Admission to AIM

EpiStem Holdings plc 04 April 2007 4th April 2007 EpiStem Holdings Plc. Fundraising and Placing by Teather and Greenwood 2.5m of new Ordinary Shares at 124 pence per share Highlights • EpiStem Holdings Plc Admission to AIM 4th April 2007 • 2.5 million shares successfully placed at 124 pence per share raising £2.6 million net of expenses • EpiStem is a biotechnology company commercialising adult stem cells in the areas of oncology and gastrointestinal diseases • Money will be used to: o enable the partnering of novel therapeutic compounds o widen the diagnostic platform of the existing cash-flow positive fee for service business o general corporate services. • Institutional investors include: o Calculus o Yorkshire Fund Managers o Rensburg Sheppards o Zeus Capital o New Star o Octopus Commenting on the completion of the placing, David Evans, Chairman of EpiStem said: 'We are delighted at the positive response that we have had from both our existing investors and new institutions in supporting the development plans of the Company. Alongside our existing list of investors including, Calculus, Yorkshire Fund Managers, Rensburg Sheppards and Jon Moulton, we welcome as new shareholders established institutional investors such as New Star and Octopus. The money raised will allow us to advance our therapeutic candidates leading to licensing partnerships. We believe candidate therapeutics will enable us to regulate and repair tissue renewal processes providing a new development approach for oncology based diseases. Epithelial cancers account for over 80% of adult cancers. Our integrated discovery and preclinical platform will enable pharmaceutical companies to access data and therapeutics based on the company's unrivalled research knowledge in stem cells which has been amassed over 30 years originally starting at the Paterson Institute at Christie's Hospital, Manchester, UK.' Commenting on his new role as CEO, Matthew Walls said: The Company has been able to build a profitable and cash generative service support business alongside an innovative discovery program based on its core technology. An AIM quotation gives us the profile to expand our service support business as well as become a leading supplier of validated candidate novel therapeutics for a pharmaceutical industry increasingly demanding such targets. The Board has a clear vision of how we will drive both sides of the business to generate shareholder value. The team is highly professional and has an acute sense of how to commercialise its technology for both short-term expansion and the long-term growth of the Company. ' History EpiStem is a biotechnology company commercialising adult stem cells in the areas of oncology and gastrointestinal diseases as well as cosmeceutical applications. EpiStem develops innovative therapeutics and diagnostic biomarkers and provides contract research services to drug development companies. The Group's expertise is focused on the regulation of adult stem cells located in epithelial tissue, which includes the gastrointestinal tract, skin, hair follicles, breast and prostate. EpiStem does not conduct research in the areas of embryonic stem cells or stem cell transplantation. Fundraising and Placing Under the Fundraising and Placing, EpiStem Holdings Plc is issuing 2.5m New Ordinary Shares representing approximately 38 per cent of the Enlarged Share Capital. Reasons for Admission and the Placing The Company intends to raise approximately £2.6 million net of expenses pursuant to the Fundraising. The net proceeds of the Fund raising will be used to: • fund further research to enable the commercial partnering of therapeutic candidate(s) from the Novel Therapies Division; • fund the development of the Company's diagnostic platform based on epithelial stem cell biology; and • general corporate purposes. The Directors also believe that the profile of the Group will be significantly enhanced as a UK quoted public company. For more information please contact: EpiStem: 0161 606 7263 Matthew Walls, Chief Executive Officer Teather & Greenwood: 020 7426 9000 Robert Naylor Thilo Hoffmann Simon Brown MC Bio-Communications Limited: 020 7744 7711 Mike Wort, Anna Dunphy In this release reference is made to the Admission Document which is available on request from the Company at 48 Grafton Street, Manchester M3 9XX or the Company's website www.epistem.co.uk. Additional Information EpiStem is a biotechnology company commercialising adult stem cells in the areas of oncology and gastrointestinal diseases as well as cosmeceutical applications. EpiStem develops innovative therapeutics and diagnostic biomarkers and provides contract research services to drug development companies. The Group's expertise is focused on the regulation of adult stem cells located in epithelial tissue, which includes the gastrointestinal tract, skin, hair follicles, breast and prostate. EpiStem does not conduct research in the areas of embryonic stem cells or stem cell transplantation. EpiStem operates two distinct