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Dharma Therapeutics

Corporate Overview

January 19, 2010

Seattle, WA





January 19, 2010 1

Overview

 Corporate Overview

 Why work with Dharma? Our internal and

external transdermal and iontophoretic expertise

 Iontophoresis

 Why iontophoretic products have not seen real

commercial success

 Dharma’s Approach

 Dharma’s Pipeline





January 19, 2010 2

Corporate Overview

 Transcu Ltd – Singapore

 Corporate headquarters

 Dharma Therapeutics, Inc – Seattle, Washington USA

 Innovative, non-invasive delivery of drugs through

the skin

 Development of state-of-the-art iontophoretic

transdermal delivery systems from pre-clinical

through approval

 TTI ellebeau, Inc – Tokyo, Japan

 R&D, passive delivery and iontophoretic electrode

technology



January 19, 2010 3

Business Model

 Internally develop novel pipeline products

 License pipeline products to pharmaceutical and non-

pharmaceutical partners for commercialization

 Establish relationships with pharmaceutical and non-

pharmaceutical companies to work on early stage

product opportunities









January 19, 2010 4

Dharma’s Internal Expertise

 17 employees with broad industry experience

 Regulatory, Quality Assurance, Quality Control, Clinical Trials

 Executive Management, Project Management

 GMP Manufacturing for early stage products

 R&D capable of both in vitro and in vivo studies

 Established quality system that is compliant with FDA

regulations for drugs and devices.

 Proven track record of moving products from early stage

development through successful Phase 2 clinical trials, with

on-going Phase 3 development





January 19, 2010 5

Dharma R&D

 Evaluation of drug targets in vitro and in vivo allowing

go/no go decisions to be made quickly

 Onsite vivarium for small animals, access to larger animals

via collaboration

 Access to human skin for model confirmation

 Experienced team of scientists

 Head of Engineering with over 15 yrs direct experience in

drug delivery science and technology (primarily

iontophoresis)

 Three additional scientists with over 16 years combined

experience in iontophoresis and passive transdermal

delivery

 Additional scientific expertise at TTI’s Tokyo laboratories



January 19, 2010 6

Hardware & Analytical Support

 State-of-the-art Permeation Systems

 Two 8-channel galvanostat/potentiostats

 One frequency response analyzer

 One 9-channel and one 3-channel in vitro permeation

systems for iontophoresis and one 8-channel passive

permeation system

 Three automated HPLC systems

 One MS system

 Radio-label tracer experience



January 19, 2010 7

Dharma’s External Expertise

 Established networks with broad capabilities

 Commercial transdermal patch manufacturing

 State-of-the-art print technology for electrodes

 Electronic development and design

 Microprocessor control (hardware and software)

 PCB layout and related component design

 Electronic manufacturing capability meeting FDA

requirements

 Access to proprietary state-of-the-art battery, ASIC and

printed circuit technology

 Analytical labs with expertise in transdermal method

development and validation

 Clinical, regulatory, compliance and product development

expertise



January 19, 2010 8

Iontophoresis

 Uses an electric field to transport charged molecules

across the skin

 Advantages of Iontophoretic Delivery

 Precise control

 Rapid delivery

 Avoids first pass metabolism

 Versatile

 Patient friendly

 Proven safe and efficient

 Track record of FDA approval



January 19, 2010 9

Why Have Iontophoretic Products

Not Been Successful?

 Initial products (from Iomed, Empi, Life-Tech) were

medical devices only

 Device and drug not designed to work in combination or

for specific application

 Formulations not optimized

 “Generic” electrode configuration not designed for specific

drug, application site or therapeutic indication

 Inadequate clinical data to demonstrate efficacy

 Bulky desktop/handheld controllers requiring tethering to

electrodes

 User filling required





January 19, 2010 10

Why Have Iontophoretic Products

Not Been Successful?

 Next generation products (from Vyteris and ALZA)

were drug/device combinations, but failed because of

one or more of the following:

