Success Story

Novel Proprietary Standardized

Healthcare Ingredient (EstroG-100)

Naturalendo Tech Co., Ltd.

 Corporate overview

Establishment May 24, 2001 Employees 80 (22 R&D Employees)

IPO 31st Oct, 2013 in KOSDAQ, now market capitalization is around USD 1.5 billion
Sales Revenue USD 124M in 2014 Capital USD 9.6M
Develop and market Transdermal Drug Delivery and Technology of herbal formula for
• Novel Proprietary Standardized Herbal Remedy (EstroG-100)
• Immune Enhancer (Welmune)
Business Lines
• IGF-1 Secretagogue (YGF-251)
• Anti-atopic & Anti-acne Formula (Derma A2)
• Other skin formula

Organizational Structure
Summary of Healthcare Industry & Our Products

Characteristics of Healthcare Industry

• Difficulty to Penetrate due to R&D time↑& Cost↑
• Addition of High Value
• Service to the Public Health
• Solid Growth Independent of Economy Fluctuation

Hospital & Clinics

Our Products
Healthcare Device &
Equipment
Industry
EstroG-100
U – Healthcare

Pharmaceutical hGH
Secretagogue
Nutraceutical Novel Ingredient

Derma A2
Cosmeceutical

Others TDDS
Insurance
Health Machine
 Executive Summary: EstroG-100

Solution for Women’s Quality of Life

features benefits
Patents, Licenses, and approvals End Users
• 17 registered and pending patents worldwide • Clinically proven efficacy and safety:
• Approved by U.S., Canada, Korea authorities -Significant improvement of 10 menopausal
symptoms out of 12 in total
-QOL improvement
Health Canada • FBMD significantly improved
NPN License • No side effects compared to other
alternatives including HRT, Black Cohosh and
isoflavone.
US FDA NDI Market Status
• Successful sales in Korea, US, Canada and expanding the
market in other countries
• Ranked No.1 over more than 45 products of
HFFI HRT & Black cohosh since 2011 in Korea
• Supplying to Korean major companies & its sales hit in
retail price: -2010 USD 9M
-2011 USD 55M
-2012 USD 105M
-2013 USD 270M
-2014 USD 400M
“EstroG-100 is dominating the market by occupying over 90% market share of
total menopause market in Korea (medicine + phytoestrogen)
 Approvals & Licenses

NHPD Product License, Health Canada (2011)

According to Health Claim, 10 Symptoms Improved!

• Date of License: July 5, 2011
• NPN(Natural Product Number):
80026169
• Helps to relieve the symptoms
associated with menopause such as
hot flashes, night sweats,
paresthesia(numbness on hands/foot),
insomnia, nervousness,
melancholia(depression),
vertigo(dizziness) , fatigue, rheumatic
pain and vaginal dryness.

http://webprod3.hc-sc.gc.ca/lnhpd-
bdpsnh/info.do?lang=eng&licence=80026169
 Approved Claims with No Side Effects
Superiority

EstroG-100: Product A:
10 specific claims with NO risk warning 1 specific claim with Risk Warning

Risk Information: Cautions and Warnings

Risk Information:
Consult a health care practitioner if symptoms persist or worsen
If you are taking ..any hormone-containing medication such as
None. progesterone ..contraceptives or HRT or blood-thinning
medication.. If you have liver troubles.
http://webprod3.hc-sc.gc.ca/lnhpd-
bdpsnh/info.do?lang=eng&licence=80026169
 NDI of US FDA (2010)
Approvals & Licenses

EstroG-100 is permitted as New Dietary Ingredient

※ The Federal Food, Drug, and Cosmetic Act (the act) requires that manufacturers and distributors who wish to
market dietary supplements that contain “new dietary ingredients” which has not been distributed in USA market
before 1994, notify the Food and Drug Administration about these ingredients. Generally, the notification must
include information that is the basis on which manufacturers/ distributors have concluded that a dietary supplement
containing a new dietary ingredient will reasonably be expected to be safe under the conditions of use recommended
or suggested in the labeling. The NDI notification process is complex. NDI notifications are most often rejected due to
insufficient evidence for safety, the absence of required elements, as well as lack of knowledge and experience for
such notifications.
 HFFI Approval by KFDA (2010)

HFFI: Health Functional Food Ingredient • Approval No: 2010-20

• Claim: Help with climacteric women’s
health

• EstroG-100 is the first approved ingredient

in Korea as Health Functional Food
Ingredient by KFDA for alleviating
menopausal symptoms such as hot flashes,
night sweats, paresthesia(numbness on
hand/foot), insomnia, nervousness,
melancholia(depression), vertigo(dizziness),
fatigue, rheumatic pain and vaginal dryness
and formication
 Growing Portion of Menopause Women

