EVOC ProbesExogenous VOC (EVOC) Probes are compounds not normally found on breath at significant levels. When introduced into the body (individually or as a cocktail), EVOC Probes can be used to explore how the body is absorbing, metabolizing or excreting specific compounds.

EVOC Probes are safe compounds, largely food additives, that when administered orally, undergo metabolism in the body and are excreted via breath.

Breath Biopsy® provides the tool to monitor the products of the metabolism under investigation.

This approach explores the development of research tests for applications where naturally occurring VOCs alone may be insu�cient, and to run smaller, focused and likely faster clinical trials for us and our customers.

Our initial focus is in liver function and health, and drug metabolism testing where we are able to target specific enzymes in the liver (e.g. CYP450 family), however they also hold the potential in a wide range of additional applications (see overleaf for examples).

EVOC® Probes

EVOC probe

EVOC product(s)

Breath Biopsy EVOC Probe Research Kit• Collect reliable non-invasive exhaled breath samples

for research on liver function and other areas

• Assess enzymatic activity by monitoring clearance ofthe EVOC probe from the system and the secretion ofmetabolic product(s) generated

• Can administer a cocktail of EVOC Probes to testmultiple targets simultaneously

• Send Breath Biopsy Cartridges to Owlstone Medicalfor targeted quantitative analysis and reporting

Absorption

ExogenousVOCs and volatile

metabolic products

Valuable, specific,quantifiable, characteristic

metabolicinformation

Disease and phenotypecharacteristic metabolic

processes

Secretionin Breath

EVOC Probes Collectionand analysis

owlstonemedical.com/evoc-probes

α-Pinene

β-Pinene

Limonene

Eucalyptol

p-Methan-3-one

AcetoneIsoprene

0.0

15.0

25.0

35.0

45.0

20.0

30.0

40.0

50.0

5.0

10.0

CTRL CTRL 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0

PE

AK

AR

EA

FO

LD C

HA

NG

E v

s. C

ON

TR

OL

TIME AFTER INGESTION OF PEPPERMINT CAPSULE (HOURS)

Peppermint Capsule Ingested

owlstonemedical.comOwlstone Medical Ltd, 183 Cambridge Science Park, Milton Road, Cambridge, CB4 0GJ, UK

Company Number 04955647 | VAT Number 260449214

Owlstone Medical's Products and Services are for research use only.Not for use in diagnostic procedures.

OW

-017

239

-MC-v1.0

-01/20

19

Example Research Applications of EVOC ProbesMonitoring Liver function

The liver is a multifunctional organ, it manages uptake and neutralization of toxic substances from the blood as well as the metabolism of drugs.

Poor liver function can be due to infection, alcohol abuse, genetic disease, transplant rejection and other factors. Liver damage is often hidden until the point of self-correction has passed.

There is a need for clinicians to reliably measure liver function to detect and monitor the progression of disease or as a predictive tool for the impact of therapy and disease treatment. A range of diagnostic tests of liver function currently exist, but none are specifically driven by liver function.

Combining Breath Biopsy with EVOC Probes has the potential to generate a measurement of liver function and to distinguish between di�erent types of liver disorders by measuring the activity of key liver enzymes.

Drug Metabolism

Approximately 40% of drugs do not work as expected leading to adverse events or to reduced therapeutic benefit.

This is largely due to drug metabolism, the biologic processing of drugs from pro-drugs into their active forms and the breaking down of drugs for excretion. When this process goes wrong, a drug can build up in the body to toxic levels or the active form never reach su�cient levels to have the desired therapeutic e�ect.

A large number of small molecule drugs are metabolized by a class of enzymes called the cytochrome P450s, of which four are responsible for metabolizing approximately 70% of small molecule drugs, including most of the most highly prescribed medications across all indications including Lipitor (cardiovascular), Zoloft (mental health), and Tramadol (pain).

CO

NC

EN

TR

AT

ION

TIME

AUC

Changes in metabolizer phenotype canlead to drug toxicity or ine�cacy

Rapid metabolism of the pro-drugto the active form leads to toxicity

Rapid metabolism of the activedrug leads to lack of e�cacy

MTC

MEC

TherapeuticRange

Durationof action

Cmax

tmaxOnsettime

30%

20.0-29.9%

10.0-19.9%

<10%

Data not available

NAFLDPrevalence

Knowledge of a patient’s drug metabolism status allows clinicians to make more informed decisions as to which drugs to prescribe and at what dose. Pharmacobreathomics with Breath Biopsy enables the investigation of drug metabolism status by phenotype.

NAFLD and NASH

Nonalcoholic fatty liver disease (NAFLD) is a condition that leads to excess fat storage in the liver. There are two subtypes of NAFLD: simple fatty liver and nonalcoholic steatohepatitis (NASH).

Simple fatty liver is the more benign, but in approximately 25% of cases however, NAFLD develops into NASH where inflammation and liver cell damage can cause fibrosis, or scarring, of the liver, and can lead to cirrhosis or liver cancer.

The global burden for these diseases is enormous, with the global prevalence of NAFLD at approximately 25% and NASH at up to 7%.

Gold standard testing for the diagnosis of these diseases involves a range of expensive and time-consuming tests followed by liver biopsy for confirmation, which is invasive and carries substantial risk for the patient. Therefore, there is a need for a reliable and non-invasive method to monitor progression of disease, identify patient subpopulations for risk profiling, and to help optimize treatment regimes.

As with other forms of liver disease, EVOC Probes o�er a promising alternative approach which can be used to investigate whether breath analysis can be deployed as a novel non-invasive approach to monitor NAFLD and NASH disease progression.