rice science3
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TRANSCRIPT
Leading Developer of Health, Wellness and Performance
Products from Stabilized Rice Bran
1Rice Science Confidential and Proprietary
Rice Science
Rice Science – The Company
Rice Science was founded in January 2008
Joint Venture Owned 80% NutraCea and 20% by
HerbalScience Group Company focused on the development
of functional ingredients from Stabilized Rice Bran (SRB)
Initial Targets - Inflammation and Diabetes Develop functional ingredients through in
vitro/in vivo studies and human clinical trials
Other Targets Immune Enhancement Cardiovascular Enhancement
2Rice Science Confidential and Proprietary
RiceScience
About NutraCea and HerbalScience
NutraCea Leader in stabilized rice bran research and dietary supplement development Manufactures and distributes rice bran based products and ingredients Company has developed proprietary rice bran stabilizing technologies that
enable the creation of food and nutrition products from rice bran NutraCea develops families of health-promoting “nutraceutricals”
HerbalScience Group Privately-held botanical technology company and a leading global producer of
evidence-based, dose-reliable functional ingredients with facilities in the United States, Singapore and Shanghai
Engaged in the discovery, development, manufacture and major brand JV-marketing of proprietary botanical –based functional ingredients for health, wellness and performance for the U.S. and international markets
Wholly owned subsidiary HSRx is a pre-clinical platform technology company that enables accelerated single molecule drug discovery from botanical and other sources
Rice Science Confidential and Proprietary3
Anti-Inflammatory and Diabetes Extracts
Individual Masses
Rela
tive
Abu
ndan
ce
Botanical Produce extracts with chemical
diversity
Generate activity data for extracts
on multiple targets for given health end-point
Dose
Resp
onse
Comprehensivechemical/activity
data set
Mine data Identify key
bioactive compounds990 3345 55 45 2789 23 2 23 2789 23 766 998 990 3345 55 45 2789 23 2 23 2789 23 766 998
258 6 6 4 2 2223 234 3 2 2223 9 33 258 6 6 4 2 2223 234 3 2 2223 9 33445 766 998 345 65 567 90 443 65 567 975 990 445 766 998 345 65 567 90 443 65 567 975 990
3 9 33 1001 565 3 456 64 565 3 23 2789 3 9 33 1001 565 3 456 64 565 3 23 27895 975 990 88 6 6 2789 23 766 998 3 2 5 975 990 88 6 6 2789 23 766 998 3 22 23 2789 23 766 998 2 2223 9 33 443 65 2 23 2789 23 766 998 2 2223 9 33 443 65
234 3 2 2223 9 33 65 567 975 990 64 565 234 3 2 2223 9 33 65 567 975 990 64 56590 443 65 567 975 990 565 3 23 2789 3 2 90 443 65 567 975 990 565 3 23 2789 3 2
456 64 565 3 23 2789 445 766 998 345 65 567 456 64 565 3 23 2789 445 766 998 345 65 5672789 23 766 998 3 2 3 9 33 1001 565 3 2789 23 766 998 3 2 3 9 33 1001 565 3
2 2223 9 33 443 65 5 975 990 88 6 6 2 2223 9 33 443 65 5 975 990 88 6 665 567 975 990 64 565 2 23 2789 23 766 998 65 567 975 990 64 565 2 23 2789 23 766 998
565 3 23 2789 3 2 234 3 2 2223 9 33 565 3 23 2789 3 2 234 3 2 2223 9 333 9 33 1001 565 3 90 443 65 567 975 990 3 9 33 1001 565 3 90 443 65 567 975 9905 975 990 88 6 6 258 6 6 4 2 2223 5 975 990 88 6 6 258 6 6 4 2 22232 23 2789 23 766 998 445 766 998 345 65 567 2 23 2789 23 766 998 445 766 998 345 65 567
234 3 2 2223 9 33 3 9 33 1001 565 3 234 3 2 2223 9 33 3 9 33 1001 565 390 443 65 567 975 990 5 975 990 88 6 6 90 443 65 567 975 990 5 975 990 88 6 6
258 6 6 4 2 2223 2 23 2789 23 766 998 258 6 6 4 2 2223 2 23 2789 23 766 998445 766 998 345 65 567 234 3 2 2223 9 33 445 766 998 345 65 567 234 3 2 2223 9 33
3 9 33 1001 565 3 90 443 65 567 975 990 3 9 33 1001 565 3 90 443 65 567 975 9905 975 990 88 6 6 456 64 565 3 23 2789 5 975 990 88 6 6 456 64 565 3 23 27892 23 2789 23 766 998 2789 23 766 998 3 2 2 23 2789 23 766 998 2789 23 766 998 3 2
