1. Nurture & Clarity

2. Market Highlights ADHD is one of the most common childhood psychiatric disorders. Approximately 50% - 70% of children with ADHD will continue to experience symptoms into adulthood. In 2000, it was estimated that 4-5 million individuals (mainly children) were diagnosed with ADHD, 75% of whom were treated with psycho stimulants. Over 8 million adults in the US may exhibit the symptoms of ADHD, while only an estimated 600,000 are being treated.

3. Market Highlights (Cont.) There has been a significant increase in ADHD diagnosis and prescription of medicine since the early 1990s. The value of the ADHD market was US$2.6 billion in 2005, and it is now the 9th largest segment of the CNS market by sales, with a growth of 8% year-on-year. In May 2006, the FDA asked drug manufacturers to revise product labeling to reflect concerns about possible adverse effects.

4. The Number of Articles on ADHD Submitted on PubMed US National Library of Health, NIH:http://www.ncbi.nlm.nih.gov/pubmed/

5. Prevalence, Diagnosis and Drug Treatment Rates of Patients with ADHD Across Seven Major Markets

6. Forecasted Revenues of Pipeline ADHD Drugs to 2015 Across the Seven Major Markets

7. Why is ADHD Controversial? Drug treatment of children Diagnosis demanded by others Undefined start and end Signs and symptoms can be detected in anyone The cause is claimed to be biological, but no biological diagnosis method has yet established Stimulant drugs are claimed to be safe, but are classified as schedule II drugs Stimulant drugs are a symptomatic treatment Signs and symptoms of this disorder may be considered an advantage for patients

8. Unmet Clinical Needs Reduced side effect profile Longer acting effect Novel mechanisms of action Lower abuse potential Improved compliance

9. Ritalin® Ritalin® is the No. 1 prescription drug for children and adults with ADD/ADHD. The side effects of these drugs are continuous; many are alarming. Ritalin® is an amphetamine, with a lengthy list of side effects, including nervousness, insomnia, nausea, abdominal pain, loss of appetite, dizziness, palpitations, headaches, irregular heart rhythm and psychic dependence; in a word – addiction (Whitaker, 2004). Ritalin has such tremendous potential for abuse that it is classified as a controlled substance by the Drug Enforcement Agency. 25%-30% ADHD cannot tolerate taking stimulant medications

10. FDA Warning Labeling Update(January 25, 2006)Methylphenidate and Amphetamine Products Sudden Death and Pre-existing Structural Cardiac Abnormalities Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in children, adolescents, or adults with known structural cardiac abnormalities.

11. Adult ADHDAttending to the Needs of the Adult Market 60% of ‘pediatric ADHD’ progress to ‘adult ADHD’ in adulthood. The adult ADHD population is potentially twice the size of the current pediatric population, and is therefore far more lucrative than the pediatric market. Only Adderall XR® and Strattera® are approved for adult ADHD, although many other stimulants are frequently prescribed off-label.

12. Adult ADHD (Cont.) Attending to the Needs of the Adult Market ADHD therapies will increasingly be used in the treatment of adult ADHD, regardless of whether the drugs have been approved for this population or not. If manufacturers wish to capitalize on this expanding patient population, it is recommended that they perform Phase III clinical trials in the adult population, either as a means to approval for adult ADHD, or to demonstrate the efficacy of the drug, driving off-label prescriptions.

15. Market Case Study (Germany and England) Demographic data 9.72 million (Germany) and 8.1 million (England) at the age 6–18 years. An estimate of the prevalence of ADHD is 6% ,assuming that DSM-IV criteria will be used in clinical practice. ADHD diagnosis rates Administrative prevalence of ADHD increased from 1.24% in 1998 to 2.95% in 2003 and 4.5% in 2010. ADHD treatment rates In 2003, 40% of children and adolescents diagnosed with ADHD were treated with stimulant medication. It was assumed that the rate of ADHD patients receiving pharmacotherapy would continue to increase through 2010

16. Market Case Study(Germany and England, Cont.) Market diffusion rates Generic market penetration was assumed to reach 60-70%. Prescribing patterns Pediatricians: 50% ; psychiatrists: 30% (data available for Germany only) In England, spending for ADHD-related pharmacotherapy increased from 1998 (₤3.1 million) to 2005 (₤24.4 million) by +695%. Average costs per prescription rose from ₤13.68 in 1998 to ₤46.94 in 2005, driven by price increases and a shift to more expensive new products. Child Adolesc Psychiatry Ment Health. 2007; 1: 13.

