www.glythera.com february 2009 limited corporate presentation

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www.glythera. com February 2009 Limited Corporate Presentation

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Page 1: Www.glythera.com February 2009 Limited Corporate Presentation

www.glythera.com

February 2009

Limited

Corporate Presentation

Page 2: Www.glythera.com February 2009 Limited Corporate Presentation

www.glythera.com

Glythera Highlights• Glythera’s Patented Permalink™ technology allows the stable linkage of PEG

or Glycan groups to proteins or peptides in vitro, while Permacarb™ technology renders carbohydrates resistant to enzymatic degradation

• Glythera technology can be applied to peptide, protein and antibody based therapeutics

• In combination, these technologies allow unprecedented control over glycosylation, greatly enhancing stability and homogeneity

• Glythera is currently working in partnership with a leading European biotechnology company

Page 3: Www.glythera.com February 2009 Limited Corporate Presentation

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Company Overview• Glythera is a spin-out biotechnology company based at the University of Bath

and in the City of London

• Glythera expertise rests in protein chemistry and biochemistry & is driven to add value to marketed biological therapeutics and biologics still in development

• Glythera adds value , efficacy and novelty to new biological entities and provides proprietary uniform, stable and controllable PEGylation linkers

• Glythera raised its first round of investment in Autumn 2008

• Glythera is an IP Group PLC portfolio company with additional investment from Bath Ventures and research funding from the government agency SWRDA

Page 4: Www.glythera.com February 2009 Limited Corporate Presentation

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Corporate StructureDr Anthony Baxter - ChairmanDr Baxter was formerly the founding CEO of Argenta Discovery Ltd, a leading drug discovery services. In less than four years from the company's start-up in 1999, he grew services revenue to over £9 million which included building a pipeline of novel therapeutic programmes. Prior to this, Dr Baxter was Chief Scientific Officer of Oxford Asymmetry International plc and helped build the business from an early stage company to its flotation on the LSE and then to its eventual merger with Evotec for £316 million. Most recently, Dr Baxter lead the turnaround of deltaDOT Ltd, which involved fundraising of £8.3 million. He is currently a Non-Exec. Chairman of Equinox Ltd., and the CEO of Cyprotex Plc, which has recently announced better than expected profits to Shareholders.

Dr Andrew G Watts – Founder and Executive DirectorAndrew is currently a Lecturer in Medicinal Chemistry with over 10 years experience in carbohydrate research, including synthesis, inhibitor design, mechanistic enzymology and development of novel technologies. After completing his PhD in Western Australia, he carried out Post-doctoral research in Vancouver, Canada (UBC) before moving to the UK.

Dr Amanda MacKenzie – Founder and Executive DirectorAmanda MacKenzie is a Lecturer in Pharmacology with over 10 years research experience in field of ion channels, immunology and hematology. Her experience include a postdoctoral fellowship position in Glaxo Wellcome and a senior fellowship funded by AstraZeneca mentored by Prof. Alan North. She has authored several high impact research papers and reviews in the field of membrane ion channel signalling and small protein cytokine signalling.

Page 5: Www.glythera.com February 2009 Limited Corporate Presentation

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Corporate Structure

Simon Youlton - Business Development

Prof. William Baines - Non-Executive Director

Dr Alison Fielding, MBA - Executive Director

Alison was the Chief Operating Officer of Techtran Group when it was acquired by IP Group in January 2005. Previously, she spent five years at McKinsey & Co where she consulted primarily to the pharmaceutical and health care sectors. Prior to McKinsey, Alison spent four years as a development chemist for Zeneca, performing technical roles in the speciality chemicals and agrochemicals divisions.

William is a scientist and entrepreneur. He has 15 years' experience in creating, valuing and implementing new technology in start-up companies, including Ark Therapeutics and Vectura, and has started 4 companies including Amedis Pharmaceuticals Ltd.. He is author of over 100 articles and3 books, teaches entrepreneurship and company financing at Cambridge University.

Simon has a 15 year career in sales and marketing in life science companies and a ten year career in international technology transfer. This has included being a Board Member of several life science companies, being a Management Team Member for the worlds largest cancer charity whilst at the tech transfer and drug development company Cancer Research Technology Ltd, & being a founding member of the CRUK translational funding committee set up to receive and review academic translational awards and review the drug development activities of CRT.

Page 6: Www.glythera.com February 2009 Limited Corporate Presentation

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The Glythera ApproachGLYTHERA’s core expertise allows the functionalisation of biological therapeutics to improve properties and efficacy of glycoproteins via the implementation of its PermaLink™ and PermaCarb™ technologies.

PermaLink™ is a biologically stable linker which attaches functional groups such as carbohydrates and PEGs to cysteine residues on proteins and peptides .

PermaCarb™ technology renders carbohydrates resistant to enzymatic degradation, maximising their biological effects in vivo.

Our modular approach enables the stable attachment of PermaCarb™ s using PermaLink™ to create drugs with improved plasma half-life, biological stability and therapeutic efficacy.

Page 7: Www.glythera.com February 2009 Limited Corporate Presentation

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Problems which can be addressed:Biologics and Biosimilars

• Biological therapeutics can be heterogeneous.