business divisions, Contract Research Services and Novel Therapies. Contract Research Services Contract Research Services provides specialised preclinical efficacy testing primarily for drug development companies on a fee for service basis. This division on a standalone basis is cash generative and profitable, with an established five-year track record of providing testing services to over 65 company clients primarily in Europe and the United States. Novel Therapies Novel Therapies is focused on developing its own innovative therapeutics and diagnostic biomarkers. Through its discovery platform, Novel Therapies has identified 250 potential drug candidates, of which a subset will undergo further evaluation as stem cell regulators for the Group's emerging drug development pipeline. Novel Therapies is also conducting feasibility studies with two drug development companies using its clinical diagnostic biomarker technology. Combined Business Model The Group is exploiting its combined business model to advance its own therapeutic candidates to late preclinical stage development. The business model integrates the discovery efforts of Novel Therapies with the efficacy testing assays of its Contract Research Services Division, to identify and characterise new drug candidates. Revenues generated by Contract Research Services will assist in offsetting Novel Therapies' investment requirements for the discovery and development of therapeutics. In February 2007, EpiStem licensed its first drug candidate to a clinical development company. With the validation of the Novel Therapies discovery platform and the achievement of discovery milestones, the Directors believe that additional licensing partnerships will be forthcoming for therapeutics, diagnostics and cosmeceuticals starting in 2008. Company background EpiStem was founded in 2000 by Professor Chris Potten and Dr. Catherine Booth, its co-founders having previously been based in the Paterson Institute at the Christie Hospital in Manchester, UK. Its offices are located in the Manchester Incubator Building, which is part of the University of Manchester. The Company's expertise is based on over three decades of experience in relation to discovery research on the behaviour of adult epithelial stem cells by Professor Potten. Professor Potten received a lifetime fellowship from Cancer Research UK and has published over 350 scientific publications, written two and edited nine books. He has received two prestigious prizes for his contributions to radiobiological research, the Madame Marie Sklodowska-Curie Medal in 1998 and the Weiss Prize in 2003. Professor Potten is the Chief Scientific Adviser to the Group. Stem cell assays developed by the founders attracted the attention of drug development companies and these assays created the core platform for the formation of the Contract Research Services Division. Dr. Booth has built a team of 13 scientists alongside a business development team of five led by Dr. Mark Bryant. Six of the Contract Research Services team have Ph.D. degrees. Dr. Gerard Brady joined EpiStem as Research Director of the Novel Therapies Division in 2001. Dr. Brady has applied over two decades of expertise developing specialised molecular biology tools, including gene profiling of individual cells, with the goal to identify the key regulators of epithelial stem cells. In September 2005, EpiStem hired Dr. Jeffrey Moore to lead the commercialisation of the Novel Therapies' technology. Prior to joining EpiStem, Dr. Moore discovered a blood stem cell regulator, founded Phylogix Inc., a therapeutics biotechnology company, and raised over $15 million to advance the drug candidate to late preclinical development. The Novel Therapies team has seven scientists, five of whom have Ph.D.degrees. In February 2007, Matthew Walls, an experienced Chief Executive most recently at Oxford Biosignals Limited, took on the role of Chief Executive Officer. Matthew has extensive experience of building and commercialising biotechnology products and services across the United States and United Kingdom. He succeeds David Evans, who had been Executive Chairman since March 2006. David will continue in the role of Non-executive Chairman, which he fulfils for three other AIM-quoted companies in the healthcare sector. John Rylands, now Financial Director, joined EpiStem in 2002 and has successfully completed several rounds of investment supporting the growth of EpiStem. Dr.Robert Nolan, the other Non-executive Director, has extensive pharmaceutical licensing experience and an active involvement with early stage healthcare companies. Contract Research Services Division Contract Research Services provides specialised preclinical assays for drug development in the areas of oncology supportive care, oncology, inflammatory bowel disease (IBD), and new emerging applications. Introduction to oncology supportive care The effectiveness of chemotherapy and radiation to eradicate cancer depends in part on oncologists' ability to manage toxic side effects