17. Combination Therapy The treatment of ADHD is a highly individualized challenge. Discovering the most effective combination of the proper medications and other forms of therapy may mean attempting to use several medications in various combinations, as well as in varying doses. What is appropriate for one child or adult may not be either appropriate or effective for another.

18. Herbal Therapy for ADHD The lifetime prevalence of herbal therapy in patients – children and adults – was 20%. Recommendations from a friend or relative resulted in the administration of herbal medicines by 61%. Almost 83% of caregivers gave herbal medicines alone, whereas 13% gave herbal medicines with prescription drugs. Most caregivers (78%) supervised the administration of herbal therapy in their children, while the children's psychiatrists (70%), pediatricians (56%), or pharmacists (74%) were not aware of the use. Pharmacotherapy. 2003 Feb;23(2):222-30

19. Herbal Therapy for ADHD (Cont.) The use of herbal medicine for treating ADHD is of high interest to the many families and professionals looking for alternatives to drug therapy or “add on” treatments. Various combinations of sedative and stimulating herbs have been widely used in naturopathic and herbal practice as one aspect of treatment for ADHD. In traditional Chinese medicine, herbal formulas are used in synergistic combination to nourish and balance the body’s systems.

20. Herbal Therapy for ADHD (Cont.) The philosophy of 'restoring balance' lends itself in particular to ADD/ADHD, in which the affected individual suffers from multiple biochemical, neurological, and behavioral symptoms for which there is no clear-cut etiology.

21. Advanced Alternatives to Ritalin or Other ADHD Medications No other natural product claimed to be a remedy for ADHD has been proven to be successful in a controlled clinical trial

22. Nurture & Clarity® Overview Unique and safe medicinal plant formulas based on traditional Chinese medicine principles. Specifically engineered to help support the function of the central nervous system via different mechanisms. Help reduce stress and frustration, focus attention and improve concentration. Validated in a scientific clinical trial. Accepted for publication by the Journal of Attention Disorders.

23. Nurture & Clarity® Overview (Cont.) Produced in adherence to pharmaceutical standards by ISO certified Frutarom Industries Ltd. Approved by the Israeli Ministry of Health as safe. Marketing By PharmaGuri Ltd. – distributor of numerous consumer health products.

24. Safety Nurture & Clarity® was approved by the Israeli Ministry of Health as safe for consumption. A pre over-the-shelf marketing test conducted with more than 1000 children as participants – none reported any adverse side effects.

25. How Does Nurture & Clarity®Work? Nurture & Clarity® contains essential nutrients that promote concentration and facilitate learning. Nurture & Clarity-H® also contains a natural calming ingredient Nurture & Clarity® also promotes the development of new neurons and reinforces existing neurons, thus improving memory retrieval. Moreover, Nurture & Clarity® supplies nutrients that are vital for proper brain growth and development in children.

26. Bio Active Therapeutic Mechanisms Nurture & Clarity®’sactive components include, for example: Withania Somnifera: Withania Somnifera has been found to stimulate growth of axons and dendrites in human neuroblastoma cells (Kuboyama et al., 2002, Tohda et al., 2000, Zhao et al., 2002), in addition to increasing acetylcholine receptor capacity (Bhattacharya et al., 1997), and acetylcholinesterase (AChE) inhibitory activity (Vinutha et al., 2007). Centella Asiatica: Centella Asiaticademonstrated increased neurite elongation, dendritic growth (Soumyanath et al., 2005 Moser, 1999), and improved learning and memory (Nalini et al., 1992, Engert & Bonhoeffer, 1999). Centella Asiatica is especially high in B-vitamins (Brinkhaus et al., 2000): cofactors in the synthesis and functioning of serotonin, norepinephrine, dopamine, acetylcholine, as well as GABA (Baynes & Dominiczak 1999, Coleman et al., 1979).

27. Scientific Validation: Clinical Trial

28. Pre- and Post-Trial Mean TOVA Scores