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 Jains 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 CharacteristicMu OpioidsKappa OpioidsPPL-103 Significant Self-Administration / CPP (Euphoria)YesNo Significant CPA (Dysphoria)NoYesNo Lethal Respiratory Depression at High DosageYesNo Significant ConstipationYesNo Withdrawal SymptomsSevereNo Sustains Without Opiate WithdrawalYesNoYes 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 7 7 PPL-103 Rat Self-administration: Progressive Ratio 8 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: , 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 LD 50 = 500x dose No constipation - at 100x dose & very limited even at 350x dose No physical dependence - in nave rodents No Long QT syndrome risk hERG assay Does not precipitate withdrawal - in dependent monkeys Orally active unlike morphine that is an injectable 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 PharmaLabs 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 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 Thank You For further information contact: Bill Crossman President and CEO Phoenix PharmaLabs, Inc. Tel: (860)