234 3 2 2223 9 33 2 2223 9 33 443 65 234 3 2 2223 9 33 2 2223 9 33 443 6590 443 65 567 975 990 65 567 975 990 64 565 90 443 65 567 975 990 65 567 975 990 64 565
456 64 565 3 23 2789 565 3 23 2789 3 2 456 64 565 3 23 2789 565 3 23 2789 3 22789 23 766 998 3 2 90 443 65 567 975 990 2789 23 766 998 3 2 90 443 65 567 975 990
990 3345 55 45 2789 23 2 23 2789 23 766 998 990 3345 55 45 2789 23 2 23 2789 23 766 998258 6 6 4 2 2223 234 3 2 2223 9 33 258 6 6 4 2 2223 234 3 2 2223 9 33445 766 998 345 65 567 90 443 65 567 975 990 445 766 998 345 65 567 90 443 65 567 975 990
3 9 33 1001 565 3 456 64 565 3 23 2789 3 9 33 1001 565 3 456 64 565 3 23 27895 975 990 88 6 6 2789 23 766 998 3 2 5 975 990 88 6 6 2789 23 766 998 3 22 23 2789 23 766 998 2 2223 9 33 443 65 2 23 2789 23 766 998 2 2223 9 33 443 65
234 3 2 2223 9 33 65 567 975 990 64 565 234 3 2 2223 9 33 65 567 975 990 64 56590 443 65 567 975 990 565 3 23 2789 3 2 90 443 65 567 975 990 565 3 23 2789 3 2
456 64 565 3 23 2789 445 766 998 345 65 567 456 64 565 3 23 2789 445 766 998 345 65 5672789 23 766 998 3 2 3 9 33 1001 565 3 2789 23 766 998 3 2 3 9 33 1001 565 3
2 2223 9 33 443 65 5 975 990 88 6 6 2 2223 9 33 443 65 5 975 990 88 6 665 567 975 990 64 565 2 23 2789 23 766 998 65 567 975 990 64 565 2 23 2789 23 766 998
565 3 23 2789 3 2 234 3 2 2223 9 33 565 3 23 2789 3 2 234 3 2 2223 9 333 9 33 1001 565 3 90 443 65 567 975 990 3 9 33 1001 565 3 90 443 65 567 975 9905 975 990 88 6 6 258 6 6 4 2 2223 5 975 990 88 6 6 258 6 6 4 2 22232 23 2789 23 766 998 445 766 998 345 65 567 2 23 2789 23 766 998 445 766 998 345 65 567
234 3 2 2223 9 33 3 9 33 1001 565 3 234 3 2 2223 9 33 3 9 33 1001 565 390 443 65 567 975 990 5 975 990 88 6 6 90 443 65 567 975 990 5 975 990 88 6 6
258 6 6 4 2 2223 2 23 2789 23 766 998 258 6 6 4 2 2223 2 23 2789 23 766 998445 766 998 345 65 567 234 3 2 2223 9 33 445 766 998 345 65 567 234 3 2 2223 9 33
3 9 33 1001 565 3 90 443 65 567 975 990 3 9 33 1001 565 3 90 443 65 567 975 9905 975 990 88 6 6 456 64 565 3 23 2789 5 975 990 88 6 6 456 64 565 3 23 27892 23 2789 23 766 998 2789 23 766 998 3 2 2 23 2789 23 766 998 2789 23 766 998 3 2
234 3 2 2223 9 33 2 2223 9 33 443 65 234 3 2 2223 9 33 2 2223 9 33 443 6590 443 65 567 975 990 65 567 975 990 64 565 90 443 65 567 975 990 65 567 975 990 64 565
456 64 565 3 23 2789 565 3 23 2789 3 2 456 64 565 3 23 2789 565 3 23 2789 3 22789 23 766 998 3 2 90 443 65 567 975 990 2789 23 766 998 3 2 90 443 65 567 975 990
COX1 5-LOX
PPAR AMPKDART TOF-MS Individual Masses
Rela
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Abu
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COX2
StabilizedRiceBran
Key Steps in the Development of Optimized SRB Extracts for Inflammation and Diabetes
Rice Science Confidential and Proprietary 4
FABP4
Rice Bran – A Rich Source of Bioactives
SRB is among the most nutrient dense food ingredient with a rich diversity of bioactive compounds More than 100 antioxidants & metabolic co-factors Vitamin E complex with complete tocotrienol profile Naturally rich in B Vitamins High in IP6 and Inositol Rich in γ-oryzanol and phytosterols Rich in essential fatty acids Complete and balanced Amino acid profile
Contains compounds known to be beneficial in down-regulating pro-inflammatory intermediates (i.e., γ-oryzanols) and maintaining blood glucose moderation
Rice Science Objective: Develop dosed assured, all natural extracts to reduce inflammation and for moderation of blood glucose levels
Rice Science Confidential and Proprietary5
Matrix of Extracts from SRB
Matrix of 14 different extracts produced from SRB feedstock
based on varying extraction conditions
Each SRB extract is chemically fingerprinted
using DART TOF-MS
