Transcript A Revolution in Pain Pharmaceuticals

A Revolution in Pain
Pharmaceuticals
1
The Problem
Opioids are the oldest and most prescribed pain drugs.
They are the most powerful analgesics for treatment of
acute as well as chronic pain.
However, their use is plagued by significant side effects:
 Euphoria / Abuse & Addiction
 Respiratory depression
 Constipation
 Death
2
2
The Problem
From the CDC mortality report released in February, 2011:
Death rates in the U.S. have declined over the past ten years for
all major causes of death - except for death from prescription
opioid abuse. “It is a major public health problem that is getting
worse, and getting worse rapidly. “
From follow-up reports by the CDC from 2012 to 2014:
More than 2 million Americans are addicted to opioids. The
epidemic of overdoses of opioid pain relievers (OPRs) has
continued to worsen. OPR deaths now represent nearly 75% of
all prescription drug overdose deaths.
3
The Solution: Phoenix PPL-103





Robust analgesic potency – 10-20x stronger than morphine
No euphoria / abuse & addiction
No dysphoria
No death from overdose (even at 350x dose)
No significant constipation (even at 350x dose)
From Jain’s Pain Therapeutics: “Phoenix [PharmaLabs Inc] is developing a
new class of opioids with partial Mu/Delta/Kappa-receptor activity allowing
them to be moderately active at all three pain receptors. This balanced
partial activity appears to allow full pain relief while eliminating or
reducing such side effects as respiratory depression and addiction...”
4
4
The Unique Profile of PPL Drugs
 High binding affinity at all three opioid receptors
 Partial agonist / antagonist activity
 More balanced receptor activity than other opioids
 Mu antagonist with weak partial agonist activity
 Relatively high, but not full, kappa agonist activity
 Moderate delta activity
5
5
PPL-103 Profile
Characteristic
Mu Opioids Kappa Opioids
PPL-103
Significant Self-Administration / CPP (Euphoria)
Yes
No
No
Significant CPA (Dysphoria)
No
Yes
No
Lethal Respiratory Depression at High Dosage
Yes
No
No
Significant Constipation
Yes
No
No
Withdrawal Symptoms
Severe
No
No
Yes
No
Yes
Sustains Without Opiate Withdrawal
A potent opioid with a profile that is neither mu nor kappa –
and is free of the serious side effects of both
6
6
PPL-103 Rat Self-administration
FR-1
Infusions (120 min)
30
A
Morphine 100 µg/kg
7
PPL-103 30 µg/kg
PPL-103 100 µg/kg
Saline
25
20
15
10
5
0
B
***
***
***
***
***
***
***
***
1
2
3
4
FR-1 sessions
7
PPL-103 Rat Self-administration:
Progressive Ratio
B
80
20
60
15
40
**
**
sa
lin
/k
10
0
µg
/k
P
P
L10
3
P
L10
3
30
µg
/k
µg
P
10
0
e
0
g
0
g
5
g
20
in
e
ph
or
M
10
**
Break Point
Total Responses
8
Progressive
Ratio
8
Predictive Validity of Rat SA Studies
The rat self-administration model has a very
high correlation to abuse liability in humans:
“In summary, the current review identified 23 opioid related drugs that
had been assessed in the rat self-administration model and which
could be contrasted with reports of positive subjective- effects in
humans and/or drug scheduling status. The large volume of literature
on the self-administration of opioids in rats together with the high
concordance of findings between non-clinical studies and the clinical
endpoints of abuse liability provides strong support for the use of the
rat model for assessing the abuse liability of opioids.” [“The predictive
validity of the rat self-administration model for abuse liability” O'Connor et al.
Neuroscience & Biobehavioral Rev. 35:912-938, 2011]
9
PPL Drug Family Study Results
Study results in monkeys and rodents done by National Institutes
of Health (NIH) and SRI International Laboratories:











Robust analgesic potency (10-20x stronger than morphine)
No euphoria / abuse potential – multiple studies
No dysphoria – in rodents and monkeys
Only limited respiratory depression – even at 150x dose
No death from overdose – even at 350x dose
LD50 = 500x dose
No constipation - at 100x dose & very limited even at 350x dose
No physical dependence - in naïve rodents
No Long QT syndrome risk – hERG assay
Does not precipitate withdrawal - in dependent monkeys
Orally active – unlike morphine that is an injectable
10
10
Strategic Objective:
To enter into a strategic alliance with appropriate
market leader(s) that have the resources and
motivation to further develop, commercialize, and
maximize the market potential of, Phoenix
PharmaLab’s family of drugs.
PPL is currently advancing its lead compound for pain through
preclinical studies and then to proof of concept (POC) in humans. At
or before that point is reached the company expects to license that
compound to a pharma company that meets the above criteria.
11
11
PPL Offers…
 A Novel Design Technology
 Multiple Therapeutic Licensing Opportunities
 A Very Large Market in Pain Therapeutics
 Relatively Low Clinical Trial Costs
 PPL Drug Family Expansion
 Multiple government grant opportunities
12
12
Thank You
For further information contact:
Bill Crossman
President and CEO
Phoenix PharmaLabs, Inc.
Tel: (860) 305-6955
Email: [email protected]
www.phoenixpharmalabs.com
13