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TRANSFORMING HEALTHCARE THROUGH REVOLUTIONARY MEDICINES FOR AGEING DISEASES

www.angelicobiotech.com. TRANSFORMING HEALTHCARE THROUGH REVOLUTIONARY MEDICINES FOR AGEING DISEASES. "We are entering a period of time where many of the smaller biotech companies have been around for ten years, and they are starting to get their products past the goal line“

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TRANSFORMING HEALTHCARE THROUGH REVOLUTIONARY MEDICINES FOR AGEING DISEASES

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  1. www.angelicobiotech.com TRANSFORMING HEALTHCARE THROUGH REVOLUTIONARY MEDICINES FOR AGEING DISEASES

  2. "We are entering a period of time where many of the smaller biotech companies have been around for ten years, and they are starting to get their products past the goal line“ Dr. Kris H. Jenner, portfolio manager T. Rowe Price Health Sciences Fund (T. Rowe Price is managing more than $269 billion in assets) "When they write the history of the world this will be mankind's greatest moment when we actually harnessed and got the understanding of life and used the understanding of biology to be transformative: it will improve environment ,it will improve health. We will theoretically live forever. It will improve the quality of our life while we are living . It is a fabulous time to be alive and it is a fabulous time to be in this industry". Steven Burill, CEO Burill & Company (Burill & Company has $900M in life sciences assets under management) " Dream as if you'll live forever. Live as if you'll die today. “ James Dean Two-time Oscar-nominated American film actor.

  3. The promise of revolutionary medicines for ageing diseases Scientists managed to extend the lifespan of C. elegans by nearly 10 times. A group of scientists from the University of Arkansas for Medical Sciences has shown that a mutation in gene that is similar with the gene that humans have (gene that does insulin-like signaling) extends lifespan of C. elegance by nearly 10 fold extension of both median and maximum adult lifespan.

  4. Some of the scientific breakthroughs that made life extension possible 1908 The Nobel Prize in Physiology or Medicine - in recognition of their work on immunity. IlyaIlyichMechnikov, Paul Ehrlich 1965Discovering that human cells divide for a limited number of times in vitro (refuting the contention by Alexis Carrel that normal body cells are immortal). This is known as the Hayflick limit. Leonard Hayflick Ph.D., is Professor of Anatomy at the University of California, San Francisco, School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. 1992 The Nobel Prize in Physiology or Medicine for discoveries concerning reversible protein phosphorylation as a biological regulatory mechanism 1993The Nobel Prize in Physiology or Medicine for their discoveries of split genes 1994The Nobel Prize in Physiology or Medicine for their discovery of G-proteins and the role of these proteins in signal transduction in cells 1995The Nobel Prize in Physiology or Medicine for their discoveries concerning the genetic control of early embryonic development 1996The Nobel Prize in Physiology or Medicine for their discoveries concerning the specificity of the cell mediated immune defence 1999The Nobel Prize in Physiology or Medicine Gьnter Blobel for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell (He is on the board of advisors of our portfolio company).

  5. 2001 The Nobel Prize in Physiology or Medicine Leland H. Hartwell, Tim Hunt, Sir Paul M. Nurse for their discoveries of key regulators of the cell cycle 2002The Nobel Prize in Physiology or Medicine Sydney Brenner, H. Robert Horvitz, John E. Sulston The Nobel Prize in Physiology or Medicine for their discoveries concerning genetic regulation of organ development and programmed cell death 2006The Nobel Prize in Physiology or Medicine Andrew Z. Fire, Craig C. Mello The Nobel Prize in Physiology or Medicine 2006 for their discovery of RNA interference - gene silencing by double-stranded RNA 2007 The Nobel Prize in Physiology or Medicine Mario R. Capecchi, Sir Martin J. Evans, Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells 2007 Making Skin Cells Into Stem Cells. Kyoto University’s Yamanaka and a University of Wisconsin team led by Junying turned human skin sells into embryonic stem cell equivalents. 2009 The safest way yet to make stem-like cells using a patient's ordinary skin cells, this time by using pure human proteins was developed by a team at Harvard University and Massachusetts-based Advanced Cell Technology Inc. Dr. Robert Lanza of Advanced Cell sees almost immediate commercial applications. He said the company would seek Food and Drug Administration permission to test the cells in people by next year. This technology is leading to the revolution in medicine and in theory will allow grow-your-own transplants with no risk of rejection and much more.