Dose response curves are generated for each extract
against each of several targets
(COX1; COX2; 5-LOX, FABP4, glucose uptake)
IC50 Curves
Rice Science Confidential and Proprietary6
SRB EXTRACT FOR INFLAMMATION AND ARTHRITIS RELIEF
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arthritis Market Place
The rate of increase of osteoarthritis and rheumatoid arthritis over the next two decades will almost double due to the aging of the world’s population
Arthritis is the most common cause of disability in the U.S. An estimated 28 million people in the US have arthritis or other
rheumatic conditions Arthritis represents a multi-billion (> $10 Billion) dollar
market globally Rx > $9B in 2007 (Primarily NSAID products) OTC $0.5B in 2007 (Primarily NSAID products) Supplements > $1.5B in 2007 (Primarily Glucosamine/Chondroitin)
8Rice Science Confidential and Proprietary
Osteoarthritis
An estimated 27 million adults in the United States live with osteoarthritis—the most common type of arthritis
Characterized by pain, inflammation, joint damage, and limited motion
Joint damage is not generally reversible Management of pain and inflammation
can restore significant joint mobility and function
Highest success for relief of symptoms is through control of pro-inflammatory response
Rice Science Confidential and Proprietary
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Images by the National Institute of Arthritis and Musculoskeletal and Skin Diseases
Healthy joint
Arthritic joint
Rheumatoid Arthritis
Rice Science Confidential and Proprietary10
http://www.niams.nih.gov/hi/topics/arthritis/rahandout.htm
An estimated 1.3 million Americans suffer from rheumatoid arthritis
Chronic, systemic autoimmune disease characterized by inflammation of the synovium in the joints, bone loss, chronic pain, loss of function and disability
No cure Like osteoarthritis, preferred means of
controlling rheumatoid arthritis symptoms is through the use of analgesics (painkillers) and anti-inflammatory drugs
Pro-Inflammatory Pathways
The major inflammatory pathways in arthritis and related inflammatory disorders are regulated by Cyclo-oxygenases (COX-1 and COX-2) and Lipooxygenases (5-LOX)
Most current drugs target COX-2 (e.g., Celebrex®) or are non-specific for COX-1 and COX-2 (e.g., aspirin and ibuprofen)
NSAIDs associated with various side-effects (e.g. ulcers)
5-LOX has been recognized recently as a key target as well
Major effort underway by Pharma to develop Dual COX-LOX Inhibitors for optimal efficacy
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Arachidonic Acid
COX-1 COX-2
5- LOX
Prostaglandins Leukotrienes
Pro-inflammatory cytokines and chemokines
Rice Science Confidential and Proprietary
Glucosamine/Chondroitin Supplements
Glucosamine/Chondroitin dominate supplements market for arthritis products $831M in sales in 2007
Glucosamine and chondroitin are not COX or LOX inhibitors NIH sponsored human clinical (GAIT) concluded that:
The results showed that combination of glucosamine plus chondroitin sulfate did not provide significant relief from osteoarthritis pain among all participants
The ancillary study results showed that glucosamine and chondroitin sulfate, together or alone, appeared to fare no better than placebo in slowing loss of cartilage in knee osteoarthritis
Market is poised for alternative supplement that is effective in providing relief from the symptoms of arthritis – All-natural botanical extracts with dual COX-LOX inhibitory activities
Rice Science Confidential and Proprietary12
Extracts with COX & LOX activities
EnzymeSRB-AI
IC50 (μg mL-1)
SRB-AII
IC50 (μg mL-1)
SRB-AIII
IC50 (μg mL-1)
COX1 305 310 48
COX2 29 19 11
5-LOX ND 396 197
Two extracts identified with very high COX-2 inhibitory activities and moderate COX-1 inhibitory activities
