Overview of the Clinical Development EMBEDA™ (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use. ASENT 12 th Annual.

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Overview of the Clinical Development EMBEDA™ (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use. ASENT 12 th Annual Meeting EMBEDA™ (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use. ASENT 12 th Annual Meeting #21 Meisner

EMBEDA ™ Extended release morphine sulfate with a sequestered core of naltrexone hydrochloride (antagonist) in a ratio of 25:1 Indicated for moderate to severe pain when a continuous, around- the-clock opioid analgesic is needed for an extended period of time Six dosage strengths (20 mg to 100 mg morphine sulfate with 0.8 to 4 mg naltrexone hydrochloride) Morphine Sequestered Naltrexone

Clinical Trials – EMBEDA ™ THE FOLLOWING 12 CLINICAL TRIALS HAVE BEEN CONDUCTED TO DATE 1)Three (3) phase 1/2 pharmacodynamic (PD) studies a)ALO-201 Naltrexone Dose Ranging b)ALO-205 Oral Drug Liking Study c)ALO-106 Euphoria Study 2)Six (6) phase 1, single dose pharmacokinetic (PK) studies in healthy subjects a)ALO-101 Fasting Bioequivalence (vs KADIAN ® ) b)ALO-102 Fasting, Fed and Sprinkled Bioequivalence c)ALO-103 Ethanol Drug Interaction d)ALO-104 Crush Bioavailability e)ALO-903 Fed, Fasted f)ALO-107 withdrawal in patients on chronic opiate therapy (study withdrawn) 3)Three (3) phase II/III efficacy and safety studies a)ALO-202 Preliminary Efficacy & Safety (vs. Kadian) b)ALO-301 Pivotal Efficacy (12 week vs. Placebo) c)ALO-302 Long Term Safety (52 week)

EMBEDA ™ – Oral Drug Liking Study (ALO- 205) 'DRUG LIKING' AND 'OVERALL DRUG LIKING' WERE SIGNIFICANTLY LOWER FOR EMBEDA ™ CRUSHED AND WHOLE COMPARED TO MORPHINE IR (MSS) 'FEELING HIGH', 'GOOD EFFECTS', AND 'BAD EFFECTS' WERE SIGNIFICANTLY LOWER FOR EMBEDA ™ CRUSHED AND WHOLE COMPARED TO MORPHINE IR (MSS)

EMBEDA ™ – Euphoria Study (ALO-106) FIGURE. MEAN RESPONSE TO DEQ #5 'HOW HIGH ARE YOU?' OVER TIME FIGURE. MEAN RESPONSE TO COLE/ARCI STIMULATION/EUPHORIA SCALE OVER TIME p-value (adjusted) Morphine 30 mg E max vs Morphine 30 mg + Naltrexone 1.2 mg (4%) < Morphine 30 mg + Naltrexone 1.2 mg (4%) vsPlacebo< Morphine 30 mg E max vsPlacebo< Time (hours) DEQ #5 Mean Score n=26 Time (hours) Cole/ARCI Euphoria Scale Mean Score p-value (adjusted) Morphine 30 mg E max vs Morphine 30 mg + Naltrexone 1.2 mg (4%) < Morphine 30 mg + Naltrexone 1.2 mg (4%) vsPlacebo< Morphine 30 mg E max vsPlacebo< 0.001

EMBEDA ™ – Preliminary Efficacy & Safety (ALO-202) STUDY DESIGN: Double-blind, two way crossover of EMBEDA™ and KADIAN® [extended release morphine sulfate (ERMS)] ERMS initiated at 20 mg BID and titrated to a maximum of 160 mg BID 113 patients with Chronic Pain Due to Osteoarthritis of the Hip or Knee enrolled into Period 1, 72 randomized into Period 2 and 69 completed RESULTS: Plasma morphine from KADIAN® (ERMS) and EMBEDA™ formulations are bioequivalent limited to extent of exposure at steady state (AUC0-12h) The minimal release of naltrexone and its metabolite, 6-β-naltrexol, from EMBEDA™ after chronic dosing did not increase pain scores EMBEDA™ appears to be safe and effective in treating chronic pain of osteoarthritis of the knee and hip Most patients rated both medications as good or excellent (KADIAN® (ERMS), 78.9%; EMBEDA™, 91.5%)

EMBEDA ™ – Pivotal Efficacy Study (ALO-301) STUDY DESIGN: Patients with Moderate to Severe Chronic Pain Due to Osteoarthritis of the Hip or Knee EMBEDA™ initiated at 20mg BID and titrated to maximum of 80mg BID RESULTS: Statistically significant improvements in efficacy (primary and secondary) were seen compared to placebo EMBEDA™

System Organ Class Preferred Term EMBEDA™ (N=465) n (%) Any TEAE 378 (81.3%) Any Related TEAE 288 (61.9%) Gastrointestinal disorders 219 (47.1%) Constipation 145 (31.2%) Diarrhea 10 (2.2%) Dry mouth 17 (3.7%) Nausea 103 (22.2%) Vomiting 37 (8.0%) General disorders and administration site conditions 51 (11.0%) Fatigue 19 (4.1%) Nervous system disorders 99 (21.3%) Dizziness 19 (4.1%) Headache 32 (6.9%) Somnolence 34 (7.3%) Psychiatric disorders 42 (9.0%) Anxiety 10 (2.2%) Insomnia 13 (2.8%) Skin and subcutaneous tissue disorders 52 (11.2%) Hyperhidrosis 16 (3.4%) Pruritus 26 (5.6%) TEAEs Related to Study Drug Reported by ≥2% of Subjects—Safety Population EMBEDA ™ – Long Term Safety Study (ALO-302)

EMBEDA™- Phase IV Plans Clinical Trials Pediatric studies in ages 2- <12 years and years (post-approval commitment) Effects of crushed EMBEDA™ in opioid tolerant patients (withdrawal study) Abuse potential of EMBEDA™ via intranasal route Role of EMBEDA™ in the Universal Precautions approach to pain management Specific patient populations e.g. fibromyalgia, neuropathic pain EMBEDA™ Epidemiology Program-To determine if there is a lower rate of EMBEDA™ abuse compared to other ER opioids, with particular focus on the method of abuse.