to the gastrointestinal tract, a condition called mucositis. Destruction of the epithelial lining, leading to ulceration and functional impairment, increases the risk of infection and treatment delays and causes suffering for the patient manifested by loss of appetite, diarrhoea, and wasting. Pain induced by ulceration in the mouth (oral mucositis) is a major reason why patients either delay or halt chemotherapy and radiotherapy. Better management of mucositis during cancer treatment would decrease the risk of serious, sometimes life-threatening infections, reduce overall treatment costs and patient suffering. Reducing the toxic side effects of cancer therapy remains a major unmet clinical need. Oncology supportive care The core intestinal stem cell assays used by EpiStem evaluate efficacy, optimise drug dose/scheduling, and elucidate mode of action in the area of oncology supportive care. These assays, established over the past decade, have been used to evaluate more than a dozen supportive care drug candidates in preclinical development. Following earlier testing involving Professor Potten and Dr. Booth, two drug candidates have gone on to enter clinical trials, one of which (Amgen's Kepivance(R)) is the first and currently the only drug approved to reduce oral mucositis. Oncology and Inflammatory Bowel Disease Contract Research Services provides a range of established preclinical efficacy testing services to assess anticancer compounds on tumour growth in oncology and the severity of tissue damage in IBD. The team has developed a variety of analytical tools to evaluate drug candidates and is also extending its services in oncology and IBD to better assess the nature of these chronic diseases. New emerging areas Intestinal injury is a major component of radiation sickness and the National Institutes of Health in the United States is funding the development of drugs that will prevent and treat radiation sickness following a nuclear terrorist event. EpiStem is currently evaluating the efficacy of candidate drugs to protect and/or repair intestinal injury in the radiation/nuclear medical countermeasure development programme. Contract Research Services has a specialised understanding and expertise in the area of skin testing. It provides bespoke skin assays, designed to assess a drug's ability to protect against tissue damage from chemical and ultraviolet sources. The group has a specific competence in growth and differentiation of various skin tissue types. Market overview and opportunity The Directors believe that Contract Research Services' core assays for oncology supportive care and biodefence will provide the foundation for the division's future sustainability and growth. Oncology supportive care The worldwide market for supportive care products exceeds £6 billion per annum, primarily from Amgen and Johnson & Johnson's blood cell growth regulators. The growing sales of Amgen's Kepivance(R) for oral mucositis reflect an opportunity for additional therapeutics in this area. Contract Research Services is currently evaluating several anti-mucositis candidates. Biodefense EpiStem's biodefense subcontract, which is funded through the University of Maryland School of Medicine's prime contract with the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, in the United States, involves screening of drug candidates to protect and/or repair intestinal injury followed by more comprehensive studies on selected drugs and is anticipated to continue over three years. EpiStem is currently the primary laboratory in the University of Maryland consortium that is evaluating the efficacy of candidate drugs to protect the epithelial lining in the gut from radiation damage for the radiation /nuclear medical countermeasure development programme. Independently two drug development companies with biodefence compounds have contracted EpiStem to conduct parallel studies in oncology supportive care. Competition The Directors believe that the Group's intestinal stem cell assays in supportive care and biodefence have few competitors. The Directors believe that limited oral mucositis models are conducted through a private contract research organisation in the United States. Contract Research Services' oncology and IBD assays operate in a more competitive market with success based on providing an established quality of interactive service leading to repeat business. The team has built a track record and profitable business based on its expertise in assay design, execution and interpretation of results with its customers. Novel Therapies Division EpiStem intends to unlock the commercial value of adult epithelial stem cells by discovering the key regulators of stem cells and developing candidate therapeutics through commercial partnerships with drug development companies. The core value generator in this division is its high resolution, gene expression profiling technology used to analyse the behaviour of epithelial stem cells. This know how has been generated over five years, profiling a wide