FlexNow®
with 100% SheaFlex70TM
brought to you by BSP Pharma Inc.
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1
Table of Contents
•
•
•
Value Proposition
Testimonials
Clinical Review
– Destructive Inflammation Cascade
– Alternative Interventions
– Selected Clinical Trial Review
•
•
FlexNowppt081509b
Safe / All Natural / Sustainable
Summary
2
The Next Generation of Joint Care:
Quadruple Action Joint Solution
Proven: Over 30 clinical trials and studies prove
FlexNow with 100% SheaFlex70:
1. Reduces inflammation by 9 times
2. Improves cartilage retention by 44%
3. Increases bone retention by 10%
4. Alleviates pain by 45%
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The Next Generation of Joint Care:
FlexNow
with 100% SheaFlex70
New, Unique and Incremental:
– Not a building block (like GS), Not a lubricant (like HA), Not a COX-inhibitor
– Single ingredient product, Not a compound formula
– Exclusive, Patented and available only through BSP Pharma
Safe and All Natural:
– No contraindications, No side effects, No allergies
– Active material: High Triterpene Shea Nut Extract [HTSNE]
– Source material: Shea Nuts
• not a nut, but the pit of the shea fruit
• used to make shea butter, common in cosmetics
• Shea butter contains less than 6% shea triterpenes; FlexNow with 100%
SheaFlex70 contains 70% shea triterpenes
Sustainable:
– Wild-crafted/harvested
– Processed in concert with the UN Development Programme
4
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Target Consumers
•
Target Market: Joint Health
– 60+mm joint care consumers;
– 45+mm Osteo-Arthritis sufferers;
– 30+mm GS users
• FlexNow® with 100% SheaFlex70™ is effective for individuals who
experience or are experiencing joint discomfort or pain, stiffness, loss of
flexibility or mobility – anyone who may not be as active as they would like,
due to joint issues:
–
–
–
–
–
Arthritis sufferers
Athletes: Professional, amateur and occasional
Menopause
Accident prone consumers
Genetic predisposition to joint issues
– GS/CS and other joint care product users who have not realized
complete relief – Add FlexNow to existing regimen (not a replacement
solution)
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Dose Regimen:
FlexNow with 100% SheaFlex70
• Take one dose of 3 softgels per day,
with or without food;
• Effective with or without other joint
care products. Recommended with
building block products (eg, GS/CS)
• 4-6 week dosing cycle required for
clinical benefits
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Table of Contents
•
•
•
Value Proposition
Testimonials
Clinical Review
– Destructive Inflammation Cascade
– Alternative Interventions
– Selected Clinical Trial Review
•
•
FlexNowppt081509b
Safe / All Natural / Sustainable
Summary
7
Testimonials:
FlexNow with 100% SheaFlex70
• Hundreds of consumers have contacted us
and shared stories of how FlexNow has
changed their lives:
– Arthritis: Hands, Knees, Shoulders, Feet, Neck,
Elbows, Spine
– Chronic and Acute Pain
– Bone repair
– Endurance
• Representative testimonials may be found at
www.PowerOfShea.com/testimonials
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Testimonials: FlexNow with 100% SheaFlex70
The Skeptic
Being an RN with over 30 years experience...
I decided to try it for the horrible inflammatory arthritic condition I was experiencing in my hands.
I had tried all the over the counter and prescription NSAIDs and nothing worked to relieve the pain and
swelling. I was desperate for help, and I could no longer turn the key to start my car, open a jar, turn a door
knob, or hold a hair dryer.
After 7 days the swelling had improved, and I was close to making a fist again. Now, after taking FlexNow®
with 100% SheaFlex70™ for 3 months, my hands are pain free and I can wear my rings again. I am so
glad I tried FlexNow® with 100% SheaFlex70™…
Maridel - AL
Joint Replacement/Replacement
My left knee was rebuilt twice. My last surgery was in 1999.
