Slide 1: Phase 2 Studies of HTX-011 in the Management of Post-Operative Pain
HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM Phase 2 Studies of HTX-011 in the Management of Post-Operative Pain Positive Top-Line Results across Bunion and Hernia Studies August 1, 2016 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. We caution investors that forward-looking statements are based on management’s expectations and assumptions as of the date of this presentation, and
Slide 3: The Ideal Therapeutic for Post-Operative Pain
The Ideal Therapeutic for Post-Operative Pain The ideal therapeutic for post-operative pain would: Significantly reduce pain for several days after surgery Significantly reduce opioid use: Reduce total amount of opioids consumed Increase number of patients who NEVER need an opioid Demonstrate these
Slide 4: Market Opportunity for HTX-011 in Post-Operative Pain Management
Market Opportunity for HTX-011 in Post-Operative Pain Management Procedures Requiring Post-Operative Pain Relief 2016-20211 Procedures (Millions) 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 27.8 28.5 29.2 29.9 30.6 32.5 2016 2017 2018 2019 2020 2021 Post-Operative Pain Market Share Last 12 Months2 3% 18%
Slide 5: Biochronomer Bupivacaine Produced Significant Reductions in Pain in Preclinical Models
Biochronomer® Bupivacaine Produced Significant Reductions in Pain in Preclinical Models1 Pig Post-Operative Pain Model Saline Control Biochronomer Bupivacaine Bupivacaine Liposome Injectable Suspension (2) Percentage of Maximal Force (60 gm) Tolerated by Animal 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30
Slide 6: Local Anesthetics Exist in a Balance Between Water-Soluble and Lipid-Soluble Forms
Local Anesthetics Exist in a Balance Between Water-Soluble and Lipid-Soluble Forms Water-Soluble Ionized Form Lipid-Soluble UnIonized Form BUPH+ BUPN + H+ Diffusable Form Active Form Outside Membrane Inside Membrane Nerve Cell Membrane BUPH+ BUPN + H+ Local anesthetics have pKa values > 7.4, so at n
Slide 7: When Tissue Is Inflamed, Local Anesthetics Cannot Effectively Enter the Nerve Membrane
When Tissue Is Inflamed, Local Anesthetics Cannot Effectively Enter the Nerve Membrane Inflammation Produces an Acidic Environment Which Shifts the Balance to Ionized Form Unable to Penetrate Nerve Cell Membrane BUPH+ BUPN + H+ Diffusable Form Active Form Outside Membrane Inside Membrane Nerve Cell
Slide 8: HTX-011's Combination of Bupivacaine and Meloxicam Produced Anesthesia through 72 Hours
HTX-011’s Unique Combination of Bupivacaine and Meloxicam Produced Marked Anesthesia through 72 Hours1 Pig Post-Operative Pain Model Saline Control HTX-011 Biochronomer Meloxicam Biochronomer Bupivacaine Bupivacaine Liposome Injectable Suspension (2) Percentage of Maximal Force (60 gm) Tolerated 100
Slide 9: HTX-011 Is the First and Only Long-Acting Anesthetic Addressing Pain and Inflammation
HTX-011 IS THE FIRST AND ONLY LONG-ACTING ANESTHETIC THAT ADDRESSES BOTH POST-OPERATIVE PAIN AND ACCOMPANYING INFLAMMATION 9 HERON THERAPEUTICS Developing Bes-in-Class Medicine. Improving Lives.TM
Slide 10: Previously Presented Preliminary Results HTX-011-201 Phase 2 Bunionectomy
PREVIOUSLY PRESENTED PRELIMINARY RESULTS HTX-011-201 PHASE 2 BUNIONECTOMY 10 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 11: HTX-011 Study 201: Bunionectomy Study Design
HTX-011 Study 201: Bunionectomy Study Design Part A HTX-011 200 mg Injection Saline Injection N = 20 Part B Saline Injection HTX-011 400 mg Injection Pooled N = 24 N = 22 Part C HTX-011A 200 mg Injection N = 5 11 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 12: Pain Intensity Not Adjusted for Opioid Use: HTX-011 Significantly Better Than Unlimited Opioids