  6. Technology push: Beginning the 2nd Half of the Gartner Curve 2009 Obama removes the «partial ban» on HESCs Visibility 2001: 3300 jobs, 73 firm, mkt cap > $2.5 billions 2000 Time Magazine: TE №1 job 2001 Ortec FDA approved 2001 TE blood vesel enter clinic 2001 Dermagraft FDA approved 2002 ISSCR founded 1999 Intercifex founded 2003 UK Stern Cell Bank set up 2005 CIRM founded 2006 Carticel – 10 000 patients 2006 hESCs derived without harming embryo 2006 Batten’s Disease trial 2006 Reneuron file IND for stroke trial 2007 Apligraf – 200 000 patient therapies 2007 Human iPSCs Derived 2007 Intercytex start Phase 3 ICX Pro 2007 $1.2M+ Patients Treated 2007 $1.5B RM Product Revenues 2007 800 FDA Clinical Trials Ongoing 2007 50 Public Companies: $4.7B Mrkt Cap 1999 TE bladders in clinic 1999 First TE product FDA approved (Apligraf) 2002 Bush «partial ban» on HESCs 1998 Plan to build human heart in 10 years 1998 Human ESCs first derived 1997 Dolly the Sheep 1997 First cell therapy FDA approved (Carticel) 1992 Geron founded 1988 SySternix founded 1986 ATS & Organogenis founded 1985 Team TE coined 2002 ATS + Organogenesis file Chapter 11 Time 1980 Early TE research (MIT)

  7. Human Genome Project Human Genome Project (HGP) Completed in 2003. HGP the was a 13-year project coordinated by the U.S. Department of Energy and the National Institutes of Health. During the early years of the HGP, the Wellcome Trust (U.K.) became a major partner; additional contributions came from Japan, France, Germany, China, and others. See our history page for more information. Project goals were to identify all the approximately 20,000-25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA, The Human Genome Project took 10 years and cost $3 billion USD  Celera genome sequencing project took two years and cost just $300 million USD Gene sequencing costs have been dropped exponentially since the sequencing of the human genome in 2000. In 2001, the genome sequencing of James Watson, a co-discoverer of the structure of DNA, was completed at a cost of $2 million USD. In 2008, the first full genome sequencing services were sold commercially to customers for a cost of $100,000 USD. By March 2008, one company, Applied Biosystems, completed a human genome sequencing in two weeks for $60,000 USD, the best cost yet. Another company, Intelligent Bio-systems, has developed a system that can sequence a full human genome in 24 hours for $5,000 USD. A price has been offered for the first to sequence 100 human genomes for $10,000 USD each in ten days or less. The $10 million USD prize, donated by diamond prospector Steward Blusson, will continue to be available until the deadline of 4 October 2013. Many scientists around the world think it is highly likely that the prize will be claimed before the deadline, probably substantially before.

  8. If the cost of genome sequencing falls below $1,000 USD, or better yet, $500 USD, many futurists have predicted qualitative changes in the way we do medicine. If millions of genomes are sequenced and made publicly available, the potential knowledge to be gained for the science of genetics would be massive. Cancer Genome Project Cancer is now understood to include more than 200 different diseases. In all forms of cancer, genomic changes cause disruptions within cellular pathways that result in uncontrolled cell growth. One in three people in the Western world develops cancer. One in five will die of the disease. Cancer is, therefore, the most common genetic disease. The Cancer Genome Project seeks to explore the entire spectrum of genomic change in cancer through the application of genome analysis technologies, including large-scale genome sequencing. The Cancer Genome Atlas Pilot Project (TCGA), was initiated in 2006 to identify important genetic changes involved in lung, brain, and ovarian cancers. TCGA is a comprehensive effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, especially large-scale genome sequencing. The project will delve more deeply into the genetic changes leading to origins of this complex set of diseases and, in doing so, will enable new discoveries and tools that will provide the basis for a new generation of cancer therapies, diagnostics, and preventive strategies.

