Slide 1: A Phase 2 Study of HTX-011 in the Management of Post-Operative Pain: Positive Top-Line Results
HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM A Phase 2 Study of HTX-011 in the Management of Post-Operative Pain Positive Top-Line Results September 22, 2015 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking statements” as defined by the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve risks and uncertainties, including uncertainties associated with the development, regulatory approval, manuf
Slide 3: Heron Post-Operative Pain Program
Heron Post-Operative Pain Program Objective: Develop a best-in-class therapeutic for post-operative pain that can substantially reduce dependence on opiates Target Product Profile: Maximal pain relief that lasts for 2-3 days Maximal reduction of opioid use Maximal reduction of length of hospital sta
Slide 4: Introducing HTX-011
Heron Post-Operative Pain Program Introducing HTX-011: – An injectable pain therapeutic that utilizes proprietary Biochronomer® polymer-based drug delivery platform technology – Contains bupivacaine and low concentration of meloxicam – Designed to deliver both drugs evenly over 2-3 days Drug + Polym
Slide 5: Post-Operative Pain Market
Post-Operative Pain Market Surgeries Per Year 69 Million in U.S. 234 Million Worldwide 65% Will Experience Moderate-to-Severe Post-Operative Pain Deaths Due to Opioid Overdose: U.S., 2000-2013 20,000 15,000 10,000 5,000 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Years An
Slide 6: Procedures Eligible for Long-Acting Local Anesthetic
Procedures Eligible for Long-Acting Local Anesthetic Estimated Number of Procedures in the U.S. Eligible for Long-Acting Local Anesthetic Number of Procedures (Millions) 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 22.5 28.9 2012 2021 Sources: Decision Resources, Commercial Market Assessment: Post-Operativ
Slide 7: Superior Efficacy Would Address Major Unmet Medical Need
Superior Efficacy Would Address Major Unmet Medical Need Value Exparel (WAC $315) Ofirmev (WAC $426) Target Product Profile Degree of Pain Relief and Opiate Sparing Source: PriceRx HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 7
Slide 8: A Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study of HTX-011
A Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study of HTX-011 in the Management of Post-Operative Pain in 64 Patients Undergoing Bunionectomy HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 8
Slide 9: Study Design
Study Design Screening Subjects requiring bunionectomy Treatment (96-hour evaluation) Part A - HTX-011 200 mg bupivacaine (n=20) Placebo - All subjects pooled for endpoint analysis Part A (n=10), Part B (n=10) Part B - HTX-011 400 mg bupivacaine (n=20) Primary Endpoint SPI 0-24 hrs Secondary Endpoin
Slide 10: Historical Context: Exparel Pivotal Bunionectomy Study
Historical Context: Exparel Pivotal Bunionectomy Study Figure 2. Mean Pain Intensity versus Time plot for bunionectomy study (C-317) PI 10 9 8 7 6 5 4 3 2 1 0 placebo exparel 0 12 24 36 48 60 72 time (hours) Source: FDA Clinical Review of NDA 022-496, page 48 10
Slide 11: Pain Intensity Difference at Low Dose
Pain Intensity Difference at Low Dose Mean Pain Intensity Score* 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00 SPID0-24 -25%, p=0.022 HTX-011 200 mg Placebo 0 10 20 30 Hours 40 50 60 70 *Standard LOCF method used to account for use of rescue medications from Golf et al, Adv Ther, 28(9):776-788, 2011 HERON
Slide 12: Pain Intensity Difference at High Dose
Pain Intensity Difference at High Dose Mean Pain Intensity Score* 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00 SPID0-24 -69%, p<0.0001 SPID0-48 -52%, p<0.0001 SPID0-72 -40%, P=0.0064 HTX-011 400 mg Placebo 0 10 20 30 Hours 40 50 60 70 *Standard LOCF method used to account for use of rescue medications fr
Slide 13: Summed Pain Intensity and Summed Pain Intensity Difference over Time
