Relieving Pain….Improving Lives Exhibit 99.2 |
Special Note Regarding Forward-Looking Statements 2 This presentation includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements, among other things, relate to our business strategy, goals and expectations concerning our product candidates, future operations, prospects, plans and objectives of management. The words "anticipate", "believe", "could", "estimate", "expect", "intend", "may", "plan", "predict", "project", "will" and similar terms and phrases are used to identify forward-looking statements in this presentation. Our operations involve risks and uncertainties, many of which are outside our control, and any one of which, or a combination of which, could materially affect our results of operations and whether the forward-looking statements ultimately prove to be correct. These forward-looking statements should be considered together with the risks and uncertainties that may affect our business and future results included in our filings with the Securities and Exchange Commission at www.sec.gov. These forward- looking statements are based on information currently available to us, and we assume no obligation to update any forward-looking statements except as required by applicable law. |
Company Highlights • Dex-IN – intranasal, non-opioid in Phase II for acute pain following surgery - significant market opp’y • Multiple clinical studies demonstrate analgesic effect, fast onset of action and well tolerated • Phase II post op pain trial ongoing – Day 1 dosing • Multiple clinical and regulatory milestones over next few years • Experienced team with significant development, regulatory and commercial experience 3 |
Experienced Management and Board 4 • Gerri Henwood – President and CEO Founded Auxilium Pharmaceuticals (AUXL, NASDAQ) and IBAH (former NASDAQ Co. – acquired 1998); GSK • Chuck Garner – CFO, CBO and Treasurer Over 14 years of life sciences investment banking experience – Deutsche Bank, Burrill & Co., Inverness Advisors; PwC • Randy Mack – SVP, Development Over 20 years of clinical development experience – Adolor, Auxilium, Abbott Labs and Harris Labs Board of Directors Wayne B. Weisman – Chairman SCP VitaLife Partners Winston J. Churchill SCP VitaLife Partners Gerri Henwood – CEO William L. Ashton Harrison Consulting Group; frmly Amgen Abraham Ludomirski, M.D. SCP VitaLife Partners Alfred Altomari CEO, Agile Therapeutics Michael Berelowitz Former SVP, Specialty Care Business Unit, Pfizer |
Clinical Stage Pipeline Product PC I II III Rights Dexmedetomidine (“Dex”) WW, exc. Europe, Turkey, CIS* Dex- IN (intranasal) Acute post-operative pain Cancer breakthrough pain Dex-SL (sublingual) Transdermal Fadolmidine (“Fado”) WW, exc. Europe, Turkey, CIS* Intrathecal Post-operative pain Topical Neuropathic pain 5 * CIS currently includes Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, and Uzebekistan. |
Post Op Pain Market Underserved 6 • $5.9 billion market (1) • Predominantly opioid use • Significant side effects / issues associated with opioids • Dearth of non-opioid drugs in development Inpatient procedures Total procedures (2009) 47.9M Addressable >25M Ambulatory procedures Total procedures (2006) 53.3M Addressable >25M Note: Addressable includes procedures expected to utilize pain medication. Source: National Center for Health Statistics and management estimates. (1) GBI Research, 2010 sales. |
Limited Pain Relief Options for Patients 7 Pain Severity Class Compounds Advantages Disadvantages Mild Acetaminophen Antipyretic properties; Oral; no opioid AEs Only effective for mild pain NSAIDs Ketorolac, ibuprofen, aspirin Mild to moderate analgesia; oral; no opioid AEs Bleeding risk; GI and renal complications Moderate Sodium channel blockers Bupivacaine, lidocaine Use directly at pain site; mostly peri- operative Limited duration of action; some are concerned about local tissue impact Moderate to Severe Alpha 2 agonists Dexmedetomidine (Recro Pharma) Good pain relief; anxiolytic properties; no respiratory depression, impaired GI or addictive properties In development – potential for first in class to be approved for post- operative pain Opioids Morphine, hydrocodone, oxycodone, fentanyl Good pain relief Respiratory depression, impaired GI motility after even one dose; frequent nausea and vomiting; abuse/addiction potential Note: Pain severity based upon market research / physician feedback |
