Atlas Genetics Limited: a University of Bath spin-out company providing novel technology for rapid diagnosis of infectious diseases.
Submitting Institution
University of BathUnit of Assessment
Biological SciencesSummary Impact Type
TechnologicalResearch Subject Area(s)
Technology: Medical Biotechnology
Medical and Health Sciences: Clinical Sciences, Medical Microbiology
Summary of the impact
Atlas Genetics Ltd is a University of Bath spin-out company established
in 2005 by Dr John Clarkson, a former lecturer in the Department of
Biology and Biochemistry (DBB). In collaboration with DBB researchers,
Atlas Genetics developed novel technology for rapid (<30 minute) and
robust detection of infectious diseases at the point-of-care. Atlas
Genetics has raised over £22m funding specifically to develop the Atlas ioTM
detection system, which combines a patented electrochemical detection
system with probes for specific micro-organisms within a small disposable
cartridge. Different probe cartridges are used to detect a range of
pathogens that have critical clinical importance and large-scale
socio-economic significance, including Candida, methicillin
resistant Staphylococcus aureus (MRSA), bacterial meningitis, and
sexually transmitted diseases (STDs) Trichomonas, Chlamydia and Gonorrhoea.
Candida research in DBB underpinned the specificity, sensitivity
and application of the technology to clinical samples and was used in
seeking capitalization for Atlas.
Atlas Genetics re-located from the University to a nearby business park
and employs 35 full-time staff, some having moved from academia into the
company largely thanks to the synergistic relationship with University of
Bath researchers. The ioTM platform has undergone successful
clinical tests on Chlamydia and Trichomonas at Johns
Hopkins University, USA. The ioTM platform and Chlamydia
test is scheduled for clinical trials in 2014, with roll out in Europe and
the USA, pending regulatory approval, providing global reach within the
$42bn in vitro diagnostics market.
Underpinning research
The prompt diagnosis and treatment of life-threatening diseases not only
improves clinical outcomes but impacts on the cost of healthcare provision
and can lead to changes in clinical practice. The Atlas system comprises
test-specific disposable cartridges containing all reagents to extract and
amplify DNA from a clinical sample, and detect target organisms. Existing
DNA sensor technology is largely based on fluorescence detection, whereas
the Atlas ioTM (formerly VeloxTM) system is based on
electrochemistry. The core electrochemistry was being developed in Dr John
Clarkson's laboratory in the Department of Biology and Biochemistry (DBB)
in 1996 by a post doctoral researcher, Dr B. Cobb, who became an early
employee of the first company formed, Molecular Sensors Ltd, which listed
in 1999 as Molecular Sensing plc.
The detection assay technology was taken further and adapted in
collaboration with the University of Bath Department of Chemistry. The
basis of the assay is that the T7 exonuclease exhibits 5'-3' exonuclease
activity on double strand (ds) DNA, thereby cleaving the terminal
nucleotide at the 5' end of the probe. The higher diffusion mobility and
enhanced access of the enzymatically cleaved ferrocene label to the
electrode surface results in an increase in ferrocene oxidation current at
an electrode, allowing for sensor applications. It was soon realised that
this approach could be used for recognition of any oligonucleotide
sequence. Atlas Genetics has patented these unique and powerful assays for
detection of DNA and RNA using target-specific probes labelled with an
electro-detectable tag [see Section 5].
Subsequent developments by the DBB team involved further research using
this assay for detection of sequences which identify infectious diseases
that are both clinically and economically important, including bacterial
meningitis and methicillin-resistant Staphylococcus aureus (MRSA),
and the pathogenic yeast Candida. In parallel and in Atlas funded
collaboration, in DBB Dr Wheals developed methods for simultaneous
detection of multiple pathogens in a single reaction [1]. In the case of Candida,
five species (C. albicans, C. glabrata, C. parapsilosis complex,
C. tropicalis and C. krusei) account for over 90% of fungal
infections in the UK (Linton et al., 2007, J Clin Microbiol 45:
1152-1158) and are associated with mortality rates of up to 70% (Krcmery
et al., 2002, J Hosp Infect 50: 243-260). In the USA,
fungal pathogenic diseases are the fourth most common cause of
death from infections.
Importantly, electrochemical probes developed by Atlas/DBB reliably
distinguish the five Candida species from each other, and
from other fungal pathogens, in the presence of human DNA [2]. Probe
sensitivity allows detection of one genome equivalent in one ml of
sample [3] or around 10 yeast cells in one ml of human blood
[2], values which are suitable for application to clinical samples
(Loeffler et al., 2000, J Clin Microbiol 38: 586-590). The
development of this into point of care application was driven by the
current situation, where most hospital microbiological laboratories are
usually unable to detect and/or identify fungal pathogens. Consequently,
samples are sent by post to the National Mycology Reference Laboratory in
Bristol. This delays diagnosis by up to a week which has considerable
implications for patient outcomes.