2000 2010 2050

 Average Onset Age of Menopause is 49.7 in Korea

 Estimated Menopause Population is *32(22)% of Korean Women in 2000,
Raised to 45(30)% in 2010, and to 60(50)% in 2050
*32%=10% of surgical and pre-mature menopause + 22% of natural menopause
 Function of Estrogen

• Growth and development of uterus and mammary gland

• Expression of secondary sex characteristics
• Control of menstrual cycles and supporting pregnancy

• Bone metabolism and increase of BMD

• Cardiovascular health and lipid metabolism
• Anti-dementia, trophic factor for neuron

• Colon cancer prevention

• Teeth health
• Prevention of macular degeneration

• Fat distribution to subcutaneous fat tissue

• Collagen production and maintaining human skin
 Menopause Classification

 Premature Menopause
• About 8% Women (US) stop having period before age 40
• Same symptoms as Menopause

 Peri-menopause
• Average women go through this phase age 45~49
• Wildly fluctuating Estrogen Level
• Same symptoms as Menopause

 Menopause
• Estradiol level<50 pg/mL; FSH>50 mIU/mL; no period for >1 yr*
• Average age for onset of menopause is 52 in US
• Symptoms last 2~19 years, many more than 5 years

 Surgical Menopause
• After Hysterectomy/Bilateral surgery

* Definition: Dr. Joel Harglove, MD, Chairman, Vanderbilt Menopause Center, Nashville, TN
 After Menopause Women Suffer ….

 Physiological /Psychological Changes During Menopause

• Hot flashes, Night sweats
• Vaginal dryness & thinning of vaginal wall
• Inelastic skin and dry eye, Insomnia, nervousness, depression, paresthesia(numbness),
vertigo(dizziness), fatigue, rheumatic pain(joint), pounding of heart, headaches

 Long Term Post-Menopausal Health Risks

• Cardiovascular Diseases (CVD’s) : 2 times higher risk of CVD’s after menopause
• Osteoporosis

Women spend almost 1/2 of their lives post-menopause

 EstroG-100

Science of New Herbal Ingredient

 Herbal extracts screened out of 71 herbal extracts via non-

reproductive tract target tissue response (E-screen test)
 3 herbal extracts were chosen: Cynanchum wilfordii, Phlomis
umbrosa, and Angelica gigas Nakai
 Proven Safety
• About 400 years of documented use in Korea as folk medicine
• Registered as safe main food ingredient in Korea Food Standard Codex
• Cynanchum wilfordii & Phlomis umbrosa are reported to be liver-protective
plants to WHO
• No increase of uterus weight in ovariectomized rat tests
• Inhibition of proliferation of human breast cancer cell (MCF-7)
• No binding Affinity to both Estrogen Receptor α and β, cancer-inhibitory
• Safe: Acute & Multi-dose toxicity tests , Genetic toxicity tests

 Proven Efficacy in vitro, in vivo, and in 3 human group (Asian and

non-Asian) clinical studies
 Efficacy of EstroG-100

• Clinically proven efficacy : 62% significant improvement of QOL

• 10 out of 12 climacteric symptoms significantly improved compared to Placebo

Hot flash/
Night sweats
Vaginal
dryness Paresthesia

Formication
Improve Insomnia
62%
menopausal Improvement

symptoms
of symptoms

Rheumatic
Nervousness
pain

Fatigue Melancholia
Vertigo
Clinical Study Ⅰ- Protocol
Efficacy of EstroG-100

Randomized Double-blind Placebo-controlled study

(School of Medicine, Sungkyunkwan Univ. Samsung Cheil Hospital)

Dosing period 12 months (May 2003-April 2004)

Evaluation Style Long Term Safety Evaluation

Patients (n=47) 23 subjects in placebo group &

24 active group

Inclusion Criteria Age of 46 ~ 66 & Diagnosis of menopausal

syndromes
(average age=54)
 Clinical Study I - Efficacy
Efficacy of EstroG-100

Climacteric Symptoms After 3 months

5 times better improvement than OR=5.04 (95% C.I.=1.4-18.1)
placebo with significance Fisher’s Exact Test

Femoral Bone Mineral Density After 12 months

Significant improvement 0.746±0.10 → 0.763±0.13 (P<0.05)

Serum hGH Level After 12 months

Significant improvement 0.25±0.21 → 0.92±0.97 (ng/mL) (P<0.05)

Serum Osteocalcin Level After 12 months

Significant improvement 6.02±2.74 → 5.66±3.01 (ng/mL) (P<0.05)

