GastroPanel Innovation

Pentti Sipponen, MD, PhDProfessor

Biohit Oyj, Helsinki

GastroPanel for the unmet need (1)

Gastrointestinal disorders are a growing medical, ethical and

economic global problem and they are among the most common

types of complaints made to primary care physicians worldwide

and are associated with a substantial healthcare and economic burden

Despite being one of the world’s largest therapeutic areas many of the diseases of the gastrointestinal tract are still poorly understood and diagnosis and therapy options are far from optimalleaving many patients dissatisfied with their current treatment

GastroPanel for the unmet need (2)

In addition, the ageing of the population is accompanied by severe diseases such as gastric, oesophageal and colorectal cancers as well as peptic ulcers, dementia, depression, polyneuropathy, heart attacks, strokes, anemia and osteoporosiswhich are causing an increasing burden for well-being and even a threat to sustainable health care

GastroPanel for the unmet need (3)

Biohit’s mission is to alleviate and solve these huge medical and economic problems

and to become a leading supplier of unique diagnostic products and analyzing systems

as well as turnkey, comprehensive GastroPanel Laboratories

with special focus on the development of safe, ethical and cost-efficient diagnosis of diseases and cancer prevention of the gastrointestinal tract (www.biohit.com/Diagnostics/Product Brochures /GastroPanel Laboratories)

GastroPanel for the unmet need (4)

The prevalence of dyspepsia is 20-40% of whole populationDyspepsia is not a specific symptomCorrect diagnosis is not possible by symptoms aloneGastroscopy with biopsies or GastroPanel are the only diagnostic alternatives of very often symptomless atrophic gastritis (loss of glands and function of the stomach mucosa) caused by H.pylori infection or autoimmune disease GastroPanel blood tests will help in rationalizing of the endoscopic investigations

Dyspepsia and the physician

Simple and reliable blood biomarker examination for primary care Safe, ethical cost-efficient stomach health test Non-radioactive ELISA tests based on highly specific monoclonal antibodies - assays can be automatized avoiding human errorsGastroPanel: pepsinogens I and II, amidated gastrin-17, and H.pylori antibodies Dyspetic patients: Enable reliable diagnosis of “healthy” stomach mucosa, H.pylori gastritis and atrophic gastritis with related risks, such as gastric and oesophageal cancer

GastroPanel

GastroPanel Primary examination

for physicians at Basic Health Care

Pepsinogen I or Pepsinogen I /II - biomarkers of corpus (oxyntic mucosa)

Gastrin - 17 - biomarker of antrum (antral G cells)

H.pylori antibodies - biomarker of gastritis

Biohit GastroPanel Examination – “Genuine Laboratory Test”

Venous blood sample. Sample needs centrifugation and stabilizer

Corpus

Pylorus Antrum

Esophagus

Amidated gastrin-17

Acid

+

-

Gastrin – Acid – Feedback Control Mechanism

Oxyntic (corpus) glands

Antral (pyloric) D and G cells

Food proteins+

Atrophic corpus gastritis: Low acid output and low serum pepsinogen I

GastroSoft computer

program helps and

assists in interpretation

of the GastroPanel data

Healthy, normal stomach: No risk of gastric disorders. Gastroscopy does not give additional

information from stomach.

Non-atrophic H.pylori (Hp+) gastritis: High ulcer risk, low cancer risk. Gastroscopy may be

helpful – decision by patient and physician.

Atrophic gastritis (Hp+ or Hp-): High cancer risk, low ulcer risk. High risk of malabsorption

of vitamin B12, calcium, iron and zinc. Unexpected malabsorption of pharmaceutical drugs. Stomach is acid-free – will be colonized with bacteria and fungi from oro-pharynx and

gut. Gastroscopy is mandatory.

Healthy, normal stomach: All biomarkers are normal.

Non-atrophic H.pylori (Hp+) gastritis: Only H.pylori antibody test is positive.

