical development of cutting edge vaccine candidates with a need for
immunopotentiators or advanced delivery systems. Under a partnership agreement we would jointly
invest in the preclinical and, potentially, phase I/II clinical product development and then license them
either to a strategic partner or a third party for completion of clinical development, registration, and
product marketing. These deals will generate multi-million upfront payments, milestones and double
digit royalties.
The company will also pursue licensing agreements with multinational vaccine producers that
are in the need of advanced immunopotentiators and delivery systems for multiple antigens. We would
provide rights to our intellectual property in exchange for license fees, milestone development
payments and royalties tied to product sales. Target deal profile may include exclusive or semi-exclusive
arrangement, use with 3 to 6 antigens in defined field (infectious disease, allergy or cancer), upfront
payment ($10M-20M), milestones ($5M - 15M per antigen), royalties (5 - 15% depending upon disease,
exclusivity), subsidized research, and follow-on or extension deals with other antigens or fields.
Apogee may enter into collaborations with Global Health organizations for the development of
vaccines for developing countries. The Company anticipates these efforts to be subsidized, with a
potential technology transfer fee upon completion of preclinical or clinical evaluation. Since, each
immunopotentiator or delivery system can be used or tested with a variety of antigens, this provides an
opportunity to generate valuable, including clinical data and benchmarking against competing systems
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at little or no cost to the Company. Apogee intends to pursue similar opportunities for Public Health
vaccines in US actively seeking government subsidized R&D studies, also involving commercial partners.
In the Animal Health vaccine industry we plan to enter into a short term joint evaluation studies
and sell our rights to one or two leading companies in the field, generating significant short term
revenues targeting Q4 2012, which will allow us to more aggressively, pursue other high value added
partnerships.
Apogee has already initiated discussions with several potential partners. Apogee’s strategy for
establishing strong partnership deals include selecting antigens and animal models of relevance to
vaccine developers, compatibility with other immunopotentiators and delivery systems, and
benchmarking our systems against our competitors.
Product Pipeline
Apogee’s product pipeline consists of the following proprietary systems: ImmunoMer H,
immunopotentiating and antigen stabilizing polyphosphazene agent for parenteral and mucosal human
vaccines, ImmunoMer AH, immunopotentiating and antigen stabilizing polyphosphazene agent for
parenteral and mucosal animal health vaccines, and IgloPatch, advanced immunopotentiated
microneedle patch for the application of vaccine to the skin. We plan to integrate these systems with
novel vaccine antigens in partnerships with industry leaders developing new vaccines, governmental and
world health organizations to develop breakthrough vaccines with enhanced protective immunity,
improved safety profiles, and superior term shelf-life, with IgloPatch product potentially offering self-
applied vaccines with reduced dependence on cold chain distribution.
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Table 1. Projected Product Development
Apogee identified a number of novel vaccine candidates that are currently in clinical or pre-
clinical development, which we believe are ideally suited to be enhanced by our immunopotentiating
systems with many proof-of-concept in vivo experiments already completed. Apogee anticipates
entering into the agreements on the co-development of these vaccines within approximately 6 months
after receiving funding and conduct preclinical and clinical development of Public Health and World
Health vaccines under the terms of appropriate funding from potential partners.
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Table 2. Identified Target Antigens
1 A.K. Andrianov et al., Proc. Natl. Acad. Sci. USA, 2009, 106:18936 2 G. Mutwiri, in “Polyphosphazenes for Biomedical Applications” A.K. Andrianov, Ed., John Wiley & Sons, 2009, 77 3 A.K. Andrianov et al., J. Pharm. Sci., 2011, 100 (4), 1436 4 K. Johansen, in “Polyphosphazenes for Biomedical Applications” A.K. Andrianov, Ed., John Wiley & Sons, 2009, 85
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In order to execute commercial development of ImmunoMer H, ImmunoMer AH, and
polyphosphazene related part of IgloPatch in the proposed timeframe, Apogee believes that it needs to
gain access to certain patents of Parallel Solutions, Inc. (PSI), which it plans to acquire upon receipt of
funding proceeds. Intellectual property of PSI also includes other biomedical polyphosphazene
technologies, such as therapeutic protein stabilization methods, which can be highly complementary to
Apogee’s microneedle system, IgloPatch, and can enhance characteristics of our patch systems for the
delivery of therapeutics. Upon acquisition of PSI, Apogee plans to seek externally funded partnership to
conduct in vivo proof-of-concept studies of these technologies.
Intellectual Property
Apogee has already established a strong intellectual property position through licensing and filing of several patent applications in the field. Patent application related to microneedle device, related compositions and manufacturing methods was licensed from Georgia Institute of Technology (Professor M.R. Prausnitz):
Coated Microstructures and Methods of Manufacture Thereof H.S. Gill, Harvinder Singh, M.R. Prausnitz US 11/917705 (06.19.2006); Pub. No. US 2008/0213461 A1; provisional No. 60/691,857 (06.17.2005), No
60/732,267 (11.1.2005); PCT/US2006/023814 (06.19.2006); Int. Publ. No. WO 2006/138719 A2;
EP20060785110.
