kibow’s educational webinar - probiota asia · kibow’s educational webinar natarajan...
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Working outside the box. Pre and probiotics for
beyond-the-gut conditions including Chronic Kidney Disease
Kibow’s Educational Webinar
Natarajan Ranganathan, PhD. (Dr. Rangan)
The PPT is proprietary compilation of Kibow Biotech Inc, 2017.
22-24 October, 2019 || Singapore
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
• 2005 - Innovation Corridor Abstract Winner, Boston, MA
• 2014 “Buzz of Bio Awards” – The First dietary supplement Company to win this award. International Bio conference, San Diego, CA
• 2018 - Invited Company for Presentation, Boston, MA
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019 2
Award winning and
patented technology
• The speaker is one of the key founders of Kibow Biotech Inc.
• Continues to be employed as key management and scientific personnel.
• Has substantial financial interest in the company.
• Roots from India, Fruits from USA
3
Disclosure Statement
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Biochemical /Metabolic Pathways in the
Human Body
4This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
This presentation is the proprietary compilation of Kibow Biotech Inc. 20195
Comparing Old vs.
New Technologies
1. Calling
2. Computer
3. Video
4. Music
5. Messaging
6. Banking
7. Monitoring health
8. Camera
9. Social Media
1. Only for calling
Ranganathan , N., & Vyas , U. (2012).
Probiotics, Prebiotics and Symbiotic: Gut and Beyond. Gastroenterology Research and Practice
This presentation is the proprietary compilation of Kibow Biotech Inc. 20196
Diseases Influenced
by Gut Microbiota
This presentation is the proprietary compilation of Kibow Biotech Inc. 20197
Microbiome Everywhere
Image Src: http://theconversation.com/the-human-microbiome-is-a-treasure-trove-waiting-to-be-unlocked-118757
This presentation is the proprietary compilation of Kibow Biotech Inc. 20198
Gut microbiome
profile in various diseases
Comparison of Human Genome
and Gut Microbiome
Human Genome10 Trillion cells23,000 Genes
Gut Microbiome100 Trillion cells
3.3 Million Genes
❑ Over 1000 different bacterial species in the intestines
❑ Microbiota has 100 times greater metabolic capacity than humans
‘the microbiota can be viewed as a metabolic organ exquisitely tuned to our physiology that performs function we have not had to evolve on our own’
Backhed et al. 2004. PNAS 101: 15718-157239
“WILL THE BOWEL BE THE KIDNEY OF THE FUTURE”
• SYMPOSIUM AT THE INTERNATIONAL SOCIETY OF ARTIFICIAL INTERNAL ORGANS IN EDINBURGH, SCOTLAND
Aug 04, 1999
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019 10
The Vision is Born
• 1. Heart disease• 2. Cancer• 3. Respiratory Diseases (COPD)• 4. Accidents • 5. Stroke• 6. Alzheimer’s disease• 7. Diabetes• 8. Influenza and pneumonia• 9. Kidney Disease• 10. Suicide
This presentation is the proprietary compilation of Kibow Biotech Inc. 201911
The top 10 Leading
Causes of Death*
2.6 million deaths annually(75%) is due to top 10 diseases.
* In United States
Urine
Healthy Kidney Function
Urea, Uric Acid,
Creatinine
Healthy Kidney
Function is to
Remove
Nitrogenous
Wastes
12This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Impaired Kidney Function
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Urine
Urea, Uric Acid,
Creatinine
Toxins Increase Uremic
Syndrome Fatal if Untreated
Waste Accumulation
Toxins Retained❑ Urea❑ Uric acid❑ Creatinine❑ Other guanadino compounds❑ Spermine and spermidine❑ Parathyroid hormone❑ Indoxyl sulphate❑ Phenol ❑ P-cresol❑ β2-microglobulin❑ Oxalate❑ Leptin❑ Tumor necrosis factor alpha❑ Hipurric acid❑ Pentosidine❑ Glyoxal
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Stage I Stage II Stage IVStage III Stage V
This presentation is the proprietary compilation of Kibow Biotech Inc. 201914
A Significant Unmet Market Need
(GFR > 90 ml/..) (60-90 ml/..) (30-59 ml/..) (15-29 ml/..) (<15 ml/..)
