Droplet ExteNsion (DEN) Technology for the Commercial Microarray Patch Manufacturing

MICRONEEDLE 2020

10th, Nov., 2020

RAPHAS Co., Ltd.Medical Business Division

Juyeop, SHIN

1. Introduction of RAPHAS & IP

2. Technology as DEN microarray

3. Business Model : Cosmetic, Medical Device & Medical field

4. Automatic In-line mass production for DEN

5. Production Yield and Capacity

6. Quality Control for Commercialization

CONTENTS

RAPHAS HQs & Research CenterPharmaceutical / Cosmetic GMP

HQs,Pharmaceutical GMP Factory in Seoul

1st GMP Factory in Cheonan, Korea

2nd GMP Factory in Shizuoka, Japan

Patent Status

Method & Equipment for DEN Microarray Core Technology

Raphas has 43 granted patents and Keep try to build evergreen strategy

Covered in USA, JAPAN, EU, CHINA and Korea(51 patents within Application)

Dispensing on the Adhesive Patch

Contacting Elongation And Drying

Separation of a couple patch

DEN MAP FABRICATION TIME

Dispensing on the Adhesive Patch

Contacting Elongation And Drying

Separation of a couple patch

1 min 3-4 min3 min 100-array based

1 process time needs just 8 minutes

One Layer DEN MAP

Double Layer DEN MAP

COMMERCIALIZATION PRODUCTS OF RAPHASAntiaging & Skin Care Products

PARTNERS

Trouble Cure PigmentationCare

Wrinkle care Dark Circle Care

Basement 2 hours (1-app.) After 4-weeks

0 Day 4 Day 7 Day

0 Week 4 Weeks

0 Week 4 Weeks

Accumulated over Ten million patches

Sales

On/Off-line Channel Distribution of Microneedle Dermacosmetic product

TOTAL ACCUMULATED SALES HISTORY of RAPHAS Microneedle Dermacosmatic Products

(2015- 2019)

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2015 2016 2017 2018 2019

x 10

0000

00

ACROPASS ODM

MEDICAL PRODUCTS OF RAPHASFirst Dissolving MAP Medical Device

The rapas s ®

Psoriatic plaques improved significantly after 1 week of MAP application. The circle indicated by the white dotted line is a plaque treated with MAP. The modified Psoriasis Area Severity Index (mPASI) decreased from 7 to 1 in patient 1 (A and E), from 9 to 3 in patient 5 (B and F), from 5 to 0 in patient 6 (C and G) and from 6 to 2 in patient 9 (D and H). These patients were very satisfied with the additional application of the MAP application.

Clinical improvement of prurigo nodularis. Photograph of prurigo nodularis lesions before (A) and after (B) the application of dissolving MAP following topical steroids, and before (C) and after (D) the application of topical steroids alone (without the MN patch). The dissolving MAP side exhibited greater improvement with regards to size and height, compared to the control side.

Patch for absorption of transdermal medicine

Psoriasis Treatment

Prurigo nodularis Treatment

Eur J Dermatol 2018; 28(1): 71-7

J Dermatol. 2018 Jan;178(1):e24-e25

MEDICAL PRODUCTS OF RAPHASVaccine & Therapeutic area

Airway Hyper-Responsiveness

TuberculosisVaccine

COVID-19Vaccine

Hepatitis type BVaccine Immunotherapy

ACNE CareOTC

SCAR CareMedical device

Neutralization Antibody

7 weeks treatment

What is the most urgent issue for the Microneedle patch at this moment?

AUTOMATIC IN-LINE MANUFACTURING FACILITYCommercialization GMP

CAPACITY & YIELD OF RAPHAS MANUFACTURING SITE

12,000patches/single equipment/day

Automatic In-line Capacity (Present in 2020)

31,000patches/day

MT 20,000 Blister pack/day

Production Capacity of Individual Machine (Condition: day = 8hours, Yield 90%, Spot patch)

21,000patches/day

21,000 patches / line / day (8 hours)App. 420,000 patches / Line / Month (working day)

SPECIFICATION FOR QUALITY OF DEN MICROARRAY

Automatic Inspection of Appearance

Physical Strength of each Array/Needle

Microorganism ControlAerobic live & Specific M/O

(CFU/ml)

00.050.1

0.150.2

0.250.3

0.350.4

-0.04 0.01 0.06 0.11 0.16

Sta

ndar

d F

orce

(N

)

Travel from Touching Onwards (mm)

THERAPASS®

650um needle length

Microarray can puncture into skin and deliver drug into body. This image shows real skin puncture on our forearm by OCT.

MAKING CHANNEL BY MICRONEEDLE SKIN SURFACE

Stratum corium250um length of Microarray 600um length

of Microarray

Epidermal Dermal Junction

Epidermis

Dermis

These images are shown that skin penetrate depth depends on length of microarray.

SPECIFICATION FOR QUALITY OF DEN MICROARRAYSkin Puncture

SPECIFICATION FOR QUALITY OF DEN MICROARRAY

Basic Quality Control Points of Rapahs

Manufacturing is not the end, it's just the beginning. The ultimate goal is customer satisfaction.

We has Real Experiences form production to C/S managing of Microneedle commercial products.

PARTNERSHIP

“We innovate by starting with the customer and working backwards. That becomes the touchstone for how we invent”

We hope that many Microneedle inventors and developers will work together to help the market demand the productization and successful entry into the market.Thank you to the organizers of the Micronedle2020.