Dexmedetomidine (“Dex”) |
Dex Has Demonstrated Analgesia & Safety • Alpha 2 agonist (non-opioid) – Injectable form (Precedex) marketed by Hospira in US as sedative – Multiple studies demonstrating analgesia of alpha 2 agonists • Intranasal formulation in clinical development for acute pain – In-licensed non-IV rights from Orion – Worldwide rights except Europe, Turkey, and CIS • Multiple studies demonstrate Dex pain relief and safe profile – Including our completed placebo controlled trials • Expect strong IP position – Pending IP coverage could run through 2030 • Expect to file 505(b)(2) NDA shortly after completion of Ph III 9 |
Dex Efficacy and Safety in Multiple Studies 10 Beneficial effects Source Approved sedative and safe profile NDA filing / pivotal trials - Abbott/Hospira, Orion Morphine sparing NDA studies plus Literature Analgesia by IV route Chan, 2010; Grosu, 2010; Lin, 2009, Arain, 2010 Demonstration of pain relief (VAS) Placebo controlled trials; L. Webster, MD (Utah) CLBP study (Recro sponsored) Positive PK/PD plasma levels demonstrating analgesic potential Clinical trials run by Recro Relieves morphine “Max” (‘hyperalgesia’) University of Minnesota; M. Belgrade, MD |
Significant Advantages Over Opioids 11 Dex Fast-acting Opioids Non-opioid (Not controlled substance) Opioid - DEA scheduled product No habituation effects Addictive Does not cause respiratory depression Respiratory depression Not associated with constipation, nausea, or vomiting Unwanted side-effects of constipation, nausea and vomiting Enhances morphine effectiveness without morphine dose increase Additive effect requires higher dose More cognitively intact Frequently “Foggy”/ may be confused Anxiolytic properties Not anxiolytic Effective Analgesic Effective Analgesic |
Dex Has Been Well Studied by Recro 12 • Evaluated proprietary formulations of Dex in 9 trials Trial Form Design Outcome REC-13-012 Dex-IN Acute pain following bunionectomy surgery (n=85 evaluable) Within a subset of patients (n=42), with baseline pain intensity of 6 or below, there was a trend towards analgesia in 50 mcg and reduced opioid use versus placebo REC-11-010 Dex-IN Chronic lower back pain POC study (n=24) Statistically significant pain relief within 30 minutes demonstrated in placebo controlled trial – single use device REC-09-003 Dex-SL Chronic lower back pain POC study (n=21) Statistically significant reduction in pain intensity demonstrated in placebo controlled trial REC-11-008 Dex-IN Multi-dose PK study (n=12) Safety & tolerability of IN dosage form |
Dex-IN Study REC-13-012 (US placebo controlled trial) 13 • Phase II bunionectomy study in approx. 150-200 pts • Three dosing groups – 50 mcg, 35 mcg and placebo • Preplanned interim analysis – Randomized, placebo controlled study • Primary endpoint – summed pain intensity difference (SPID) over 48 hours • Rescue therapy allowed • Post Op Day 0 dosing – Scheduled after half of patients enrolled – Allowed for possible sample size adjustment – 85 pts evaluable in interim analysis – approx. 28 pts per group |
Results of Phase II Interim Analysis • Analgesia and opioid reduction seen in subset of patients – Patients with baseline pain score equal to 6 or lower – Approximately half of patients enrolled • However, trial was not expected to reach statistical significance with current design – Post Op Day 0 dosing • Revised trial design – Post Op Day 1 dosing – Stable / declining pain trajectory 14 |
Summary of Key Safety Data – No SAEs Event Dex-IN 50 mcg arm Placebo arm Drowsiness 17 (53%) 17 (53%) Nausea 8 (25%) 14 (44%) Vomiting 2 (6%) 6 (19%) Dizziness 3 (9%) 5 (16%) Nasal Irritation 2 (6%) 3 (9%) Epistaxis 2 (6%) 3 (9%) 15 • 4 patients discontinued due to symptomatic hypotension (3 in 50 mcg arm, 1 in 35 mcg), 1 due to fever (35 mcg) and 1 due to nausea and vomiting (placebo) • Adverse event of asymptomatic “BP decrease” in 10 Dex-IN patients (6 in 50 mcg arm) • 1 patient in 50 mcg arm and 2 patients in placebo arm had heart rate below 50 bpm and notable change from baseline |