The different stages of CKD are assessed by Glomerular Filtration Rate (GFR)
Causes of CKD: Obesity, Diabetes, Hypertension,
HIV, Lupus, Tuberculosis, and other diseases.
$32 BillionMarket
$40 Billion Market
Target Market
Pre-dialysis(8 million patients)
ESRD(.6 million patients)
$74 Billion $40 Billion
Different Stages of Chronic Kidney Disease (CKD)
BAD
GOOD
Imbalanced Ecosystem has higher number of pathogens
and lower number of beneficial microbes
Clostridia
Proteus
Staphylococci
Pseudomonas
Bifdobacteria
Eubacteria
Lactobacilli
Bacteroides
E. coli
Enterococci
Streptococci
❑ CKD Patients
❑ Accumulation of uremic
toxins
❑ LOW levels of Lactobacilli,
Bifidobacteria
❑ Larger amount of pathogenic
bacteria
Healthy population• High levels of
Lactobacilli.• High levels of
Bifidobacteria
BAD
GOOD
Nosratola D Vaziri et al.Kidney International 19th Sept 2012Stephen Dunn and Michael Simenhoff. J of Am Soc Nephrol 9:146-A, 1998 15
Intestinal flora in Normal and
CKD population
This presentation is the proprietary compilation of Kibow Biotech Inc. 201916
Kidneys Three
Primary Functions
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Restoration of Dysbiosis-production of
bacteriocins with antibiotic like effect
Less protein putrefaction products-uremic toxins,
gut generated toxins
Metabolic Effects-serum cholesterol, lactose
tolerance,colon cancer risk
Inflammation Control-IBD, food allergy
Quality of Life (QoL)
Mechanism of Action
of Probiotics
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
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Inflammation
Markers of oxidative stress-NADPH oxidase, lipoxygenase,
xanthine oxidase, etc.Anti-inflammatory markers-IL-4,IL-6,IL-10, IL-11,IL-13
Production of Proinflammatorymarkers IL-1B,IL-6,IL-18,IL-23,TNF-a
Renadyl Mode of Action >>
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
C-Reactive Protein
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Mode of Action❑ Secretory
❑ Excretory
❑ Regulatory
Metabolism of Nitrogenous Wastes
Modulation of Inflammation
Production of Bacteriocins and (reduction of pathogens)
Renadyl Mode of Action >>
Renadyl - Possible Modes of Action
20
Hemo/Peritoneal/Enteric Dialysis -
Comparison
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
We Are Passionate About
Humans, Cats, and Dogs Alike!
21
Azodyl - Licensed to veterinary
pharmaceutical company
Vetoquinol Paris, France, Since 2006
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
This presentation is the proprietary compilation of Kibow Biotech Inc. 201922
Drug Like Validation
SHIME Gut Flora Adaptation Studies
23This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Human Clinical Trials Performed
Multi Site - CKD III & IV: Canada, Argentina, Nigeria, USA
Advances in Therapy Volume 27: Issue 9: Sept. 2010
Dose Escalation – CKD III & IV: Thomas Jefferson Univ, Philadelphia, PA
Journal of Nephrology & Therapeutics Volume 3: Issue 3: 2013
ESRD – Dialysis: Down State Medical Center, SUNY Brooklyn, NY
BioMed Research International Volume 2014, Article ID 568571
24This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Reduction was seen in blood urea nitrogen(BUN), uric acid and creatinine
Improved quality of life (QOL) with respect to physical activities, emotional wellbeing and
decrease in pain was observed
270 B CFU dosing per day is well tolerated without any adverse effects1
2
3
Clinical Trial Findings
Clinical Trial Findings
Levels of the inflammatory biomarker CRP decreased4
In the dialysis population, levels of indoxyl glucuronide which result out of gut dysbiosis and
protein putrefaction decreased5
25This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Internationa
l Journal of
Medical and
Applied
Sciences
Volume 3,
Issue 3,
2014
pages 183-
205
Cur Med Res
Open
Vol. 25, No.
8: 1919–1930,
Aug 2009
Kibow’s – Scientific Publications
BioMed
Research
International
Volume 2014,
Article ID
568571, 9 pages
“Journal of Nephrology & Therapeutics”
Volume 3: Issue 3: 2013
“Journal of Nephrology & Therapeutics”
Volume 5: Issue 4: 2015
“Advances in
Therapy”
Volume 27:
Issue 9: Sept.