When I blew out my “good” knee in 2007, I realized it was time to put away my bike for good. Very depressing –
but I figured it’s just part of getting old.
My health food store talked me into trying FlexNow® with 100% SheaFlex70™.
In two weeks I felt good enough to try my stationary bike. By the end of March, I could ride my bike outdoors
again. Without PAIN.
Both of my knees are pain-free. I have built up muscle tone, finally. My limp is gone, finally. I’ve lost almost 20
pounds due to the exercise. I FEEL GOOD. Your product is fantastic. At age 50, I feel like I have a new
lease on life. I feel healthy…
Sharon - PA
Relapse:
I once ran out of your product, and had trouble finding it. By the time I got re-supplied, I had slipped back into
agony….
Kathy - FL
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Table of Contents
•
•
•
Value Proposition
Testimonials
Clinical Review
– Destructive Inflammation Cascade
– Alternative Interventions
– Selected Clinical Trial Review
•
•
FlexNowppt081509b
Safe / All Natural / Sustainable
Summary
10
Inflammation: the root of disease
Diseases of the heart—blood vessel inflammation
Malignant neoplasms—inflammation proven to contribute to
oncogenesis
Cerebrovascular disease—blood vessel inflammation
Chronic lower respiratory disease—bronchi chronic inflammation
Diabetes—especially Type II, excessive inflammation impacts
blood sugar metabolism
Influenza and pneumonia—over-expression of inflammation at
immune system trigger
Alzheimer’s Disease—inflammation predisposes neurofibrilary
plaques and tangles
Nephritis and nephroses—chronic kidney inflammation
Chronic liver disease/cirrhosis—chronic liver inflammation
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Source: National Vital Statistics Report, Volume 53, Number 5 (October 2004)
Joint Structure
muscle
synovial fluid
tendon
bone
bone
Joint
capsule
(ligaments)
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synovial tissue
cartilage
Stages of Osteoarthritis
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Destructive Inflammation Cascade
•
When the body is injured or infected with a pathogen, the immune system releases
cytokines
•
Cytokines target the area of concern, increase vascularity (allowing the body access
to fight and repair) and drive inflammation
•
Joint stress (eg, wear and tear: micro cartilage tear or bone fissure) often results in a
destructive inflammation cascade
– Cytokines released; vascularity increases
– Inflammation builds in the affected area
– Pain, tenderness and discomfort are evident
– Cytokines strip cartilage and erode bone tissue
• Body sends bone tissue and cartilage repair elements to affected area
• Inflammation impedes proper repair:
» bone spurs and/or hard/dense bone build up, further damaging
already weakened and inflamed cartilage
» Inflamed cartilage is challenging to repair properly; raw material
may be challenging to deliver to the inflamed areas, increasing
likelihood of additional bone damage
• incremental damage occurs through use of poorly repaired site
– More cytokines are released -- cytokine production can multiply 1000 fold when
activated
– Inflammation builds further, and the destructive inflammation cascade
continues…
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Cytokines drive inflammation in the body, can ramp up 1,000 fold
when activated, often resulting in a destructive inflammation cascade
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How it works: FlexNow® with 100% SheaFlex70TM
•
Managing cytokines and the destructive inflammation
cascade is key to reducing pain and effectively
repairing the affected areas.
•
FlexNow with 100% SheaFlex70 modulates the
production of cytokines and controls the destructive
inflammation cascade:
Cytokine management: FlexNow with 100% SheaFlex70
reduces cytokine production: IL-6 by 31% and TNFa by 24%, resulting in:
1.
2.
3.
4.