  9. In the last 5 years large pharma lost half of it’s value

  10. Success in biotech investing Capitalization 48.71B This slide is created by Angelico and is about Amgen. It not endorsed by or affiliated with Amgen.  Amgen is a leading human therapeutics company in the biotechnology industry. For more than 25 years, the company has tapped the power of scientific discovery and innovation to advance the practice of medicine. Amgen pioneered the development of novel products based on advances in recombinant DNA and molecular biology and launched the biotechnology industry’s first blockbuster medicines. Today, as a Fortune 500 company serving millions of patients, Amgen continues to be an entrepreneurial, science-driven enterprise dedicated to helping people fight serious illness.

  11. Success in biotech investing In just over 20 years, Gilead has become one of the largest biopharmaceutical companies in the world. Gilead’s primary areas of focus include HIV/AIDS, liver disease and serious cardiovascular and respiratory conditions. Company has a portfolio of 12 market leader drugs including the first single-tablet regimen for HIV infection and  the treatment of chronic hepatitis B. In 2008, Gilead’s annual revenues surpassed $5.3 billion. BusinessWeek  has ranked Gilead #1 in its 2009 listing of the 50 best-performing companies, up from #2 last year. Capitalization 40.04B This slide is created by Angelico and is about Gilead. It not endorsed by or affiliated with Gilead. 

  12. Success in biotech investing Capitalization 19.03B Revenue 2.4B

  13. Success in biotech investing Capitalization 4.5B Revenue 2.05B This slide is created by Angelico and is about Cephalon. It not endorsed by or affiliated with Cephalon. 

  14. Success in biotech investing This slide is created by Angelico and is about Dendredreon. It not endorsed by or affiliated with Dendredreon. 

  15. Market After 40 years of development, regenerative medicine (RM) technologies are maturing and the market is at a key inflection point. Driven by a technology push from the RM programs now proliferating at major universities throughout the world and a market pull from large Pharmaceutical companies seeking to fill their diminishing pipelines, the field is poised for rapid expansion. Fueling this expansion are the demographics of an aging population seeking cures for many previously incurable degenerative diseases, like diabetes, heart disease and Parkinson’s disease. The key metrics confirm the opportunity: • 80+ RM research programs in universities around the world • 400+ private RM companies and more are formed every month • 30+ public RM companies • 800+ ongoing FDA clinical trials involving RM technologies The current market for Regenerative Medicines is $5.5B, and it is projected to reach $11.5B in 2010 for a projected CAGR of 27.5%. The DHHS predicts that the market for Regenerative Medicines will reach $300B by 2020. Life Science Intelligence (LSI), predicts that the largely untapped global market potential for tissue engineering and regenerative medicine products will exceed $118 billion by 2013. The world skin care market had sales of $65.7 billion in 2007, up 40% from 2002 (and up 7% from 2006 ) Within facial care, anti-aging products were the fastest growing with 67% growth from 2002-2007 to reach $14.9 billion in 2007 Cell Culture Tools Market: Coatings & Additives. The size of the market in 2005 was estimated to be $714.5 million. Forecasted to grow to $1.2 billion by 2012 Tissue Engineering Market / Tissue Regeneration patches for Wound Care, Hernia Repair, Pelvic Floor Repair, Rotator Cuff/Ligament Repair, Periodontal There are approximately 700,00 hernia repairs yearly. There are over 230,000 rotator cuff repairs yearly. Approx. 500,000 operations for Pelvic Floor Repair US hair regrowth market is estimated at $2.5 billion . Current obesity products totaling sales of around US$0.5.1 billion. Lack of significant efficacy and medical rationale, along with unacceptable side effects. Type 2 diabetes US$10+ billion market in the key markets worldwide. Alzheimer's market exceeds US13 billion USD. The total global value of the medical devices market is estimated to be more than $165 billion in 2006, with annual growth at 5.5% World pharmaceutical market is over $1 trillion. Despite the maturation of RM, the industry has been underserved by the venture capital community. Concerns about political risk, and the length of the technology development cycle have caused most VC’s to stay out of the field. We believe that the political risks are diminishing, and the extraordinarily rapid pace at which the technology is developing mitigates the technology risk. This market dislocation presents a very attractive investment opportunity, which we will exploit.