Apogee has filed the following patent applications related to microneedle technology and the use of polyphosphazenes as intradermal immunopotentiator and as coating reagents for microneedle technology.
Methods and Systems for Coating a Microneedle with a Dosage of a Biologically Active Compound A.K. Andrianov, A. Marin US 12/133,505 (06.05.08); Pub. No. US 2009/0017210 A1; provisional 60/948,500 (07.09.07);
PCT/US2008/007200 (06.09.08); Int. Publ. No. WO2009/008951 A2; EP20080768269.
Coating Formulation Including Polyphosphazene Polyelectrolytes and Biologically Active Agents and Asperities Coated with Such Formulations A.K. Andrianov, A. Marin US 12/217,437 (07.02.08); Pub. No. US/0016935 A1, provisional 60/948,540 (07.09.2007)
PCT/US2008/008265 (07.03.08); Int. Publ. No. WO 2009/009004 A1; EP20080768862.
Immunostimulating Polyphosphazene Compounds for Intradermal Immunization A.K. Andrianov, D.P. DeCollibus, H.A. Gillis, H.H. Kha, A. Marin US 12/217,402 (07.03.08); Pub. No.2009/0041810 A1; provisional 61/125,576 (04.25.2008) and
60/948,540 (07.09.07); PCT/US2008/008230 (07.03.08); Int. Publ. No. WO 2009/008988A1;
EP20080779950.
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In order to execute commercial development of ImmunoMer H, ImmunoMer AH, and
polyphosphazene related part of IgloPatch in the proposed timeframe, Apogee believes that it needs to
gain access to certain patents of Parallel Solutions, Inc. (PSI), which it plans to acquire upon receipt of
funding proceeds. Intellectual property of PSI also includes other biomedical polyphosphazene
technologies, such as therapeutic protein stabilization methods, which can be highly complementary to
Apogee’s microneedle system, IgloPatch, and can enhance characteristics of our patch systems for the
delivery of therapeutics.
Competitive Advantage
There is an unmet need for new immunoadjuvants (immunopotentiators) and alternative
administration routes for the delivery of vaccines. A major bottleneck in vaccine development is the lack
of suitable adjuvants for adult and pediatric vaccine use. Until recently, vaccine research and
development focused nearly exclusively on the antigen component of the vaccine that induces a specific
immune response in the body to protect against a particular disease. Contemporary vaccines
increasingly rely on another component – immunoadjuvant, which does not induce the immune
response on its own, but is capable of amplifying it dramatically to make the vaccine more potent,
reduce the dose of the antigen and a number of required administrations, and achieve more rapid and
longer-lasting protective immunity. Alternative delivery routes, such as intradermal vaccination, further
have a potential to simplify and decrease the cost of drug or vaccine administration, improve the
efficacy of the treatment, and increase the product shelf-life.
There are two vaccine adjuvants (immunopotentiators) currently approved in the United States
– Alum, which has been used with multiple vaccines for decades (public domain), and recently approved
ASO4 for use in Cervarix HPV Vaccine (GSK Biologicals). MF59 (Novartis Vaccines), has been also
approved in Europe. All of these immunopotentiators are heterogeneous (biphasic) systems that are
either incompatible with many advanced delivery systems, such as microneedles, or reactogenic or
inefficient when delivered intradermally or mucosally, important delivery modalities. Although there are
a number of immunopotentiators that are currently under development, such as AF03 (Sanofi Pasteur),
ASO3 (GSK Biologicals), IC31 (Intercell), various TLR agonists (3M), and others, they have similar
limitations and may face other challenges in the approval process.
Polyphosphazene immunopotentiators, PCPP and newer generation molecules have the
following features, distinguishing them from other similar systems:
Well-defined synthetic molecular immunopotentiator;
Vaccine Stabilization Agents for prolonged shelf life;
Proven Parenteral, Mucosal, Intradermal Immunopotentiator with higher, sustained immune
response with quick onset and improved immunological memory;
Antigen sparing effect;
Strong safety and tolerability track record in clinical trials;
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Compatibility with solid microneedles;
Can be formulated in nanoparticulates for synergistic vaccine delivery effect;
Technology platform with newer, more potent immunopotentiators through High Throughput
Discovery;
Excellent compatibility with other immunopotentiating systems.
There are a number of companies developing solid microneedle technologies for biomedical
applications, such as Zosano, Corium, Theraject, and 3M, however most of them focus on therapeutic
applications and lack compatible immunopotentiators. Published report by Zosano on the use of small
molecule immunopotentiator (GMDP, not suitable as a microfabrication material), indicated that the
adjuvant worked intradermally, but its effect was 10 times less than when it was used parenterally. In
contrast, Apogee’s system showed at least order of magnitude higher performance of polyphosphazene
immunopotentiator when administered intradermally compared with intramuscular administration.
