Apogee Corp Presentation By Hans David De Beer

1,639 views

Published on

APOGEE PRESENTATION BY THE DEBEER FUND MANAGAMENT GROUP LLC
INFO: 954-588-0761 (usa)

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,639
On SlideShare
0
From Embeds
0
Number of Embeds
9
Actions
Shares
0
Downloads
21
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Apogee Corp Presentation By Hans David De Beer

  1. 1. DE BEER FUND MANAGEMENT LLC 619 ORTON AVE, PENTHOUSE 601, FORT LAUDERDALE, FLORIDA 33304 Email:dada7772@hotmail.com, USA TEL: 1-954-306-6545 IS PROUD TO INTRODUCE Apogee TECHNOLOGYH.D. De Beer
  2. 2. A Biotechnology Company Pioneering Vaccine and Drug Delivery Technologies via Intradermal and Polyphosphazene Platforms August 2011
  3. 3. Forward-Looking StatementsThis presentation contains forward-looking statements as defined inthe Private Securities Litigation Reform Act of 1995. For thispurpose, any statements contained in this presentation that are notstatements of historical fact may be deemed to be forward-lookingstatements. Without limiting the foregoing, the words “believes”,“anticipates”, “plans”, “expects”, and similar expressions areintended to identify forward-looking statements. Actual results maydiffer significantly from results discussed in the forward-lookingstatements. Factors that might cause such differences include thoseset forth from time to time in the Companys SEC filings, including inour annual report on Form 10-K.
  4. 4. Apogee Technology Inc.Vision: To develop advanced and patient friendly technologies for theprevention and treatment of infectious diseases and chronic conditions• 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
  5. 5. 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
  6. 6. The Opportunity 145 Vaccines Under Development* 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 solutionSource*Pharmaceutical Research and Manufacturers of America. 2010 Report. Medicines indevelopment for Infectious Diseases |http://www.phrma.org/sites/default/files/422/infectiousdiseases2010.pdf
  7. 7. Polyphosphazenes as Biomedical Macromolecules Dial-In Biodegradability R (P N) RUnprecedented Structural Diversity – 1,000+ DerivativesTunable Properties – Various Potential Applications Vaccine Adjuvants, Biodegradable Carriers, Nanoparticulates, Microencapsulation and Modulated release, Microneedles, BiomaterialsHigh Throughput DiscoveryManufacturing Friendly Chemistry
  8. 8. Polyphosphazene Immunoadjuvants – ImmunoMer Platform PCPP • 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
  9. 9. 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 Antigen Dose Sparing Effect (up to 25x) Improves Vaccine Shelf-Life Demonstrated Potency in Large Animals with Animal Health Vaccine AntigenClinical 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
  10. 10. IgloPatch Technology Band-Aid-Like Microneedle Patches To PCPP - VACCINE Deliver Vaccine in The Skin Scalable Production Process Enhanced with Metal Support Microneedle Array
  11. 11. IgloPatch - In Vivo Proof-of-Concept StudiesHBsAg specific IgG Titers In Vivo POC studies in a relevant animal model - pigs 5 4 3 IgloPatch 2 Adjuvanted IM 1 Non-adjuvanted Microneedles Non-adjuvanted IM Weeks Single Dose
  12. 12. Potential Benefits of IgloPatch Technology• 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
  13. 13. Apogee’s Intellectual Property Portfolio Microneedle Technology Licensed from Georgia Tech: 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; Apogee’s filings on Microneedle Technology and Adjuvanted Formulations: Methods and Systems for Coating a Microneedle… A.K. Andrianov, A. Marin US 12/133,505 (06.05.08); Pub. No. US 2009/0017210 A1; Coating Formulation Including Polyphosphazene… A.K. Andrianov, A. Marin US 12/217,437 (07.02.08); Pub. No. US/0016935 A1 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;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.
  14. 14. Product Pipeline•ImmunoMer H, immunopotentiating and antigen stabilizingpolyphosphazene agent for parenteral and mucosal humanvaccines•ImmunoMer AH, immunopotentiating and antigen stabilizingpolyphosphazene agent for parenteral and mucosal animalhealth vaccines•IgloPatch, advanced immunopotentiated microneedle patchfor the application of vaccine to the skin. Potentially offers self-applied vaccines with reduced dependence on cold chaindistribution
  15. 15. Product Pipeline -TimelineApogee 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.
  16. 16. Strategy Assumption for 3 non-exclusive arrangements for 1-2 antigens, $2 million access fee, $1 million and $6 millionPartnerships with vaccine developers milestones, royalties on sales of 5-15%.(ImmunoMer H) Anticipated milestone timelines:1-2013/2014/2015; 2nd- 2014/2015/2016; 3rd- 2015/2016/2017 Generate valuable preclinical and clinical data at little or no cost to company (funded R&D) retaining rights forCollaboration with Global Health commercial use of developed vaccine. One fundedorganizations (all product candidates) collaboration is currently under way, assumption for two more in 2011 ($1.1M) and in 2014 ($2M) Target deal profile: 1.5 million upfront payment in 2012, atLicensing agreement with Animal Health least one milestone payment of $3 million in 2013, andvaccine company (ImmunoMer AH) royalties on net product sales starting in 2014. Target deal profile: exclusive or 3-6 antigens in a definedLicensing agreement with a multinational field, upfront payment of $7 million (2015) and milestonesvaccine company (IgloPatch) of $3 million and $7 million in 2016, royalties on sales of 5-15%.
