· Molecular Pharmacology based on “weighting” biological pathways and ... Added value to the...

www.aureliabio.com

Aurelia Bioscience © 2020

( +44 (0) 115 8370503

1

Who are we? – Over 100 years of experience in Pharma pre-clinical

research and technology development

Gary Allenby (CEO), Kathy Dodgson (CSO)

Ph.D. level staff

Currently 8 staff (B.Sc. and Ph.D. level)

5 research labs, 2 offices on site

Location – Biocity, Nottingham, United Kingdom

Bio-incubator with over 70 bio-based businesses including CRO / CMO,

specialised expertise including Med Chem, DMPK, Pathology, In-Vivo

Aurelia clients include top 50 Pharma, Biotech SME’s, other CRO’s, Research

Institutes (Life ARC, CRUK)

Disease areas include oncology, neurobiology, musculoskeletal, respiratory and

inflammation, novel disease targets

Targets types include Kinases, GPCR’s, cell surface second messenger,

epigenetic, enzyme, protein-protein, ion-channel

Over 95% repeat business rate with our clients

Aurelia Bioscience

2Aurelia Bioscience © 2020

Biology CRO - Our Services

Aurelia

Bioscience

• Instrument/Reagent Consultancy and Validation

Expertise

New technology Biology

+ +

Data • Application Development

• Validation for Client

• Benchmarking

• Fee for service

Assay Development

State of the art technology

+

Data Data

Data

Data

Series of compounds with appropriate properties

• Discovery Project using FTE resource

Assay Development, Pharmacological Profiling and Screening

• Hit Identification (no chemical precedent therefore need HTS)

• Hits-to-Lead (chemical precedent in literature)

3

Aurelia

Bioscience


Case Study – Hit to Lead example

Target disease area - oncology

Client (e-Therapeutics)

Molecular Pharmacology based on

“weighting” biological pathways and

interactions to identify key nodes

Selected 1100 compounds to

screen from propriatory in silico

modeling software

4

Two potential targets based in literature precedent for the biology (not

traditional DD) – both assays cell-based

Initial aim – screen 1100 compounds through assays then IC50 determination

of actives

Also needed to measure cyto-toxicity

Project objective was to generate compounds with novel IP for future

collaboration with Pharma or sale of assets

Project sponsor was e-Therapeutics who employed Aurelia Bioscience to perform

the biology and a chemistry CRO to deliver medicinal chemistry support


Initial Biology Delivery

>10% Hit rate from the initial 1100 set

Excellent correlation between the two assays

SAR tables for active compounds in both assays

Select desirable chemotypes for hit-to-lead optimization work

Chemical design and library enumeration work around five chemotypes

5

• ds

Differentiation assay

Reporter assay

1100 compoundsDifferentiation Assay (10µM) Ave % Inhibition

Cytotoxicity (10µM) Ave % Toxicity

144 compounds (>50% cut off)Differentiation Assay IC50 (nM)

Reporter Assay IC50 (nM)

SAR analysisChemotypes active in both assay

Selection of a further 440 compounds based on 2D/3D similarity

Biology resource – project initiated as “fee for service” but once hits identified then

transitioned to resource based, initially one then two biologists total length = 18 months


6

Developed an FP binding assay for discrimination of hits based on

binding of a fluorescently tagged standard agonist

Ideal profile was a non-binder

All of the 144 hits were tested as conc-response in this assay

Approximately half were non-binders

Selectivity Assay

Series A

Series B

Cell differentiation assay

FP

Bin

din

g A

ssay

• The FP binding assay was added to the

screening cascade

• Series A had the desired profile


A number of mutations in a key pathway protein were known to exist in patient population and affect drug resistance Horizon generated 3 mutant cell lines (using

CRISPR) in the same cell background as the differentiation assay

Anti-proliferative effects on multiple cell lines – basal cell carcinoma, lung, ovarian, pancreatic (squamous cell carcinoma), medulloblastoma

ELISA assay for assaying changes in levels of a potential target protein in multiple cancer cell lines Also identified a Cisbio HTRF assay for the

target protein with improved sensitivity

Protein Simple Western blot Cell lysates from 4 cancer cell lines

QPCR for changes in key transcription factor on the target pathway

Mode of Action Studies

WT cell + TestMutant 1+ TestMutant 1+

Std

WT cell + Test

Mutant 2+

Std

Housekeeping gene

Target gene


Identified 3 series of compounds with activity on the target pathway

Developed secondary assays to discriminate between molecules

Aiming to achieve one lead series with LO properties

• Potency in cells pIC50>8

• Clear IP position

Added value to the project with the addition of other MOA assays including

working with the mutant cell lines and measuring changes in protein/mRNA

Identified compounds taken forward into in vivo tumour models

HtL – Measuring Success

The client has 3 patents on the IP generated in this project and is

looking for risk share to move onto the next stage


Target = TRESK – 2 pore non-voltage gated potassium channel

Disease indication = Migraine (prevalent, debilitating and costly)