The Company believes that the advantages of Apogee’s microneedle technology are as follows:
Proven synergy of adjuvant and intradermal delivery;
Dual role of polyphosphazene as microfabrication material provides higher loading
Stabilization effect of polyphosphazene and improved microfabrication rate reduces stress on
vaccine antigen improving efficiency of loading;
Reduced reliance on surfactants in the microfabrication process;
Precise dosing of antigen to overcome one of the most critical challenges of the technology.
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Market Analysis
Others
Sources:
* Kalorama Information | http://www.kaloramainformation.com/about/release.asp?id=1693
** 12th annual World Vaccine Congress Lyon 2010, J. Almond, Sanofi pasteur | http://www.terrapinn.com
Vaccine Market Overview
Presence of current Top
Pharma Companies**
2005 - 3 of 10
2009 - 8 of 10
**
Global Market for preventive vaccines:
$22.1 billion in 2009*
Predicted Growth:
9.7% *compound annual rate (next five years)
The global market for preventative vaccines topped $22 billion in 2009 and is predicted to
increase at a compound annual rate of 9.7% during the next five years, as new product introductions
continue and the use of current products expands further in all regions. Vaccines are commonly
segmented into two target markets, adult and pediatric. The pediatric vaccine market is larger,
accounting for more than half of the total market and is also growing at a faster rate than adult vaccines
and this is expected to continue over the next five years. Geographically US will continue to lead the
vaccines market followed by Europe. Japanese vaccine market has also started to open up further from
regulatory and political barriers. The large population in countries like India and China, high prevalence
of diseases and emergence of new pandemics are some of the important factors posting tremendous
growth in vaccine market. This sector is expected to grow at a rate of 14% during 2009-2012.
In 2009, pandemic influenza vaccines were the best selling vaccines with sales of over $ 5 billion
followed by hepatitis B vaccines. The worldmarket of Hepatitis B Vaccine was $ 1.2 billion. Of the 350
million to 400 million individuals worldwide infected with the hepatitis B virus (HBV), one-third reside in
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China, with 130 million carriers and 30 million chronically infected. Pneumococcal vaccine (Prevnar) has
crossed the sales of US$ 1 Billion in 2007 and became the first vaccine to reach nearly US$ 3 Billion
annual sales by 2009. Pneumonia is the world's leading killer of children younger than 5 years, and is
one of the foremost vaccine-preventable killers of children today. Every year, pneumococcal disease kills
about 1 million children worldwide. The Advanced Market Commitment (AMC) initiative for
pneumococcal vaccine was launched in June, 2009 with the intention to help prevent pneumonia. With
$1.5 billion funding from Canada, Italy, Norway, Russia, the UK, and the Bill & Melinda Gates
Foundation, the initiative is aiming to create a market to ensure demand for, and supply of,
pneumococcal vaccines for developing countries. Sales of Cervical cancer vaccines (HPV) have crossed $
1 Billion by 2007 and are forecasted to cross $ 4 Billion mark by 2012. Market for Rotavirus and polio
vaccines has crossed $ 1 Billion each in 2009. Malaria vaccine market for public is expected to cross $
400 Million by 2025.
Due to existing threat of terrorism Bio-protection vaccines are an important segment of the
market. US government poured billions into building strategic stockpiles of these vaccines (influenza,
bioterror) and R&D funding for new production technologies. The Bio-protection vaccines market is
expected to grow with an annual rate of 12.08% percent from 2009 to 2015.
Pharmaceutical Research and Manufacturers of America lists 145 vaccines under development
in US only, to prevent a variety of infections. A large number of vaccines that are currently under
development, both in US and worldwide, are designed to combat important emerging or neglected
diseases, for which there is currently no preventive treatment. Norovirus infection, more commonly
known as the “stomach flu”, is the most common cause of acute gastroenteritis in the U.S. A systematic
review of studies performed by the CDC estimated that norovirus causes an annual 64,000
hospitalizations and 900,000 clinical visits among children in industrialized nations and up to 200,000
death of children < 5 years of age in developing countries. Chlamydia is a common sexually transmitted
disease (STD) caused by the bacterium, Chlamydia trachomatis. Chlamydial infections in women, which
are usually asymptomatic, can result in pelvic inflammatory disease, which is a major cause of infertility,
ectopic pregnancy, and chronic pelvic pain. CDC reports high prevalence of chlamydial infections in the
general U.S. population. Among young adults (aged 18–26 years) who participated in the nationally
representative National Longitudinal Study of Adolescent Health (Add Health) during 2001–2002,
chlamydia prevalence was 4.2%. A vaccine against recurrent vulvovaginal candidiasis (VVC) would
benefit a large number of women who suffer from this debilitating syndrome. The disease has a
significant effect on quality of life and poses a huge burden to the health care system. CDC estimates
that 75% of women will have at least one episode of VVC, and 40%–45% will have two or more episodes
within their lifetime. Approximately 10%–20% of women will have complicated VVC that necessitates
diagnostic and therapeutic considerations. Global candidiasis therapeutics market was valued at $1.57
bn in 2009. Hand, foot, and mouth disease (HFMD) is another common viral illness in infants and
children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although
most HFMD do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71)
can present with a high rate of neurological complications, including meningoencephalitis, pulmonary
complications, and possibly death. HFMD caused by EV71 has become a major emerging infectious
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disease in Asia with approximately 1,155,000 new cases of HFMD in mainland of China only, and 353
deaths. A number of commercial entities and academic groups are working on the development of
vaccines in these areas and Apogee’s immunopotentiating, delivery, and stabilization systems can
potentially play an important role in enabling these vaccines, accelerating their development, reducing
required doses, improving shelf-life and enhancing their protective immunity.