Serum Triglyceride Level After 12 months

Significant improvement 119.1±54.72 → 92.16±49.94 (mg/dL) (P=0.066)

Serum Alkaline Phosphatase Level After 12 months

Significant improvement 73.35±21.02 → 60.42±14.87 (IU/L) (P=0.08)
Clinical Study II (Non-Asian) - Protocol
Efficacy of EstroG-100
Randomized, Double-blind, Placebo-controlled study (CA, USA)

Dosing period 3 months

Patients (n=61) 32 subjects in placebo group & 29 active group

Inclusion Criteria Age of 42 ~ 70
Diagnosis of menopausal syndromes(average age = 53)

Ad for Volunteers for US Clinical Study

 Results
Efficacy of EstroG-100

Kupperman Menopause Index and Vaginal Dryness (Difficulties in Sexual Intercourse)

Improved Significantly

Vaginal Dryness (Difficulties in Sexual Intercourse)

- Hot flush/ Night sweat

Somatic / - Paresthesia (numbness on hands/foot)
physical - Vertigo (dizziness)
- Fatigue
- Muscular skeletal pain

- Nervousness
Physiological / - Insomnia
Psychological - Depression
- Formication

EstroG-100 was confirmed to improve both somatic and physiological symptoms

with statistic significance.
 Result : Vaginal Dryness
Efficacy of EstroG-100

Vaginal Dryness Improved Unlike Black cohosh and Isoflavone

EstroG-100 Placebo
Mean±SE Mean±SE

Vaginal dryness scores

Week0 (Baseline) 1.45±1.02 1.75±1.11
Week6 0.72±0.88 1.50±1.11

Change from baseline -0.72±0.84**††## -0.25±0.57#

Week12 0.59±0.87 1.28±1.02

Change from baseline -0.86±0.88*## -0.47±0.72##

P=0.0536

Fig. 1. Changes of vaginal dryness and reduced libido during 12 weeks administration of EstroG-100 and placebo.
SE: Standard Error
*: Statistically significant compared between groups; p<0.05 by t–test(ITT)
**: Statistically significant compared between groups; p<0.01 by t–test(ITT)
††; p<0.01 compared between groups by Wilcoxon rank sum test
#; p-<0.05 compared to baseline, ##; p<0.01 compared to baseline by paired t-test
 Result : KMI (Kupperman Index)
Efficacy of EstroG-100

35
EstroG-100 Placebo

Kupperman index scores

Mean±SE Mean±SE 30 **
**
Week0 (Baseline) 29.45±7.39 29.16±6.55 25
Week6 13.62±7.61 23.31±8.96 20

Change from baseline -15.83±9.10**††## -5.84±6.15## 15

10
Week12 11.31±5.78 23.66±7.68
EstroG-100
5
Placebo
Change from baseline -18.14±8.46**††## -5.50±5.34##
0
0 6 12
Time (weeks)

Fig. 2. Changes of Kupperman Menopause Index(Mean±SE) during 12 weeks administration of EstroG-100 and placebo.

SE: Standard Error

**: Statistically significant compared between groups; p<0.01 by t–test(ITT)
††; p<0.01 compared between groups by Wilcoxon rank sum test
##; p<0.01 compared to baseline by paired t-test

Kupperman Index for Moderate or Severe Menopausal Symptoms Improved

Result: Individual Menopausal Symptoms
Efficacy of EstroG-100

EstroG-100 (n=29) Placebo (n=32)

Week 0 Week 6 Week 12 Week 0 Week 6 Week 12
Vasomotor 2.24±0.69 1.03±0.82**††## 0.79±0.73**††## 2.22±0.66 1.78±0.75## 2.06±0.76

Paresthesia 1.31±0.85 0.59±0.78*†## 0.55±0.74*†## 1.41±0.91 1.13±0.94# 1.09±0.96##

Insomnia 2.28±0.84 1.28±0.96**†## 0.97±0.82**††## 2.03±0.86 1.63±1.01# 1.63±0.87#

Nervousness 1.72±0.88 0.76±0.69**††## 0.66±0.67**††## 1.56±0.84 1.22±0.83 1.34±0.75
Melancholia 1.93±0.88 1.03±0.68**††## 0.83±0.71**††## 1.59±0.95 1.31±0.93 1.31±0.74

Dizziness 0.97±0.82 0.21±0.49**††## 0.21±0.41**††## 0.75±0.72 0.72±0.77 0.59±0.80

Fatigue 2.21±0.77 0.90±0.77**††## 0.72±0.70**††## 2.00±0.88 1.69±0.90# 1.59±0.80#