The potassium channel TRESK is abundant in trigeminal ganglia. The mutation causes loss of function, thereby increasing TG excitability. TRESK is therefore a viable therapeutic target for migraine

TRESK is activated strongly by second messengers such as calclum and volatile anaesthetics such as halothane

At resting membrane potential, channel is closed but activated by calcium. As a membrane depolarizes, potassium outflow through open TRESK channels tends to restore the membrane potential

Compound targeting TRESK and to increase TRESK opening in the resting state would reduce excitability and responsiveness

Case Study – Hit Identification example

9

Project Sponsor had no prior art or knowledge of chemistry,

therefore wanted HTS of target (50,000 compounds)


HI Assay Protocol – 50K compounds

10

HTS Assay Format

Fluorescence-based [Thallium]i detection

as a surrogate of [potassium]o influx

FluxOR™ Potassium Ion Channel Assay in FLIPR Tetra

Target was transiently expressed in U2OS cells using a Bacmam construct

10000

13300

16600

19900

23200

26500

29800

33100

36400

39700

43000

00 1 2 3 4Time(seconds)

Multiple Well Overlay

Flu

ore

scen

ce C

han

ge (

Co

un

ts)

Test compounds– normal

(yellow)

Inhibited channel

activity (blue)

Activated channel

activity (red)

5ul

Range = ( 7800, 55000 )

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Mini Graphs

Test Compounds


Hit Confirmation, IC50 and Selectivity

11

Hit confirmation rate ~65%

Highly reproducible

Retest of hits (n=2) followed by IC50 of hits

Selectivity required against TREK channel

(heart) therefore selectivity assay developed

BL-1249

Control

TPA

Time (secs)

Response (

max-m

in/b

asal)

Almost all hits are

‘TRESK specific’

TRESK-mediated increase inThallium flux

log [Compound] (M)

% R

esponse

-8 -7 -6 -5 -40

100

200

300

400Cmpd 1

Cmpd 2

Cloxyquin

Cmpd 3


Aurelia Bioscience

Lab Technology and Assay Capabilities


EnSpire (PerkinElmer)

Multimodal (label free)

FLIPR –

(Molecular Devices)

Kinetic fluorescence

Envision –

Fluorescence

/Luminescence

Capabilities - Readouts

CX5 – ThermoFisher (Cellomics)

High content screening assays

13

WES & JESS – Protein Simple

High throughput Westerns

QuantiStudio 6 – Life Tech

High throughput RT qPCT

Guava PCS-96 FlowCyte


Capabilities – Liquid Dispensers

14

HP digital dispenser

(non-contact dispenser)

Cybiwell

(well to well dispensing)

Multidrops and Combi’s

(bulk reagent dispensing)


Case Study - Positive AllostericModulator (PAM) Recombinant cell assay – calcium

mobilisation 384 well adherent assay using HEK-293

cells expressing a G-protein coupled receptor as a “frozen cell assay” – cells grown by us for screen

FLIPR – Flux Ca2+ or K+ Kinetic Imaging

15

1ul 'Standard' Compound

1ul test compound

1ul DMSO (negative control - agonist read + PAM read)

1ul 10mM Carabchol (positive contrl - agonist read)

1ul DMSO (positive contrl well - PAM assay)

Human primary cell assay – Neutrophils Fresh neutrophils isolated by density gradient

centrifugation, loaded with dye, dispensed into plates in suspension in presence of compounds, incubated then agonist is added on-line

Determine agonist EC20 on the day

Test compounds added on-line

(agonist / antagonist activity)

Incubate 30 mins

Add EC20 for PAM activity (also run EC100)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

EC20 Carbachol

EC100 Carbachol (40uM)

EC0 (Base buffer)

Agonist/Antagonist TemplatePAM Template


Fluorescence and Luminescence Assays

16

Client required a comparison of AlphaScreen,

Lance and HTRF for Epigenetic Enzyme

JMJD2C. Assays were developed / purchased

and a number of commercially available

compounds were profiled and plates screened

for statistical quality (Z’ factors)

HTRF Lance AlphaLISA

IC50 for 2,4-

PDCA

187 nM 234 nM 41 nM

IC50 for NOG 2.15 uM 2.2 uM 0.36 uM

HTRF LANCE AlphaLISA

R e p ro d u c ib ility fo r H T R F - 3 h o u rs d e te c t io n

W e ll n o .