range of epithelial tissues to elucidate the fundamental mechanisms of stem cell regulation. The Directors believe that control over the regulation of intestinal stem cells will enable EpiStem to develop novel therapeutics to treat mucositis, cancer, IBD, and other epithelial stem cell disorders. The Directors believe that the regulators of intestinal stem cells are largely unknown due to the difficulties in accessing and evaluating intestinal tissues. Through the combination of its gene profiling technology and its intestinal stem cell expertise, the Directors believe that they will be able to overcome these technical obstacles. At the initial proof-of-concept stage, this technology approach resulted in the identification of ten potential cell receptor targets regulated by small molecule drugs. Biological activity was demonstrated in three out of the ten receptors. One small molecule drug was then selected and characterised. In 2004, EpiStem applied for patent protection for its application as an anti-mucositis therapy. In February 2007, EpiStem entered into its first licensing partnership with a clinical stage company to develop this small molecule drug for oncology supportive care and biodefence applications. With the confirmation in 2004 that EpiStem's discovery technology could successfully identify relevant therapeutic targets, the Novel Therapies team embarked on a comprehensive programme to identify the key regulators of intestinal stem cells. The stem cell regulators will themselves be novel protein therapeutic candidates. In June 2006, the division completed its gene profiling programme of intestinal stem cells and selected 250 genes that are likely to include candidate stem cell regulators. EpiStem engaged Eden Biodesign, a contractor at the National Biomanufacturing Centre in Liverpool, to produce the recombinant proteins. These proteins will initially be evaluated directly in the Contract Research Services Division's intestinal stem cell assays. EpiStem intends to apply for patent protection of candidate therapeutics identified and characterised in these assays. The Directors believe that it is likely that some of the 250 proteins will also regulate epithelial stem cells in other tissues, such as hair follicles to turn on and off hair growth for use in cosmeceutical applications. Developing innovative diagnostic biomarkers EpiStem is applying its gene expression profiling technology to determine the feasibility of using plucked human hairs to guide the clinical development of new oncology drugs. Specifically, it is focusing on obtaining proof-of-concept for this diagnostic biomarker method to determine drug exposure, dose and dose scheduling, onset of intestinal toxicity, and patient selection. EpiStem already has two feasibility studies supported by drug development companies to determine the diagnostic biomarker's technical and biological robustness. The Directors believe that these initial feasibility studies are likely to lead to development partnerships in which EpiStem's plucked hair diagnostic biomarker will be evaluated as part of oncology clinical trials starting in 2007. Market overview and opportunity EpiStem's business model for therapeutics draws on the scientific and commercial validation of Amgen Inc.'s blood cell growth regulators. Both companies exploit the body's own regulators that bind cellular receptors to activate cells. Amgen generates over £5 billion in annual worldwide revenue from blood regulators that stimulate production of the oxygen-carrying red blood cells and the infection fighting white blood cells. The Directors believe that Amgen has sustained and extended its market position over nearly two decades by introducing improved versions of their patented protein therapeutics. The Directors believe that this intellectual property strategy coupled with the complexity of protein manufacturing processes has protected Amgen from generic drug competition. EpiStem intends to adopt a similar strategic approach for its epithelial stem cell regulator programmes. Wide range of tissue targets and clinical opportunities The potential commercial opportunity to exploit the body's own regulators of epithelial stem cells could surpass that of the blood cell growth regulators. The epithelium offers a wide range of tissue targets, clinical disorders, and routes of drug delivery. In oncology alone, over 80 per cent. of all adult cancers originate from the epithelium. Commercialisation strategy for therapeutics EpiStem intends to advance its candidate therapeutics to the stage of proof-of-concept in late preclinical development and then enter into commercial partnerships with clinical stage development companies. This strategy leverages the Company's strengths - discovery through to preclinical efficacy - and provides an early opportunity to obtain scientific and commercial validation of its therapeutic business model. The Directors believe the Company is on track to identify 1-4 candidate stem cell regulators for preclinical development in 2007 