• Chemical heterogeneity is a concern for regulatory compliance and often necessitates multiple purification steps.

• Current production methods can result in heterogeneity of post-translational modification patterns, particularly glycosylation, which can effect the PK properties:- eg Bioavailability, biological activity, solubility (including the propensity for aggregation) and immunogenicity.

• Glycans are degraded by glycosidases in vivo, which can increase rate of clearance and reduce plasma half-life.

• Glythera’s patented technologies minimises these risks by providing a ‘better designed’, homogeneous and stable product.

Page 8: Www.glythera.com February 2009 Limited Corporate Presentation

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PermaLink™

• PermaLink™ uses novel chemistry to functionalise surface cysteine residues through a thio-ether bond, stable to biological and chemical degradation.

• Range of reagents customized for different sized proteins or peptides.

• Improved selectivity and control of PEGylation over maleimide methodology.

• High yields (>95%) for glycosylated/PEGylated peptides with the Glythera process.

Customized functional group

Carbohydrate, PEG,Affinity tag

Linker GroupChemistry modulates reactivity

Page 9: Www.glythera.com February 2009 Limited Corporate Presentation

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PermaCarb™

• PermaCarb’s are novel glycosylation groups resistant to enzymatic degradation by exo-glycosidases (during production and in vivo)

• Glycans can be added synthetically to modify protein function: such as improved plasma half-life, enhanced efficacy and solubility

• Can be used in combination with Permalink™ for stable attachment to proteins and peptides at defined locations

• Wide range of endogenous glycosylation patterns are available

Linker Reactive

Flexibility and ControlSynthesis of the carbohydrate prior to conjugation assures homogeneity and efficiency.

Engineered ResistanceUnique ability to introduce resistance to enzymatic degradation ensuring maximum benefit from glycosylation is conferred to the therapeutic.

Page 10: Www.glythera.com February 2009 Limited Corporate Presentation

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Application of Glythera Technologies

• Pegylated PermaLink can be used to replace Maleimide based methods of Pegylation

• PermaLink targets cysteine residues similar to Maleimide, but provides greater specificity and increased stability without needing to make changes to the target protein

Companies currently using Pegylation

• PermaCarb technology can be applied directly to endogenously glycosylated therapeutics produced in cell-based systems

• Glycosylated therapeutics can be modified with PermaCarb to produce homogenous glycoforms which are then inert to enzymatic degredation in vivo, thus improving half-life

Companies currently using cell-based glycosylation methods

• The Pegylation of small peptides, or introduction of natural glycosylation sequences into peptides, can result in loss of functional activity.

• The application of PermaLink to small peptides requires only a single a.a. substitution (Ser, Thr, Ala →Cys) to allow functionalisation by low molecular weight PermaCarb

Companies developing peptide-based therapeutics

Page 11: Www.glythera.com February 2009 Limited Corporate Presentation

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Glythera PARTNERSHIPS

•Glythera supplies know-how to produce homogeneous glycoforms with stable glycosylation for biologicals manufactured in bacterial, yeast or mammalian cell based systems, to enhance pharmacokinetic properties.

•Glythera can introduce chemical stability and/or glycosidase resistance to your drug.

•Novel substitutions allow the controlled and stable linkage of PEG’s without the need for maleimide chemistry.

• IDF™ - Improved Drug Functionality : through the ability to incorporate novel glycan modification points.

Page 12: Www.glythera.com February 2009 Limited Corporate Presentation

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Glythera Internal Projects

• We will be moving certain exemplar peptides and protein biotherapeutics in to Proof-of-Concept animal models at the end of this year

• Such agents will include Permalink™ and Permacarb ™ modified G-CSF, an HIV peptide protein fusion inhibitor and Interferon β1a

• Preliminary data on PEGyltated Interferon β1a using Permalink has given encouraging results

Page 13: Www.glythera.com February 2009 Limited Corporate Presentation

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Glythera PARTNERSHIPS

Partner delivers test peptide or protein

• We welcome enquiries for all types of biological therapeutics

• We will help you in the first steps to make Permalink™ and Permacarb™ variants for you to perform biological evaluation

Glythera delivers sample of partner peptide/protein after functionalisation/protection

Partner evaluates Glythera version of peptide/protein cf original form

Page 14: Www.glythera.com February 2009 Limited Corporate Presentation

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Summary• Our two patented technologies – Permalink™ and Permacarb™ are both

applicable to functionalising proteins, peptide and antibody based biologicals

• Functionalisation can:• improve stability and serum half-life through stable glycosylation• provide homogeneous glycosylation

• We can PEGylate proteins without Maleimide and in a more defined and controlled manner, producing a chemically stable product

• New formulations, biomanufacture methods and novel IP allow for extensions of class lifespan and market penetration for follow-on biologics

• We are a young company ‘hungry’ for partners

Page 15: Www.glythera.com February 2009 Limited Corporate Presentation

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Thank you

For further information regarding Glythera Limited, please contact:

• Simon Youlton on +44 (0)7588 410868 ([email protected])

Glythera Limited, 24 Cornhill, London, EC3V 3ND, Registered Number 6433235