Inflammation reduction: Reduces inflammation by 9X
Cartilage retention: Decreases breakdown in collagen /
cartilage by 44%
Bone regulation: Reduces Osteocalcin (a measure of bone
destruction) by 10%
Pain management: Alleviates pain by 45%
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Joint Structure
muscle
synovial fluid
tendon
bone
bone
Joint
capsule
(ligaments)
synovial tissue
cartilage
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Composition of Joint Cartilage
• The least abundant part of cartilage is
proteoglycans, representing 30%
– The shock absorbing part of the
cartilage matrix
– Glucosamine/chondroitin impacts
proteoglycans
• The most abundant part of cartilage
is collagen, representing 70%
– The meshwork that holds
proteoglycans in place in cartilage
– FlexNow with 100% SheaFlex70 [High
Triterepene Shea Nut Extract] impacts
the collagen portion of the cartilage
matrix
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Healthy Joint Cartilage
Healthy Cartilage structure:
• Collagen: Golden bands
– 70% of cartilage
– Impacted by FlexNow with
100% SheaFlex70 [High
Triterepene Shea Nut Extract]
• Proteoglycans: Turquoise
– 30% of cartilage
– Impacted by GS/CS
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Damaged Joint Cartilage
When joint injury occurs:
•
Collagen meshwork (golden bands) breaks and
shreds
•
Proteoglycans (turquoise) leak out, reducing
joint lubrication / shock absorbing qualities
•
Destructive inflammation cascade:
–
Cytokines are released
–
Inflammation increases
–
Proper repair of the joint is challenged…
–
Additional damage occurs, and the cycle
continues
FlexNow with 100% SheaFlex70 [High Triterepene
Shea Nut Extract] has been proven to reduce
cytokine production, resulting in:
1.
Inflammation reduction: Reduces
inflammation by 9X
2.
Cartilage retention: Decreases
breakdown in collagen / cartilage by 44%
3.
Bone regulation: Reduces Osteocalcin (a
measure of bone destruction) by 10%
4.
Pain management: Alleviates pain by
45%
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Inflammation: Categories of
Allopathic Intervention
1.
Non-steroidal anti-inflammatory drugs
(NSAIDS)--COX 1 and 2 blockade: ibuprofen
(Motrin), naproxen (Aleve), ketoprofen (Orudis)
2.
Steroids—broad spectrum suppression of
immune and inflammation response: prednisone,
dexamethasone (Decadron), hydrocortisone
3.
COX 2 Inhibitors: celecoxib (Celebrex)
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FlexNow vs Alternatives
Relative to other remedies, FlexNow with 100%
SheaFlex70 offers more relief and is better for the
body than:
• Steroids: Clinical benefits are similar, without the side
effects
• Analgesics: Taken every day, FlexNow joint-specific
pain management exceeds the benefits of analgesics,
without the side effects
• Glucosamine:
– 48% better than GS; even better with GS.
– GS targets 30% of the cartilage matrix (proteoglycan); FlexNow
impacts the other 70% (collagen)
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Over 30 Clinical Trials
and studies prove:
FlexNow
with 100% SheaFlex70
•
•
•
•
Reduces inflammation by 9 times
Improves cartilage retention by 44%
Increases bone retention by 10%
Alleviates pain by 45%
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ACCMER Trial Parameters
Randomized Placebo Controlled Trial on the Safety and
Efficacy of BSP-201 in Osteoarthritis. ACCMER.* Cheras PA,
Myers SP, Outerbridge K, Nielsen G. Sept. 4 2007.
A randomized, double-blind, placebo-controlled single center
study.
• Active: FlexNow with 100% SheaFlex70
• Subjects:
– 117 participants, 58 active, 59 placebo
– Radiologic and clinical evidence of osteoarthritis of the knee and/or
hip
• Measures:
– WOMAC (Western Ontario and McMaster Universities OA index)
– COAT Scores (Comprehensive Osteoarthritis Test)
• Duration: 15 weeks
• Note: At the end of the study, scores were not at plateau,
trending downward. Longer studies in the future may yield
even more optimal results.