Summed Pain Intensity (SPI) and Summed Pain Intensity Difference (SPID) over Time Patients receiving HTX-011 had significantly lower pain scores for all three time periods of interest SPI Placebo SPI HTX-011 400 mg SPID 0–24 hours 124.2 38.5 -85.7 (-69%) p<0.0001 0–48 hours 224.8 106.9 -117.9 (-52%)
Slide 14: Percent of Patients Pain Free
Percent of Patients Pain Free Percent of Patients Pain Free (PI < 1) 100 90 80 70 60 50 40 30 20 10 0 p<0.0001 HTX-011 400 mg Placebo 0 10 20 30 40 50 60 70 80 Hours HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 14
Slide 15: Historical Context: Percent of Patients Pain Free, Cross-Study Comparison to Exparel
Historical Context: Percent of Patients Pain Free, Cross-Study Comparison to Exparel Percent of Patients Pain Free (PI £ 1) 100 90 80 70 60 50 40 30 20 10 0 HTX-011 400 mg Placebo 0 12 24 36 48 60 72 Hours Percentage of Patients pain-free (NRS £ 1) 80 60 40 20 0 Depofoam bupivacaine 120 mg Placebo 2
Slide 16: Mean Time to First Use of Opiate Rescue Medication
Mean Time to First Use of Opiate Rescue Medication 488% longer time to first use of rescue medications Placebo HTX-011 200 mg HTX-011 400 mg 8.2 hours 20.8 hours p=0.15 48.2 hours p<0.0001 Cross-study comparison: Mean time with Exparel was 7.2 hours versus 4.3 hours on placebo Source: Golf et al, Ad
Slide 17: Percent of Patients Who Received No Opiate Rescue Medication
Percent of Patients Who Received No Opiate Rescue Medication Percent of Patients Who Received No Opiate Rescue Medication 0 10 20 30 40 50 60 70 80 90 100 p<0.0001 32% HTX-011 400 mg Placebo 0 10 20 30 40 50 60 70 80 Hours HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 17
Slide 18: Historical Context: No Opiate Rescue Medication, Cross-Study Comparison to Exparel
Historical Context: Percent of Patients Who Received No Opiate Rescue Medication, Cross-Study Comparison to Exparel Percent of Patients Who Received No Opiate Rescue Medication 100 90 80 70 60 50 40 30 20 10 0 HTX-011 400 mg Placebo 0 12 24 36 48 60 72 Hours Percentage of patients who did not receiv
Slide 19: Pain Intensity NOT Adjusted for Opiate Use
Pain Intensity NOT Adjusted for Opiate Use: HTX-011 Significantly Better Than Unlimited Opiates* Mean Pain Intensity Scores 7 6 5 4 3 2 1 0 SPID0-24 p<0.0001 SPID0-48 p=0.0001 SPID0-72 p=0.0051 HTX-011 400 mg Placebo 0 10 20 30 40 50 60 70 Hours *Patients were permitted to take 5 mg oxycodone every
Slide 20: Preliminary Safety
Preliminary Safety HTX-011 was generally well tolerated The most common adverse events were: headache, nausea, vomiting, constipation, erythema, cellulitis, dizziness, and hypoxia, none of which were considered drug-related HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 20
Slide 21: HTX-011b: Second Formulation with Distinct Properties
HTX-011b: Second Formulation with Distinct Properties HTX-011b is our second formulation Designed to possess distinct properties that may be ideal in certain surgical procedures: – Greater volume – Slightly faster onset Phase 1 study in healthy volunteers showed: – Therapeutic drug levels achieved f
Slide 22: HTX-011b Provides Faster Onset and Substantially Greater Bupivacaine Levels
HTX-011b Provides Faster Onset and Substantially Greater Bupivacaine Levels Mean Bupivacaine Plasma Concentrations (ng/mL) 600 500 400 300 200 100 0 HTX-011 200 mg HTX-011 400 mg HTX-011b 200 mg 0 20 40 60 80 100 120 140 160 Hours HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives
Slide 23: Pain Intensity: HTX-011b vs. HTX-011
Pain Intensity: HTX-011b 200 mg vs. HTX-011 400 mg Mean Pain Intensity Scores* 7 6 5 4 3 2 1 0 HTX-011b 200 mg (n=5) HTX-011 400 mg (n=22) 0 12 24 36 48 60 72 Hours *Not adjusted for use of rescue medications HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM 23
Slide 24: Summary and Future Directions
Summary and Future Directions Phase 2 results demonstrate unprecedented level of efficacy for a local anesthetic in the management of postoperative pain – Major reduction in pain intensity – True opiate-sparing activity – One-third of patients required no opiates at all over first 72 hours Strong pr