The worldwide vaccine market is dominated by five major competitors: Merck & Co,
GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Novartis. Examples of other vaccine companies include
AlphaVax, Inc., Bavarian Nordic A/S , Baxter Healthcare, Bharat Biotech, Celldex Therapeutics, Crucell,
Emergent Biosolutions, Medimmune, Nabi Biopharmaceuticals.
Global Veterinary Vaccines Market to reach $5.6 Billion by 2015. The market is split between
Livestock Vaccines (Porcine Vaccines, Bovine Vaccines, Poultry Vaccines, Ovine Vaccines, Equine
Vaccines, & Other Animal Vaccines) and Companion Vaccines (Canine Vaccines, & Feline Vaccines) with
the first representing the largest product segment of about 63% in 2006. Growth in the Livestock
Vaccines market is essentially driven by Porcine Vaccines market, which not only accounts for a majority
share of the total market but is also one of the fastest growing segments. Revenues from porcine
vaccines market are estimated to be approximately $1 billion mark in 2010. United States and Europe
collectively capture more than 60% of the worldwide Veterinary Vaccines market. United States
companion animal vaccines market is estimated to be approximately $410 million in 2010. Europe is a
major market for veterinary vaccines and medicines across the globe. France, Germany and United
Kingdom account for over 40% of the veterinary vaccine sales in Europe.
Key players in the marketplace include Bayer HealthCare AG, Biogenesis-Bago, Boehringer
Ingelheim GmbH, Heska Corporation, Imugene Limited, Indian Immunologicals Ltd, Lohmann Animal
Health, Merck & Co. Inc., Intervet/Schering-Plough Animal Health, Merial Ltd., Pfizer Inc., Embrex Inc.,
Fort Dodge Animal Health, Virbac Corporation, among others.
Operational Plan
Progress to Date
Since the start of our biomedical project, the Company has reached a number of important
milestones including:
Establishment of the laboratory and the initiation of R&D work in 2006;
Completion of the licensing agreement for the microneedle technology from Georgia Tech;
Development of the prototype microneedle fabrication process, arrays, and patches, and
identification of critical external suppliers and main quality control methods;
Completion of in vivo proof-of-concept study (in collaboration with Vaccine and Infectious
Disease Institute) for Apogee’s microneedles which demonstrated superior potency of IgloPatch
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and synergy between polyphosphazene and intradermal delivery and resulted in a publication in
Proceedings of National Academy of Sciences U.S.A.;
Filing of 3 patent applications;
Completion of in vivo proof-of-concept study (in collaboration with St. Jude Hospital) of
immunopotentiation technology and pandemic influenza vaccine, which demonstrated the
ability of Apogee’s formulations to protect animals in a lethal challenge study at a significantly
reduced dose;
Demonstration of the stabilizing effect of Apogee’s technology on vaccine and other biologics as
a proof-of-concept for the improved shelf-life;
Award of R&D contract from Children Hospital Boston for the development of
immunoadjuvanted formulations of vaccines for newborns, and successful and timely
achievement of milestones to date.
Facilities and Equipment
Apogee Technology is headquartered in Norwood, MA and established state-of-the art research
facilities include a formulation and characterization laboratory (360 sq.ft.) and an additional 670 sq.ft. of
lab support space.
The analytical section of the laboratory is equipped with Hitachi LaChrom Elite High Performance Liquid
Chromatography (HPLC) system with multi-detection capabilities (L-2I3OHTA pump and degasser, L-
2200 autosampler, L-2455 Diode array detector, and L-2490 refractive index detector), UV/Vis
spectrophotometer (HITACHI U-2810), analytical balance (AL204, Mettler Toledo), pH Meter (SevenEasy,
Mettler Toledo), a stereo zoom microscope (STZ-45-BS-FR) with a digital camera (Caltex Scientific, Irvine,
CA), Bunton MACROZOOM-FL microscope system (Bunton Instrument Company, Inc.), and a
stereomicroscope (model ML-40STER, Home Science tools).