and enter into additional commercial partnerships in 2008. Future strategy The Company's future strategy is predicated on the continued growth of its Contract Research Services and Novel Therapies Divisions. Based on the already profitable Contract Research Services Division, the new funding will primarily underpin drug development in the Novel Therapies Division. Where appropriate, the Company may consider the acquisition of complementary technologies to strengthen its business model and accelerate product and service development. Summary financial information 6 months ended Year ended 30 June 31 December 2004 2005 2006 2006 £000's £000's £000's £000's Turnover 704 1,245 901 667 PBT (250) 48 (756) (481) Net assets 99 1,634 1,095 714 Cash at bank 90 1,517 681 328 Current trading statement Since 31 December 2006, the trading of EpiStem's Contract Research Services Division has been in line with management expectations and the Novel Therapies Division has concluded an agreement with a clinical stage company to commercialise its first therapeutic candidate. The Board remains confident that overall trading will continue to meet internal expectations. Directors and employees The Board consists of eight Directors in respect of whom brief biographies are set out below. David Evans (aged 46), Non-Executive Chairman David was executive Chairman of EpiStem from 2006 until February 2007. As the former CFO he guided Shield Diagnostics Ltd. through its IPO and then, as its CEO, through its merger with Axis Biochemical ASA to form Axis-Shield plc, a Fully Listed diagnostics company. In addition to being Chairman of the Company he is currently non-executive Chairman of BBI Holdings plc, Immunodiagnostic Systems Holdings plc and Omega Diagnostics Group plc, all of which are AIM listed diagnostic companies. MatthewWalls (aged 43), Chief Executive Officer Matthew joined EpiStem in February 2007 as Chief Executive Officer. Matthew is an experienced CEO most recently with Oxford BioSignals Limited where he led the strategic 'diagnostic' collaboration with Rolls Royce Plc and Covance Inc and completed the recent fundraising and repositioning of the medical diagnostic business to the United States. Matthew spent the early part of his career with ICI plc progressing through the executive development programme and several senior management positions. Matthew headed up the corporate financial and commercial development of plant biotechnology at AstraZeneca plc prior to its merger with Novartis to form Syngenta plc. Matthew has led the growth and development of several technology and biotechnology companies as CEO including Internexus Limited and Zylepsis Limited. Matthew holds a non-executive role at Riyada Oxford Investments Limited and is a chartered accountant and a member of CIMA. John Rylands (aged 52), Financial Director John originally joined EpiStem in 2002 as an investor and non-executive director and in 2005 he took over his current role. Mr. Rylands worked at Northern Venture Management, providing corporate finance advice to private companies before joining EpiStem. Until 1999 he was an investor in and consultant to the SDS group of companies. John holds a degree in Economics and Accountancy from Manchester University and is a member of ICAEW. Jeffrey Moore, Ph.D. (aged 47), Managing Director, Novel Therapies Jeffrey joined EpiStem in 2005 in his current role. Prior to joining EpiStem he had been at Phylogix, a US biotech company based in the Boston area that he had founded in 1998. Phylogix business was based on a stem cell preservation factor that he discovered while leading a team at ImClone Systems Incorporated. Until 1992, when he joined ImClone, he had held two postdoctoral fellowships at different research institutes, DNAX Research Institute of Molecular and Cellular Biology, Inc. and the Walter and Eliza Hall Institute of Medical Research. Throughout his career Jeffrey has kept a strong interest in stem cell regulation and the potential commercial application of these factors. He holds a Ph.D. from George Washington University. Professor Chris Potten, Ph.D. (aged 67), Chief Scientific Adviser Chris is a co-founder of EpiStem and the Company capitalises on the results of the research that was produced by him and his team at the Paterson Institute over the past three decades. While not involved in the day to day management of EpiStem Chris keeps a strong interest in the progress and success of EpiStem and prior to Admission has been its biggest individual shareholder. Catherine Booth, Ph.D. (aged 41), Managing Director, Contract Research Services Catherine is a co-founder of EpiStem and prior to starting EpiStem she worked for 10 years with Professor Chris Potten at the Paterson Institute. While at the Paterson Institute she developed many of the pre-clinical assays that today are the core of EpiStem's Contract Research Services Division. Catherine received her Ph.D. from the Emmanuel College, University of Cambridge. Gerard Brady, Ph.D. (aged 50), Research Director, Novel