Atrophic gastritis (AG) - (Hp+ or Hp-):

PGI (g/L) and/or PGI / PGIIMild AG: 50 - <70 5 - <7Moderate AG: 30 - <50 3 - <5Severe AG: <30 <3

Atrophic gastritis is limited to corpus alone if gastrin-17 is 10 pmol/L

or more, otherwise atrophic gastritis is in both antrum and corpus

(highest known risk condition for gastric cancer!)

Healthy, normal stomach: Immediate gastroscopy is unnecessary because the risks of gastric diseases are practically

non-existing.

Non-atrophic H.pylori (Hp+) gastritis: Patient and physician may decide of further treatment and examinations.

Consider eradication of H.pylori!

Atrophic gastritis (Hp+ or Hp-): Gastroscopy is mandatory because of the

cancer risk. Eradication of H.pylori is necessary if present.

Healthy Stomach H.pylori gastritis Atrophic gastritis

GastroPanel examination

No risks – gastroscopy not the first

option

Treatment of H.pylori and gastroscopy

optional

Gastroscopy necessary

Developing populations (age 50 or more): 30% 50% 20%Developed populations (age 50 or more): 70% 25% 5%

Healthy Stomach H.pylori gastritis Atrophic gastritis

GastroPanel examination. “China study” on 81 patients

No risks – gastroscopy not the first

option

Treatment of H.pylori and gastroscopy

optional

Gastroscopy necessary

9 (11%) 27 (33%) Mild: 34 (42%) Moderate: 8 (10%)

Severe: 3 (4%)

______________________________________________________________ Endoscopy histology (N of cases)

Normal H.pylori AtrophicTotalgastritis gastritis

GastroPanel

Normal 541 34 4 579

H.pylori 64 255 24 343gastritis

Atrophic 5 15 34 54gastritis

Total 610 304 62 976

”Kalixanda” population sample from Sweden (Agreus

et al). Overall accuracy of GastroPanel 85%.

H.pylori G-17 PGI PGII Antrum Corpus EIU pmol/l microg/l microg/l <30 2-15 >30 <15

29 363 5 3.5 N A3

PGI is low indicating that corpus is severely atrophic. This conclusion is supported by low PGI/PGII ratio and high G-17.

Amidated G-17 is high indicating that antrum in normal

No H.pylori antibodies. H.pylori infection is lost or atrophic gastritis is “autoimmune” of origin.

Gastroscopy is mandatory for cancer risk. Risks of malabsorption of vitamin B12, calcium (risk of osteoporosis), iron and zinc. Stomach is likely totally achlorhydric (no acid).

GastroPanel - examples

Severe atrophic gastritis in gastric corpus

H.pylori G-17 PGI PGII AntrumCorpus EIU pmol/l microg/l microg/l <30 2-20 >30 <15

2 18 75 10.1 N N

All GastroPanel biomarkers are normal

Risk of cancer or peptic ulcer is nil – irrespective of age.

Gastroscopy will not give any additional information. Colonoscopy or other clinical examinations are more useful.

GastroPanel - examples

Stomach mucosa is normal and healthy

Healthy versus diseased (”sick” gastric mucosa):

Tohoku – Japan: Accuracy : 94% Sensitivity: 95% Specificity: 93%

Atrophic gastritis versus non-atrophic gastritis

Kalixanda – Sweden: Accuracy: 96% Sensitivity 71% Specificity 98%

GastroPanel examination

Is stomach mucosa ”healthy” or ”sick”?

GastroPanel provides diagnosis of H.pylori infectionbut also gives the diagnosis of very often symptomless atrophic gastritis in corpus and/or antrumwith related risks, such as gastric and oesophageal cancer, peptic ulcer disease and the deficiency of vitamin B12, iron and calcium. Atrophic gastritis is caused by H.pylori infection or autoimmune disease,and diagnosed only by GastroPanel or gastroscopy

GastroPanel vs. GastroscopyThe quality of the gastroscopy is strongly dependent on the experience and competence of the gastroenterologist and the pathologist

