The document discusses a potential collaboration between LifeArc and Biocartis to develop a circulating tumor ESR1 Mutation Test using Biocartis' Idylla platform. The test would detect mutations in the ESR1 gene indicative of resistance to endocrine hormone therapy in metastatic breast cancer. LifeArc has expertise in diagnostic development and Biocartis has an automated molecular testing platform. The test could help guide treatment decisions for breast cancer patients by monitoring their risk of resistance to hormone therapies.

1. A partnered development of a circulating
tumour ESR1 Mutation Test for the detection
of metastatic breast cancer mutations
indicative of resistance to endocrine
hormone therapy
08 November 2018
Head of Diagnostics
Ciaran Fulton

2. Who are LifeArc?
A UK registered charity
Translating academic research
Life Science specialist
Founded in mid 1980s
25+ years in the ‘technology transfer’ business
Key Client: UK Medical Research Council
Collaborating widely - UK, Europe, USA, China

3. What LifeArc Does
Technology Transfer
Identification, protection, management and licensing IP
Centre for Therapeutics Discovery
Small molecule drug discovery team
Antibody engineering team
Centre for Diagnostics Development
Molecular Dx assay development
Pre-clinical & clinical validation
Business Development - scouting for great science
Scouting activities on 3 continents
Due diligence team

4. Our Organisation Today
Our ambitions driven by our Charitable ‘Objects’
‘To promote the public benefit by improving
human health and medical research…
‘Accelerate the progress of these discoveries and
technologies to the stage at which they are (i)
capable of being made generally available to the
medical profession and the public for practical
application for the improvement of health
and/or (ii) are transferred or licensed to a third
party to progress development of such
discoveries or technologies towards such goals’
Over 180+ Staff, spread over our three sites including…
30 in Technology Transfer (London)
80 Drug Discovery scientists (Stevenage)
10 Diagnostics scientists (Edinburgh)
We are financially self sufficient -
Revenue (2017/18) £25.85m
Expenditure (2017/18) £26.54m
With our R&D spending, we have invested over (2017/18)-
Drug Discovery £16.2m
Diagnostics Development £2.2m
We have also invested over £19m in a new Drug Discovery
Complex & Diagnostics Development Centre in Stevenage
and Edinburgh.

5. Products on the Market

6. LifeArc’s Centre for Diagnostic Development, Edinburgh
Set-up in 2014
We help translate early stage diagnostic opportunities
We work collaboratively with academics & industry partners
We do this at our own risk – providing the resources, expertise
& investment to effect this development
Our focus is in developing molecular diagnostics
Work across wide ranging disease areas
We’re interested in novel ways, new or enabling technologies
Look to find the best path to bring new & novel tools to the clinic
Our focus in diagnostics

7. Commercial Collaboration – Biocartis
co-development of a liquid biopsy assay
Biocartis is a molecular diagnostics company based in Mechelen, Belgium.
The Company’s proprietary Idylla platform is a fully automated, real time qPCR
system offering accurate, highly-reliable molecular information from any clinical
sample.
The Idylla system covers the entire process from sample to result in about 35 to 150
minutes with less than 2 minutes hands-on time.
Biocartis developed assays in oncology (KRAS, NRAS, EGFR & BRAF, RUO & CE-IVD)
and infectious diseases (IFV-RSV, FDA cleared); the platform is FDA waived & CE-IVD
marked.

8. Fully automated molecular testing with Idylla™Instrument
Console
Cartridge
(consumable)
Scan
sample
Scan
cartridge
Load
sample
Insert
cartridge
Clinically-
actionable
results
Superior sensitivity and ease-of-use, combined
with sample to result turnaround time of
90 to 150* minutes
* Based on turnaround times of current on-market oncology tests

9. Breast Cancer and ESR1 Mutations
First-line treatment of estrogen receptor (ER+) metastatic Breast Cancer (MBC) is
endocrine hormonal therapy: hormone treatments lower the levels of estrogen in the
body, or block their effects.
70% of Breast Cancers (BC) express estrogen receptors which makes them sensitive to
hormonal blockage.
Endocrine hormone treatments include selective estrogen receptor
modulators/down-regulators (SERMs/SERDs) or by estrogen agonists/antagonists, and
aromatase inhibitors (AIs).
The ESR1 gene codes for the estrogen receptor. Mutations in this gene have been
associated with acquired endocrine resistance in patients with ER-positive metastatic
breast cancer (MBC) previously treated with endocrine therapy.
ESR1 mutations are rare in primary breast cancers at the time of diagnosis (<2%).

10. ctESR1 Mutation Assay
The Biocartis Idylla ctESR1 Mutation Test will be developed
for the detection of 10 point mutations within the ligand-
binding domain (LBD) of the ESR1 (estrogen receptor 1) gene.
The assay will target patients with ER-positive metastatic
breast cancer who may be at risk of acquiring resistance to
endocrine hormone therapy.
Mutation SNP Sequence
E380Q [n1138] G -> C CTTCTACAATGTGCC
S463P [n1387] T -> C TTTCTGCCCAGCACC
L536H [n1607] T -> A GTGCCCCACTATGAC
L536R [n1607] T -> G GTGCCCCGCTATGAC
L536P [n1607] T -> C GTGCCCCCCTATGAC
L536Q [n1607_1608] TC -> AG GTGCCCCAGTATGAC
Y537N [n1609] T -> A GTGCCCCTCAATGAC
Y537S [n1610] A -> C GTGCCCCTCTCTGAC
Y537C [n1610] A -> G GTGCCCCTCTGTGAC
D538G [n1613] A -> G GTGCCCCTCTATGGC
E380Q S463P
AF-1 DBD Hinge LBD
L536H
L536R
L536P
L536Q
Y537N
Y537S
Y537C
D538G
5

11. Initiated breast cancer menu development with partners
Resistance
monitoring test
Therapy selection
test
1. On 15 June 2017 MRC Technology changed its name in LifeArc. LifeArc has been involved in helping deliver a number of therapies including Keytruda (pembrolizumab, marketed by MSD) which is an important immunotherapy treatment for various cancers
2. Partnership is with ETPL, the commercialization arm of A*STAR
• Liquid biopsy test
• Monitoring of metastatic breast cancer
patients for resistance to hormone
therapy
UK based medical research charity1
Description Partner
• Solid biopsy test
• Supporting optimal therapy selection
decisions for breast cancer patients
Singapore’s Agency for Science, Technology and
Research2
Partnership structure
• Development multiple Idylla™ tests
• LifeArc acts as development contractor
• Biocartis responsible for commercialization under
own label
• Parties will co-invest in development of selected
Idylla™ tests
• A*STAR acts as development partner
• Biocartis responsible for commercialization under
own label
Oncotype Dx Breast
Recurrence Score®
test US based provider of genomic-based diagnostic tests in
cancer
• Solid biopsy test
• Tailoring treatment of breast cancer
patients based on the biology of their
individual disease
• Genomic Health to develop Idylla™ versions of
proprietary Genomic Health tests
• Genomic Health responsible for
commercialization under own label
• Biocartis acts as supplier of tests