The formulation section of the facilities is equipped with a fume hood, FreeZone 2.5 Lyophilizer
(Labconco), an incubated orbital shaker (model 4450), vortex mixers (12-810-1, Fisher Scientific;VM-
3000,VWR), an orbital shaker (model 51300-00, Cole Parmer), heated magnetic stirplates (models
12620-982, 12365-82 VWR), a vacuum oven (model 1410, VWR), a refrigerated vapor trap (model
RVT4104 Savant), vacuum pumps (VP 100, Savant and 8907, Welch), a centrifuge (model 5702,
Eppendorf), an ultrasonic water bath (model 50HT, VWR), and a heated water bath (model 182,
Precision). The microneedle coating facility is equipped with coating apparatuses, syringe pumps, and X-
Y-Z micro-positioning systems. Supporting facilities include flammable safety storage cabinet, gas supply
lines and manifolds (nitrogen, carbon dioxide and compressed air), B-Pure deionization and water
filtration system, a microwave oven, a freezer, and refrigerators.
Deal Throughput
Apogee intends to finalize the acquisition of PSI technology as soon as funding is complete. The
Company plans to enter at least 3 research and commercialization collaboration in Q4 2011 and Q1-Q2
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2012, one with the animal health vaccine company, another for a funded R&D collaboration with Global
Health or Government organization, and one with the commercial developer of vaccine of interest. Each
collaboration envisaged will give the partner access to ImmunoMer for use with their antigens. These
collaborations are expected to provide significant cash flow to the company in the medium term. Based
on these and other collaborations, Company envisions one licensing agreement in Q4 2012, one in Q3
2013, and another in Q1 2014.
Projected growth
To meet our stated objectives and deliverables the Company will need to add personnel, equipment and
acquire additional laboratory and office space.
Employees: We project our total staff will increase to 24 employees by 2016. In the business operations
group, significant emphasis will be placed on adding individuals with partnering capabilities, program
management, business development, and regulatory experience. On the R&D side, expertise will be
added in immunology, polymer and biochemistry, various areas of assay development, formulation and
manufacturing. The ratio of PhD to Technician (BS or MS level) for our laboratory staff will be roughly
1:2. Many upstream capabilities will be accessed through the Company’s corporate alliances and
through a strong network of outside advisors and vendors.
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Business Model
• Product development partnerships with pharmaceutical and biotechnology
companies worldwide, license out application rights, maintain manufacturing
rights
• IgloPatch Technology: licensing model with multinational vaccine producers:
• Exclusive arrangement for 3-6 antigens
• Upfront payment of $5 - $20 million
• Milestone payments of $5 - $15 million per antigen
• 5 - 15% royalties on net product sales
• ImmunoMer H Technology: licensing model with smaller vaccine producers
or biotechnology companies:
• Non-exclusive arrangement for 1-2 antigens
• Upfront payment of $1 - $2 million (“Access Fee”)
• Milestone payments of $1 - $2 million per antigen
• 10 - 25% of proceeds upon acquisition of vaccine by a multinational company
• 5 - 15% royalties on net product sales
• ImmunoMer AH Technology: collaboration with Animal Health company
• Other: collaboration with Global Health or Government organizations
generating technology transfer fees
Company Products Applications Customers Finances
Celonova Bioscience(Peachtree City, GA)
PolyphosphazeneNanoparticlesEmbozeneTM
EmpolizationPP coated stent
Physicians Private
Competition
Company Products Applications Customers Finances
IntercellPatch
Vaccines/Bacterial Adjuvant
Pandemic Influenza and Traveler's
Diarrhea Vaccine Patches
Discovery- MarketPublic-$500MM
Market Cap
3MMicroneedles
(plastic)/TLR AdjuvantMultiple Clinical
Public-$61B Market Cap
Zosano PharmaMicroneedles with
PTH, EPO, GM-CSF/GMDP Adjuvant
Osteoporosis Phase IIPrivate-$90MM NEA,
Numera
Becton DickensonMicroinjection device/Alum
Soluble Vaccines On the marketPublic-$17B Market
Cap
Corium InternationalMicroCor™ Micro Delivery System
Small and large molecular weight
moleculesPrivate Private
Polyphosphazene Company
Intradermal Delivery/Adjuvant Companies
Other examples of Immunoadjuvants: AF03 (Sanofi Pasteur), ASO3 (GSK Biologicals), MF 59 (Novartis), IC31 (Intercell)
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• Worldwide exclusive license from Georgia Tech for coated
microneedle technology
• Know-how and world’s expert scientists in
polyphosphazene field
• Drug Master File for PCPP as an adjuvant *
• cGMP produced PCPP*
• Polyphosphazene immunoadjuvant library,
polyphosphazene drug delivery library, and biomaterial
product candidates*
* Upon closing PSI transaction after funding
Competitive Advantages
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Partnering
Company envisions one licensing agreement in Q4 2012, two in Q3 2013, and another in Q1
2014.
Leverage external resources
The Company does not plan to establish in-house capabilities to execute in-vivo evaluation of
our immunopotentiation and intradermal delivery. In addition to planned partnership, Apogee has
already established collaborations with Children Hospital Boston, and can reactivate previous
collaborations with VIDO and St. Jude Hospital and enter new R&D agreements to provide cost-effective,
flexible and timely access to animal models needed to evaluate our systems. The relationships with
governmental and university researchers provides a low cost (no cost) mechanism to investigate
broader applications of our platform.