  16. Market Annual sales growth in biotech industry has been approx. 29,55% for the last 5 years. Annual sales growth in pharmaceuticals industry has been approx. 7,71% for the last 5 years.  EPS growth in biotech industry has been approx. 38,57% for the last 5 years.  EPS growth in pharmaceuticals industry has been approx. 6,55% for the last 5 years. A total of 199 mergers and acquisitions were announced in the health care industry during the first quarter of 2009, based on preliminary figures, however, a total of $127.4 billion was committed to fund the first quarter’s M&A activity, the highest level of dollars ever spent during a single quarter. This breaks the previous record of $118.4 billion set nearly 10 years ago in the fourth quarter of 1999. The health care technology segment attracted the largest amount of capital, capturing nearly 99 cents out of every dollar invested in health care M&A. The major driver of this activity was the Pharmaceutical sector, which by itself accounted for 89% of the first quarter’s dollar volume. • Key market drivers for medicines for ageing diseases: • Diminishing populations of developed countries • Aging population of successful business people • Large unmet medical needs • Increased healthcare spending • Government funding increasing • Large pharmaceutical companies pipelines diminishing • 80+ Academic Programs Worldwide Pharmaceutical Market by Sectors through 2008  ($ Billions)

  17. Big Pharma Faces Tidal Wave of Patent Expirations

  18. It takes one good drug to make over $4 billion in sales revenues

  19. Large pharmaceutical companies buy biotech companies to make up for a scarcity of new medicines and expiring patents for best-selling products $720 M $68 bn $90.8 bn Sirtris is focused on discovering and developing proprietary, orally available drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Its drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that control the aging process. $725 M Dimebon made in Russia $6.5bn $550 M $64 M $85 M $300 M $41 bn $15.6bn $800 M

  20. Public Markets Are Rewarding Clinical Progress

  21. Big Pharma is Actively Engaged GSK & HSCI $25M Deal Merck, Pfizer & Lilly Launch Enlight Bioscience Pfizer Forms Regenerative Medicine Division GSK, AZN (AstraZeneca) & Roche Help Launch Stem Cells for Safer Medicine in UK Johnson&Johnson invest in Tengion & NovoCell

  22. Market Regenerative Compounds: already 50% of Biotech Sales

  23. Population ageing is bad for the nations Population growth rates. CIA World Fact Book • USA • Aging population threatens USA’s "AAA" credit rating • Korea • Currently one of the youngest populations out of all OECD countries • By the middle of this century it will have one of the oldest • Around half of all workers will be aged 50 and over • Population ageing will lead to a slowdown in labor force growth • Within 20 to 30 years the labor force may begin to contract • Australia • Coastal regions will experience growth of 210% in the number of seniors between now and 2045. Inland regions will also experience significant growth in the number of seniors with 179.7%. With the delivery of human services now representing 49% of total local • government expenditure, local councils are more likely to face budgetary pressures from population ageing than from traditional activities such as road and infrastructure provision • and maintenance.

  24. Population as a competitive advantage Things don’t look good for Europe

  25. Populations decline 2009

  26. Government & NGO’ support • Obama gives green light to stem cell research • Anti-ageing organizations in the USA and the rest of the world are becoming more active • NIH grants heavily towards developing novel cures for age related diseases • Most of the governments have developed plans to foster development of biotech clusters by tax incentives and investment.