One of the extracts (SRB-AII) also demonstrated moderate 5-LOX inhibitory activity
SRB-AI extract had no measurable 5-LOX inhibitory activity
An SRB-AI and SRB-II proprietary blend (SRB-AIII) was produced to optimize the Dual COX-LOX inhibitory activities
Rice Science Confidential and Proprietary13
Optimized SRB-AIII Extract
Stabilized Rice Bran extract (SRB-AIII) from Rice Science possesses COX-1, COX-2 and 5-LOX inhibitory activities COX-1 IC50 value = 48 μg mL-1
COX-2 IC50 value = 11 μg mL-1
5-LOX IC50 value = 197 μg mL-1
First-in-class all-natural extract with dual COX-2/5-LOX inhibitory activities
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Arachidonic Acid
COX-1 COX-2
5-LOX
Prostaglandins
INFLAMMATORY RESPONSE
SRB Extract
Leukotrienes
Rice Science Confidential and Proprietary
Identification of Bioactives
Importance of Identifying Anti-Inflammatory Bioactives
Intellectual Property Composition-of-Matter Methods-of-Making Methods-of-Use
Ingredient Production Verify presence of bioactives in feedstock Optimize extraction to enrich for bioactives Guarantee presence of bioactives in all batches at doses that deliver
efficacy Provides a “dose assured” functional ingredient Ingredients that work
Rice Science Confidential and Proprietary15
Bioactive Chemistries in SRB-AIII
16Rice Science Confidential and Proprietary
Compound NameMolecular Formula
Molecular Mass (M)
Chemical Class
Relative Abundance (%)
Wt per 100 mg (mg)
Theoretical IC50
(mM) (COX1)Theoretical IC50
(mM) (COX2)Theoretical IC50
(mM) (5-LOX)
norcamphor/heptadienal C7H10O + H+ 110.08 terpene 0.45 452 197 45 8096-methyl-5-hepten-2-one C8H14O + H+ 126.11 terpene 3.24 3,237 1232 282 5057
ocimene/camphene/adamantane C10H16 + H+ 136.12 terpene 1.42 1,418 500 115 2052
histidinol C6H11N3O + H+ 142.11 imidazole 2.86 2,863 967 222 3969
lysine C6H14N2O2 + H+ 146.12 amino acid 0.42 421 138 32 568tryptamine C10H12N2 + H+ 160.12 amino acid 0.39 388 116 27 477Nonanedioic acid anhydride C9H14O3 + H+ 170.11 fatty acid 1.81 1,815 512 117 2102Nonanedioic acid diamide C9H18N2O2 + H+ 187.14 fatty acid 1.92 1,920 492 113 2021Epiloliolide C11H16O3 + H+ 196.12 alkaloid 5.74 5,745 1406 322 5771Farnesatrienetriol C15H26O3 + H+ 254.36 terpene 5.08 5,076 958 220 3931Farnesylacetone C18H30O + H+ 262.43 terpene 27.13 27,131 4962 1137 20367Octadecatrienol C18H32O + H+ 264.45 fatty acid 16.61 16,614 3016 691 12376octadecatrienoic acid C18H30O2 + H+ 278.43 fatty acid 100.00 100,000 17240 3951 70754hydroxyoctadecatrienoic acid C18H30O3 + H+ 294.43 fatty acid 28.57 28,571 4658 1067 19117hydroxyoctadecenoic acid C18H34O3 + H+ 298.46 fatty acid 15.37 15,374 2473 567 10148epoxyhydroxyoctadecanoic acid C18H32O4 + H+ 312.27 fatty acid 12.67 12,671 1948 446 799412-shoagol C23H36O3 + H+ 360.28 gingerol 4.35 4,348 579 133 2377
In addition to 17 bioactives with “known” structure, 4 novel bioactives with previously unknown structures have been identified in SRB-AIII that have
significant COX-1/COX-2 and 5-LOX inhibitory activities
Pharmacokinetics of SRB-AIII
Vegetable capsules with SRB-AIII extract given to 5 human subjects
Uptake of key bioactives into serum and appearance in urine was monitored using DART TOF-MS
Uptake of key bioactives occurred within 40 minutes of oral dose
Key bioactives appeared in urine within first hour
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Rice Science Confidential and Proprietary
Uptake of 3 SRB-AIII bioactives into human
serum
Appearance of 3 bioactives into urine
Structure-Function Claims*
Enriched in bioactives that inhibit the activity of pro-inflammatory enzymes COX-1-, COX-2 and 5-LOX in vitro
Dual-function extract that targets the two major pathways controlling inflammation and pain associated with arthritis and related inflammatory diseases