HT

RF

ra

tio

66

5/6

20

0 1 0 2 0 3 0 4 0 5 0

0

2 0 0 0 0

4 0 0 0 0

6 0 0 0 0

8 0 0 0 0

N o in h ib it io n

IC 8 0

IC 1 0 0

R e p ro d u c ib ility fo r L A N C E

W e ll n o .

LA

NC

E s

ign

al

at

66

5n

m

0 1 0 2 0 3 0 4 0 5 0

0

2 0 0 0 0

4 0 0 0 0

6 0 0 0 0

8 0 0 0 0

1 0 0 0 0 0

1 2 0 0 0 0

1 4 0 0 0 0

N o in h ib it io n

IC 8 0

IC 1 0 0

R e p ro d u c ib ility fo r A lp h a L IS A

W e ll n o .

Alp

ha

Lis

a s

ign

al(

co

un

ts)

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0 0 0

1 0 0 0 0 0

1 5 0 0 0 0

2 0 0 0 0 0

2 5 0 0 0 0

3 0 0 0 0 0

3 5 0 0 0 0

4 0 0 0 0 0

4 5 0 0 0 0

N o in h ib it io n

IC 8 0

IC 1 0 0

• Case Study - JMJD2C Histone H3 Demethylase detection technology comparison

Client had a 96 well cell-based reporter assay using response element controlling luciferase production –

required us to re-start assay to screen compounds

• Found that some compounds interfered with the luciferase activity

• Designed, developed and implemented a selectivity assay to detect these interference compounds

• Iterative screening on a weekly basis

• Case Study - Luminescence Reporter Assay

Cell based assayBiochemical assay

Developing AlphaScreen

assay to measure protein

DMSO


Kinase screening using Target Engagement

Bioluminescence Energy Transfer (BRET) measureS

compound engagement with the kinase target. The kinase

cDNA plus the Nanoluc enzyme cDNA are transiently

transfected (24hrs) on a single plasmid. In the presence of

a cell permeable Nanoluc substrate, photons are

generated. Cells treated with a cell-permeable

fluorescently tagged tracer bind the tracer bringing the tag

into close proximity and excite the fluorescent tag

resulting in BRET. Compound engagement is measured

in a competitive format of tracer versus compound

-1 1 -1 0 -9 -8 -7 -6 -5

0

1 0

2 0

3 0

4 0

E ffe c t o f in h ib ito rs o n A B L k in a s e

[c o m p o u n d ] (M )

Ra

tio D a sa tin ib - IC 5 0 1 1 nM

N ilo tin ib - IC 50 340nM

F o re tin ib - IC 5 0 E s t 2 uM

P o na tin ib - IC 50 48 0nM

Cells were transfected with each of four kinase; ABL, FGR, EPHA8 and DDR-1 and treated with

exemplar kinase compounds including dasatinib, nilotinib, foretinib and ponatinib as a dose response

for each compound competed against a fixed concentration of fluorescent tracer K4 at the

concentration depicted in orange

0 5 0 1 0 0 1 5 0 2 0 0

0

1 0

2 0

3 0

A s s o c ia t io n R a te A B L K in a s e

T im e (m in s )

BR

ET

Ra

tio

A B L F o r t in ib

A B L D a s a t in ib

A B L N ilo t in ib

A B L P o n a tin ib

A B L D M S O

0 5 0 1 0 0 1 5 0 2 0 0

0

2 0

4 0

6 0

8 0

A s s o c ia t io n R a te D D R 1 K in a s e

T im e (m in s )

BR

ET

Ra

tio

D D R 1 F o rtin ib

D D R 1 D a s a tin ib

D D R 1 N ilo tin ib

D D R 1 P o n a tin ib

D D R 1 D M S O

0 5 0 1 0 0 1 5 0 2 0 0

0

2 0

4 0

6 0

8 0

A s s o c ia t io n R a te E P H A 8 K in a s e

T im e (m in s )

BR

ET

Ra

tio

E P H A 8 F o rt in ib

E P H A 8 D a s a tin ib

E P H A 8 N ilo tin ib

E P H A 8 P o n a tin ib

E P H A 8 D M S O

0 5 0 1 0 0 1 5 0 2 0 0

0

2 0

4 0

6 0

8 0

A s s o c ia t io n R a te F G R K in a s e

T im e (m in s )

BR

ET

Ra

tio

F G R F o rtin ib

F G R D a s a tin ib

F G R N ilo tin ib

F G R P o n a tin ib

F G R D M S O

Left: HEK-293 cells transiently expressing ABL, FGR, EPHA8

or DDR-1 were incubated for 2hrs at 37oC with a nominal

tracer K4 to allow the tracer to bind to the kinase.