Arthritic Pain 1.59±1.02 0.79±0.94**†## 0.55±0.78*†## 1.84±0.95 1.63±0.83 1.47±0.88

Headache 1.34±1.04 0.69±0.76## 0.66±0.77## 1.53±0.95 1.13±0.91# 0.84±0.72##
Palpitation (heart poundering) 1.00±0.96 0.48±0.69# 0.55±0.63# 1.31±0.93 0.91±0.82## 0.75±0.84##

Formication 0.83±0.85 0.14±0.44* ## 0.28±0.45## 1.25±1.05 0.88±1.01## 0.72±0.96##

*;p-<0.05 compared between groups, **; p<0.01 compared between groups by t –test †; p-<0.05 compared between groups, ††; p<0.01
compared between groups by Wilcoxon rank sum test, #; p-<0.05 compared to baseline, ##; p<0.01 compared to baseline by paired t-test
Clinical Study III - Multi-Center Randomized
double-blind placebo-controlled study
Efficacy of EstroG-100

Clinical Study III

Multi Center,
Test Method
Randomized double-blind placebo-controlled study

Aju University Medical Center

Study Location Anam Hospital of Korea Univ.
Severance Hospital of Yonsei Univ.

Test period 12 weeks

Dosage 638 mg tablet orally twice a day

Study 96 female participants of age of 40~70 with menopausal symptoms (105

Participants enrolled and 9 drop out)

Inclusion Criteria Age of 40 ~ 70 with menopausal symptoms

Clinical Study III- Result

 The result almost duplicate the 2nd Clinical

Significantly Improved! Study (Non-Asian) by improving as many as
9 different symptoms.
 Hot flash
 Paresthesia  No significant differences or changes
observed when measured endometrial
 Nervousness thickness.
 Melancholia
 No change in weight, BMI, and the level of
 Vertigo estrogen and FSH without any adverse event
 Fatigue reported during the study. The endometrial
 Formication thickness was measured to be observed not
to change in addition.
 Rheumatic pain
 Vaginal Dryness
 Clinical Study III- Result

KMI
Kupperman Menopause Index Improved Significantly
Placebo ESTROG-100
N=47 N=49
Mean±SD Mean±SD
Week0 (Baseline) 32.89±7.75 35.14±8.11
Week4 24.72±9.48 23.20±9.25
Change from
-8.17±8.58 -11.94±10.41 <0.05
baseline
p-value** <0.01 <0.01
Week12 20.35±10.31 14.84±9.94
Change from
-12.54±12.92 -20.31±12.07 <0.01
baseline Fig. 1. Changes of Kupperman Menopause Index (Mean±SE) during 12 weeks
p-value** <0.01 <0.01 administration of EstroG-100 and placebo.
SE: Standard Error, *: Statistically significant compared between groups; p<0.05
**: Statistically significant compared between groups; p<0.01 by t–test(ITT)
 Clinical Study III- Result

Vaginal Dryness
Vaginal Dryness (Difficulties in Sexual Intercourse) Improved Significantly

Placebo ESTROG-100
N=47 N=49
Mean±SD Mean±SD
Week0 (Baseline) 2.02±0.91 2.10±0.82
Week 4 1.46±1.11 1.43±1.10
Change from
-0.57±1.15 -0.67±0.94 >0.05
baseline
p-value** <0.01 <0.01
Week 12 1.48±1.05 1.10±1.12
Change from
-0.54±1.15 -1.00±0.98 <0.05
baseline
p-value** <0.01 <0.01 Fig. 2. Changes of vaginal dryness (Mean±SE) during 12 weeks administration
of EstroG-100 and placebo.
SE:Standard Error, *: Statistically significant compared between groups; p<0.05
by t–test
 Estrogenicity
Efficacy of EstroG-100
In e-screen test, the estrogen-specific alkaline phosphatase has significantly increased and
synergetic effects of EstroG-100 has been confirmed

 E-screen test: Screen herbal extracts for Estrogenicity

 Synergetic Effects of 3 Constituent herbal extracts
confirmed
- Lee at al., Lab. Anim. Res. 24(2): 167-172 (2008)

 Significantly improved in serum osteocalcin and FBMD in OVX rat

 No change in weight, liver, kidney, and uterus weight in OVX rat
Uterus weight Serum osteocalcin FBMD
7 0.9

0.8 *
6 *
Osteocalcin (ng/mL)

0.7
* *
5 * * * *

FBMD * (g/㎠)
* 0.6 *
*
4 0.5
* *
0.4
3
0.3
2
0.2

1 0.1

0
0
G1 G2 G3 G4 G5 G6 G7 G8 G9
G1 G2 G3 G4 G5 G6 G7 G8 G9
Group
Group

-Kim at al., Kor. J Food Sci. Technol. 40(3): 316-320 (2008)