Government funding
Apogee plans to apply for grant funding from Global health organizations and governmental
agencies to support preclinical and clinical development of its technologies. The Company has already
applied this strategy in an ongoing collaboration with Children Hospital of Boston, which allowed to get
support for some of Companies vital R&D efforts.
Royalties paid on licenses
The Company entered in a 50 year exclusive worldwide licensing agreement in March of 2007
for a microneedle technology with Georgia Institute of Technology.
Financial model assumptions – Revenues:
Apogee has already generated revenues external collaborations and believes it can continue and
increase generation of revenues from partnerships. In the early years, revenue is projected to come
from milestone payments and royalties. Baseline business projections foresee the completion of 3
corporate deals by early 2014.
Each deal gives a partner the right to use PSI’s technology with the antigen of interest, although in the
animal health vaccine area we expect to give exclusive rights to our technology for livestock and
companion market segments. The deal structure envisions a series of success-based milestones and
subsequent product royalties for each of the antigens.
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PROJECTED REVENUES AND EXPENSES 2010-2016
($10,000,000)
($5,000,000)
$0
$5,000,000
$10,000,000
$15,000,000
$20,000,000
1 2 3 4 5 6 7
2010 2011 2012 2013 2014 2015 2016
Revenues
Operating Loss/Gain
Total Expenses
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Investment Rationale
• A strong balance sheet will strengthen Apogee’s negotiating
position with potential strategic partners
• Acquisition of certain assets of Parallel Solutions, Inc. (PSI)
for 700,000 shares of Apogee stock and 25% of future joint
venture payments will provide Apogee with access to
• PSI’s intellectual property portfolio
• Drug Master File
• cGMP produced material
• Polyphosphazene libraries (new adjuvants, drug delivery) and
other polyphosphazenes for potential biomedical and industrial
applications
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Management Team
Herbert Stein, CEO and Chairman: Mr. Stein brings over fifty years of management experience to
Apogee and has served on the boards and in executive management positions at several life sciences
companies, including as Chairman and CEO of Organogenesis.
Paul J Murphy, Chief Financial Officer and Vice President of Finance: Mr Murphy has 25 years of
experience as Chief Financial Officer of public and private companies. Prior to joining Apogee, Mr
Murphy was an independent contractor with JH Cohn, LLP, where he worked on engagements with
public companies to design, assess and test controls for compliance with Section 404 of the Sarbanes-
Oxley Act of 2002.
Alexander K. Andrianov, Ph.D., Vice President of Research and Development: Dr. Andrianov has ~20
years of experience in the biotechnology industry having served as Chief Scientific Officer of Parallel
Solutions, Inc., and in various management positions at Avant Immunotherapeutics and Virus Research
Institute Inc (VSI). He has unique expertise in polymer chemistry and is the inventor of the
polyphosphazene immunoadjuvant technology. Dr. Andrianov is an author of more than 60 scientific
papers and book chapters, an inventor on 41 issued and pending patents, and an editor of the book
“Biomedical Applications of Polyphosphazenes”. Dr. Andrianov also has extensive academic experience
as a faculty member in Moscow State University (MSU) and visiting scientist at Massachusetts Institute
of Technology (MIT) with Professor Robert Langer.
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Summary
• Apogee Technology is a biotechnology company pioneering advanced
vaccine and drug delivery systems via its proprietary technology platform
• Core expertise: biomedical polyphosphazenes and their integration into
value added products
• Vaccine antigens stabilized and adjuvanted by polyphosphazenes and
delivered via Apogee’s microneedle technology have demonstrated to
confer a more potent immune response using reduced amounts of antigen
and provide an extended shelf life
• Potential self-administration and reduced dependence on cold chain