  17. 17. Vaccine Market Overview Global Market for preventive vaccines: $22.1 billion in 2009* Others Predicted Growth: 9.7% * compound annual rate (next five years) ** Presence of current Top Pharma Companies** 2005 - 3 of 10 2009 - 8 of 10Sources:* 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
  18. 18. Competitive Advantages • 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
  19. 19. CompetitionPolyphosphazene Company Company Products Applications Customers Finances Polyphosphazene Celonova Bioscience Empolization Nanoparticles Physicians Private (Peachtree City, GA) PP coated stent EmbozeneTMIntradermal Delivery/Adjuvant Companies Company Products Applications Customers Finances Pandemic Influenza Patch and Travelers Public-$500MM Intercell Vaccines/Bacterial Discovery- Market Diarrhea Vaccine Market Cap Adjuvant Patches Microneedles Public-$61B Market 3M Multiple Clinical (plastic)/TLR Adjuvant Cap Microneedles with Private-$90MM NEA, Zosano Pharma PTH, EPO, GM- Osteoporosis Phase II Numera CSF/GMDP Adjuvant Microinjection Public-$17B Market Becton Dickenson Soluble Vaccines On the market device/Alum Cap Small and large MicroCor™ Micro Corium International molecular weight Private Private Delivery System moleculesOther examples of Immunoadjuvants: AF03 (Sanofi Pasteur), ASO3 (GSK Biologicals), MF 59 (Novartis), IC31 (Intercell)
  20. 20. Go to Market Strategy• 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
  21. 21. 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
  22. 22. 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)
  23. 23. PROJECTED REVENUES AND EXPENSES 2010-2016$20,000,000 Revenues$15,000,000 Operating Loss/Gain$10,000,000 $5,000,000 $0 1 2 3 4 5 6 7 Total Expenses ($5,000,000)($10,000,000) 2010 2011 2012 2013 2014 2015 2016
  24. 24. PROJECTED CONSLIDATED BALANCES 2010-2016 $20,000,000 Assets $15,000,000 $10,000,000 $5,000,000 $0 1 2 3 4 5 6 7 ($5,000,000) Liabilities ($10,000,000) 2010 2011 2012 2013 2014 2015 2016Financial Assumptions 2010-20161. $10 Million Private Placement2. Restructuring of bridge loans (all but $156K) has been effected in the Financials.3. Legal fees of $1.5 MM being settled for $600k.
  25. 25. 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
  26. 26. 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.
  27. 27. 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
  28. 28. Apogee Technology Inc. ConfidentialApogee Technology, Inc. Business Plan August 2011 1
  29. 29. Apogee Technology Inc. ConfidentialCertain 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. Theseforward-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, knownand unknown risks and uncertainties, which could cause the actual results, performance orachievements of the Company to be materially different from those that may be expressed or implied.Please refer to the Companys risk factors as set forth in the Companys filings with the Securities andExchange Commission, including its report on Form 10-KSB, as amended, for the year ended December31, 2008, as updated in its quarterly reports on Form 10-Q. The information contained in this pressrelease is believed to be current as of the date of original issue. The Company does not intend to updateany of the forward-looking statements after the date of this document to conform these statements toactual results or to changes in the Company’s expectations, except as required by law. 2
  30. 30. Apogee Technology Inc. ConfidentialThis business plan does not constitute an offer to sell or a solicitation of any offer to buy the securitiesto which it relates in any jurisdiction in which, or to any person whom, it is unlawful to make such anoffer or solicitation. Neither the delivery of this business plan nor any offer of sale made hereundershall, under any circumstances, create any implication that there has been no change in the informationset forth herein or in the affairs of Apogee Technology since the date hereof. This business plan contains confidential and proprietary information of Apogee Technology, whichis for the sole use of its intended recipient. Any unauthorized review, use, disclosure or distribution isprohibited. The financial projections in this business plan were developed by the management of ApogeeTechnology and are based on a number of assumptions, some of which are listed here. Theseassumptions include the timing and success of our future development efforts, acceptance of ourproducts, our ability to successfully implement our hiring goals, our average sales price, the size of themarket, our market share, general industry conditions and other matters. Although Apogee Technology believes that these assumptions are reasonable, they may beincomplete or incorrect, and unanticipated events and circumstances are likely to occur. The assumptionsinvolve significant elements of subjective judgment and analysis, and no representation can be made asto their attainability. The projected financial information has not been examined, reviewed or compiledby independent accountants. The projections were not prepared with a view to public disclosure and donot comply with the published guidelines of the SEC or any state securities commission or the guidelinesestablished by the American Institute of Certified Public Accountants. Actual results achieved during anyfuture 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 existingafter the date hereof or to reflect the occurrence of future events, even if the assumptions or estimatesunderlying the projections are shown to be in error. Prospective investors should not rely on, and will bedeemed not to have relied on, the projections in making an investment decision. 3
  31. 31. Apogee Technology Inc. ConfidentialCompany 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 preventionand 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 aredesigned to enhance biological activity of vaccines or drugs, and display synergistic effect whenintegrated with non-conventional administration routes, such as topical (intradermal) delivery usingmicroneedle enhanced patches. The technology has the potential to enhance protective immunityinduced by vaccines, simplify and decrease the cost of drug or vaccine administration, improve theefficacy of the treatment, and increase the product shelf-life. Apogee has established a strongintellectual property position through licensing and filing of several patent applications in the field andplans to extend it through the acquisition of Parallel Solutions, Inc. The Polyphosphazene approach canbe applied across a range of other disease areas and biomedical applications providing a broad andflexible 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 infectiousdiseases, cancer, and allergies using advanced immunopotentiating and microneedle deliverytechnologies - ImmunoMer H, ImmunoMer AH, and IgloPatch.TechnologyPolyphosphazenesPolyphosphazenes, 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 applicationsand also distinguish them from other classes of biomedical polymers. Firstly, the inorganic backbone iscapable of hydrolytical degradation, which can be modulated through the selection of the appropriateside group. Secondly, the unique synthetic pathway to these polymers, the so-called macromolecularsubstitution, allows a huge selection of substituents to be introduced by common organic chemistrymethods, 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 andsupramolecular assemblies create new opportunities for the interface with biological systems. 4