  27. Revolutionary medicines for ageing deseases A Broad Field: 8 Key Sectors Cell Therapies Heart Diseases Diabetes Vision Disorders Neurological Disorders Tissue Engineering Organ Replacement Tissue Regrowth Bone & Cartilage Wound Healing Regenerative Compounds Compounds that trigger endogenous regeneration Anemia Advanced Wound Healing Advanced Fracture Healing Drugs Vitamins & Supplements Healthy foods Diagnostics, Tools & Devices Delivery Devices Cells Assays for DD&D Predictive Toxicology Bioinformatics Aesthetic Medicine Dermal Fillers Hair Restoration Anti-Aging/Anti-Wrinkle Tooth Regeneration

  28. Why the Time to Invest is Now Companies Emerging to Fill the Gap Technology Push Market Pull Technology maturing after 40 years of Development Research program proliferating: 80+ Technology maturing Clinical activity accelerating (800+ FDA trials) Increased Government Funding Healthcare spend is 17% of US GDP Heading Towards 23% Demographics: aging populations Large unmet medical needs Pharma pipeline diminishing Public markets receptive 400+ companies

  29. Investment Process Overview Angelico systematic approach leads to… Substantial Proprietary Deal Flow Industry Leadership Extensive Network Proprietary Database Identify Best Opportunities 1. Proprietary Deal Flow Rigorous Due Diligence Process 2. Due Diligence & Deal Structuring Initial Screen &Primary Due Diligence Structure Deal to Maximize Returns & Minimize Risk Deep Due Diligence Build Value trough Active Management Build Team & Construct Optimal Business Model 3. Build Company Value & Maximize Exist Structure Exit to Maximize Value Drive Execution & Manage Risk … greater value for our portfolio companies & higher returns for our LPs.

  30. Angelico Investment Approach Deal Flow Due Diligence Build Value Competitive Land- -scape Size of Market External Ecosystem Analysis Options To Enhance Value Unmet Need TargetSegment/ Approach Top Down Strategy Companies Proprietary Database Build Company Value Universities Company Selection Intellectual Property Bottom Up Strategy Target Companies Clinical Trials Internal Company Analysis Drivers Of Value Patents / IP Universities

  31. Investment Selection Criteria • Outstanding scientist recognized by Nobel prize award and/or large NIH grant • Scientific advisory board is excited about the technology 3. Technology market screening has shown that our scientist is the leader in this technology and that there is no evidence that this technology will not work but on the other side all evidence shows the contrary • There is a substantial over $1 bln market for this technology and a strong market demand for the product or services • Technology must be disruptive: far ahead of all existing technologies • Technology must prolong maximum life span by 1/3 and more • In general, most of the investments are expected to be in the startup through mezzanine stage. The largest number of investments are targeted to Series A and B rounds, and we do invest in public entities.  • Angelico principally invests in the United States and Europe, but has strategic interests globally. The average investment made by Angelico is $1-5M over the life of any one company. Angelico professionals almost always serve on the Board of Directors of each portfolio company, and assist with operational activities

  32. Science Gets Funded + 1972 Alcor Life Extension Foundation, L. Ellison - 10M for a company that studied centurions, O. Deripaska - 16M for SkQ project, T. Artemiev – 1M undisclosed, P. Thiel – 3.5M, May 2009, energy sector investor - 4M undisclosed

  33. Recent Pre-clinical Licensing Deals The Marketplace

  34. Success in Longevity Drug Investing “Alzheimer’s Disease drug sales can easily surpass $13 billion in sales of Pfizer's cholesterol drug, Lipitor, to become the biggest drug of all time.“ According to health-care investor Larry Feinberg, whose flagship health-care hedge fund has averaged 21% over the past 18 years Medivation is getting a healthy $225 million in upfront cash, potential future milestone payments of $500 million or more, plus 40% of any profits on Dimebon if approved in the U.S. and royalties on its sales elsewhere in the world. Medivation will be responsible for 40% of the U.S. development and commercialization expenses. $725 M Dimebon made in Russia 2008deal