distribution open up developing countries as attractive target markets
• Licensing agreements with vaccine developers, an animal health company
and Global Health or Government organizations are expected to generate
significant revenue from upfront, milestone, and royalty payments, as well
as funded collaborations
• In addition to vaccine and drug delivery applications, potential uses of
polyphosphazenes extend to biomaterials
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Appendix 1. References
[1] Singh M, editor. Vaccine Adjuvants and Delivery Systems. Hoboken, New Jersey: Wiley-Interscience, 2006. [2] Andrianov AK, Marin A, Chen J. Synthesis, properties, and biological activity of Poly[di(sodium carboxylatoethylphenoxy)phosphazene]. Biomacromolecules 2006;7(1):394-9. [3] Andrianov AK, Marin A, Roberts BE. Polyphosphazene polyelectrolytes: A link between the formation of noncovalent complexes with antigenic proteins and immunostimulating activity. Biomacromolecules 2005;6(3):1375-9. [4] Andrianov AK, Sargent JR, Sule SS, Le Golvan MP, Woods AL, Jenkins SA, et al. Synthesis, physico-chemical properties and immunoadjuvant activity of water-soluble phosphazene polyacids. Journal of Bioactive and Compatible Polymers 1998;13(4):243-56. [5] Mutwiri G, Benjamin P, Soita H, Townsend H, Yost R, Roberts B, et al. Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens. Vaccine 2007;25(7):1204-13. [6] Payne LG, Jenkins SA, Andrianov A, Roberts BE. Water-soluble phosphazene polymers for parenteral and mucosal vaccine delivery. Pharmaceutical biotechnology 1995;6:473-93. [7] Payne LG, Jenkins SA, Woods AL, Grund EM, Geribo WE, Loebelenz JR, et al. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) is a potent immunoadjuvant for an influenza vaccine. Vaccine 1998;16(1):92-8. [8] Lu Y, Salvato MS, Pauza CD, Li J, Sodroski J, Manson K, et al. Utility of SHIV for testing HIV-1 vaccine candidates in macaques. J Acquir Immune Defic Syndr Hum Retrovirol 1996;12(2):99-106. [9] Payne LG, Van Nest G, Barchfeld GL, Siber GR, Gupta RK, Jenkins SA. PCPP as a parenteral adjuvant for diverse antigens. Dev Biol Stand 1998;92:79-87. [10] Payne LG, Jenkins SA, Andrianov A, Langer R, Roberts BE. Xenobiotic polymers as vaccine vehicles. Advances in Experimental Medicine and Biology 1995;371(B):1475-80. [11] Andrianov AK. Polyphosphazenes as vaccine adjuvants. In: Singh M, editor. Vaccine Adjuvants and Delivery Systems. Hoboken, New Jersey: John Wiley & Sons, 2007: 355-78. [12] Andrianov AK, Chen J. Polyphosphazene microspheres: Preparation by ionic complexation of phosphazene polyacids with spermine. Journal of Applied Polymer Science 2006;101(1):414-9. [13] Andrianov AK, Chen J, Payne LG. Preparation of hydrogel microspheres by coacervation of aqueous polyphosphazene solutions. Biomaterials 1998;19(1-3):109-15. [14] Andrianov AK, Chen J, Sule SS, Roberts BE. Ionically cross-linked polyphosphazene microspheres. ACS Symposium Series 2000;752:395-406. [15] Andrianov AK, Payne LG. Polymeric carriers for oral uptake of microparticulates. Advanced Drug Delivery Reviews 1998;34(2-3):155-70. [16] Andrianov AK, Payne LG. Protein release from polyphosphazene matrices. Advanced Drug Delivery Reviews 1998;31(3):185-96. [17] Andrianov AK, Marin A, Peterson P, Chen J. Fluorinated polyphosphazene polyelectrolytes. Journal of Applied Polymer Science 2007;103(1):53-8. [18] Andrianov AK, Chen J, LeGolvan MP. Poly(dichlorophosphazene) as a precursor for biologically active polyphosphazenes: Synthesis, characterization, and stabilization. Macromolecules 2004;37(2):414-20. [19] Andrianov AK, Le Golvan MP. Characterization of poly[di(carboxylatophenoxy)-phosphazene] by an aqueous gel permeation chromatography. Journal of Applied Polymer Science 1996;60(12):2289-95. [20] Andrianov AK, Svirkin YY, LeGolvan MP. Synthesis and biologically relevant properties of polyphosphazene polyacids. Biomacromolecules 2004;5(5):1999-2006. [21] Andrianov AK, Marin A. Degradation of polyaminophosphazenes: Effects of hydrolytic environment and polymer processing. Biomacromolecules 2006;7(5):1581-6. [22] Andrianov AK, Marin A, Peterson P. Water-soluble biodegradable polyphosphazenes containing N-ethylpyrrolidone groups. Macromolecules 2005;38(19):7972-6.