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ACCMER Overall Trial Results
• Cytokine Reduction:
– 17.9% TNF-a overall reduction; 23.9% reduction in group with
elevated TNF-a
– IL-6 fell by 30.9%
– CRP was reduced by 20.6%
• Cartilage retention: CTX-II cartilage marker:
– Reduction of 28.7% in subjects with elevated levels,
– Placebo group increased 17.6%
– 46.3% reduction in cartilage destruction
• Bone retention: Osteocalcin (marker of bone
destruction) 9.2% reduction in elevated group
• Pain management: statistically significant pain reduction for
both men and women
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HTSNE and Dexamethasone (steroid) produce
similar Arthritis Clinical Scores:
Controls Arthritis
6
Vehicle control
Mean score Day 28
5
4
High Triterpene Shea Nut
Extract 1000 mg/kg*
3
2
Dexamethasone 0.025
mg/kg*
1
0
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High Triterpene Shea Nut Extract: Screening for Effect on Rat; Type II
Collagen Arthritis. Jorgensen JD, Weidner MS. Unpublished
pharmacological report. April 10, 2003
Level of statistical significance: * p<0.0001, Mann-Whitney U test
HTSNE and Dexamethasone (steroid) exhibit
similar infammation reduction properties:
Reduces inflammation
Level of statistical significance: * p<0.0001, Mann-Whitney
U test
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*HTSNE = High Triterpene Shea Nut Extract
HTSNE and Dexamethasone (steroid) exhibit
similar infammation reduction properties:
Reduces inflammation by 9-times
0.2
0.18
Vehicle control
Paw swelling, ml
0.16
0.14
BSP-201 250 m g/kg****
0.12
0.1
BSP-201 500 m g/kg****
0.08
0.06
BSP-201 1000 m g/kg****
0.04
0.02
Dexam ethasone 0.025
m g/kg****
0
Level of statistical significance: **** p<0.0001, Mann-Whitney U test
BSP 201 Screening for Antiinflammatory effect in the Ratcarrageenin induced paw edema assay. Jorgensen JD, Weidner
MS. Unpublished pharmacological report. Dec. 20, 2002
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HTSNE and Ibuprofen produce similar
inflammation control:
Reduces inflammation
BSP 201 Screening for Antiinflammatory effect in the Rat-carrageenin induced paw
edema assay. Jorgensen JD, Weidner MS. Unpublished pharmacological
report. Dec. 20, 2002
Levels of statistical significance: * p<0.001, Mann-Whitney U test
** p<0.0001, Mann-Whitney U test
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HTSNE and Ibuprofen produce differentiated Stomach
and Intestinal Ulcers/Damage profiles:
No gastrointestinal damage
Gastrointestinal lesions
2
Vehicle control
Mean score
1.5
HTSNE* 2000 mg/kg
1
0.5
Ibuprofen 200 mg/kg*
0
Gastric
lesions
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Intestinal
lesions
Level of statistical significance: * p<0.0001, Mann-Whitney
U test
*HTSNE = High Triterpene Shea Nut Extract
HTSNE: Exercise Induced Pain and Inflammation Trial
with Visual Analog Scale (VAS):
Significantly reduces pain and inflammation
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A Double-Blind Randomized Placebo Controlled Parallel Group Study Demonstrates
Analgesic Effects of Sheanut Oil Extract [BSP-201] in Exercise Induced Muscle
Tenderness. Srendt-Nielsen L, Rosetzsky A, Weidner MS. Sept 15, 2003 *HTSNE
= High Triterpene Shea Nut Extract
HTSNE: Better than Analgesics and GS –
Significantly reduces pain and inflammation
PEMS Pain comparison*
80
70
Absolut pain score VAS
60
50
Placebo
Glucosamine Sulphate (1500mg)
40
Ibuprofen (1200mg)
BSP 201 (3000mg)
30
20
10
0
day 0pre
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day 0post
day 1
day 2
day 8
A Double-Blind Randomized Placebo Controlled Parallel Group Study Demonstrates
Analgesic Effects of Sheanut Oil Extract [BSP-201] in Exercise Induced Muscle
Tenderness. Srendt-Nielsen L, Rosetzsky A, Weidner MS. Sept 15, 2003 *HTSNE
= High Triterpene Shea Nut Extract
FlexNow® with 100% SheaFlex70TM
The Next Generation of Joint Care
Over 30 clinical trials and studies
Reduces cytokine production 24-31%, producing breakthrough
results:
1) Reduce inflammation by 9 times
2) Improve cartilage retention by 44%
3) Increase bone retention by 10%
4) Alleviate pain by 45%
Safe and Natural substitute for Steroids and Analgesics
Better than GS; even better with GS
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Table of Contents
•
•
•
Value Proposition
Testimonials
Clinical Review
– Destructive Inflammation Cascade
– Alternative Interventions
– Selected Clinical Trial Review
•
•
FlexNowppt081509b
Safe / All Natural / Sustainable
Summary
35
Safe & All Natural
•
Clinically proven: FlexNow® with 100% SheaFlex70™ has been the subject of over
30 clinical trials and studies, and has been commercially available for a few years.
