December 1, 2005

1
The BYEF Experience

• Bart Nelissen
• Department of Chemistry
• University of York
• BioScience York 10th Anniversary
• December 1 2005

2
Our Technology in a Nutshell
1 Select Molecular Target
3 Immobilise Best Receptor on Polymer Support

• High Capacity Selective Affinity Resins
• Potential Applications
• Therapeutics
• Separations

2 Design Small Library of Synthetic Receptors
3
Current Therapeutic Targets

• Phosphate Lowering Medication
• End Stage Renal Failure Patients
• Supported by Wellcome Trust University
  Translation Award (UTA)
• Cholesterol Lowering Medication
• Supported by BYEF

4
Bioscience Yorkshire Enterprise Fellowship

• A scheme by Yorkshire Forward to stimulate
  Bioentrepreneurs in the Yorkshire area
• Proof of Concept Funding for 1 year
• 15.000 to develop the science
• 15.000 to develop the business
• Monthly Workshops on topics such as IP, Finance,
  Market Analysis
• Network of Advice
• Learning how to translate a scientific idea to a
  product

5
BYEF Support

• Market Research
• Better understanding of how our product fits into
  the future market
• Patentability Study
• Take away concerns about infringements
• Student Support
• Two summer students for 8 weeks each to take the
  science forward

6
BYEF Support

• Tap into Local Network of Support
• Mentors Graham Fagg and Peter Bentley
• Exposure
• Personal Skills Development
• Commercially versed
• Better networked

7
Cardiovascular disease (CVD)
WHO by 2010, CVD will be the leading cause of
death in developed countries
Biological Risk Factors
Changes in Lifestyle
8
Current Therapies

• Statin Drugs
• Inhibit synthesis of cholesterol in the liver
• Bile Acid Sequestrants
• Inhibit re-uptake of bile acids produced by the
  liver from cholesterol
• Cholesterol Absorption Inhibitors
• Inhibit the absorption of dietary cholesterol

9
Anti-dyslipidemic Drugs Market

• Total value worldwide in 2004 25 billion
• Market dominated by statins
• Bile Acid Sequestrants only take 1 of the market

10
Statin Drugs, Associated Problems

• Efficacy
• 60 of patients do not reach their cholesterol
  goals

Percentage of patients reaching goal
Risk Category
11
Statin Drugs, Associated Problems

• Efficacy
• 60 of patients do not reach their cholesterol
  goals
• Dose-response curve for statins is non-linear

12
Trend Combination Drugs

• Two drugs that lower cholesterol via
  complementary mechanisms
• Keeps dose of statin at a save but still
  effective level
• E.g. Statins Bile Acid Sequestrants

13
Bile Acid Sequestrants, Materials

• Cross linked polymers
• Cationic ion-exchange resins
• (positively charged)
• Bind negatively charged bile acid
• (via electrostatic interactions)

14
Bile Acid Sequestrants, Problems

• Dose
• High doses (multigram) needed because of low
  affinity for bile acids cause constipation
• Selectivity
• Potential removal of essential nutrients, e.g.
  vitamins, because of lack of selectivity for bile
  acids
• Patient compliance
• Materials are gritty resins and swell when taken
  with water

15
Our Approach

• Requirements
• Higher affinity for Bile Acids
• Selectivity for Bile Acids
• Enhanced Material Properties
• Solution
• Develop synthetic receptors for Bile Acids
• Incorporate units into cross linked polymer
  network
• Control Material Properties

16
Our Approach
Current Bile Acid Sequestrants
Our Receptor Containing Bile Acid Sequestrants
17
The Near Future
2005
2006
2007
2008
Phosphate
In Vitro Data
In Vivo Data
Preclinical Safety
Phase I