  32. 32. Apogee Technology Inc. Confidential DIVERSITY BIODEGRADABILITY HT COMPATIBLE INTERACTIVE Scheme 1. PolyphosphazenesPolyphosphazene ImmunoadjuvantsThe search for potent, well characterized, and safe vaccine adjuvants and delivery vehicles has beenwidely recognized as a key strategic factor in the development of new and improved vaccines [1]. In thisregard, an emerging class of well defined macromolecules, based on a polyphosphazene backbone(Scheme 2), offers a number of important advantages, both from immunostimulation and deliverystandpoints. Impressive immunopotentiation activity and dose sparing effects of these water-solublemolecules [2-11] are augmented with the ease of their assembly into supramolecular microparticulatestructures to achieve optimal delivery performance [12-17]. The synthetic origin of polyphosphazeneadjuvants and their well characterized molecular structures assure a high level of reproducibility andease 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 agood safety profile, which includes the results of clinical trials in humans, are among other advantagesof 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 ofphysiologically benign compounds [4, 21-23]. The commercial development of the lead compound issustained by the existence of a robust GMP manufacturing process and the availability of a drug masterfile to support regulatory applications. A substantial research effort has already been invested in thefield, including work in multiple animal models and with various antigens, both synthetic andmechanistic studies [2-10]. It becomes evident that the polyphosphazene adjuvant technology evolvesthrough the discovery of new, more potent derivatives [24-26], development of microparticulatedelivery 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 theirnon-polyphosphazene counterparts [3, 9], is still largely under discussion. It has been established thatadjuvant activity of PCPP is not associated with a depot formation, as the excision of the injection sitehad no detectable effect on the kinetics of antibody induction [7]. The adjuvant activity of PCPP appearsto be linked to its ability to form water-soluble non-covalent complexes with the antigen, a processwhich may enhance their interaction with antigen presenting cells [3]. This can be an important factor 5
  33. 33. Apogee Technology Inc. Confidentialtaking 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 innateimmunity 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 AdjuvantIntradermal ImmunizationSkin 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 thatprotect against infectious and chronic diseases caused by intra-cellular pathogens. The unique antigenpresenting function of skin draining lymph node DCs has been the focus of intense studies for thepurpose of vaccine development [27]. Intradermal vaccination approaches have a potential to facilitateinduction of more potent immune responses and provide the basis for a significant antigen sparingeffect [29-34]. The latter can be highly desirable during times of vaccine shortages, such as epidemicemergencies, and can also reduce the cost of vaccine manufacturing, which is especially important forexpanding vaccine use in less developed areas of the world [33, 35]. This could increase the possibility ofmass intradermal vaccination programs and result in major global health benefits, particularly in areaswhere access to healthcare personnel is an issue.Microneedle Technology for Intradermal Administration of VaccinesAlthough the intradermal immunization approach appears to be promising, its technical realization facessignificant challenges, such as special training of personnel who would be needed to administervaccinations through the intradermal route effectively [36]. Microneedles and micro-injection devices 6
  34. 34. Apogee Technology Inc. Confidentialcan provide a convenient alternative potentially offering ease of application and distribution, possibilityof self-administration and pain-free delivery [37].Apogee Technology, Inc. is engaged in the development of microneedle systems (Fig. 1), which utilizesub-millimeter structures to pierce the stratum corneum and deliver vaccines in the epidermis or dermiscompartments [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 theskin, these formulations dissolve to release vaccine antigen in the skin compartment. Solid vaccineformulations used in such systems are especially attractive since they also potentially offer improvedshelf life and reduced dependence on temperature-controlled supply chains [41, 42]. Thesemicroneedles can also potentially be self-administered and safely disposed of. Thus thetechnology can significantly reduce biohazardrisks and drastically lowers the cost ofdisposal as compared to contaminatedneedles and syringes.Polyphosphazene Immunoadjuvants forIntradermal ImmunizationA significant barrier on the way to a successfuldevelopment of microneedle vaccines is areliance of modern vaccine technologies onimmune-enhancing additives, i.e.,immunoadjuvants, to engender the desirableprotective immune responses [1].Unfortunately, many of the currentlyemployed vaccine adjuvants may not becompatible with intradermal deliveryapproaches. For example, alum, which is themost common adjuvant used in the vaccinemarket globally [1] and one of only twoadjuvants currently approved in the UnitedStates, was shown to induce serious adverseeffects, such as formation of granulomas, when administered intradermally [43]. Other advancedadjuvants, which contain biphasic systems, such as oil emulsions or liposomes, may not be sufficientlystable to withstand the microneedle coating and drying processes. Although there are clear indicationsthat intradermal immunization can potentially offer significant improvements over intramuscular 7