Synergistic bioactives that promote healthy joints Key bioactives taken up rapidly, within 40 minutes
Rice Science Confidential and Proprietary18
* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any diseases
Human Clinical trial
Rice Science plans to sponsor a human clinical trial (2010) to examine efficacy of SRB-AIII in relieving symptoms of arthritis
Primary outcome will measure onset of pain relief in arthritic knee during course of exercise and measure levels of cytokine pro-inflammatory markers following oral dosing with SRB-AIII in a randomized double-blind placebo controlled study
Secondary outcome will monitor joint health and function in a 30-day open label study in which subjects will self-monitor joint function in 6 minute walks and filling out of questionnaires. Pro-inflammatory cytokine markers will also be monitored at end of 30 days
Rice Science Confidential and Proprietary19
SRB EXTRACT FOR DIABETES
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Diabetes Market Place
Type 2 diabetes related to age and obesity, characterized by insulin resistance which elevates blood sugar
Over 23 million Americans suffer from type 2 diabetes Of these, over 16 million are diagnosed The American Diabetes Association estimates that 1 in 3
Americans will be diagnosed with diabetes in their lifetime Medical expenses related to diabetes exceed $ 132B in the
U.S. annually Diabetes is a subset of what is called Metabolic Syndrome
which includes cardiovascular disease and obesity
Type 2 Diabetes
Symptoms include: Abnormally high blood sugar Fatigue and lack of energy Frequent urination Unexplained weight loss Blurred vision that can lead to blindness Slow healing of wounds Cardiovascular disease
Metabolic Syndrome
Metabolic Syndrome is a combination of disorders that increase the risk of developing cardiovascular disease and diabetes
Diabetes is a major disorder of Metabolic Syndrome
The SRB extract developed by Rice Science addresses two key processes in Metabolic Syndrome, glucose and fat utilization
SRB Extract for Diabetes
A number of SRB extracts were tested for diabetes endpoints with one indentified as most effective and designated SRB-D1
Effect of SRB-D1on Glucose Uptake
SRB-D1 stimulated glucose uptake in adipocytes more effectively than insulin
Effect of SRB-D1 onFABP4 Protein
SRB-D1 has a moderating effect on FABP4 protein which plays a role in type 2 diabetes, atherosclerosis and obesity
Pharmacokinetics of SRB-D1
Vegetable capsules with SRB-D1 extract given to 5 subjects
Uptake of key bioactives into serum was monitored using DART TOF-MS
Uptake of key bioactives occurred within 20 – 45 minutes
VALUE PROPOSITION
28Rice Science Confidential and Proprietary
Rice Science
Value Proposition
All-natural first-in-class dose-reliable botanical extract with dual COX-LOX inhibitory activities for inflammation and arthritis
All-natural, dose reliable extract for moderating glucose serum levels in diabetics
Strong structure-function claims backed by solid in vitro and human clinical studies
Significant product differentiation Dose assured functional SRB extracts manufactured through
proprietary methods that ensure the presence and functional levels of key bioactives in every batch
Comprehensive and strong IP and patent position • Composition-of-matter, methods-of-making, and methods-of use (mode-of-
action)
29Rice Science Confidential and Proprietary
Contact Information
NutraCea
Leo GingrasPresident and Chief Operating
6720 N. Scottsdale Road, Suite 390Scottsdale, AZ 85253
Office: 602-522-3011Fax: 602-522-7575
NutraCea
Colin GarnerSr. Vice [email protected]
6720 N. Scottsdale Road, Suite 390Scottsdale, AZ 85253
Cell: 602-909-0327Office: 877-723-1700