Bionexus Gene Lab Corp · NASDAQ:BGLC
Bionexus Gene Lab — Technical Presentation (December 2020)
41 slides from Bionexus Gene Lab's technical presentation, Dec 22, 2020
Slide 1: RNA as a Screening Tool and Biomarker for Disease: A Paradigm Shift
RNA AS A SCREENING TOOL AND BIOMARKER FOR DISEASE: A PARADIGM SHIFT IN MEDICAL RISK STRATIFICATION DR STEPHEN PONNAMPALAM
Slide 2: Outline of presentation
Characteristics of an ideal biomarker DNA vs RNA as biomarker for risk stratification Sentinel principle: its applications for disease detection Epidemiology of disease mortality in Malaysia with a focus on cancer Current biomarkers: drawbacks ColonSentry: a trail blazer of the Sentinel principle ap
Slide 3: Characteristics of an ideal tumour marker
(1) Highly sensitive (2) Highly specific (3) Long lead-time (4) Levels correlate with tumour burden (5) Short half-life (6) Simple and cheap test (7) Easily obtainable specimens Characteristics of an ideal tumour marker
Slide 4: DNA vs RNA Screening
DNA vs RNA Screening DNA & RNA DNA vs. RNA Wid Uf ein srantes Cavern see seared
Slide 5: Messenger RNA (mRNA)
Messenger RNA (mRNA) ( fl DNA H mRNA Our genetic nvormation | Instructions for making a Basic building blocks ofall t protein from a gene cells in the body
Slide 6: Blood is in intimate contact with all human tissues including cancerous tissue
Blood is in intimate contact and interacts with all human tissues including cancerous tissue Peripheral blood cells (white blood cells: leukocytes) have the ability to respond to changes in the physiology and microenvironment of the body. Bloodomics: function of blood in regulation of gene expressio
Slide 7: Early detection of changes in the microenvironment and systems biology of the body
Early detection of changes in the microenvironment and systems biology of the body Gene expression: RNA levels which are dynamic vs DNA which is relatively static Sentinel Principle: can be used as an early biomarker to detect changes in the body including the earliest of changes that occur in cance
Slide 8: Epidemiology of Disease Burden in Malaysia
Top 5 causes of death in men: heart disease, pneumonia, road accidents, stroke, lung cancer Top 5 causes of death in women: pneumonia, heart disease, stroke, breast cancer and road accidents Epidemiology of Disease Burden in Malaysia
Slide 9: Percentage of most common cancers in Malaysia
Percentage of 10 most common cancers in Malaysia (Cancer Registry 2017/2018)
Slide 10: Malaysia: cancer statistics
Malaysia: cancer statistics (Cancer Registry 2017/2018)
Slide 11: Cancer statistics: Malaysia
Currently: 100,000 new cases per year By the age of 75, risk is 1:4 in developing cancer By 2020, there will be a 15% increase in cancer cases Cancer statistics: Malaysia Cancer Registry 2017/2018
Slide 12: Cancer Statistics 2018 Malaysia
Top 5 cancers: (1) Breast (17.3%) (2) Colorectal (14.0%) (3) Lung (10.7%) (4) Cervical (5.7%) (5) NPC (4.8%) Second major cause of death in Malaysia Cancer Statistics 2018 Malaysia
Slide 13: Late presentation despite existing screening programmes
Despite existing screening facilities and programmes, the results are dismal: Those presenting late (Stage III or IV disease): Breast cancer (41.3%) Cervical cancer (38.5%) Colorectal cancer (63.8%) Five year survival rate is less than 30% Cancer statistics 2017/2018: Malaysia
Slide 14: Early detection theme adopted by Ministry of Health, Malaysia
Theme form 2019 to 2021 adopted also by Ministry Of Health, Malaysia (MOH) is “ I am and I will” The purpose is to empower people to voice their commitments in taking action to overcome cancer. Our health minister has stressed the importance of EARLY DETECTION in cancer prevention and control 60% of
Slide 15: Screening for cancer at MOH hospitals
