Kibow’s Educational Webinar - Probiota Asia · Kibow’s Educational Webinar Natarajan...

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


Biochemical /Metabolic Pathways in the

Human Body

4This presentation is the proprietary compilation of Kibow Biotech Inc. 2019


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


Diseases Influenced

by Gut Microbiota

http://genomemedicine.com/content/3/3/14/figure/F1?highres=y


Microbiome Everywhere

Image Src: http://theconversation.com/the-human-microbiome-is-a-treasure-trove-waiting-to-be-unlocked-118757

http://theconversation.com/the-human-microbiome-is-a-treasure-trove-waiting-to-be-unlocked-118757


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


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


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


Impaired Kidney Function

13

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


Stage I Stage II Stage IVStage III Stage V


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


Kidneys Three

Primary Functions

17

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


18

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 >>


C-Reactive Protein

19

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


We Are Passionate About

Humans, Cats, and Dogs Alike!

21

Azodyl - Licensed to veterinary

pharmaceutical company

Vetoquinol Paris, France, Since 2006



Drug Like Validation

SHIME Gut Flora Adaptation Studies


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


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


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



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


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


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



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



3.3 Million Genes

Dr. Rangan

and Dr. Kolff

(Inventor of dialysis

machines 1943)

Dr. Rangan and Dr. Kolff



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


Urea and chronic kidney disease: the

comeback of the century?



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.


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


Our poster presentation with Dr Jeff Gordon

at Harvard Medical School-2018

39

Fecal microbiome analysis- Challenges

40

1. Experimental designs and procedures

2. Sample collection and storage

3. NGS platforms4. DNA isolation procedures

and kits



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

[email protected]


“Hope never abandons you, you abandon it”

~ George Weinberg, American Writer, Psychologist and Activist

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