Transcript Guerrilla Tactics in Pharmaceutical Innovation and

Life beyond Science
Early Work
1986
1986
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Early Work
Years at Sterling Drug Company
Products Developed
Pro-Drug Approach
Hydroxychloroquine Formulations
Danazol Pro-Drugs
Life Beyond Science
Bold Move to Business 1989 - 2002
• Electrician Loan + Proctosol is same as Anusol
• State of the Art liquid Manufacturing + Sell when on Top of the game
Guerrilla
Warfare
Guerrilla
Marketing
Guerrilla
Innovation
Guerrilla Tactics in
Pharmaceutical Innovation and Testing
Dr. V. Ravi Chandran
R&D Practitioner
Life Enhancing Technologies, LLC.
Allen, TX
USA
Normally to create an IPR of a large Pharma Company
requires:
+
+
Army of Good
Creative Scientists
R&D Funding equal
to top 10 Pharma
Companies combined
A Decade or
more years
But what we really have:
One Scientist
(myself)
Enough resources for
a lavish retirement
in Caribbean Islands
Getting old –
not much time left
Questions in my mind:
Do I develop
one Molecule
at a time?
Do I develop
all the Drugs
at one shot?
Platform
Technology?
What area
do I apply this
Technology?
Status in the early 2000
Efficacious
Toxic
I wanted to increase the
efficacy and reduce the
toxicity i.e. Increase the
Therapeutic Index
Drugs entering market
Examples
Hail in the Guerrilla!
Areas of human endeavor responsible
for enhancing Quality of Life*
1. Computer Hardware and Software
2. Advances in Medicine
* APhA Conference in Seattle, Washington, USA
Circa year 2000
Leading Causes of Death
650,000
559,000
250,000
143,000
Heart Diseases
Cancer
Doctors*
Stroke
131,000
Chronic
Respiratory
Diseases
*JAMA Vol. 284, No.4, July 26, 2000
Guerrilla Tactic – 1 :
Narrow area of attack with maximum impact
Among Heart
Diseases, Heart
Attack is the leading
cause of death in
both men and
women*
*World Health Report 2004. Changing History, WHO 2004 pp 120-124 ISBN 92-4-156265-K
Tribute to a Legend
CLASSICAL AGE OLD DRUG
• Was Omar Sharif on Low Dose Aspirin?
• What is Aspirin?
• Chemically it is Acetyl Salicylic Acid
Guerrilla Tactic – 7 :
Creativity turns Problems into Opportunities
How to rapidly advance a NCE
without an IND from Lab to Clinical Trials
Guerrilla Tactic – 8 :
Simple Techniques are sometimes most useful
What can be an effective, simple and
reliable technique to measure effectiveness
of anti-platelet drugs in humans
Beautiful & Handsome Arabs
Doc, Can you Sing & Dance?
Doc, Can you Act?
Outsource Hollywood?
Bollywood Dream Busted!
Guerrilla Tactic – 12 :
Expand upon what worked earlier
Expansion of OH
Containing AA
platform
technology to
improve
Ibuprofen
Synthesized 3 Amino Acid
Esters of Racemic Ibuprofen
L – Threonine
L – Hydroxy Proline
L - Serine
Numerous Surprises on Raviprofen®
Surprising
Racemic
Separation
L–
Threonine
Platform
Technology
Proven
Works
similar to
Ibuprofen
No
Ibuprofen
released
Effective
in Human
Trials
No Systemic
Toxicity
Not a
Pro - Drug
Guerrilla Tactic – 13 :
Open to surprises & turn them into advantages
Yes!
Can we
separate
racemic
mixtures with
L-Threonine?
Ketoprofen &
Ketorolac
separated
Embedded
Platform
Inside our
Platform
Technology
Painkiller Extraordinary
L-Threonine Ester of S(-)Ketorolac
Separates
Racemic
Mixtures
Non
Toxic
No Addiction
Potential
Threonine
Ester of S
(-)
Ketorolac
Highly
Effective in
Human
Trials
Narcotic
Strength Pain
reliever
L-Threonine – Nature’s Wonder
Surprising
Racemic
Separation
Platform
Technology
Proven
Simple
Separation
Method
Versatile
Properties
Effective
for Non
Racemic
Drugs
Resulting
Isomer has
high TI
Not a
Pro - Drug
Applications of Chiral Separation
using L-Threonine
Racemic Hydroxychloroquine
S(-)R(+) Carvedilol
Problems of Hindered Alcohols – Cyclosporine-A
Poor
Solubility
Poor
Absorption
Hindered
OH Group
Variable
Pharmacokinetics
Inconsistent
Pharmacological
Activity
KeraKlear - Numerous Surprises
Hindered
Alcohol
Problems
Solved
TI of 4.5
Showed
better
Prophylaxis
Versatile
Application
Amino Acid
Ester of
Cyclosporine
Keraklear
No ocular
irritation
Highly Soluble
in Water
Formulation
stable over
18 months
Life
Enhancing
Technologies
Tribute to a Legend
Prodrugs(?) of Propofol
Mr. Jackson wanted a
good night sleep
US Patent No. 8,173,840
Propofol Dose Selection
Drug
Low
Mid
High
Propofol
10 mg/kg
15 mg/kg
20 mg/kg
Lysine Ester of
Propofol
40 mg/kg
45 mg/kg
50 mg/kg
Proline Ester of
Propofol
25 mg/kg
30 mg/kg
35 mg/kg
Glycine Ester of
Propofol
30 mg/kg
35 mg/kg
40 mg/kg
10 Rats each, all doses, Propofol molar equivalent
Propofol Efficacy Studies
Mr. Jackson wanted low toxicity
Drug
Low (min)/
No. died
Mid (min)/
No. Died
High min)/
No. Died
Propofol
0
0
123 ± 34
0
178 ± 30
0
Lysine Ester of
Propofol
0
0
0
5
546 ± 0
9
Proline Ester of
Propofol
282 ± 162
1
421 ± 113
0
641 ± 138
2
Glycine Ester of
Propofol
532 ± 217
0
300 ± 211
0
641 ± 138
1
Time of righting reflex (seconds)
Conclusions – Propofol Studies
• Mr. Michael Jackson only wanted a good
night sleep
• Doses administered to him were toxic.
• If he had used Glycine Ester of Propofol,
he would have had a long night sleep, and
would come out of the sleep unscathed.
• Further studies in humans are warranted.
Summary
Largest Drug
Pipeline in the
World
9000 molecules
in 3 years
Creative
processes and
Guerrilla tactics
Numerous
Patents
covering 80% of
the market
Better
Alternatives
for 6 out of
top 10 – $ 41
Bill in sales
Better
Alternatives
for 68 out of
top 200 –
$ 120 Bill in
sales
Be on the lookout for
AAA – Once a day
capsules, nontoxic, safe and
effective cardioprotective agent
S(-)Ketorolac- LThreonine Ester, a
superior pain killer
of narcotic
strength, but with
no addiction
potential
KeraKlear optic
drops for dry
eyes …
You Can Achieve Anything
Isn’t it
Truly Life
Enhancing!
Thank You