 75% Higher Satisfaction Rate
Efficacy of EstroG-100

 75% higher satisfaction rate compared to the existing Isoflavone product

 69% picked “Better Efficacy” for the top reason for the higher satisfaction

* One month Open Label Clinical Study by Hiliving, the No.1 MLM firm among local capital MLM companies in Korea
with 119 participants
 86% Decrease in Menopausal Symptoms
Efficacy of EstroG-100

 86% decrease in menopausal symptoms compared to 39% of the Isoflavone product

 Sales volume increased 2.5 times, satisfaction/repurchasing/ recommendation rate soared

Satisfaction Rate Sales Volume/Month

100% 250%
80% 200%
60% 150%
40% 100%
20% 50%
0% 0%
Isflavone EstroG-100 Isflavone EstroG-100

Repeat Order Rate Recommendation Rate

80 80%
60 60%
40 40%
20 20%
0 0%
Isflavone EstroG-100 Isflavone EstroG-100

* One Month Open Label Clinical Study by Pulmuone Health Care with 31 participants
 Wrinkles, Hot Flashes, and Moisture
Significantly Improved
Efficacy of EstroG-100

* One month Open Label Clinical Study by LG Household & Health Care for 6 weeks with 30 participants
 Hot Flashes and Vaginal Dryness
Mostly Improved
Efficacy of EstroG-100

Hot flush and vaginal dryness, 33 % of total improved cases.

Symptoms cases %
Out of 20 participants, 10 participants
Hot flush 11 20%
showed the improvement of
Paresthesia 4 7% menopausal symptoms within 7 days
Insomnia 3 6% after taking EstroG-100. The main
Nervousness 3 6% improvement symptoms were hot flush
Melancholia 3 6% and vaginal dryness, 33 % of total
Vertigo 4 7% improved cases.
Fatigue 5 9%
Rheumatic pain 3 6%
Formication 2 4%
Headache 2 4%
Palpitation 2 4%
Vaginal dryness 7 13%
PMS 2 4%
Menstrual pain 2 4%
Restarting menstruation 1 2%
Total 54 100%

* Open Label Clinical Study by Kim Jung Moon Aloe for 4 weeks with 20 participants
Safety of EstroG-100

Safety in three human clinical studies

 No serious adverse effects – not even a single case of vaginal bleeding /
spotting
 No change in body weight
 No significant changes in E2 and FSH
 No change in blood pressure, blood sugar, cholesterol, LDL/HDL
 No change in endometrial thickness

Other Proven features

• All three herbs have been documented for use as herbal remedy for +400 years in
Korea
• All are registered as safe food ingredient in Korea Food Standard Food Codex
• Cynanchum wilfordii & Phlomis umbrosa are reported to be liver-protective
plants to WHO
MCF-7 cell & ER Binding Affinity
Safety of EstroG-100

MCF-7 proliferation inhibition

Cynanchum wilfodii extract
P hlomis umbros a extrac t
120 80
100
80 60
60
40
40
20 20
0
0
10㎍/㎖ 50㎍/㎖ 100㎍/㎖ 500㎍/㎖ 1000㎍/㎖
10㎍/ ㎖ 50㎍/ ㎖ 100㎍/ ㎖ 500㎍/ ㎖ 1000㎍/ ㎖

Estrogen receptor binding affinity test

Affinity of EstroG to ER beta

1.2
E2
Absorbance (450 nm)

0.9 FGF271
EstroG-100

0.6

0.3

0.0
10 -6 10 -5 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 10 4

Concentration (ug/ml)

EnBio Estrogen Receptor / Coactivator, Ligand Assay System

 Toxicology
Safety of EstroG-100

 Single oral toxicity study

• No specific toxic symptoms in relation to test substance were observed

• Minimal lethal dose (MLD) > 4,000 mg/kg (HED = 648.6mg/kg)

 Thirteen-week repeated (91 day) oral dose toxicity study of in Sprague-Dawley rats

• No observed adverse effect level (NOAEL):

upward 1,000 mg/kg in the male and female group

 Genetic Toxicity Study – proven non-toxicity

• Ames (Bacterial Reverse Mutation), Micronucleus, Chromosome Aberration

 Mechanism of Action
There are 4 different traditional methods of screening candidate plants for
estrogenecity
a. E-screen assay to see non-reproductive tract target tissue response for a certain plant
extract to induce alkaline phosphotase or ALP √ confirmed
b. Reproductive tract response for a certain plant extract to change uterus weight of
ovariectomized rats (now, just for safety) √ confirmed
c. Receptor binding affinity test (now, just for safety) √ confirmed
d. Gene reporter vector assay (now, just for safety)