  35. Team Built to Succeed in Creating Revolutionary Medicines for Ageing Deseases Technology Team Maxim Skulachev Stan Polozov Eugeny Nudler Alexey Ryazanov Konstantin Severinov Business Team Ed Kanalosh Yury Oreshin Science Finance Regulatory Operations • Science/Technology • Broad Expertise in medicines for ageing diseases • Conducting pioneer research • Deep academic ties • Regulatory • Nuanced understanding of clinical trial design within the context of medicines for ageing diseases • Operations • Extensive management experience in large pharma • McKinsey background • Finance • Build a pharma business from $10M to 100M in sales and sold it for 100M to a strategic investor

  36. Scientific Advisory Board Evgeny Nudler, Ph.D. Evgeny is a Molecular Biology professor at New York University. Evgeny operates New York University and Geron Lab research facilities, where Evgeny’s research is focused on searching for substances with small molecules that prolong life. Excellent results have been produced: the regular life span of nematodes has more than doubled and Evgeny is working on reproducing the effect in mammals. Evgeny is an author of more than 30 publications on molecular biology in the most prestigious scientific journals. At 25 Evgeny became the youngest professor of New York University. Evgeny’sGeron Lab research facility was financed by the Dynasty Foundation that belongs to the founder of the leading cellular operator in Russia VimpelCom (NYSE: VIP). Alexey Ryazanov Ph.D., D.Sc. Alexey is a professor of Pharmacology at University of Medicine & Dentistry of New Jersey - Robert Wood Johnson Medical School and a member of The Cancer Institute of New Jersey. Alexey is an honorary recipient of numerous National Institutes of Health (NIH) grants including most recent $10M grant for developing a new approach to treat chronic diseases . Alexey has discovered a novel type of the signaling proteins that play a key role in the regulation of magnesium homeostasis in the cells. Understanding how those proteins function could lead to new treatments for a wide range of conditions, including heart, kidney and neurological diseases. Alexey is also the founder of Longevica Pharmaceuticals Inc. with a patented technology that prolongs life of mammals.

  37. Investment Team Ed Kanalosh MBA, M.D., Ph.D. Ed is the honorary chairman of ANGELICO Biotechnology Investment Fund. Ed has been Vice-President of Investment Bank Trust, a large Moscow-based investment bank. His carrier included McKinsey & Co, Private Equity Funds: QuadrigaCapital and Steinberg Fund, Bill and Melinda Gates Foundation, MPP/ Pharmatec, SmithKline Beecham Pharmaceuticals, Pharmacia & UpJohn. Ed has worked on a wide variety of financing transactions, including M&A and LBO. Ed graduated from Harvard Business School with an MBA, got his Ph.D. from the National Medical University, and M.D. from Kiev Medical Institute. Andrey Mladentsev MBA Andrey is the Senior Partner of ANGELICO Biotechnology Investment Fund. Andrey has been several times nominated as the best CEO in Russia and he is known to be the best CEO in the pharmaceutical sector. Andrey increased the revenues of the pharmaceutical company Nizhpharm from $19M in 1999 to $124M in 2007 and successfully sold the company to the German pharmaceutical company STADA AG for 80,5M EUR including his own stake. Andrey has been also the Vice President of STADA AG and Deputy of the Head of the Russian Drug Administration. Andrey got his MBA at IEDC Bled School of Management.

  38. Investment Team Yury Oreshin Yury is the CEO and founder of ANGELICO Biotechnology Investment Fund. Prior to launching ANGELICO, Yury has been an Investment Banking Director at Art Capital investment group, Advisor at London based investment banking boutique Edelau and a Sales Director at IBMED, a stem cell research and medical center. Yury holds his Bachelor of Science in Business Administration degree from the University of South Carolina.