2010
26
International
Journal of
Research
Studies in
Medical and
Health Sciences
Volume 2,
Issue 1, 2017,
PP 11-24
International
Journal of
Nephrology and
Kidney Failure
(ISSN 2380-
5498)
Volume 4 Issue
1,2018
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
This presentation is the proprietary compilation of Kibow Biotech Inc. 201927
Consumer Survey Data
Parameters 2013 2015 2017
Number of Responders (N) 147 168 200
Male (M) 84 80 117
Female (F) 57 71 83
No data (M/F) 6 17 14
Response Rate(%) 16 20 35
Quality of life- (QoL)Increased sense of well being(Mood , energy,
fitness)107(73%) 121(72%) 176(88%)
Improvement after taking Renadyl 108(73%) 120(72%) 176(88%)
Consumer survey data
Pharma like Validation
28This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Bifidobacteria longum (KB 31)
Lactobacillus acidophilus (KB 27)
Streptococcus thermophilus (KB 19)1
2
3
Hope in a Bottle
Deploy
probiotic bacteria
to consume
toxins in the bowel
Probiotic bacteria
29
Comparison of different treatments for
reduction of uremic toxins
30This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
May Re-establish the Equilibrium
Enteric Uremic Toxin Reduction
Continuous and steady removal of nitrogenous
waste metabolites
Qu
alit
y o
f lif
e
Time
Quality of life
Reduced yo-yo effect andImproved quality of life
Qu
alit
y o
f lif
e Quality of life
24
/731
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Gut Microbiome100 Trillion cells
3.3 Million Genes
Dr. Willem Jonathan
Kolff
(Inventor of dialysis
machines 1943) with
Dr Eli Friedman
(Inventor of portable
dialysis machine)
Dr. Willem Jonathan Kolff
32This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Gut Microbiome100 Trillion cells
3.3 Million Genes
Dr. Rangan
and Dr. Kolff
(Inventor of dialysis
machines 1943)
Dr. Rangan and Dr. Kolff
33This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Gut Microbiome100 Trillion cells
3.3 Million Genes
A Time to Remember
Dr. Eli Friedman’s
Foresight!
World Congress of
Nephrology, Singapore.
2005.
Human Safety Studies
A Time to Remember
34
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Urea and chronic kidney disease: the
comeback of the century?
35This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
This presentation is the proprietary compilation of Kibow Biotech Inc. 201936
Rat studies for hyperuricemia
using probiotics and prebiotics-
Results
Plasma uric acid levels were reduced in the probiotic fed groups at week 5
Rat studies for hyperuricemia using probiotics
and prebiotics - Results
37
Systolic blood pressure rose in the oxonic and placebo fed groups. In the probiotic fed groups with and without Curcumin the increase in the SBP was prevented from rising.
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Rat studies for hyperuricemia using probiotics
and prebiotics- Results
38
Urinary N-acetyl-beta-D-glucosaminidase (NAG) urinary activity which is a marker of tubular injury was also lower in the probiotic groups
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
Our poster presentation with Dr Jeff Gordon
at Harvard Medical School-2018
39
Fecal microbiome analysis- Challenges
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1. Experimental designs and procedures
2. Sample collection and storage
3. NGS platforms4. DNA isolation procedures
and kits
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019
This presentation is the proprietary compilation of Kibow Biotech Inc. 201941
KIBOW - MEANS HOPE (WORLD WIDE)Bringing hope to CKD patients worldwide
KIBOW - MEANS HOPE (WORLD WIDE)
Understanding the Cause not the Symptoms in
CKD - Chronic Kidney Disease
FUTURE-❑ Gut Microbiome modulation
❑ Use of probiotics and prebiotics,
❑ Dysbiosis-Stabilization
PRESENT-❑ Indoxyl sulfate,
❑ p-Cresyl sulfate
❑ Other Aromatic metabolites
PAST-❑ Urea,
❑ Uric Acid,
❑ Creatinine
Once
upon a time in
dialysis: the last
days of Kt/V urea.
Kidney International:
Raymond Vanholder,
June 2015
42
Dr. Natarajan Ranganathan
This presentation is the proprietary compilation of Kibow Biotech Inc. 2019 43
“Hope never abandons you, you abandon it”
~ George Weinberg, American Writer, Psychologist and Activist