EstroG-100:
In a non-reproductive tract target tissue response for e-screen assay, all of the 3
constituent herbal extracts of EstroG-100 found to promote estrogen-specific ALP activity
to show estrogenic action while EstroG-100 promoted more than any of the individual
herbal extract (Lee et al. Anti-menopausal effect of the newly-developed phytoestrogen,
FGF271 (=EstroG-100), in vitro and in vivo. Lab. Anim. Res. 24(2): 167-172(2008).) In the
earlier study that has not been published, the 3 constituent herbal extracts of EstroG-100
were selected out of 71 different herbal extracts by this e-screen assay.
 Mechanism of Action
The following available evidences suggest that some phytochemicals in EstroG-100 act as estrogen
agonists and/or antagonists without influencing the levels of estradiol (E2) and follicle stimulating
hormone or FSH:
• In two researches for the reproductive tract target tissue response, EstroG-100 did not
increase the uterus weight of ovariectomized rats while it increased femoral bone mineral
density. (Kim et al. Korean J. Food Sci. Technol., 2008 and Lee et al. Lab. Anim. Res. 2008)

• EstroG-100 did not show any affinity to both estrogen receptor alpha and beta in the receptor
binding affinity test reported by Chungbuk National Univ. of South Korea

• Each herbal extract of EstroG-100 showed inhibitory effect of the proliferation of human
breast cancer (MCF-7) cells

• In a randomized double-blind placebo controlled clinical study, EstroG-200(A finished product

containing EstroG-100 as main active) improved menopausal symptoms, bone density of
femoral bone neck, oseteocalcin level without any serious side effects with no increase of
body weight and BMI and without influencing level of E2 and FSH (Lee et al. Evaluation of
effectiveness and safety of natural plants extract (Estromon(=EstroG200)) on
perimenopausal women for 1 year. J of Korean Society of Menopause. 11(1): 116-26 (2005)

• In other clinical study performed in U.S. that was finished on Feb. 2010, EstroG-100
significantly improved menopausal symptoms of non-Asian American women without any side
effect (Chang et al. The Effect of Herbal Extract (EstroG-100®) on Pre-, Peri-, and Post-
Menopausal Women: A Randomized Double-Blind Placebo-Controlled Study. Phytother. Res.
26: 510-516 (2012)).
 Other Estrogen Alternatives

HRT
Women’s Health Initiative Study (WHI)
National Institute of Health (NIH) sponsored 8.5-year study with 16,000 subjects
to estimate the benefits and risks of HRT

The Study was terminated early at 5 years with increased risks of breast cancer (26%),
CVD (22%), stroke (41%), coronary heart disease (29%), blood clots (100%), Alzheimer's (100%)
US FDA required “Black Box Warning”
Prescribed ONLY for <4 weeks

JAMA July 2002

5,000

4,500

4,000

3,500

3,000

2,500

2,000

1,500

1,000

500

-
'01 '03 '05 '07 '09 '11 '13E '15E '17E
 Vulnerability of Black Cohosh
Other Estrogen Alternatives
The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) advised that a
warning label would be placed on the all black cohosh products due to 21 reported cases of
liver problems associated with black cohosh use (MHRA, 2006)

The committee reviewed case reports suggesting a potential

link between ingestion of the extracts and liver damage
01/15/2007
07/30/2007

At the end of one year, there was no significant

difference seen between the number of daily hot flashes
and/or night sweats in any of the herbal groups compared to
the placebo group, with an average of 0.6 less vasomotor
symptoms per day in the herbal groups. There was a significant
difference-4.06 fewer symptoms per day-in the hormone
therapy group compared to the placebo groups
 Vulnerability of Black Cohosh
Other Estrogen Alternatives
As of Oct 2012, due to 36 out of 53 case reports related to black cohosh involved liver
problem, MHRA has warned manufacturers of black cohosh products that the herbal
supplements must contain warnings about potential liver problems (MHRA 2012).

10/30/2012

http://www.nutraingredients.com/Regulation/UK-tells-black-cohosh-makers-to-add-warnings-and-backs-THMPD
 Risk of Black Cohosh

Liver Toxicity Reports Worldwide

47 cases by 2005  82 cases by 2009

United Kingdom (MHRA) Australia (TGA)

21 cases  36 cases (2012) 9 cases  11 cases (2006)
Product-label warning required (2012) TGA warning label required

Germany: 7 cases
Sweden: 6 cases

United States (USP DSI-EC) Canada (HC)

3 cases Brief notice & follow-up consumer
Labeling required advisory issued
 Risks of Isoflavone
Other Estrogen Alternatives

 Genistein (a major isoflavone aglycone) may

cause Cancers ( NIH & FDA – National Toxicology Program,
Genistein Final , Jan, 2008)
Exposure to Genistein for 2 years caused mammary gland /
pituitary gland adenoma in female rats.
Exposure to Genistein for shorter duration following birth
was also possibly associated with increased rates of
pituitary gland and mammary gland tumors.