  39. Venture Partners Business Advisory Stan Polozov Stan  is a venture partner of ANGELICO Biotechnology Investment Fund. Prior to joining ANGELICO, Stan has been conducting research in the area of molecular biology and genetics focusing on anti-ageing for over 6 years. Stan is an inventor of 3 life extension technologies. Stan is also an owner of electronic manufacturing company Comforta ltd. Stan holds a Masters degree in Molecular Genetics from the Kyiv National Taras Shevchenko University, and did his practice work in Molecular Medicine at Hannover Medical School in Germany. Radka Milanova, Ph.D.  With over 15 years of experience in the pharmaceutical industry Dr. Milanova possesses expertise in the leadership of drug discovery and development programs, technology assessment, licensing, and manufacturing. Throughout her career she has also served as a senior officer in companies like Forbes Medi-Tech and IGT Pharma, a board member of several companies and a member of technical and grant approval committees. As a Director and senior manager, Dr. Milanova has been involved with the due diligence process for several licensing activities as well as technology transfer and commercialization. She has been responsible for the technology transfer and upscaling of the multibillion steroid intermediates AD and ADD with generic pharmaceutical manufacturers in Europe and North America. Dr. Milanova negotiated and completed the first venture funding for LinkCore with a UK venture group, secured additional private financing and completed the licensing of LinkCore’ first technology XC-1100.

  40. Pre Angelico Experience

  41. Our Deal Pipeline Geron Lab GeronLab is a high-end research laboratory focusing on basic and applied studies in the area of aging. We design technologies to delay normal aging and postpone the onset and progression of age related diseases. The ultimate goal is to understand the basic molecular mechanisms of human aging and develop drugs that could slow down this process and also delay/treat age-related diseases such as atherosclerosis, neurodegenerative diseases, cancer, etc. Structure: GeronLab exists as a private biomedical laboratory based in Moscow. It supervises and coordinates studies performed in several research institutes, including the State Research Institute of Genetics (Moscow), Institute of Molecular Biology (Moscow), Biomedical Department of the Moscow State University, Institute of Cell Biophysics (Puschino) and New York University (USA). Team: Principal Investigator and Director - Evgeny Nudler, PhD, Professor of Biochemistry (NYU). Senior Research Stuff: Prof. Alexander Mironov (SRIG); Prof. Mikhail Evgen’ev (IMB); Prof. Ivan Gusarov (NYU); Dr. NataliyaBobkova (ICB); Research Stuff: 15 people (multidisciplinary PhD/MD team). Major Preclinical Results: 1) Treatment for the Alzheimer’s disease (AD). AD is a prevalent neurodegenerative illness affecting millions of people worldwide. Currently, there is no effective therapy to prevent or halt the progression of the disease, although symptomatic treatments are available. We have developed a rodent model of sporadic AD, which induces AD-like behavioral and neurochemical features including spatial memory impairment, regional loss of neurons, a cholinergic deficit and increased brain beta-amyloid levels. Using this model we screened for neuroprotective molecules and found a polypeptide, witch prevented AD-related memory loss and regional neuronal degeneration after intranasal administration. Moreover, the polypeptide significantly extended the lifespan of both AD and healthy animals (mice and rats). We are preparing the patent application to cover this technology and looking for partners to move the technology into clinics. 2) Anti-aging therapeutics. We have developed the high-throughput screen of small molecule compounds that extend the lifespan of a round worm (nematode) Caenorhabditiselegans. C.elegans is a well-established animal model to study aging mechanisms. It has a short lifespan (~2 weeks) and is easy to maintain and manipulate genetically. Many genes that control normal aging are conserved in evolution. Mutations that prolong life of C.elegans do so in yeast, flies, mice, and humans by affecting the same genes. Consistently, small molecules that have been shown to extend the lifespan in C.elegans (e.g. resveratrol) do so in yeast and mice. Therefore, C.elegans represents the most convenient live test system for screening libraries of small molecule compounds for their ability to slow down the aging process. In the last two years we have identified several such compounds that increased the average and maximum lifespan of the worm for more than 2 times which is significantly greater than any previously reported pharmacological effects. Some of those compounds are known drugs and/or supplements that have been used in clinics for unrelated indications. We are planning to evaluate the most potent compounds from the screen in mice to establish their anti-aging effect in mammals. Financial Information: Capital Raised – 1,300,000; Capital Seeking – 2,000,000.