Over the course of hundreds of clinical trial subjects and tens of thousands of
consumers, just like you, there have been:
– no adverse effects (no side effects)
– no allergies (the shea nut is not a nut, but the pit of the shea fruit)
– no contraindications (no interactions with pharmaceutical or OTC products)
•
FDA-approved: FlexNow® with 100% SheaFlex70™ is accepted by the FDA as
having met every safety and toxicological requirement for a dietary supplement.
FlexNow® with 100% SheaFlex70™ was one of only seven dietary supplements
accepted by the FDA in 2004, given the overwhelming evidence supporting the
product’s efficacy and safety.
•
Centuries of use: All natural shea oil and shea butter, the raw materials used to
produce FlexNow® with 100% SheaFlex70™ have been used as a food and food
ingredient in Africa and Europe, for hundreds of years – shea oil and shea butter are
common ingredients in both baked goods and chocolate production.
•
Et al: FlexNow® with 100% SheaFlex70™ contains no added sugars (sucrose,
fructose, or lactose), no salt (sodium chloride), no nuts, yeast, wheat (gluten-free),
corn, fish, or milk, and no artificial colors or preservatives.
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Sustainable/Green
Good for the plant/Green farming:
• Shea trees grow wild in West Africa, where all of our shea nuts are grown. The shea
nuts (actually the pit of the shea fruit) used in the manufacture of FlexNow® with
100% SheaFlex70™ are wild-crafted/harvested and processed in concert with the UN
Development Programme.
• Wild-crafted plants are carefully gathered from their natural, wild habitat, where they
have not been sprayed with pesticides or fertilized with synthetic fertilizers.
• Wild-crafting is a sustainable agricultural process that respects the living plant. Only
the shea fruit is taken during harvest; the tree is left unharmed.
Good for the community:
• Local villagers collect ripe shea fruit which has fallen to the ground, process a portion
for local use and sell the bulk of the shea nuts to our company, food companies and
skin care companies.
• The UN Development Programme has established education and training programs
to support the commercialization and management of the wild-craft farming,
harvesting, processing and sale of shea fruit and shea nuts.
• The UN Development Programme has helped tens of thousands of villagers,
particularly West African women, to become independent and improve their economic
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position.
Shea nut harvesting in
Burkina Faso, Ghana, and the
Ivory Coast
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Table of Contents
•
•
•
Value Proposition
Testimonials
Clinical Review
– Destructive Inflammation Cascade
– Alternative Interventions
– Selected Clinical Trial Review
•
•
FlexNowppt081509b
Safe / All Natural / Sustainable
Summary
40
FlexNow
with 100% SheaFlex70:
Quadruple Action Joint Solution
•
Proven: Over 30 clinical trials and studies prove FlexNow:
1.
2.
3.
4.
