TECHNOLOGY

Phoenix Characteristics Vs. Others

CHARACTERISTICMU OPIOIDSKAPPA OPIOIDSPPL-103PPL-138
Significant Euphoria ("High" Feeling)
( CPP/SA )
Significant Dysphoria ("Bad" Feeling)
(CPA)
Lethal Respiratory Depression (Slowed Breathing) at Moderate Dose
Significant Constipation
Withdrawal Symptoms
Sustains Without Opiate Withdrawal
Drowsiness
CHARACTERISTICMU OPIOIDSKAPPA OPIOIDSPPL-103PPL-138
Significant Euphoria ("High" Feeling)
( CPP/SA )
Significant Dysphoria ("Bad" Feeling)
(CPA)
Lethal Respiratory Depression (Slowed Breathing) at Moderate Dose
Significant Constipation
Withdrawal Symptoms
Sustains Without Opiate Withdrawal
Drowsiness

Potent opioids with profiles that are neither mu nor kappa – and are free of the serious side effects of both.

All of the leading opioids on the market today like morphine, oxycodone, hydrocodone, methadone, fentanyl, etc. –as well as heroin – bind to the mu receptor in the brain and then aggressively stimulate that receptor. Mu produces potent pain relief, but it also produces a euphoric “high” – which leads to abuse and addiction.

OTHER OPIOIDS

Morphine, Oxycodone, Hydracodone,

Methadone, Fentanyl, etc. – and Heroin

agonize the Mu receptor

PPL-103

PPL-103 is unique because it binds strongly to three receptors: mu, kappa and delta – and then just partially stimulates those receptors in a much more balanced manner. That partial stimulation derives analgesic benefit from all three receptors, but it is not sufficiently strong to produce the serious opioid side effects associated with any of the receptors. The reason that all of those other opioids are addicting is because they produce a euphoric “high”. Without that euphoria, drugs would not be abused and would not be addicting.

This profile results in first-ever opiate analgesics that appear to be non-addicting and free of significant dangerous side effects.

PPL-103

partially stimulates all three opioid receptors

PPL-103 has clearly demonstrated in various animal studies that it does not produce euphoria (or dysphoria) and does not produce the other mu opioid side effects like withdrawal, constipation and death from overdose.

PPL-103 Product Profile:

  • Robust analgesic potency – >10x the potency of morphine

  • Little or No Euphoria or Abuse-Liability – >No self-administration preference [1]

  • No Dysphoria – >No aversion – unlike kappa opioids

  • No Physical Dependence – No withdrawal symptoms

  • No Death from Overdose – At elevated dose levels

  • No Constipation – At elevated dose levels

Further Technical Details

PEER REVIEWED PAPER:

Frontiers in Psychiatry, 12 April, 2017.

Technical Narrative

PPL-138

Recently Phoenix acquired the closest competing technology to PPL-103: a portfolio of Nociceptin compounds from the University of Bath (England) including the drug that we now call PPL-138. This compound meets all of PPL’s criteria for a potent, safe, non-addicting analgesic for effective treatment of moderate to severe pain. It has demonstrated long duration of action, effective bioavailability in sublingual administration and no development of tolerance after four weeks of chronic administration. Since PPL-138 has such a long duration of action, it has excellent potential for development as a non-addictive treatment for chronic pain.

PPL-138

partially stimulates all two opioid receptors

PPL-138 Studies in Non-Human Primates:

  • Robust analgesic potency – >100x the potency of morphine

  • Long Duration of Action – >24 Hours

  • Little or No Euphoria or Abuse-Liability – >No self-administration preference [1]

  • No Physical Dependence – No withdrawal symptoms

  • No Respiration Depression – Low risk of lethal overdose

  • No Tolerance – After 4 weeks of chronic administration

  • No Constipation – At elevated dose levels

Further Technical Details

PEER REVIEWED PAPER:

British Journal of Anaesthesia, 122 (6): e146ee156 (2019)

Studies of the drugs have been conducted by prominent scientists at leading institutions including Virginia Commonwealth University (VCU), the University of Michigan, Wake Forest University, SRI International, Torrey Pines Institute for Molecular Studies, ITR Canada, the University of Montreal, University of Bath and Florida Atlantic University (FAU).

Few drug classes have more longitudinal testing data than opioids for use as a predictor of success in trials. Therefore, the risk of pharmaceutical product development is significantly reduced compared to the risk of developing less understood and potentially problematic drug classes.

Furthermore, a vast amount of opioid testing data is available concerning the transition of effects of pure opioid compounds from animals to humans.  Consequently, our scientific experts and advisors predict that the risk of problems in toxicology and safety pharmacology is very low.  The predictive validity from animals to humans is very high, and thus there is a high level of confidence that the compounds will be safe, effective and beneficial for humans. [1]

Recently our drug family has also attracted attention for Animal Health applications, primarily due to the lack of respiratory depression and GI tract side effects as well as the likelihood that the drugs would likely be unscheduled (or at most scheduled as Class IV).

[1] O’Connor EC, Chapman K, Butler P, Mead AN (2011) The predictive validity of the rat self-administration model for abuse liability Neurosci Biobehav Rev. 35:912-938.