 Cancer Causing Risks

Isoflavone Could be Toxic because its high level of hormone-like action.
It could be Hormone Dependent Cancer Causing Material due to its high binding affinity to Estrogen Receptor α,
and β

Relative Binding Affinity

α β
Estradiol 100 100
Coumestrol1) 94 185
Genistein2) 4 87
1) Kuiper et al, Vol 139, No. 3, Endo 1997 2) Vol 138, No. 10, Endo 1998,
 EstroG-100’s Superiority over Others
EstroG-100 Compared with Other Alternatives
EstroG-100 Pomegranate Soy Isoflavones Black Cohosh HRT

Improved 1
10 2 (Hot Flush, Fatigue) Partially Some Improved
Symptoms (Hot Flush)
Improvement of
O X O
Vaginal dryness
Bone metabolism
O X O X O
index

Bone density O (FBMD) X O X O (Backbone)

Triglycerides O X

Cancer Related Fatal Side

Side Effects X X Liver Damage
(limitation on dosage) Effects

Increase of Body
X X O
Weight & BMI

E2, FSH Changes X X O

Development In the 2000s In 1998 In the 1990s In the 1940s

17 registered and
Related Patents X
pending patents
New History on Healthcare Ingredients

Sales of Major Herbal Medicines

(million USD)
100  Stillen: the Korean Blockbuster Herbal
80
Medicine of Dong-A Pharm sold in US$85
mil.
60
Joins Tab.
 Joins: the Korean Major Herbal Medicine
40 Stillen Tab.
of SK Chemical in US$35 mil. (Ministry of
Health & Welfare, 2012)
20

 Factive: the 1st Korean Drug approved by

0
2005 2007 2009 2012 U.S. FDA sold in US$17 mil in 2011 but
decreased to US$9 mil. in 2012 (Asia Economics,
Sales of EstroG-100 in Retail Price 2013)

(million USD)
350
 EstroG-100 has been supplied for Korean
300
majors and its sales hit in Retail Price:
250
 2010 USD 9 mil.
200
 2011 USD 55 mil.
150
 2012 USD 105 mil.
100
 2013 USD 270 mil
50  2014 USD 400 mil
0
2010 2011 2012 2013 2014
 Target
Strategies & Current Status
Market
FDA Approval from USA and Canada. North America market has
North
40% of market share in Health Functional Foods Market.  Scientific evidence is mandatory. 3
Being supplied for #1 & #2 pharmacy chains, Walgreens and CVS clinical studies studies
America and #2 Infomercial company called Ideal Living.
In negotiation with 2~3 global big pharma companies.  FDA approval is a must
To be approved in 2015. Contracted with Swiss pharma company as
EU a n exclusive distributor for EU market; EU controls 30% of market  Testimonial is essential for buyers
world wide. to judge the efficacy.
To be approved in 2015. Japan is the market accounts 11% of
Japan  Proven track record in local market
global market share of the world.
is necessary to confirm the
To be approved in 1Q 2016. Plan to expand into China with efficacy of a new ingredient.
China finished products. Currently, China dominates 12% of the market
and expected to grow as the 2nd largest market in the world.
Approved and being sold in Singapore, Malaysia, Thailand and
Pakistan.
South East
Joint marketing with the multinational companies to be carried out
Asia to get an approval in Indonesia, Philippines, Vietnam, and the rest
(etc).
S.America
Approval process underway in Brazil, Iran, Saudi Arabia and so on.
M.East

CIS In the middle of getting an approval in Russia

 Expected
Countries Category Authority ‘14 2H ‘15 1H ‘15 2H ‘16 1H
approval date
USA Food supplement FDA Completed in 2010
Health Functional
Korea MFDS Completed in 2010
Food Supplement
Natural Health
Canada Health Canada Completed in 2011
Product
Malaysia Food supplement NPCB Completed in 2013
Singapore Health Supplement HAS Completed in 2013
Thailand Food supplement MOPH Completed in 2014
Pakistan Food supplement DRAP Completed in 2014
EU Food supplement EU Commission 3Q 2015 Expected Date
Iran Food supplement MOHME 4Q 2015 Expected Date
Iraq Food supplement MOH 2Q 2015 Expected Date
India Food supplement FSSAI 2Q 2015 Expected Date
Colombia Food supplement MHSP 2Q 2015 Expected Date
Vietnam Food supplement VFA 3Q 2015 Expected Date
Japan Food supplement MHLW 3Q 2015 Expected Date
Natural Health
New Zealand NZFSA 3Q 2015 Expected Date
Product
Brazil Food supplement ANVISA 4Q 2015 Expected Date
Indonesia Food supplement BPOM 4Q 2015 Expected Date
Russia Food supplement MOPH 4Q 2015 Expected Date
Philippines Traditional Medicine BFAD 4Q 2015 Expected Date
China Food supplement CFDA 1Q 2016 Expected Date
 Current Status in N. America Market