  35. 35. Apogee Technology Inc. Confidentialvaccination [37], it appears that the majority of studies have been conducted using non-adjuvantedvaccine formulations.Apogee Technology develops microneedle systems, which utilize polyphosphazene adjuvants, both asimmunostimulant and microfabrication material. Polyphosphazene polyelectrolytes are one of the mostremarkable classes of vaccine adjuvants due to their macromolecular nature, well-defined structure, andsynthetic origin and have demonstrated excellent immunomodulating potential when tested in multipleanimal 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] andPCPP formulated vaccines were reported to be safe and immunogenic in humans [45, 46]. Mostimportantly, the macromolecular nature of PCPP ensures excellent film forming and microencapsulatingproperties [12, 13]. It has been also demonstrated that PCPP can protect and stabilize vaccine antigens 8
  36. 36. Apogee Technology Inc. Confidentialduring the microfabrication process [48, 49]. PCPP is a water-soluble molecule, which can be formulatedwith proteins in aqueous solutions under mild conditions [3] and has the potential to be dissolved easilyin a highly hydrated environment, such as skin. Finally, dual functionality of such a molecule, as animmunoadjuvant and film forming/microfabrication material, eliminates the need for the use ofadditional macromolecular excipients and thus can potentially result in a higher vaccine loadingcapacity.Synergy between Polyphosphazene Immunoadjuvant and Microneedle Technology Creates NewApproach to Intradermal ImmunizationRecent studies conducted by Apogee have demonstrated that a macromolecular adjuvant, PCPP,exhibits potent immunoadjuvant activity when delivered intradermally and also enables efficientincorporation 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 Residual activity, % dose immunization (Fig. 2a). They also provide significant 100 antigen sparing ability (Fig. 2b). These results appear 80 especially significant as the anatomy of pig skin presents a 1 reasonable model for human skin [50]. In fact, a powerful 60 synergistic effect between microneedle system and polyphosphazene adjuvants observed in these 40 immunization studies requires further mechanistic studies focusing on the specifics of immunological pathways 20 associated with delivery to skin and the role of PCPP. 2 0 0 5 10 15 20 PCPP is not only compatible with solid state microneedle Time, days technology, but can potentially eliminate the need for Fig. 3. Residual enzymatic activity of inert “engineering” polymers, such as CMC, whose sole HRP encapsulated on microneedles (1) and in aqueous solution (2) during role is to serve as a microfabrication material. Since both accelerated thermal stability studies as immunostimulating and “engineering” functionalities can a f unction of time (80° C). now be integrated in a single compound - PCPP - the approach creates opportunities for maximizing antigendoses or achieving faster dissolution profiles using the same amount of the formulation. The results alsosuggest that PCPP can potentially provide surfactant-free or low surfactant coating solutions allowingmore flexibility in formulation development, which is especially important when high contents ofsurfactant are undesirable [42, 51].The micro-dip coating process utilized by Apogee is anticipated to be scaleable and inexpensive. Anumber of proprietary methodologies have been developed to assure accurate and reproducible dosingof the vaccine formulation [52]. The results of recent studies also showed no loss of activity in the 9
  37. 37. Apogee Technology Inc. Confidentialcoating process utilizing model protein compounds, which indicated high efficiency of encapsulation inthe process of microneedle fabrication [52].One of the most significant potential advantages of solid state microneedle technology, being developedby Apogee, is an expected improved shelf life of solid state formulations as compared to their solutioncounterparts. Stability of microneedles containing model biological, Horse-Radish Peroxidase (HRP) wascompared to the same enzyme in aqueous formulation at 80 °C (Fig.3). The accelerated degradationprofiles show a dramatic improvement in the stability of a solid state formulation as compared to HRP insolution [52]. As mentioned above, the stability and better shelf-life of the microneedle formulationscan 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 onunique polyphosphazene technology synergized with advanced delivery approaches. Our core expertiseis the development of novel biomedical, immunopotentiating and protein stabilizing polyphosphazenesand their integration into value added products. Due to high costs of vaccine development andregulatory approval, we intend to develop products thru partnerships, further licensing out applicationrights 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 forimmunopotentiators or advanced delivery systems. Under a partnership agreement we would jointlyinvest in the preclinical and, potentially, phase I/II clinical product development and then license themeither to a strategic partner or a third party for completion of clinical development, registration, andproduct marketing. These deals will generate multi-million upfront payments, milestones and doubledigit royalties. The company will also pursue licensing agreements with multinational vaccine producers thatare in the need of advanced immunopotentiators and delivery systems for multiple antigens. We wouldprovide rights to our intellectual property in exchange for license fees, milestone developmentpayments and royalties tied to product sales. Target deal profile may include exclusive or semi-exclusivearrangement, use with 3 to 6 antigens in defined field (infectious disease, allergy or cancer), upfrontpayment ($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 ofvaccines for developing countries. The Company anticipates these efforts to be subsidized, with apotential technology transfer fee upon completion of preclinical or clinical evaluation. Since, eachimmunopotentiator or delivery system can be used or tested with a variety of antigens, this provides anopportunity to generate valuable, including clinical data and benchmarking against competing systems 10