Dr John Clarkson, a member of staff in DBB from 1985-2000, and Dr Alan
Wheals (DBB) developed the technology for Atlas Genetics, together with
colleagues from the Department of Chemistry. Dr Clarkson's company was
based in DBB laboratories from September 2005 to January 2008. He
continues to interact with several members of DBB, including Dr Wheals on
Candida species and Dr Ruth Massey on MRSA.
References to the research
[1] Muir A., Harrison E, Wheals, A. (2011) A multiplex set of
species-specific primers for rapid identification of members of the genus
Saccharomyces. FEMS Yeast Res, 11: 552-563. DOI:
10.1111/j.1567-1364.2011.00745.x
[2] Muir AD, Forrest G, Clarkson J, Wheals AE (2011)
Detection of Candida albicans DNA from blood samples using a novel
electrochemical assay. J Med Microbiol 60: 467-471. DOI:
10.1099/jmm.0.026229-0
[3] Muir A, Jenkins ATA, Forrest G, Clarkson J, Wheals AE
(2009) Rapid electrochemical identification of pathogenic Candida
species. J Med Microbiol 58: 1182-1189. DOI: 10.1099/jmm.0.009183-0
Funding to Department of Biology and Biochemistry:
1997 Hybaid funded post doctoral RO.
2006-2009 BBSRC CASE with Atlas; 2006-2009 BBSRC CASE with Unilever plc.
2005 University of Bath Sulis Seedcorn Fund £250,000.
Details of the impact
The novel technologies initiated in the DBB, together with subsequent
research involving DBB staff, has (i) provided proof of principle for the
application of Atlas Genetics technology to clinical diagnostics (ii)
assisted in capitalization of Atlas (iii) led to expansion of Atlas
Genetics activity to include bacterial and fungal pathogen targets, for
which clinical evaluation has been reached (Chlamydia, Trichomonas)
or is planned (Candida). The Atlas CEO commented:
"The creation of Atlas Genetics was only possible thanks to research
carried out in the Department of Biology and Biochemistry (DBB).
University of Bath support came as: funding (departmental BBSRC
studentship and University Sulis Fund); encouragement from the incumbent
HoD (Prof. S. Reynolds) and provision of laboratory space. Early patents
to Molecular Sensing arose during this period. Long term and ongoing
collaborations with academic staff, in particular Dr A. Wheals, have
contributed to the development of intellectual property and essential
capitalization. Atlas funded a BBSRC Case studentship to DBB in 2006 and
the resulting Candida research confirmed the speed of the technology and
its ability to be adapted to detect general groups (pan-fungal probe)
and distinct pathogen species. Exquisite sensitivity, even
from blood samples was a crucial demonstration.
Multiplexing will enable simultaneous detection of diverse pathogens.
Associated DBB links with the National Mycology Reference Laboratory
Bristol provided critical access to and advice from clinicians. Candida,
as a major cause of sepsis, was used as one of several targets when
seeking venture capital, before the eventual focus post-2011 on
Chlamydia as STDs grew in importance. Candida remains a future
potential Atlas target for hospital acquired infections and Atlas
remains committed to providing diagnostics solutions for sepsis.
This novel technology will enter clinical trials in 2014 and we are
confident that its speed and accuracy means that it will change
practices by allowing point of care application to result in direct and
rapid treatment of patients" [A].
Impacts from this work: company, investment, people and a new
technology
- A spin-out or new business has been created [B]. Jobs have been
created.
- Industry (including overseas industry) has invested in research and
development.
- Highly skilled people have taken up specialist roles in companies
- The health sectors in USA and Europe are trialling a new technology
Background
Molecular Sensors Ltd was the initial University of Bath spin-out
company, formed in 1996, listed as Molecular Sensing plc in 1999, then
sold in 2004 to the US-based diagnostics business Osmetech plc. Atlas
Genetics was launched with £500,000 initial funding, 50% of which came in
part from the Sulis Seedcorn Fund, established by the University of Bath
to provide support for new businesses. Atlas was founded as a spin-out
from the University and Osmetech plc in 2005. In 2007 Atlas completed
Series A financing of £2 million and the company relocated to a 2,500 sq.
ft. site on a business park close to Bath (Trowbridge, Wiltshire). The
number of full time staff increased to 12 and a commercial programme to
develop the Atlas system was initiated. STDs and sepsis and in particular
Candida, were proposed as key targets to potential investors.
Impact — development of the company arising from DBB underpinning
research
In 2010 Atlas obtained a grant from the Regional Development Agency grant
for the development of a Syphilis assay. Atlas was also awarded a
Technology Strategy Board grant for £1.6m in partnership with Randox
Laboratories and the Health Protection Agency (HPA). In early 2011 Atlas
secured £1.5m Series B funding from Consort Medical plc and other
investors in a synergistic partnership, to utilise the plastic device
manufacturing expertise of one of Consort's group companies, Bespak Europe
Ltd. Atlas then raised £16.9 million later in 2011 from a syndicate of new
and existing investors led by Novartis Venture Funds to further develop
the ioTM system, including a molecular Chlamydia test.
The new investors in this Series B financing are Novartis Venture Funds,
Life Sciences Partners (LSP), BB Biotech Ventures and Johnson &
Johnson Development Corporation.