First bio company in Korea to receive the approvals and successfully signed
the contracts to supply ingredients to major industries in North America.

On the shelves of # 1 & 2 pharmacy chains, Walgreens & CVS

Major infomercial company Ideal Living launched Profemin

On the shelves of Whole Foods Market, the largest organic food

supermarket

Solidified contracts with top 10 pharmacy chains in US

Solidified contract with Natural Factors, #1 health supplement company in

Canada

Currently in negotiation with 2~3 global big pharma companies

US products

Multi Symptom 8 Symptom Advanced Advanced Natural Sex

Herbal Pause Best EstroG-100
Menopause Relief Menopause Relief for Women 50+
(NOW Foods) (Doctor's Best)
(Walgreens) (CVS Pharmacy) (Life Extension)

Advanced 8-Symptom
Ultra EstroG-100 Profemin Intimate Comfort Zestrogen
Menopause Relief
(Swanson) (TheraBotanics LLC) (Healthy Directions ) (Purity Products)
(Meijer)

Venus and Mars EstroPrime Plus Flashes No More n-fuzed Estro-Fem HerbaEst Balance
(Dr. John Gray, Inc) (Allergy Research Group) (Nutricology) (Harmonic Innerprizes Inc. ) (New Spirit Naturals)
Major products & partners

BAEKSUOQUEEN
DongaBAEKSUO
(Lotte& CJ Home
(DongaPharm)
Shopping)

KT&G
(HwaaelakQueen)

NOWFOODS
(HerbalPause)
 Awards

Best Botanical Award at Natural Products Expo West in US (2014)

 Korea’s top 10 most innovative technologies (2013)

EstroG-100 was awarded for “Korea’s top 10 innovative technologies” in 2013. This
award is given only for the product that is the most promising and potential of the year
in all industry.

For ‘EstroG-100’ by Ministry of Trade, Industry and Energy

Korean World-class Product Award (2011)

World-class Product Award is honorable recognition given to top-tier Korean

companies including Samsung, Hyundai, and LG.

For ‘EstroG-100’ by Ministry of Knowledge & Economy

Presidential Citation (2011)

Presidential Citation
In recognition of the
company’s integrated
contribution to the growth of
the industry through edge-
state technology
development in agro-fishery
food sector.
Oct. 13, 2011

President Myung-bak Lee

IR52 Chang Young-Sil Award(2009)

This Award is normally and in most cases for conglomerates such as

Samsung, Hyundai, LG, and for the suppliers for the big companies from
Ministry of Education, Science and Technology (2009).
[Other Awardees of IR52
Award in 2009]
 Other Awards from Korean Government

Korea Health Industry Award by KFDA 2009 Health Technology Award 2008
 Gold Medal Prize in the Exhibition of Inventions of
Geneva (2008)

The International Exhibition of Inventions of Geneva is one of the three largest

invention expo in the world.
 Product Merit Award-NBJ (2006)

Awarded to the Promising Brand-new Functional Food of the Year

 Press Coverage
Life Extension Magazine, May 2012

“EstroG-100™, this multi-compound

extract supports balanced estrogenic
activity, which in turn inhibits the many
symptoms of menopause including
female sexual dysfunction”

Oprah Winfrey Magazine, 2014

Press Coverage
 Press Coverage
SBS Special : Rediscovery of Korean Herb(Mar. 3rd ,
2013) The most popular privately owned TV
channel, SBS Special Documentary featured
EstroG-100 for 1 hour: its history, science &
technology, testimonials from MDs and end
users, and other distinctive aspects.

“Traditional Korean herb extracts pulling

Global attention and being exported to the
World.

KBS Science Café – Science of Hormone (April 9th, 2012)

The largest and state-run Korea Broadcasting
System or KBS reported on hormone in their
program called Science Café. It dealt the
science of hormone and introduced EstroG-100
as a safe new product for menopause.
 Thank you
for
your attention

Naturalendo Tech Co., Ltd.