Reduces inflammation by 9 times
Improves cartilage retention by 44%
Increases bone retention by 10%
Alleviates pain by 45%
Safe and Natural substitute for Steroids and Analgesics
Better than GS; even better with GS
•
New, Unique and Incremental:
– Single ingredient product, Not a compound formula
– Exclusive, Patented and available only through BSP Pharma
– Acts uniquely, and synergistically, with other joint care
•
Safe and All Natural:
– No contraindications, No side effects, No allergies
– Source material: Shea Nuts (not a nut, but the pit of the shea fruit)
•
Sustainable:
– Wild-crafted/harvested
– Processed in concert with the UN Development Programme
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41
Table of Contents
Back-Up
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42
BSP Pharma Inc.
•
BSP Pharma Inc. is a North American pharmaceutical, OTC and dietary
supplement developer/marketer, focused on identifying and commercializing
novel, natural substances with the following characteristics:
– Clinically proven to have substantial and meaningful clinical benefits
– Safe and approved by the FDA
– Derived from nature and naturally occurring materials
•
BSP Pharma Inc. is:
– incorporated in Delaware,
– a subsidiary of BSP Pharma A/S:
• conducts business in Europe, Asia and North America
• owned by Innoventure, a private equity firm, based in Denmark.
•
BSP is an acronym for ButyrSpermum Parkii, the latin name for shea butter,
the source material for our first commercial product, FlexNow® with 100%
SheaFlex70™, the subject of over 30 clinical trials and studies.
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43
Contact
If you have any questions/issues or would like to order, please contact:
BSP Pharma Inc.
500 Scarborough Drive
Suite 301
Egg Harbor Twp., NJ 08234
Office: 1-877-778-1212
CustomerService@BSPPharmaInc.com
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44
Clinical Dossier
1)
The efficacy of FlexNow on Rheumatoid Arthritis – Full Trial;” Dr. K, University Hospital, Japan;
2010: Study in development.
2)
“The efficacy of FlexNow on Rheumatoid Arthritis – Pilot Study;” Dr. K, University Hospital,
Japan; 2009: Pilot trial/in progress, 3 month duration, positive trend required and confirmed.
3)
“FlexNow and Glucosamine Synergism in Osteo-Arthritis;” Duke University, Durham, NC, USA;
2009: Study in development. 10-month, guinea pig OA animal model. 4 study arms: placebo,
FlexNow, Glucosamine and FlexNow + Glucosamine. Outcome measures: inflammatory, bone
and cartilage biomarkers together with histological examination.
4)
“Safety and Efficacy on Japanese Osteo-Arthritis Patients;” Dr. K, University Hospital, Japan;
2009: Safety parameters, plus pain and stiffness measures. Results pending.
5)
“Meta Analysis of BSPPEMS + GIBPEMS;” Tonny Jorgensen, CSO; BSP Pharma A/S; 2009:
Preliminary results show the pain level in the glucosamine group is 73% higher than in the
FlexNow group.
6)
“Randomised placebo controlled trial on the safety and efficacy of BSP-201 in Osteo-Arthritis,”
Dr. Phillip Cheras; ACCMER, University of Queensland, Brisbane, Australia; 2007: Substantial
and statistically significant anti-inflammatory effect in humans, plus chondroprotective and
bone remodelling effects.
7)
“GIB: Evaluation of Glucosamine Sulphate and Ibuprofen versus Placebo;” Dr. Allan
Rosetzsky; Klifo, A/S, Copenhagen, Denmark; 2005: Treatments revealed no significant effect
except from Glucosamine Sulphate which had a higher VAS pain score compared to placebo,
which is the opposite of what was expected.
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45
Clinical Dossier
8)
“Evaluation of The Efficacy and Safety of a Sheabutter Extract on Cold Sores (Acute and
Prophylactic);” Dr. Phillip A. Cheras; ACCMER, Brisbane, Australia; 2005: The product was
able to significantly reduce the reoccurrence of cold sores.
9)
“A Randomized Double-Blinded Placebo Controlled Study of BSP-103 for the Treatment of
Patients With Moderate To Severe Plaque Psoriasis;” Dr. Frederic Boudjema; Pharmascan,
Villeurbanne, France; 2004: Post hoc data analysis revealed that the subgroup with initial
PASI>20 achieved a statistical reduction of >30% after 3 months.