  38. 38. Apogee Technology Inc. Confidentialat little or no cost to the Company. Apogee intends to pursue similar opportunities for Public Healthvaccines 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 studiesand sell our rights to one or two leading companies in the field, generating significant short termrevenues targeting Q4 2012, which will allow us to more aggressively, pursue other high value addedpartnerships. Apogee has already initiated discussions with several potential partners. Apogee’s strategy forestablishing strong partnership deals include selecting antigens and animal models of relevance tovaccine developers, compatibility with other immunopotentiators and delivery systems, andbenchmarking 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 humanvaccines, ImmunoMer AH, immunopotentiating and antigen stabilizing polyphosphazene agent forparenteral and mucosal animal health vaccines, and IgloPatch, advanced immunopotentiatedmicroneedle patch for the application of vaccine to the skin. We plan to integrate these systems withnovel vaccine antigens in partnerships with industry leaders developing new vaccines, governmental andworld 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. 11
  39. 39. Apogee Technology Inc. Confidential 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 immunopotentiatingsystems with many proof-of-concept in vivo experiments already completed. Apogee anticipatesentering into the agreements on the co-development of these vaccines within approximately 6 monthsafter receiving funding and conduct preclinical and clinical development of Public Health and WorldHealth vaccines under the terms of appropriate funding from potential partners. 12
  40. 40. Apogee Technology Inc. Confidential Table 2. Identified Target Antigens1 A.K. Andrianov et al., Proc. Natl. Acad. Sci. USA, 2009, 106:189362 G. Mutwiri, in “Polyphosphazenes for Biomedical Applications” A.K. Andrianov, Ed., John Wiley & Sons,2009, 773 A.K. Andrianov et al., J. Pharm. Sci., 2011, 100 (4), 14364 K. Johansen, in “Polyphosphazenes for Biomedical Applications” A.K. Andrianov, Ed., John Wiley &Sons, 2009, 85 13
  41. 41. Apogee Technology Inc. Confidential In order to execute commercial development of ImmunoMer H, ImmunoMer AH, andpolyphosphazene related part of IgloPatch in the proposed timeframe, Apogee believes that it needs togain access to certain patents of Parallel Solutions, Inc. (PSI), which it plans to acquire upon receipt offunding proceeds. Intellectual property of PSI also includes other biomedical polyphosphazenetechnologies, such as therapeutic protein stabilization methods, which can be highly complementary toApogee’s microneedle system, IgloPatch, and can enhance characteristics of our patch systems for thedelivery of therapeutics. Upon acquisition of PSI, Apogee plans to seek externally funded partnership toconduct in vivo proof-of-concept studies of these technologies.Intellectual Property Apogee has already established a strong intellectual property position through licensing andfiling of several patent applications in the field. Patent application related to microneedle device, relatedcompositions and manufacturing methods was licensed from Georgia Institute of Technology (ProfessorM.R. Prausnitz):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; provisional No. 60/691,857 (06.17.2005), No60/732,267 (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 theuse of polyphosphazenes as intradermal immunopotentiator and as coating reagents for microneedletechnology.Methods and Systems for Coating a Microneedle with a Dosage of a Biologically Active CompoundA.K. Andrianov, A. MarinUS 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 andAsperities Coated with Such FormulationsA.K. Andrianov, A. MarinUS 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 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; provisional 61/125,576 (04.25.2008) and60/948,540 (07.09.07); PCT/US2008/008230 (07.03.08); Int. Publ. No. WO 2009/008988A1;EP20080779950. 14
  42. 42. Apogee Technology Inc. Confidential In order to execute commercial development of ImmunoMer H, ImmunoMer AH, andpolyphosphazene related part of IgloPatch in the proposed timeframe, Apogee believes that it needs togain access to certain patents of Parallel Solutions, Inc. (PSI), which it plans to acquire upon receipt offunding proceeds. Intellectual property of PSI also includes other biomedical polyphosphazenetechnologies, such as therapeutic protein stabilization methods, which can be highly complementary toApogee’s microneedle system, IgloPatch, and can enhance characteristics of our patch systems for thedelivery of therapeutics.Competitive Advantage There is an unmet need for new immunoadjuvants (immunopotentiators) and alternativeadministration routes for the delivery of vaccines. A major bottleneck in vaccine development is the lackof suitable adjuvants for adult and pediatric vaccine use. Until recently, vaccine research anddevelopment focused nearly exclusively on the antigen component of the vaccine that induces a specificimmune response in the body to protect against a particular disease. Contemporary vaccinesincreasingly rely on another component – immunoadjuvant, which does not induce the immuneresponse 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 andlonger-lasting protective immunity. Alternative delivery routes, such as intradermal vaccination, furtherhave a potential to simplify and decrease the cost of drug or vaccine administration, improve theefficacy 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 approvedASO4 for use in Cervarix HPV Vaccine (GSK Biologicals). MF59 (Novartis Vaccines), has been alsoapproved in Europe. All of these immunopotentiators are heterogeneous (biphasic) systems that areeither incompatible with many advanced delivery systems, such as microneedles, or reactogenic orinefficient when delivered intradermally or mucosally, important delivery modalities. Although there area 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 similarlimitations and may face other challenges in the approval process. Polyphosphazene immunopotentiators, PCPP and newer generation molecules have thefollowing 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; 15
  43. 43. Apogee Technology Inc. Confidential 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 biomedicalapplications, such as Zosano, Corium, Theraject, and 3M, however most of them focus on therapeuticapplications and lack compatible immunopotentiators. Published report by Zosano on the use of smallmolecule immunopotentiator (GMDP, not suitable as a microfabrication material), indicated that theadjuvant worked intradermally, but its effect was 10 times less than when it was used parenterally. Incontrast, Apogee’s system showed at least order of magnitude higher performance of polyphosphazeneimmunopotentiator 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. 16