Simultaneously both Nanoluc substrate and 10X IC50

concentrations of dasatinib (red), nilotinib (green), foretinib

(blue), ponatinib (purple) or DMSO (orange) were added to

the media surrounding the cells and the plates read every 5

mins. Compounds compete for binding to the kinase by

displacing the tracer, as such the rate of association (Kon)

can be determined.Right: HEK-293 cells transiently expressing ABL, FGR,

EPHA8 or DDR-1 were incubated for 2hrs with a 10X IC50

concentrations of dasatinib (red), nilotinib (green), foretinib

(blue), ponatinib (purple) or DMSO (orange), washed then

treated with a fixed concentration of tracer K4 in the

presence of the Nanoluc substrate. Readings were taken

every 5 mins. Data suggest that tracer K4 competes for

binding to the kinase targets and therefore the rate of

dissociation (Koff) of each compound can be determined.

Protein:Protein Interactions - NanoBRET

18

Depiction of energy transfer from

Protein A NanoLuc® fusion donor

to fluorescently labelled HaloTag®

acceptor Protein B upon

interaction of Proteins A & B

Competition of an ERK-2 inhibitor binding to ERK-2 and preventing the

binding of Shn-3

Screen was for inhibitors of the Schnurri-3 (Shn-3) ERK-2 PPI in HEK-293 cells. Shn-3

is a potent and essential regulator of adult bone formation. Mice lacking Shn3

profoundly increase bone mass. Shn-3 suppresses ERK phosphorylation of GSK-3

beta leading to suppression of beta-catenin activity. By blocking Shn-3 interaction with

ERK-2 we hope to remove this brake and increase bone formation in osteoporetic

patients.

Frequency Distribution of Compound Inhibition of the Shn-3 – ERK-2 Interaction

0

0.2

0.4

0.6

0.8

1

1 5 9 13 17 21 25 29 33 37 41 45 49 53

Z factor

Z F

acto

r

Plate Number

Fre

quency

Percentage Inhibition

0

1000

2000

3000

4000

5000

-30 -15 0 15 30 45 60 75 90 105

Series1

30% cutoff used

(1.3% hits = 233

compounds)

A PPI screen was

performed in 384 well

plates screening 50,000

compounds for inhibitory

activity on Schnurr-3 ERK-

2

Z factors for

assay consistency

and reproducibility

were 0.5 or above

Hit confirmation n=2 retest correlation

Successful identification of active PPI inhibitors

Dynamic Mass Redistribution/

morphological changes

Change in

Refraction index

Final read

monitored as response (pm)

Label free Cell-based assays - Concept

Broad band light sourceReflected

wavelength

Substrate

Wave Guide

Surface

Baseline Read

Cell

Detection

Window

Ligand binding to the

receptor

The advantages of cell-based assays are; generic, requires no genetic

manipulation, phenotypic, non-invasive, no interference

from auto-fluorescence


Label Free Combination –

Multiplexed Assay

20

• Case Study - Histamine H1 PathHunter (DiscoveRx) beta-arrestin cell line

Time (secs)

Res

po

nse

(p

m)

Cells treated with Histamine and

label free measured over 30 mins

[Histamine] (uM)

10-5 10-4 10-3 10-2 10-1 1 101

Re

sp

onse

(p

m)

20

40

60

80

100

120

140

160

180

200

220

240

EC50 = 50nM

[Histamine] (uM)

10-4 10-3 10-2 10-1 1 101

Re

sp

onse

(R

LU

)

40000

60000

80000

1e5

1.2e5

1.4e5

1.6e5

1.8e5

2e5

2.2e5

2.4e5

2.6e5

2.8e5

3e5

EC50 = 61nM

Res

po

nse

(p

m)

Time (secs)

Antagonist addition

Agonist addition

DiscoveRx detection

technology (equilibrium)