10)
“A Double-Blind Randomized Placebo Controlled Parallel Group Study Demonstrates Analgesic
Effects of Sheanut Oil Extract [BSP-201] in Exercise Induced Muscle Tenderness (BSPPEMS);”
Lars Arendt-Nielsen, DmedSci, Ph.D.; Aalborg University, Denmark; Journal of Musculoskeletal
Pain, Vol. 17, Issue 1, February 2009, pages 8-14; 2003: Study found a significant 49% pain
reduction in the active group compared to placebo. Product was found to be safe.
11)
“Mouse Micronucleus;” Karin Kaaber, DVM; ScanTox; 2003: No genotoxicity observed.
12)
“Ames Test;” Karin Kaaber, DVM; ScanTox, Denmark; 2003: No genotoxicity observed.
13)
"Acute Oral Toxicity;" Karin Kaaber, DVM; ScanTox, Denmark, 2003: LD50 >2000mg/kg
46
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Clinical Dossier
14)
"Ulcerogenic Effect;“ Karin Damm Jorgensen, DVM, Study Director; BioAdvice, Vedbaek,
Denmark; 2003: This ulcerogenic safety study confirmed that BSP201 caused no
gastrointestinal lesions in contrast to Ibuprofen, which was used as the control.
15)
“Determination of Anti-Inflammatory Properties of Topical Formulations Containing Shea Butter
Extract on Lesional Skin of Patients With Atopic Dermatitis;” J. Gassmüller, MD; BioSkin Institute
for Dermatological Research, Hamburg, Germany; 2003.
16)
“Evaluation of the irritating and sensitizing potential by repeated 48-hours epicutaneous
applications under patch-tests (Marzulli & Maibach method);” Dr. Yvette Weltert, dermatologist;
Pharmascan, Villeurbanne, France; 2003: The product can be considered hypoallergenic. The
product was not associated with any clinically significant photo allergenic response.
17)
“Cutaneous Irritancy by MTT Assay on Human Skin Biopsies;” Alain Deguercy; Laboratoire
Dermscan, Villeurbanne, France; 2003: The product is non-irritant in this model.
18)
“Evaluation of Ocular Irritancy. (HET-CAM Assay);” Alain Deguercy; Laboratoire Dermscan,
Villeurbanne, France; 2003: The product is non-irritant in this model.
19)
“Topical Safety Study; Photosensibility;” Dr. Marlena Nowakowska, MD; Group Dermscan,
France; 2003: The product is non-photosensitising.
47
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Clinical Dossier
20)
“Evaluation of The Acute Cutaneous Tolerance. 48h Occlusive Patch Test Under
Dermatological Control;” Dr. Yvette Weltert; Palmer Research-Dermscan Group; St. Etienne,
France; 2003: Product is non-irritant.
21)
“Screening of Anti-Inflammatory Effect in The Repeated Oxazolone Mouse Ear Oedema Assay;”
Morten Sloth Weidner, Ph.D.; Department of Dermatology, Bispebjerg Hospital, Copenhagen,
Denmark; 2003: This model simulates chronic inflammatory conditions. When administered
systemically, the product demonstrated a dose dependent anti-inflammatory response. The
highest concentration was approximately twice the response as the positive control 10/mg
methyl prednisolone.
22)
“Screening For Anti-Iinflammatory Effect in The TPA Subchronic Mouse Ear Oedema Assay;”
Hans Christian Wulf, Dr. Med.; Morten Sloth Weidner, Ph.D.; Department of Dermatology,
Bispebjerg Hospital, Copenhagen, Denmark; 2003: This model simulates chronic inflammatory
conditions. The product had a statistical significant inhibitory effect on repeated TPA induced
oedema (very strong inflammation) (x4) formulation optimisation tests.