  44. 44. Apogee Technology Inc. ConfidentialMarket Analysis Vaccine Market Overview Global Market for preventive vaccines: $22.1 billion in 2009* Others Predicted Growth: 9.7% * compound annual rate (next five years) ** Presence of current Top Pharma Companies** 2005 - 3 of 10 2009 - 8 of 10 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 The global market for preventative vaccines topped $22 billion in 2009 and is predicted toincrease at a compound annual rate of 9.7% during the next five years, as new product introductionscontinue and the use of current products expands further in all regions. Vaccines are commonlysegmented 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 vaccinesand this is expected to continue over the next five years. Geographically US will continue to lead thevaccines market followed by Europe. Japanese vaccine market has also started to open up further fromregulatory and political barriers. The large population in countries like India and China, high prevalenceof diseases and emergence of new pandemics are some of the important factors posting tremendousgrowth 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 billionfollowed by hepatitis B vaccines. The worldmarket of Hepatitis B Vaccine was $ 1.2 billion. Of the 350million to 400 million individuals worldwide infected with the hepatitis B virus (HBV), one-third reside in 17
  45. 45. Apogee Technology Inc. ConfidentialChina, with 130 million carriers and 30 million chronically infected. Pneumococcal vaccine (Prevnar) hascrossed the sales of US$ 1 Billion in 2007 and became the first vaccine to reach nearly US$ 3 Billionannual sales by 2009. Pneumonia is the worlds leading killer of children younger than 5 years, and isone of the foremost vaccine-preventable killers of children today. Every year, pneumococcal disease killsabout 1 million children worldwide. The Advanced Market Commitment (AMC) initiative forpneumococcal 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 GatesFoundation, 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 poliovaccines 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 themarket. 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 isexpected to grow with an annual rate of 12.08% percent from 2009 to 2015. Pharmaceutical Research and Manufacturers of America lists 145 vaccines under developmentin US only, to prevent a variety of infections. A large number of vaccines that are currently underdevelopment, both in US and worldwide, are designed to combat important emerging or neglecteddiseases, for which there is currently no preventive treatment. Norovirus infection, more commonlyknown as the “stomach flu”, is the most common cause of acute gastroenteritis in the U.S. A systematicreview of studies performed by the CDC estimated that norovirus causes an annual 64,000hospitalizations and 900,000 clinical visits among children in industrialized nations and up to 200,000death of children < 5 years of age in developing countries. Chlamydia is a common sexually transmitteddisease (STD) caused by the bacterium, Chlamydia trachomatis. Chlamydial infections in women, whichare 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 thegeneral U.S. population. Among young adults (aged 18–26 years) who participated in the nationallyrepresentative National Longitudinal Study of Adolescent Health (Add Health) during 2001–2002,chlamydia prevalence was 4.2%. A vaccine against recurrent vulvovaginal candidiasis (VVC) wouldbenefit a large number of women who suffer from this debilitating syndrome. The disease has asignificant effect on quality of life and poses a huge burden to the health care system. CDC estimatesthat 75% of women will have at least one episode of VVC, and 40%–45% will have two or more episodeswithin their lifetime. Approximately 10%–20% of women will have complicated VVC that necessitatesdiagnostic and therapeutic considerations. Global candidiasis therapeutics market was valued at $1.57bn in 2009. Hand, foot, and mouth disease (HFMD) is another common viral illness in infants andchildren caused by viruses that belong to the enterovirus genus of the picornavirus family. Althoughmost 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, pulmonarycomplications, and possibly death. HFMD caused by EV71 has become a major emerging infectious 18
  46. 46. Apogee Technology Inc. Confidentialdisease in Asia with approximately 1,155,000 new cases of HFMD in mainland of China only, and 353deaths. A number of commercial entities and academic groups are working on the development ofvaccines in these areas and Apogee’s immunopotentiating, delivery, and stabilization systems canpotentially play an important role in enabling these vaccines, accelerating their development, reducingrequired 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 includeAlphaVax, 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 betweenLivestock Vaccines (Porcine Vaccines, Bovine Vaccines, Poultry Vaccines, Ovine Vaccines, EquineVaccines, & Other Animal Vaccines) and Companion Vaccines (Canine Vaccines, & Feline Vaccines) withthe first representing the largest product segment of about 63% in 2006. Growth in the LivestockVaccines market is essentially driven by Porcine Vaccines market, which not only accounts for a majorityshare of the total market but is also one of the fastest growing segments. Revenues from porcinevaccines market are estimated to be approximately $1 billion mark in 2010. United States and Europecollectively capture more than 60% of the worldwide Veterinary Vaccines market. United Statescompanion animal vaccines market is estimated to be approximately $410 million in 2010. Europe is amajor market for veterinary vaccines and medicines across the globe. France, Germany and UnitedKingdom account for over 40% of the veterinary vaccine sales in Europe. Key players in the marketplace include Bayer HealthCare AG, Biogenesis-Bago, BoehringerIngelheim GmbH, Heska Corporation, Imugene Limited, Indian Immunologicals Ltd, Lohmann AnimalHealth, Merck & Co. Inc., Intervet/Schering-Plough Animal Health, Merial Ltd., Pfizer Inc., Embrex Inc.,Fort Dodge Animal Health, Virbac Corporation, among others.Operational PlanProgress to Date Since the start of our biomedical project, the Company has reached a number of importantmilestones 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 19
  47. 47. Apogee Technology Inc. Confidential 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 researchfacilities include a formulation and characterization laboratory (360 sq.ft.) and an additional 670 sq.ft. oflab support space.The analytical section of the laboratory is equipped with Hitachi LaChrom Elite High Performance LiquidChromatography (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/Visspectrophotometer (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 astereomicroscope (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 (models12620-982, 12365-82 VWR), a vacuum oven (model 1410, VWR), a refrigerated vapor trap (modelRVT4104 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 supplylines and manifolds (nitrogen, carbon dioxide and compressed air), B-Pure deionization and waterfiltration 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. TheCompany plans to enter at least 3 research and commercialization collaboration in Q4 2011 and Q1-Q2 20