IC50 values (nM)

AntagonistLabel free

Beta arrestin(in LF plate) FLIPR

Certirizine 120 22 90

Chlorpheniramine 160 12 76

Triprolidine 40 4 26

Pyrilamine 50 4 34

• Human Primary Cells - Neutrophils

Res

po

nse

(p

m)

0.01 0.1 1 10

-200

0

200

400

600

800

1000

1200

Re

sp

on

se

(p

m)

[IL8] (nM)

EC50 = 1nM

Neutrophils isolated using density gradient

centrifugation, incubated in label free plates

(non-adherent) and treated with agonist /

antagonists


WES & JESS – High Throughput Western Blotting

21

WES and JESS (from Protein Simple) can be used for “high throughput” Western blotting

looking at protein generation, secretion and degradation from cells

Between 12 and 24 samples can be run in 3 hours together with molecular weight markers

WES is chemi-luminescence alone while JESS is both chemi and fluorescence allowing for

multiplexing of target and loading controls

Screen of 10 PROTAC

compounds. Negative

control (untreated cells)

and the positive control

were run in duplicate.

Positive control is a known

active PROTAC molecule.

Loading control is Vinculin

PROTAC Study:Compounds have a warhead that binds to

the target and a warhead that binds to an E3

ligase joined by a linker. Binding of the

compound to both the target and E3 ligase

brings the target into close proximity

resulting in ubiquitination and removal of the

target protein from the cells

Untreate

d

Positive C

on 1 2 3 4 5 6 7 8 9 10

0

25

50

75

100

125

PROTAC Compound Screen

Nor

mal

ised

Che

milu

nine

scen

ce


CellInsightT – High Content Screening Platform

• The CellInsightTM CX5 is a widefield imaging platform

• There are more than 30 pre-built applications including

cell cycle, autophagy, apoptosis and angiogenesis.

Custom analysis algorithms can also be established

Imaging

Analysis

Data

• Simultaneous image acquisition and data collection allows

high-throughput quantitative microscopy

• The CellinsightTM CX5 contains a bright-field channel plus

5 lasers allowing the multiplexing of fluorophores

-9 -8 -7 -6

0

2 0

4 0

6 0

L o g [A g o n is t] (M )

%H

IGH

_C

irc

Sp

otT

ota

lAre

aC

h3

Nuclei RFP Composite

Case Study: A client wanted to measure the movement of an

RFP-tagged protein from the cytoplasm to the

nucleus following agonist addition. The RFP

tagged protein was imaged and the fluorescence

quantified to give a dose-response curve

EC50 = 54nM


Spheroid Biology

23

Mitomycin C

WYE687

Staurosporine

10mM 5mM 2.5mM 1.25mM 62.5nM 31.3nM 15.6nM DMSO

100nM 50nM

25nM

12.5nM 6.25nM 3.13nM 1.56nM DMSO

10mM 5mM 2.5mM 1.25mM 62.5nM 31.3nM 15.6nM DMSO

100000

200000

300000

400000

-10 -9 -8 -7 -6 -5 -4

U87 Size

Log [Compound] (M)

Sp

hero

id A

rea

Nocodazole

Paclitaxel

mitomycin C

WYE 687

Staurosporin

Camptothecin

Control

Spheroid area (in pixels) plotted against compound

concentration in the presence of U87 cells, data is taken

from an 8-day time point. The cytotoxic effects of

staurosporine can be seen over time

Spheroids were allowed to form in ULA plates for 4-days, this was an

optimum time for cell compaction prior to drug treatment. To assess cellular

viability, spheroids were cultured and then treated with an increasing

concentration of compound. Each cell line showed a dose-dependent

decrease in viability with an increasing concentration of compound

0

1000000

2000000

3000000

4000000

5000000

6000000

-10 -9 -8 -7 -6 -5 -4

U87 Cells

Log [Compound] (M)

Lu

min

escen

ce (

RL

U)

Nocodazole

Paclitaxel

Mitomycin C

WYE 687

Staurosporine

Camptothecin

Untreated Cells

Spheroid Size Cell Titre GLO 3-D

Flow Cytometry Guava EasyCyte plus

96 well and tube

488nM laser can excite in green, yellow and red

Number of compatible fluors inc FITC, Alexa 488, R-

Phycoerythrin (PE), PE-TexasRed, PerCp, Propidium

Iodide, 7-AAD,

Assays include: cell health, cell cycle, apoptosis, surface

marker staining, cytokine release

Apoptosis markers…

Contr

ol

Nocodazole

5 u

M

Nocodazole

1 u

M

Nocodazole

0.2

uM

Nocodazole

0.0

4 u

M

Nocodazole

0.0

08 u

M

Nocodazole

0.0

016 u

M

0

2 0

4 0

6 0

8 0

1 0 0

T H P -1 c e lls t re a te d w ith N o c o d a z o le fo r 2 4 h o u rs

T re a tm e n t

Ce

lls

C

ou

nt (%

)