GastroPanel doesn’t have such quality problems, irrespectively who ever does the GastroPanel blood testsHowever, the diagnosis of atrophic gastritis obtained with GastroPanel is in good agreement with gastroscopy performed by skilful gastroenterologists and pathologists

H.pylori tests alone are uselessand may result in malpractice

13C urea breath test, stool antigen test and antibody tests do not diagnose atrophic gastritis with related risks, such as gastric and oesophageal cancer

13C urea breath test and stool antigen test may give even 50% of false negative results in patient with atrophic gastritis, MALT lymphoma, bleeding peptic ulcer or in patients with PPI or antibiotic treatments

GastroPanel does not include any of these serious medical and ethical problems

Serious Medical and Ethical ProblemsMalpractice and even unnecessary deaths, for example, due to gastric cancer and peptic ulcer bleedingsThese serious medical and ethical problems of the “test-and-treat strategy” can be solved simply and economically by omitting the 13C urea breath test, the stool antigen test or only antibody testsand replacing them with the GastroPanel examination, which provides abundant information of dyspepsia patients and healthy people for diagnosis and treatment

Enables non-endoscopic diagnosis and assessment of: Gastritis and H.pylori (Hp) infection Atrophic gastritis, both Hp+ and Hp- Risk for gastric and oesophageal cancer and peptic

ulcer dicease Risk for malabsorption of vitamin B12 (dementia,

depression, polyneuropathy), dietary calcium (osteoporosis) and iron (iron deficiency anemia) as well as some drugs

Hyperacid stomach: risks of the complications of gastroesophaceal disease, such as erosive oesophagitis and Barrett’s oesophagus

Healthy stomach

GastroPanel from blood plasma

GastroSoft Interpretation

GastroPanel Laboratory

All GastroPanel microplate reagents: Pepsinogen I, Pepsinogen II, Gastrin-17 and H.pylori IgG ELISA kits

Vertical measurement principle based instruments; manual or automatic

Pipettes and disposable tips Education and training After sales and service supportwww.biohit.com/Diagnostics/Product

Brochures/GastroPanelLaboratories

The History of Biohit’s GastroPanel Innovation (1)

The Finnish Gastritis Research Group, professors Max Siurala and Pentti Sipponen, and co-workers, on chronic gastritis and atrophic gastritis from the 70’s and 80’s

helped professors Barry J. Marshall and J. Robin Warren to realize that the infection and gastritis are connected to development of peptic ulcer diseases and stomach cancer

The History of Biohit’s GastroPanel Innovation (2)

The Nobel Prize in Physiology or Medicine for 2005 jointly to Barry J. Marshall and J. Robin Warren for their discovery of "the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease" in 1982

(http://nobelprize.org/medicine/laureates/2005/press.html )

The History of Biohit’s GastroPanel Innovation (3)

Professor Osmo Suovaniemi’s innovations, such as vertical measurement principle for micoroplates and very first microplate reader Titertek Multiskan, from the 60’s and 70’s, have

revolutionized microplate analyses worldwide and have been utilized so extensively and successfully since the 70’s, that they can justifiably be called global laboratory and industrial standards (www.google.com / Search “Osmo Suovaniemi vertical measurement principle”). His innovations resulted, among other things, in rapid and massive development of reliable and safe non-radioactive microplate immunoassays, on which the GastroPanel biomarker ELISA-tests (pepsinogen I and II, gastrin-17 and Helicobacter pylori antibodies) are based (www.biohit.com/About Us/History, www.biohit.com / Diagnostics).

Theranostic GastroPanel diagnosis and Acetium preventive treatment

GastroPanel Diagnose atrophic gastritis – Acid-free stomach: low PGI and/or low PGI/PGII and high G-17 Acid-free stomach is a risk factor of gastric and

oesofageal cancer

Acetium capsule Binds and inactivates carcinogenic acetaldehyde

(class 1 carcinogen for humans/WHO-IARC Oct 2009) in an acid-free stomach caused by atrophic gastritis or autoimmune disease

Thank You for Your Attention.