  48. 48. Apogee Technology Inc. Confidential2012, one with the animal health vaccine company, another for a funded R&D collaboration with GlobalHealth or Government organization, and one with the commercial developer of vaccine of interest. Eachcollaboration envisaged will give the partner access to ImmunoMer for use with their antigens. Thesecollaborations are expected to provide significant cash flow to the company in the medium term. Basedon these and other collaborations, Company envisions one licensing agreement in Q4 2012, one in Q32013, and another in Q1 2014.Projected growthTo meet our stated objectives and deliverables the Company will need to add personnel, equipment andacquire additional laboratory and office space.Employees: We project our total staff will increase to 24 employees by 2016. In the business operationsgroup, significant emphasis will be placed on adding individuals with partnering capabilities, programmanagement, business development, and regulatory experience. On the R&D side, expertise will beadded in immunology, polymer and biochemistry, various areas of assay development, formulation andmanufacturing. The ratio of PhD to Technician (BS or MS level) for our laboratory staff will be roughly1:2. Many upstream capabilities will be accessed through the Company’s corporate alliances andthrough a strong network of outside advisors and vendors. 21
  49. 49. Apogee Technology Inc. Confidential Business Model Competition • Product developmentPolyphosphazene Company partnerships with pharmaceutical and biotechnology companies worldwide, license out application rights, maintain manufacturing Company Products Applications Customers Finances rights Polyphosphazene Celonova Bioscience Empolization Nanoparticles Physicians Private • IgloPatch Technology: (Peachtree City, GA) EmbozeneTM licensing coated stent multinational vaccine producers: PP model with • Exclusive arrangement for 3-6 antigensIntradermal Delivery/Adjuvant Companies • Upfront payment of $5 - $20 million Company • Milestone payments of $5 - $15 million per antigen Products Applications Customers Finances • 5 - 15% royalties on net product sales Pandemic Influenza Patch and Travelers Public-$500MM • ImmunoMer H Technology: licensing model with smaller vaccine producers Intercell Vaccines/Bacterial Diarrhea Vaccine Discovery- Market Market Cap Adjuvant or biotechnology companies: Patches Microneedles • Non-exclusive arrangement for 1-2 antigens Public-$61B Market 3M Multiple Clinical (plastic)/TLR Adjuvant Cap • Upfront paymentwith$1 - $2 million (“Access Fee”) Microneedles of • Private-$90MM NEA, Zosano Pharma Milestone payments of $1 - Osteoporosis PTH, EPO, GM- $2 million per antigen Phase II Numera • 10 -CSF/GMDP Adjuvant upon acquisition of vaccine by a multinational company 25% of proceeds • Microinjection Becton Dickenson 5 - 15% royalties on net product sales Soluble Vaccines On the market Public-$17B Market device/Alum Cap • ImmunoMer AH Technology:Small and large with Animal Health company collaboration MicroCor™ Micro Corium International molecular weight Private Private • Other: Delivery System collaboration with Global Health or Government organizations molecules generating technology transfer feesOther examples of Immunoadjuvants: AF03 (Sanofi Pasteur), ASO3 (GSK Biologicals), MF 59 (Novartis), IC31 (Intercell) 22
  50. 50. Apogee Technology Inc. Confidential Competitive Advantages • 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 23
  51. 51. Apogee Technology Inc. ConfidentialPartnering Company envisions one licensing agreement in Q4 2012, two in Q3 2013, and another in Q12014.Leverage external resources The Company does not plan to establish in-house capabilities to execute in-vivo evaluation ofour immunopotentiation and intradermal delivery. In addition to planned partnership, Apogee hasalready established collaborations with Children Hospital Boston, and can reactivate previouscollaborations 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 withgovernmental and university researchers provides a low cost (no cost) mechanism to investigatebroader applications of our platform.Government funding Apogee plans to apply for grant funding from Global health organizations and governmentalagencies to support preclinical and clinical development of its technologies. The Company has alreadyapplied this strategy in an ongoing collaboration with Children Hospital of Boston, which allowed to getsupport 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 2007for a microneedle technology with Georgia Institute of Technology.Financial model assumptions – Revenues: Apogee has already generated revenues external collaborations and believes it can continue andincrease generation of revenues from partnerships. In the early years, revenue is projected to comefrom milestone payments and royalties. Baseline business projections foresee the completion of 3corporate deals by early 2014.Each deal gives a partner the right to use PSI’s technology with the antigen of interest, although in theanimal health vaccine area we expect to give exclusive rights to our technology for livestock andcompanion market segments. The deal structure envisions a series of success-based milestones andsubsequent product royalties for each of the antigens. 24
  52. 52. Apogee Technology Inc. Confidential PROJECTED REVENUES AND EXPENSES 2010-2016$20,000,000 Revenues$15,000,000 Operating Loss/Gain$10,000,000 $5,000,000 $0 1 2 3 4 5 6 7 Total Expenses ($5,000,000)($10,000,000) 2010 2011 2012 2013 2014 2015 2016 25
  53. 53. Apogee Technology Inc. Confidential 26
  54. 54. Apogee Technology Inc. Confidential 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 27
  55. 55. Apogee Technology Inc. ConfidentialManagement TeamHerbert Stein, CEO and Chairman: Mr. Stein brings over fifty years of management experience toApogee and has served on the boards and in executive management positions at several life sciencescompanies, including as Chairman and CEO of Organogenesis.Paul J Murphy, Chief Financial Officer and Vice President of Finance: Mr Murphy has 25 years ofexperience as Chief Financial Officer of public and private companies. Prior to joining Apogee, MrMurphy was an independent contractor with JH Cohn, LLP, where he worked on engagements withpublic 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 ~20years of experience in the biotechnology industry having served as Chief Scientific Officer of ParallelSolutions, Inc., and in various management positions at Avant Immunotherapeutics and Virus ResearchInstitute Inc (VSI). He has unique expertise in polymer chemistry and is the inventor of thepolyphosphazene immunoadjuvant technology. Dr. Andrianov is an author of more than 60 scientificpapers 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 experienceas a faculty member in Moscow State University (MSU) and visiting scientist at Massachusetts Instituteof Technology (MIT) with Professor Robert Langer. 28