23)
“Screening of Anti-Iinflammatory Effect in The Oxazolone Mouse Ear Oedema Assay;” Hans
Christian Wulf, Dr. Med.; Morten Sloth Weidner, Ph.D.; Department of Dermatology, Bispebjerg
Hospital, Copenhagen, Denmark; 2003: Confirmed topical anti-inflammatory effect as well as a
significant dose dependent systemic anti-inflammatory effect equal in the highest dose to
30mg/kg methyl prednisolone.
48
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Clinical Dossier
24)
“Screening For Anti-inflammatory Effect in The Arachidonic Acid Mouse Ear Edema Assay;”
Hans Christian Wolf, Dr. Med.; Morten Sloth Weidner, Ph.D.; Department of Dermatology,
Bispebjerg Hospital, Copenhagen, Denmark; 2003: Product provided anti-inflammatory effect.
25)
“Collagen II Rat Arthritis Assay;” Karin Damm Jorgensen, DVM, Study Director; BioAdvice,
Vedbaek, Denmark; 2003: This chronic joint inflammation model confirmed the alleviation of
joint specific chronic inflammation to a level equal to dexamethasone.
26)
“Carrageenin Induced Rat Paw Oedema assay;” Karin Damm Jorgensen, DVM, Study Director;
BioAdvice, Vedbaek, Denmark; 2002: This acute inflammatory model confirmed the dose
dependent anti-inflammatory effect of BSP201. The effect of a daily dose was comparable to a
moderate dose of Ibuprofen. (x3)
27)
“The Effect of Sheanut Oil on Serum Lipids and Lipoproteins in Normocholesterolemic and
Mildly Hypercholesterolemic Humans;” Eric Berg Schmidt; Department of Medicine,
Hjorring/Bronderslev Hospital; Journal of the American College of Cardiology, Abstract 2894,
May 1, 2002, Vol. 39, Issue 9, Suppl. B; 2001: LDL cholesterol decreased 8% in active group.
Product was found to be safe.
28)
“Screening For Anti-Inflammatory Effect in The Mouse Ear Oedema Assay (TPA);” Karin Damm
Jorgensen, DVM; Panum Institute, Copenhagen, Denmark; 2001: All versions of the product
demonstrated a statistically significant dose dependent anti-inflammatory effect. A dosage of
1mg demonstrated the same inhibition as 0.2mg hydrocortisone-17-butyrate. (x2)
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FlexNowppt081509b
Clinical Dossier
29)
“TNF-α/IL-6 Study;” Morten Weidner; Astion A/S, Copenhagen, Denmark; 2001: This test
showed a strong reduction of pro-inflammatory cytokines TNF-α and IL-6 equal to the effect
obtain with a comparable dosage of methyl prednisolone. (x2)
30)
“NF-κB Mechanistic Study;” PanLabs Taiwan Ltd., Taipei, Taiwan; 2000: FlexNow was shown
to inhibit NF-κB dependent transcription response.
31)
“Receptor Binding;” PanLabs Taiwan Ltd., Taipei, Taiwan; 2000: Confirmed safety. FlexNow
did not bind to the glucocorticoid receptors suggesting a different mode of action and side effect
profile than steroids.
32)
“Evaluation of Anti-Viral Effect;” James H. Gilbert, Ph.D., MDS; PanLabs Biosafety, Bothell,
WA, USA; 1999: Product demonstrated antiviral activity against herpes simplex and to a lesser
extent Influenza A. It did not show an effect against rhinovirus.
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FlexNowppt081509b
ACCMER: Highest Risk Group Results
• Cytokine Reduction:
– 24%% reduction in TNF-a
– IL-6 fell by 22%
– CRP was reduced by 22%
• Cartilage retention: CTX-II cartilage marker:
– Reduction of 39%
– Placebo group increased 31%
– 70% reduction in cartilage destruction
• Bone retention: Osteocalcin (marker of bone
destruction) 7.8% reduction in elevated group
• Pain management: statistically significant pain reduction for
both men and women
FlexNowppt081509b