Glythera Limited - Phase2Face

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




www.glythera.com


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



www.glythera.com


Corporate Structure

Dr

Anthony

Baxter

-

Chairman

Dr

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

Director

Andrew

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

Director

Amanda

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
.


www.glythera.com


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 and

3 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
.

www.glythera.com


The Glythera Approach

GLYTHERA’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.

www.glythera.com


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.

www.glythera.com


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 Group

Chemistry modulates reactivity

www.glythera.com


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 Control

Synthesis of the carbohydrate
prior to conjugation assures
homogeneity and efficiency.

Engineered Resistance

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

www.glythera.com


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

www.glythera.com


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.

www.glythera.com


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
β
1a

•
Preliminary data on PEGyltated
Interferon
β
1a using
Permalink has given encouraging results


www.glythera.com


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

www.glythera.com


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

www.glythera.com


Thank you

For further information regarding
Glythera Limited
,

please contact:



•

Simon Youlton on +44 (0)7588 410868

(
s.youlton@Glythera.com
)





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