Rice Science3

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


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

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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

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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


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


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)


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

9

Images by the National Institute of Arthritis and Musculoskeletal and Skin Diseases

Healthy joint

Arthritic joint

Rheumatoid Arthritis


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



http://upload.wikimedia.org/wikipedia/commons/7/7e/Rheumatoid_arthritis_joint.gif

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


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


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


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


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


Bioactive Chemistries in SRB-AIII


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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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


* 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


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


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)


Contact Information

NutraCea

Leo GingrasPresident and Chief Operating

[email protected]

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

mailto:[email protected]

mailto:[email protected]

Rice Science3

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