H ea lthy

N e c ro t ic

E a rly A p o p to t ic

A p o p to tic

Stained for Annexin V

and 7-AAD

Proliferation…CFSE staining

Human T cells stained with CFSE

following IL-2/CD3-CD28 exhaustion

THP-1 to macrophage

differentiation… marker

expression

CD11b expression

following PMA

treatment

THP-1 untreated

THP-1 PMA


Internal R&D – 3-D biology on ElectroSpun Scaffolds

Electrospun scaffolds made of Poly-L-Lactide of various sizes (100 to 1000 micron) that are islands to grow cells in 3-D and are: Magnetic

Cryo-perservable

Transfectable

Easy to handle

Reproduce pharmacology from cells

Labelled with fluorescence dyes

100 - 1000 micron

During manufacture Under SEM Under microscope

Environmental SEM – Epithelial cells

24hrs post inoculation

Environmental SEM – Epithelial cells

96hrs post inoculation

Fibroblasts 24hrs post inoculation

Note covering of fibres with cytoplasm Note cells completely engulf scaffold Note fibroblasts also cover scaffold

-2 -1 0 1 2

0

2 0

4 0

6 0

8 0

1 0 0

1 2 0

T ra n s fo rm o f A d h e re n t

L o g [ fo rs k o lin ] (mM )

% m

ax

re

sp

on

se

Log10 [forskolin] (µM)

1.2 µM

3D adherentExemplier

pharmacology –

response on scaffolds

by cells transfected

with CRE-luciferase

and stimulated with

forskolin % M

axim

al re

sp

on

se

-2 -1 0 1 2

0

2 0

4 0

6 0

8 0

1 0 0

1 2 0

T ra n s fo rm o f S ta b le C R E -L u c 2 P m a g n e t ic 9 6 -w e ll

L o g [ fo rs k o lin ] (mM )

% m

ax

re

sp

on

se

HEK293 cells - transient

0.5 µM

Log10 [forskolin] (µM)

72hrs post cryopreservation

25

• Assay Development and Pharmacological Validation (for iterative or

high throughput screening purposes)

• Cell-based assay

• Biochemical-based assay

• Assay Robustness (for HTS purposes)

• High Throughput Screening (HTS)

• Cell-based assay

• Biochemical assay based

• Exploratory Biology (technology or target)

• Iterative Cyclical Screening - Lead Identification (LI)

• Pharmacological Profiling of compounds

• Complete Discovery Project from Assay Development through to LI

• Reagent/equipment validation and benchmarking

Aurelia Bioscience Services


• Contracts are based on milestones with clear GO/NO GO decisions

agreed between client and ourselves

• Quote

• Costings broken down

• Agreed Schedule of Work

• Milestone 1: Feasibility study

• Basic pharmacology in the agreed assay format

• Milestone 2: Progressive study

• Plate based pharmacology looking at statistics,

robustness, QC

• Ad hoc Iterative screening – costs based per plate

• Milestone 3: Primary screen, retest and XC50

• Additional contracts for Hits to Lead (LI) work (iterative and/or

selectivity screening

• Contract can be terminated by either party at a milestone point

dependent on level of success

Contract Design


Communication – frequent and detailed through

teleconference and face-to-face meetings

Competency – high given our background

Transparency of data – provision of raw data,

interpretation and written report

Flexibility – understand and adapt protocols to

needs of client depending on results

Speed of service – able to work on projects quickly

and turn around data in design/make/test, lead

identification and lead optimisation cycles

UK-based, global outlook

Client focus


To find out more about Aurelia Bioscience go to: http://www.aureliabio.com

Gary Allenby PhD

Chief Scientific Officer

+ [email protected]

( +44 (0) 115 8370503 (UK)

For further information, please contact :-

Aurelia Bioscience


· Molecular Pharmacology based on “weighting” biological pathways and ... Added value to the...

Documents

Transcript of · Molecular Pharmacology based on “weighting” biological pathways and ... Added value to the...