 Cost

 Complexity

 Manufacturability at commercial scale

 Stability

 Marketing and reimbursement strategy

 Corporate financial status

 Ease of use, size





January 19, 2010 11

Dharma’s IDDS Solution

 Device and drug designed to work in

combination for specific application

 Formulations optimized

 Specialized electrode configuration designed

for specific drug, application site and

therapeutic indication

 Products designed with the end user in mind

 Prefilled patch

 Small controller that easily attaches to the patch

 Products designed to for commercial scale

manufacturing with a low cost of goods



January 19, 2010 12

Local Anesthesia

Market Opportunity

 Well documented opportunity for a product that induces local

anesthesia rapidly, in a cost effective manner

 Opportunities to reduce pain during a variety of procedures

 Blood draw, blood gas, IV cannulation, minor dermatological

procedures, chemotherapy administration

 Opportunities to reduce pain for numerous patient populations

 Pediatrics, those who are needle phobic or pain averse

 Existing product use is limited by undesirable characteristics

such as long onset time, high cost, or ineffectiveness

 EMLA cream claims local anesthesia 60 minutes after

application and represents a >$90MM market







January 19, 2010 13

The Dharma Solution→

Transdermal Lidocaine

 Advantages of local lidocaine product

 Reduction in pain and anxiety for pain/needle-

phobic patients

 Faster throughput of patients reduces overhead cost

to healthcare providers

 Easier to place needle post treatment

 Reduction in children’s pain and anxiety

 Reduce need for lidocaine injections in

dermatological surgeries





January 19, 2010 14

The Dharma Solution→

Lidocaine IDDS

 Our product has been designed to meet the

market demand for a low cost, fast onset local

anesthesia product

 Lidocaine IDDS will be highly competitive on price

and onset time → provides large share of the

existing local anesthesia market

 Lidocaine IDDS’s fast onset time (8 min) →

creates new markets within needle stick,

dermatology and other areas





January 19, 2010 15

Lidocaine IDDS

Product Configuration

 Small controller easily attaches to prefilled patch

via magnetic interconnect









January 19, 2010 16

Lidocaine IDDS

Key Benefits

It's Quick.

 After just an 8-minute application, provides local anesthesia



It's Easy.

 Single-use patch is pre-filled with Lidocaine & Epinephrine

 Multi-use power-supply is pre-programmed for ease of use with no dials to set or

current to adjust, provides visual feedback, attaches to patch with magnet



It's Effective.

 Proven iontophoresis technology delivers Lidocaine at the injection site

 Long duration anesthetic effect



It’s Safe.

 Both Lidocaine and Epinephrine have established safety profiles

 Drug products based on iontophoretic technology have been approved by the FDA









January 19, 2010 17

Lidocaine IDDS

Clinical Trial Summary

Phase 2A: Phase 2B:

A Double-Blind Randomized, A Multicenter Double-Blind Randomized

Placebo-Controlled, Two-Arm Study Placebo Controlled Two-Arm Study

Evaluating the Safety and Efficacy of Evaluating the Safety and Efficacy of the

the Iontophoretic Administration of Iontophoretic Administration of Lidocaine

Lidocaine and Epinephrine Versus and Epinephrine Using Lidocaine

Placebo Using the DTI/TTI IDDS to Iontophoretic Drug Delivery System

Induce Local Anesthesia Prior to (IDDS) to Provide Local Anesthesia for

Venipuncture in Healthy Adult Venipuncture in Healthy Adult Volunteer

Volunteer Subjects Subjects



 70 Subjects Treated  89 Subjects Treated

 36 Active  57 Active

 34 Placebo  32 Placebo

 Age 18-57 years  Age 18-66 years

 No SAEs  No SAEs

 3 AEs in 3 subjects – 2 mild,  8 AEs in 5 subjects – 6 mild, 2

1 moderate moderate





January 19, 2010 18

Lido IDDS Pain Scores



Median VAS Scores



25.0



20.0

VAS Score, mm









15.0



10.0



5.0



0.0

Placebo Active Placebo Active



Phase 2B Phase 2A





Phase 2B p= 0.0235, Phase 2A p <= 0.01







January 19, 2010 19

Device Was Well Accepted



Was Your Pain Eliminated? Would You Use IDDS Again?



100.00% 100%



90.00% 90%



80.00% 80%



70.00% 70%



60.00% 60%



50.00% 50%



40.00% 40%



30.00% 30%



20.00% 20%



10.00% 10%



0.00% 0%



Phase 2B Active Phase 2A Active Phase 2B Active Phase 2A Active

% Answering YES % Answering YES









January 19, 2010 20

Pipeline

Partnering Opportunities

 Seeking partners to support clinical development

and commercialization of pipeline projects

 Seeking partner for regional or world-wide

marketing, distribution and sales

 Lidocaine/ Epinephrine for local anesthesia (Phase 2

studies completed)

 Anti-inflammatory (pre-IND meeting completed)

 Anti-nausea (pre-clinical)

 Other targets under evaluation in pain, Alzheimer's and

Parkinson’s diseases





January 19, 2010 21

Contact Us Today To Learn More

About Pain Free Drug Delivery

Paul Sleath, PhD – President & CEO

206-330-2591

psleath@dharmatherapeutics.com





Dharma Therapeutics

1124 Columbia Street, Suite 450

Seattle, WA 98104

www.dharmatherapeutics.com









January 19, 2010 22



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