Apogee Technology Inc. Confidential
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[23] Andrianov AK, Payne LG, Visscher KB, Allcock HR, Langer R. Hydrolytic degradation of ionically cross-linked polyphosphazene microspheres. Journal of Applied Polymer Science 1994;53(12):1573-8. [24] Andrianov AK. Design and synthesis of functionalized polyphosphazenes with immune modulating activity. PMSE Preprints, 2003;88. [25] Andrianov AK. Water-Soluble Biodegradable Polyphosphazenes - Emerging Systems for Biomedical Applications. Polymer Preprints 2005;46(2):715. [26] Andrianov AK, Marin A, inventors; Immunostimulating polyphosphazene compounds 2.18.2005. [27] Larregina AT, Falo LD, Jr. Changing Paradigms in Cutaneous Immunology: Adapting with Dendritic Cells. J Investig Dermatol 2004;124(1):1-12. [28] Mutwiri G, Benjamin P, Soita H, Babiuk LA. Co-administration of polyphosphazenes with CpG oligodeoxynucleotides strongly enhances immune responses in mice immunized with Hepatitis B virus surface antigen. Vaccine 2008;26(22):2680-8. [29] Holland D, Booy R, De Looze F, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: A randomized controlled trial. Journal of Infectious Diseases 2008;198(5):650-8. [30] Alarcon JB, Hartley AW, Harvey NG, Mikszta JA. Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines. Clinical and Vaccine Immunology 2007;14(4):375-81. [31] Belshe RB, Newman FK, Cannon J, Duane C, Treanor J, Van Hoecke C, et al. Serum antibody responses after intradermal vaccination against influenza. N Engl J Med 2004;351(22):2286-94. [32] Hooper JW, Golden JW, Ferro AM, King AD. Smallpox DNA vaccine delivered by novel skin electroporation device protects mice against intranasal poxvirus challenge. Vaccine 2007;25(10):1814-23. [33] Kenney RT, Frech SA, Muenz LR, Villar CP, Glenn GM. Dose sparing with intradermal injection of influenza vaccine. N Engl J Med 2004;351(22):2295-301. [34] Van Damme P, Oosterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 2009;27(3):454-9. [35] Weeratna R, Comanita L, Davis HL. CPG ODN allows lower dose of antigen against hepatitis B surface antigen in BALB//c mice. Immunol Cell Biol 2003;81(1):59-62. [36] La Montagne JR, Fauci AS. Intradermal influenza vaccination--can less be more? N Engl J Med 2004;351(22):2330-2. [37] Prausnitz MR, Mikszta JA, Cormier M, Andrianov AK. Microneedle-Based Vaccines. In: Compans RW, Orenstein WA, editors. Curr Top Microbiol Immunol Vol 333: Vaccines for Pandemic Influenza Springer, 2009: 369-93. [38] Mikszta JA, Alarcon JB, Brittingham JM, Sutter DE, Pettis RJ, Harvey NG. Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nature Medicine 2002;8(4):415-9. [39] Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine 2006;24(10):1653-64. [40] McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proceedings of the National Academy of Sciences of the United States of America 2003;100(SUPPL. 2):13755-60. [41] Rexroad J, Wiethoff CM, Jones LS, Middaugh CR. Lyophilization and the thermostability of vaccines. Cell Preservation Technology 2002;1(2):91-104. [42] Wang W. Lyophilization and development of solid protein pharmaceuticals. International Journal of Pharmaceutics 2000;203(1-2):1-60. [43] Vogelbruch M, Nuss B, Korner M, Kapp A, Kiehl P, Bohm W. Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations. Allergy 2000;55(9):883-7. [44] Andrianov AK. Water-soluble polyphosphazenes for biomedical applications. Journal of Inorganic and Organometallic Polymers and Materials 2006;16(4):397-406. [45] Bouveret Le Cam NN, Ronco J, Francon A, Blondeau C, Fanget B. Adjuvants for influenza vaccine. Research in Immunology 1998;149(1):19-23.
Apogee Technology Inc. Confidential
32
[46] Kim JH, Kirsch EA, Gilliam B, Michael NL, VanCott TC, Ratto-Kim S, et al. A Phase I, Open Label, Dose Ranging Trial of The Pasteur Merieux Connaught (PMC) Oligomeric HIV-1 Gp160mn/LAI-2 Vaccine In HIV Seronegative Adults. Abstracts of the 37th Annual Meeting of the Infectious Diseases Society of America; 1999; Philadelphia, PA; 1999. p. 1028. [47] Thongcharoen P, Suriyanon V, Paris RM, Khamboonruang C, de Souza MS, Ratto-Kim S, et al. A Phase 1/2 Comparative Vaccine Trial of the Safety and Immunogenicity of a CRF01_AE (Subtype E) Candidate Vaccine: ALVAC-HIV (vCP1521) Prime With Oligomeric gp160 (92TH023/LAI-DID) or Bivalent gp120 (CM235/SF2) Boost. JAIDS Journal of Acquired Immune Deficiency Syndromes 2007;46(1):48. [48] Andrianov AK, Decollibus DP, Marin A, Webb A, Griffin Y, Webby RJ. PCPP-formulated H5N1 influenza vaccine displays improved stability and dose-sparing effect in lethal challenge studies. Journal of Pharmaceutical Sciences 2011:n/a-n/a. [49] Marin A, DeCollibus DP, Andrianov AK. Protein Stabilization in Aqueous Solutions of Polyphosphazene Polyelectrolyte and Non-Ionic Surfactants. Biomacromolecules 2010;11(9):2268-73. [50] Monteiro-Riviere NA. Comparative anatomy, physiology, and biochemistry of mammalian skin. In: Hobson D, editor. Dermal and Ocular Toxicology: Fundamentals and Methods. Boca Raton, FL: CRC Press, 1991: 3-71. [51] Katakam M, Bell LN, Banga AK. Effect of surfactants on the physical stability of recombinant human growth hormone. Journal of Pharmaceutical Sciences 1995;84(6):713-6. [52] Andrianov AK, DeCollibus DP, Gillis HA, Kha HH, Marin A. Polyphosphazene Immunoadjuvants for Intradermal Vaccine Delivery. In: Andrianov AK, editor. Polyphosphazene for Biomedical Applications. Hoboken, New Jersey: John Wiley & Sons, 2009: 101-16.