  56. 56. Apogee Technology Inc. Confidential 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 29
  57. 57. Apogee Technology Inc. ConfidentialAppendix 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(sodiumcarboxylatoethylphenoxy)phosphazene]. Biomacromolecules 2006;7(1):394-9.[3] Andrianov AK, Marin A, Roberts BE. Polyphosphazene polyelectrolytes: A link between the formation ofnoncovalent complexes with antigenic proteins and immunostimulating activity. Biomacromolecules2005;6(3):1375-9.[4] Andrianov AK, Sargent JR, Sule SS, Le Golvan MP, Woods AL, Jenkins SA, et al. Synthesis, physico-chemicalproperties and immunoadjuvant activity of water-soluble phosphazene polyacids. Journal of Bioactive andCompatible Polymers 1998;13(4):243-56.[5] Mutwiri G, Benjamin P, Soita H, Townsend H, Yost R, Roberts B, et al. Poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in miceimmunized 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 andmucosal 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. Vaccine1998;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 vaccinecandidates 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 fordiverse 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 andDelivery Systems. Hoboken, New Jersey: John Wiley & Sons, 2007: 355-78.[12] Andrianov AK, Chen J. Polyphosphazene microspheres: Preparation by ionic complexation of phosphazenepolyacids 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 aqueouspolyphosphazene solutions. Biomaterials 1998;19(1-3):109-15.[14] Andrianov AK, Chen J, Sule SS, Roberts BE. Ionically cross-linked polyphosphazene microspheres. ACSSymposium Series 2000;752:395-406.[15] Andrianov AK, Payne LG. Polymeric carriers for oral uptake of microparticulates. Advanced Drug DeliveryReviews 1998;34(2-3):155-70.[16] Andrianov AK, Payne LG. Protein release from polyphosphazene matrices. Advanced Drug DeliveryReviews 1998;31(3):185-96.[17] Andrianov AK, Marin A, Peterson P, Chen J. Fluorinated polyphosphazene polyelectrolytes. Journal ofApplied Polymer Science 2007;103(1):53-8.[18] Andrianov AK, Chen J, LeGolvan MP. Poly(dichlorophosphazene) as a precursor for biologically activepolyphosphazenes: Synthesis, characterization, and stabilization. Macromolecules 2004;37(2):414-20.[19] Andrianov AK, Le Golvan MP. Characterization of poly[di(carboxylatophenoxy)-phosphazene] by anaqueous 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 polyphosphazenepolyacids. Biomacromolecules 2004;5(5):1999-2006.[21] Andrianov AK, Marin A. Degradation of polyaminophosphazenes: Effects of hydrolytic environment andpolymer 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. 30
  58. 58. Apogee Technology Inc. Confidential[23] Andrianov AK, Payne LG, Visscher KB, Allcock HR, Langer R. Hydrolytic degradation of ionically cross-linkedpolyphosphazene 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 BiomedicalApplications. 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. JInvestig Dermatol 2004;124(1):1-12.[28] Mutwiri G, Benjamin P, Soita H, Babiuk LA. Co-administration of polyphosphazenes with CpGoligodeoxynucleotides strongly enhances immune responses in mice immunized with Hepatitis B virus surfaceantigen. Vaccine 2008;26(22):2680-8.[29] Holland D, Booy R, De Looze F, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal influenza vaccineadministered using a new microinjection system produces superior immunogenicity in elderly adults: Arandomized 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 forintradermal 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 responsesafter 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 electroporationdevice 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 influenzavaccine. 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 efficacyof a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine2009;27(3):454-9.[35] Weeratna R, Comanita L, Davis HL. CPG ODN allows lower dose of antigen against hepatitis B surfaceantigen 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 Med2004;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 immunizationvia micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nature Medicine2002;8(4):415-9.[39] Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters onimmunization 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 fortransdermal 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. CellPreservation Technology 2002;1(2):91-104.[42] Wang W. Lyophilization and development of solid protein pharmaceuticals. International Journal ofPharmaceutics 2000;203(1-2):1-60.[43] Vogelbruch M, Nuss B, Korner M, Kapp A, Kiehl P, Bohm W. Aluminium-induced granulomas afterinaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations. Allergy2000;55(9):883-7.[44] Andrianov AK. Water-soluble polyphosphazenes for biomedical applications. Journal of Inorganic andOrganometallic 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. Researchin Immunology 1998;149(1):19-23. 31
  59. 59. Apogee Technology Inc. Confidential[46] Kim JH, Kirsch EA, Gilliam B, Michael NL, VanCott TC, Ratto-Kim S, et al. A Phase I, Open Label, DoseRanging Trial of The Pasteur Merieux Connaught (PMC) Oligomeric HIV-1 Gp160mn/LAI-2 Vaccine In HIVSeronegative 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 1/2Comparative 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. JAIDSJournal 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 influenzavaccine displays improved stability and dose-sparing effect in lethal challenge studies. Journal of PharmaceuticalSciences 2011:n/a-n/a.[49] Marin A, DeCollibus DP, Andrianov AK. Protein Stabilization in Aqueous Solutions of PolyphosphazenePolyelectrolyte and Non-Ionic Surfactants. Biomacromolecules 2010;11(9):2268-73.[50] Monteiro-Riviere NA. Comparative anatomy, physiology, and biochemistry of mammalian skin. In: HobsonD, 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 humangrowth hormone. Journal of Pharmaceutical Sciences 1995;84(6):713-6.[52] Andrianov AK, DeCollibus DP, Gillis HA, Kha HH, Marin A. Polyphosphazene Immunoadjuvants forIntradermal Vaccine Delivery. In: Andrianov AK, editor. Polyphosphazene for Biomedical Applications. Hoboken,New Jersey: John Wiley & Sons, 2009: 101-16. 32

×