Therapies Gerard joined EpiStem shortly after its inception from Manchester University where he was a lecturer and was previously a Zeneca Fellow. He brought with him important technological expertise gained through working on blood stem cells. Of particular importance to EpiStem is his expertise in single cell gene analysis, which enables the examination of rare cells such as stem cells. Gerard previously held scientific positions in Canada and at EMBL, Heidelberg. Robert Nolan (aged 64), Non-executive Director Robert has been a Non-executive Director of the Company since 2004. He brings with him a wealth of expertise in partnering and licensing negotiations both with small biotech and large pharmaceutical companies. Prior to his retirement he was Director, Global Licensing at AstraZeneca. He is also a non-executive Director of f2g Ltd. The Group employs 29 staff in total all of which are based at the Company's premises in The Incubator Building, 48 Grafton Street, Manchester M3 9XX. Details of the Placing Under the Placing the Company is issuing 807,628 New Ordinary Shares. The Placing Shares represent approximately 12.35 per cent. of the Enlarged Share Capital immediately on Admission, on the assumption that all of the Placing Shares are issued. The Placing is conditional upon, among other things, Admission. The Placing is not being underwritten. Application has been made for the existing issued Ordinary Shares (including the Placing Shares and the Preflotation Fundraising Shares) to be admitted to trading on AIM. Dealings on AIM are expected to commence on 4 April 2007 in respect of the First Admission, 10 April 2007 in respect of the Second Admission and 11 April 2007 in respect of the Third Admission. In aggregate, the Directors will be interested in 33.40 per cent. of the Enlarged Share Capital following Admission, on the assumption that all of the Placing Shares are issued and completion of the Selling Shareholder Placing. Reasons for Admission and the Placing The Company intends to raise approximately £2,558,058 net of expenses pursuant to the Placing and the Preflotation Fundraising. The net proceeds of the Placing and the Pre-flotation Fundraising will be used to: • fund further research to enable the commercial partnering of therapeutic candidate(s) from the Novel Therapies Division; • fund the development of the Company's diagnostic platform based on epithelial stem cell biology; and • general corporate purposes. The Directors also believe that the profile of the Group will be significantly enhanced as a UK listed public company. The Directors believe that Admission will: • enhance the Group's status; • assist the Company in raising additional capital should this be required; and • provide liquidity for investors through the ability to buy and sell Ordinary Shares. Lock-in arrangements Under the terms of the Placing Agreement, the Directors have undertaken that, subject to certain limited exceptions, they will not sell or otherwise dispose of, or agree to sell or dispose of, any of their interests in Ordinary Shares held by them respectively until one month after the publication of the preliminary results for the year ended 30 June 2008. In addition orderly market arrangements apply for a period of 12 months following the expiry of the lock-in period referred to above, whereby the Directors have undertaken to sell Ordinary Shares through Teather & Greenwood. Dividend Policy In the medium term it is the Directors' intention to re-invest funds directly into the Company rather than to fund the payment of dividends. Thereafter, the payment of dividends will be subject to the availability of distributable reserves whilst maintaining an appropriate level of dividend cover and having regard to the need to retain sufficient funds to finance the development of the Company's activities. Employee Share Option Scheme Immediately following Admission the Company will have granted share options and warrants to subscribe for up to 1,374,850 Ordinary Shares representing 21.03 per cent. of the Enlarged Share Capital. Taking this into account, an additional 458,224 Ordinary Shares remain available for reward as options under the Share Option Schemes and any new share option schemes to be adopted by the Company in the future. The Directors intend to introduce a Save as You Earn Share Option Scheme and a new performance based EMI share option scheme for employees following Admission. Dealing arrangements Application has been made for the issued Ordinary Shares (including the Placing Shares and the Pre-flotation Fundraising Shares) to be admitted to trading on AIM and it is anticipated that Admission will become effective and that dealings will commence on 4 April 2007 in respect of the First Admission, on 10 April 2007 in respect of the Second Admission and on 11 April 2007 in respect of the Third Admission. This information is provided by RNS The company news service from the London Stock Exchange D MSCBRGDSUBGGGRX

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