  42. Our Deal Pipeline Longevica Pharmaceuticals Inc. Longevica is a new, privately held biotechnology company engaged in the development of novel, proprietary drugs with potential utility in treatment of cancer, degenerative diseases (Alzheimer’s and Parkinson’s diseases), and other ageing-related disorders. The company was formed to commercialize the discoveries demonstrating that inactivation of an alpha kinase EF2K protects normal (non-cancer) cells and tissues from the toxic effect of chemotherapy, and can retard aging. These discoveries lead to a novel approach in cancer therapy that can significantly improve the efficiency of the current methods of cancer treatments and have a strong and reliable commercialization potential. The discoveries of the functional significance of EF2K made by Longevica’s founder Dr. Alexey Ryazanov, are leading to the development of small molecule EF2K inhibitors capable of specifically protecting normal cells from toxic effect of chemotherapeutic treatment of cancer. Additionally, EF2K inhibitors are expected to have utility in treatment of patients suffering from ischemia, stroke and neurodegenerative disorders by protecting cells and tissues from stress damage. It was also demonstrated in a mouse model that inactivation of EF2K can significantly extend lifespan and delay the onset of menopause. Management. Longevica was founded by Dr. Alexey Ryazanov, a Professor of Pharmacology at the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey. Professor Ryazanov will serve as Longevica’s President while retaining his academic appointment at RWJMS for the near future. Intellectual Property (IP). Longevica has acquired an exclusive license for the technology developed in Dr. Ryazanov’s laboratories from the University of Medicine and Dentistry of New Jersey, embodied in five patents (issued or applied for). Longevica will hold exclusive rights to the above technology and patent applications relating to all subsequent developments made by Dr. Ryazanov and colleagues relevant to the company’s core technology. Financial Projections. Longevica is planning to use financing from the Foundation Venture Capital Group, NIH grants and investors to support the preclinical development of its first product, a specific EF2K inhibitor, for cancer therapy. This would support R&D operations for the first two years, when Longevica intends to submit an investigational new drug (IND) application for its first therapeutic product for cancer patients undergoing chemo- and/or radiation therapy. Longevica believes that this first product could enter the market in 2012. Taking into consideration the universal use of the product as a supplement to the most of existing chemotherapy treatments and consequently a very wide market coverage and even by conservative estimate, the sales of the drug could reach hundreds of $ MM in US and worldwide sales, in the first years after launching. Longevica is also developing an oral EF2K inhibitor that can be used to prevent Alzheimer’s desease, delay menopause, and as a general anti-aging medication.

  43. Optimal Exit at Phase 2 on Risk Adjusted NPV

  44. Summary of Angelico Value Proposition Revolutionary medicines for diseases of ageing are transforming healthcare Science moved at extraordinarily rapid rate Technologies are at a key infliction point Large and growing markets driven by demographics VC firm built from ground up to focus exclusively on medicines for diseases of ageing Team’s skills address all the major challenges to commercialization Proven record of success Existing pipeline 1st mover advantage: critical for IP, freedom to operate, knowledge base, best teams & deals Solid investment strategy Substantial quality proprietary deal flow Rigorous comprehensive due diligence process Build value through active management Develop big pharma relationships from the earliest stages Timely exits

  45. Year 7 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Q1 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 OL Development Technology 1 $12 - 30M OL Development Technology 2 OP IL $12 - 30M OL Development Technology 3 OP IL $12 - 30M OL Technology 4 OP Development IL $12 - 30M OL OP Development Technology 5 IL $12 - 30M OL OP Development Technology 6 IL $12 - 30M How We Plan to Progress

  46. Conservative Scenario Illustrative Projected Cash Flow on Investment

  47. Contacts Contact person: Yury Oreshin, CEO Angelico Biotechnology Investment Fund9-105 Esseninsky boulevard 109439 Moscow, Russia Phone: +7 916 3888355 E-mail: y.oreshin@angelicobiotech.com Web: www.angelicobiotech.com

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