According to the MOH screening is provided for 4 types of cancers: breast, cervical, colorectal and oral cancer High risk individuals: screening for liver, prostate and nasopharynx Use cancer markers or methods that are NOT OPTIMAL Screening for cancer at Ministry of Health, Malaysia (MOH) hospitals
Slide 16: Late Presentation: causes
(1) The screening is cumbersome, lack of facilities and specialists; lack of awareness and education (2) Breast cancer: mammogram, self examination, clinical examination (3) Colorectal cancer: colonoscopy, CT colonography (4) Cervical cancer: PAP smear Late Presentation: causes
Slide 17: Current tumour markers: types
Used for screening in Malaysia: (1) Colorectal carcinoma: carcinoembryonic antigen (CEA) (2) Pancreatic/gastric carcinoma: CA 19-9 (3) Ovarian cancer: CA-125 (4) Prostate cancer: prostate specific antigen (PSA) (5) Hepatocellular carcinoma: α-fetoprotein (AFP) (6) Breast cancer: CA 27.29 (previously
Slide 18: Current tumour markers: characteristics of CEA
CEA: Oncofetal glycoprotein expressed in normal mucosal cells and overexpressed in adenocarcinoma especially colorectal carcinoma (CRC) Also elevated in other malignancies and in non-neoplastic conditions (cigarette smoking, PUD, IBD, pancreatitis, hypothyroidism, biliary obstruction and cirrhosis)
Slide 19: Current tumour markers: uses of CEA
CEA is NOT useful in screening for CRC NOT to be used as a diagnostic test for CRC Useful for SURVEILLANCE after a malignancy has been confirmed Major role for CEA levels is in following patients for relapse after intended curative treatment for CRC Diagnosis of CRC surgical resection surveillance w
Slide 20: Current tumour markers: characteristics of CA 19-9
Intracellular adhesion molecule found primarily in patients with pancreatic and biliary tract cancers but also in other malignancies (colon, esophageal and hepatic) Also found in benign conditions such as pancreatitis, biliary disease and cirrhosis No value in screening because the PPV < 1% PPV valu
Slide 21: Current tumour markers: characteristics of CA-125
Expressed in coelomic epithelium during fetal development Envelopes the ovaries Elevated in less than 50% of women with Stage I disease Also found in other malignancies and benign conditions PPV of 20% NOT to be used in screening because of insensitivity in early stage disease and low disease preval
Slide 22: Current tumour markers: characteristics of PSA
Glycoprotein produced by prostatic epithelium Elevated in prostate cancer but also in benign conditions such as prostatitis, BPH, prostatic trauma PPV in Stage I and II tumours is 20-30% rises to 50% in Stage III and IV disease USPSTF has recommended that PSA NO LONGER be used as a marker for prosta
Slide 23: Current tumour markers: characteristics of AFP
AFP is the major protein of fetal serum, falls to undetectable levels after birth Elevated levels of AFP are found in hepatocellular carcinoma (HCC) and nonseminomatous germ cell tumours of the testes (yolk sac tumour). AFP is also found in viral hepatits and cirrhosis. β-hCG is elevated in nonsemin
Slide 24: Current tumour markers: characteristics of CA 27.29
Monoclonal antibody Associated with breast cancer but also found in other cancers and benign disorders of the breast, liver, kidney and in ovarian cysts Now used in favour of CA 15-3 CA 27.29 is elevated in only 30% of women with Stage I and II breast cancer and 67% in women with Stage III and IV Lo
Slide 25: Summary Slide of Current Tumour Marker Use
Current tumour markers available in Malaysia :CEA, CA 19-9, CA 125, PSA, AFP, β-hCG, CA 27.29 All are NOT suitable for screening and diagnostic use because of low sensitivity, specificity and predictive value. Basically have NO VALUE in cancer screening OBSOLETE Summary Slide of Current Tumour Marke