Atlas then relocated in 2011 to new 9,500 sq. ft. premises and following
an expansion programme has increased the number of full-time staff to 35
(and 3 part time). Most have higher educational degrees in science,
engineering or business. Alistair Muir, a PhD student in DBB is now an
employee of Atlas Genetics (from 2012). Other Atlas investors include the
South West Ventures Fund, Finance South West Growth Fund, Braveheart
Ventures, Sulis Investment Management Fund, GEIF Ventures, Consort Medical
plc, and private investors. Atlas is currently venture capital funded and
to date has raised more than £23m. Dr Clarkson has been invited to
numerous investment conferences [C]. Fifteen patents have been granted and
nine applications are pending to date [D].
Impact — the Route to Clinical Implementation
Since 2008, the Atlas ioTM system has been in further
development and clinical testing, which has established its value in
diagnosis of a range of infectious diseases in humans, including Chlamydia,
Gonorrhoea, MRSA, and bacterial meningitis. Highlights include:
- Clinical evaluation and trials for Chlamydia and Trichomonas
infections Chlamydia infection is one of the most common STDs,
causing an estimated >95 million new cases globally of genital Chlamydia
infection every year, with prevalence rates in young people at 5-10%.
Rapid diagnosis is key to preventing disease spread. An independent
evaluation was performed by Johns Hopkins University, Department of
Medicine (Baltimore, USA). Results showed the clinical sensitivity and
specificity of the ioTM rapid Chlamydia trachomatis
assay compared with slower, laboratory based Gen-Probe Aptima Combo 2™
and the Roche Cobas Amplicor™ as comparator tests. These clinical tests
yielded impressive results that supported the adoption of the test in
clinical environments and led to a collaborative agreement between Atlas
and Johns Hopkins. The published collaboration showed sensitivity and
specificity of >98% [E]; it was developed further for Trichomonas,
showing sensitivity and specificity >95% [F]. Trichomonas
vaginalis is the most prevalent, curable STD in the world, causing
around 248 million new cases annually [G]. Trichomoniasis can lead to
vaginitis, cervicitis, and urethritis, infection during pregnancy can
lead to complications and can increase the risk of contracting HIV and
other STDs.
- Clinical trials coordinated by Public Health England for the Atlas Chlamydia
detection product are due to commence late in 2013 with the final
clinical evaluation in March 2014 [A]. The platform is scheduled to
launch within Europe with CE certification in 2014, followed by roll-out
in the USA pending regulatory approval.
- Development of tests with Candida [B] will follow the success
with Chlamydia.
Impact — Scope for Growth
The in vitro diagnostics (IVD) market is $42 billion and growing
at 6% annum. The most rapidly growing areas are molecular diagnostics
(valued at $3b and growing at 15% pa) and the point of contact (PoC)
market (valued at $2.5b and growing at 12% pa). Atlas's focus on PoC STD
testing, embraces both these fast growing areas of diagnostics and offers
substantial routes for expanded future impact in terms of both economic
and clinical benefits.
Sources to corroborate the impact
[A] Testimonial from Atlas Genetics CEO.
[B] Atlas Genetics:
http://www.atlasgenetics.com/
Capitalisation — http://www.atlasgenetics.com/press/18_jul_2011.html
"Atlas Genetics Ltd completes £16.9M series B financing led by Novartis
Venture Funds" Corroborating contacts — Atlas Genetics CEO;
Managing Director, Novartis Venture Funds.
[C] Invitations as speaker at investment conferences: Healthios Investor
Conf., Los Angeles, 2012; BioCapital Europe Investor Conf., Amsterdam,
2012; Molecular Tri-Conf., San Francisco, 2012;VentureFest, Bristol, 2011;
SMI Point-of-Care Diagnostics Conf., London, 2011
[D] Patents 2003-2013: Nucleic acid probes, 8 granted, 1 pending.
Electrochemically active compounds, 5 granted, 1 pending. Protease assays,
2 granted and 7 pending on; microbial assays; novel compounds; analytical
methods. Patent (or application) codes available on request.
[E] Pearce D M, Shenton et al. (2011) Evaluation of a novel
electrochemical detection method for Chlamydia trachomatis:
Application for point-of-care diagnostics. IEEE Trans Biomed Engin
58: 755-758.
[F] Pearce DM, Styles DN, Hardick JP & Gaydos CA (2013). A new rapid
molecular point-of-care assay for Trichomonas vaginalis:
preliminary performance data. Sex Transm Infect; Published Online First:
April 20, 2013. doi:10.1136/sextrans-2012-051000. Pearce and Shenton
are Atlas employees. This resulted from an
invited collaboration with Johns Hopkins University
MD, USA, funded by US NIH.
[G] World Health Organisation (2011). Global prevalence & incidence
of selected sexually transmitted infections Chlamydia trachomatis,
Neisseria gonorrhoeae, syphilis and Trichomonas vaginalis:
methods and results used to generate 2005 estimates. WHO, Geneva.