Select Opioid Clinical Trials Side Effects Source: Stegmann et. al. (2008). The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery. Current Medical Research and Opinion Placebo Tapentadol IR 50mg Tapentadol IR 100mg Oxycodone IR 10mg Event n = 67 n = 67 n = 68 n = 67 Nausea 17.9% 46.3% 66.2% 71.6% Dizziness 14.9% 32.8% 64.7% 56.7% Somnolence 7.5% 28.4% 36.8% 26.9% Vomiting 1.5% 16.4% 35.3% 38.8% Headache 10.4% 17.9% 22.1% 20.9% Pruritus generalized 0.0% 7.5% 13.2% 10.4% Hyperhidrosis 1.5% 6.0% 8.8% 10.4% Constipation 1.5% 6.0% 7.4% 17.9% Pruritus 3.0% 7.5% 7.4% 11.9% Feeling Hot 4.5% 7.5% 2.9% 10.4% 16 |
Dex-IN Next Steps – REC-14-013 (US placebo controlled trial) • Phase II bunionectomy study in approx. 200 – 250pts • Post Op Day 1 dosing (previous trial Post Op Day 0) • Interim analysis for sample size adjustment planned • Top line results expected mid 2015 17 – Randomized, placebo controlled study – Primary endpoint – SPID over 48 hours – Rescue therapy allowed – Pain trajectory stable / declining – approximately half of the evaluable patients enrolled |
Dex-IN Study REC-11-010 (US placebo controlled POC trial) • 24 chronic lower back pain (CLBP) patients – Chronic opioid users & non-opioid users • PBO controlled, cross-over to evaluate: – Analgesia – Standard VAS for Pain Intensity and Pain Relief at multiple timepoints – Safety – Adverse Events, Vital Signs, Sedation • Single doses in a 3-way cross-over – PBO – Dex-IN 25 µg – Dex-IN 50 µg • Pain intensity measurements focused on 1 hour with patients monitored for up to 24 hours 18 |
Fast Onset Of and Prolonged Action (Clinical trial REC-11-010 – Dex-IN pharmacokinetics) Note: Administered with single unit device 19 |
Statistically Significant Pain Relief (Dex-IN – REC-11-010) Scale: 0 = No Relief, 4 = Complete Relief * p < 0.05 ** p < 0.01 20 |
Significant Pain Relief Over Time (Dex-IN – REC-11-010 – Summed Pain Intensity Difference) * p < 0.05 21 |
Dex-IN Well Tolerated (Clinical trial REC-11-010 - Adverse events†) Placebo (n=24) DEX-IN 25 µg (n=24) DEX-IN 50 µg (n=24) Dry Mouth - 2 2 Nausea 1 3 5 Vomiting - 1 2 Feeling Abnormal - 2 3 BP Decrease - - 2 Dizziness 4 5 10 Headache 1 4 4 Paraesthesia - - 2 Sinus Headache - 2 1 Somnolence - 6 18 Nasal Congestion - - 2 Nasal Discomfort - 1 3 Hypotension - 4 7 †Reported by more than one subject 22 |
Dex-IN Repeat Dosing Well Tolerated (Clinical trial REC-11-008) • 7 consecutive doses of 35 mcg Dex-IN every 6 hours • Evaluated heart rate, blood pressure and BP upon standing every 5 minutes for two hours after dosing – Transient effect after initial dosing • None of the above effects categorized by investigators as AEs 23 |
Well Tolerated Profile – Repeated Dosing (Study REC-11-008 – 35 mcg Dex-IN formulation) Period 1 n = 12 Period 2 n = 10 Term D1 D2 D1 D2 D3 D4 D5 D6 D7 Total 7am 1pm 7am 1pm 7pm 1am 7am 1pm 7pm Back Pain - - - - 1 - - - 1 1 Muscle Spasms - - - - - - - - - 1 Dizziness - 1 2 - - - - - - 3 Headache - - - 1 - - - - - 1 Anxiety - - 1 - - - - - - 1 Nasal Discomfort - 3 - 5 - - - - - 6 Nasal Dryness - 1 - 2 - - - - - 3 Rhinalgia - - - - 1 - - - - 1 Rinorrhea - 1 - - - - - - - 1 Number of Subjects 24 |
Fadolmidine (“Fado”) |
Fado Effective in Phase II for Pain Relief • Alpha 2 agonist – more potent at the alpha 2c receptor than Dex – >20 fold less potent at the alpha 1b receptor than clonidine • Fado has demonstrated analgesia in multiple animal models • Positive Phase II analgesia study in bunionectomy patients – Intrathecal route of administration • Formulation work underway for topical prototype – Potential in regional neuropathies • WW rights to all human uses except Europe, Turkey and CIS • NCE patent w/ expected extension to 2021 / pursuing add’l IP 26 |
Corporate Overview |
Intellectual Property • Dex applications for methods for treating/preventing pain through intranasal, sublingual and transdermal formulations without sedation • Dex composition of oral transmucosal (SL) formulation and dispensing devices • Fado IP in-licensed from Orion – Composition of matter – Method of administration for analgesia – Treatment and prevention of hypotension and shock • Regulatory exclusivity – 505(b)(2) – 3 years (Dex-IN, Dex-SL) – 505(b)(1) – NCE, 5 years (Fado) 28 |
Company Highlights • Dex-IN – intranasal, non-opioid in Phase II for acute pain following surgery - significant market opp’y • Multiple clinical studies demonstrate analgesic effect, fast onset of action and well tolerated • Phase II post op pain trial ongoing – Day 1 dosing • Multiple clinical and regulatory milestones over next few years • Experienced team with significant development, regulatory and commercial experience 29 |