Slide 26: Tests developed by BGS
Based on the Sentinel Principle Very early detection Risk stratification (low, medium and high risk) Uses a panel of genes for each disease that have been rigorously tested and validated statistically (Mann-Whitney, logistic regression analysis and Bayes’ theorem) Tests developed by BGS
Slide 27: Panel of tests developed by BGS
Have a panel of 14 tests: Cancers: Nasopharyngeal (NPC), lung, liver, stomach, breast, cervical, colorectal (CRC), prostate. IBD: Ulcerative colitis (UC) and Crohn’s disease Rheumatology: osteoarthritis Mental disorders: schizophrenia, MDD, bipolar disorder Tests developed by BGS
Slide 28: Future tests
Tests being developed: Alzheimer’s disease (needs to be validated) Heart disease and stroke (future tests) Future tests
Slide 29: Sample Report: Male
Sample Report: Male fs % iz z * 4 + ” ¢ 4 Menge stmth rote del UC} Gaver Geer ner net Cee,
Slide 30: Sample Report: Female
Sample Report: Female
Slide 31: Sample Reports
Description of disease Signs and symptoms Interpretation of results: what client should do, things to do to maintain a low risk Risk factors How the disease spreads Sample Reports
Slide 32: ColonSentry: A New Screening Test for Colorectal Carcinoma
COLONSENTRY COLONSENTRY: A NEW SCREENING TEST FOR COLORECTAL CARCINOMA
Slide 33: Recommendations for Screening
Recommendations for Screening United States Preventive Services Task Force (USPSTF): Every person above the age of 50 should have the following done: (i) Fecal occult blood testing yearly (ii) Sigmoidoscopy every 5 years (iii) Colonoscopy every 10 years Those with a family history of cancer syndrome
Slide 34: Current CRC Testing Algorithm
Current CRC Testing Algorithm CRC Testing Options FOBT/FIT Fecal Test ---- Repeat every 1-2 years Not used/low compliance Colonoscopy ---- Repeat every 5-10 years Positive Result Negative Result Repeat in 1-2 years Majority of population not getting screened
Slide 35: How does ColonSentry work?
How does ColonSentry work? RNA expression profiles differ between healthy and colorectal cancer patients Note: 7-gene panel ANXA3, CLEC4D, LMNB1, PRRG4, TNFAIP6, VNN1, IL2RB
Slide 36: Sensitivity and Specificity Priorities
Sensitivity and Specificity Priorities Priorities Low-Risk score patients want to rule-out disease High specifity is therefore more important to achieve a low false negative rate. High-Risk score patients want more certainty that disease may exist before doing more invasive procedures like colonosco
Slide 37: ColonSentry risk stratification sensitivity and specificity
Specificity 99% Specificity 97% Specificity 94% Specificity 88% Sensitivity 72% Specificity 70% Sensitivity 88% Sensitivity 94% Sensitivity 97% Sensitivity 99% Increasing specificity Increasing sensitivity ColonSentry Risk Stratification provides high sensitivity and high specificity where its impor
Slide 38: CRC Testing Algorithm with ColonSentry
CRC Testing Algorithm with ColonSentry CRC Testing Options FOBT/FIT Fecal Test ---- Low compliance ColonSentry Blood Test --- Risk Stratify Patients Colonoscopy ---- Repeat every 5-10 years Motivates non-compliant patients that were previously averse to a colonoscopy Repeat at next annual physical c
Slide 39: Applications
Applications Suggestions: (i) Routine pre-screening test for all patients above the age of 50 (in Malaysia above the age of 40), earlier and more frequently for those with FH of CRC or IBD (ii) Incorporated into annual physical examination or for screening
Slide 40: Future Biomarkers
RNA is a current biomarker and also a biomarker for the future Other biomarkers for the future: (1) Decoy receptors (2) sRAGE (3) Immuno-modulators Future Biomarkers
Slide 41: Thank You
Thank You i
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