Pain Intensity NOT Adjusted for opioid Use: HTX-011 Significantly Better Than Unlimited Opioids* Mean Pain Intensity Scores 7 6 5 4 3 2 1 0 SPID24-48 p<0.01 HTX-011 400 mg Placebo SPID0-24 p<0.0001 SPID0-48 p=0.0001 SPID0-72 p=0.0051 0 10 20 30 40 50 60 70 Hours *Patients were permitted to take 5 mg
Slide 13: Pain Intensity: HTX-011A vs. HTX-011 400 mg
Pain Intensity: HTX-011A 200 mg vs. HTX-011 400 mg Mean Pain Intensity Scores* 7 6 5 4 3 2 1 0 HTX-011A 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 13 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 14: Preliminary Results HTX-011-208 Phase 2 Bunionectomy
PRELIMINARY RESULTS HTX-011-208 PHASE 2 BUNIONECTOMY 14 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 15: HTX-011 Study 208: Bunionectomy Study Design
HTX-011 Study 208: Bunionectomy Study Design HTX-011A 200 mg HTX-011B 200 mg Bupivacaine Solution Saline Injection – Closed wound (Nerve Block) Injection – Open wound (Infiltration) Injection – Closed wound (Nerve Block) Injection – Open wound (Infiltration) Injection – Closed wound (Nerve Block) In
Slide 16: HTX-011-208: Demographics
HTX-011-208: Demographics Characteristic Parameter HTX-011A 200mg HTX-011B 200mg Bupivacaine Solution Saline Age (Years) n 32 31 15 15 Mean 49.5 52.2 52.7 48 Minimum 20.0 20.0 36.0 24.0 Maximum 72.0 71.0 84.0 69.0 Gender n (%) Male 5 (15.6) 5 (16.1) 2 (13.3) 3 (20.0) Female 26 (81.3) 26 (83.9) 13 (8
Slide 17: HTX-011-208: Route of Administration Did Not Impact Efficacy
HTX-011-208: Route of Administration Did Not Impact Efficacy Mean SPI 0-24 Hours 160 140 120 100 80 60 40 20 0 HTX-011B 200mg Infiltration HTX-011B 200mg Nerve Block Bupivacaine Solution 50mg No significant difference between routes, with both routes of HTX-011B administration significantly better t
Slide 18: HTX-011-208: Mean Pain Intensity Scores, HTX-011B Is Superior to the A Formulation
HTX-011-208: Mean Pain Intensity Scores* HTX-011B Is Superior to the A Formulation** HTX-011B Is Our Phase 3 Clinical Candidate Mean Pain Intensity Scores 8 7 6 5 4 3 2 1 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 Hours HTX-011A 200mg Bupivacaine Solution 50mg HTX-011B 200mg Saline Placebo *
Slide 19: Best Reduction in Pain Was Observed with Nerve Block
While Both Routes Were Significantly Better than Placebo or Bupivacaine Solution, the Best Reduction in Pain Was Observed with Nerve Block* Mean Pain Intensity 8 7 6 5 4 3 2 1 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 Hours HTX-011B 200mg Infiltration Bupivacaine Solution 50mg HTX-011B 200m
Slide 20: HTX-011B Via Nerve Block Is Significantly Better than Placebo or Bupivacaine Solution
HTX-011-208: Mean Pain Intensity Scores* HTX-011B Via Nerve Block Is Significantly Better than Placebo or Bupivacaine Solution Mean Pain Intensity 8 7 6 5 4 3 2 1 0 HTX-011B Via Nerve Block SPI24-48 H vs P: p=0.013 H vs B: p=0.003 SPI48-72 H vs P: p=0.291 H vs B: p=0.178 SPI0-24 H v P: p<0.0001 H v
Slide 21: HTX-011B Via Open Wound Injection Is Significantly Better than Placebo or Bupivacaine Solution
HTX-011-208: Mean Pain Intensity Scores* HTX-011B Via Open Wound Injection Is Significantly Better than Placebo or Bupivacaine Solution HTX-011B Via Injection Mean Pain Intensity 8 7 6 5 4 3 2 1 0 SPI24-48 H vs P: p=0.162 H vs B: p=0.037 SPI48-72 H vs P: p=0.115 H vs B: p=0.345 SPI0-24 H v P: p<0.00
Slide 22: HTX-011-208: Secondary Endpoint Mean Use of Opioid Rescue Medication
HTX-011-208: Secondary Endpoint Mean Use of Opioid Rescue Medication Mean opioid Rescue Over Time Placebo (P) Bupivacaine Solution (B) HTX-011B 200 mg Percent Reduction 5.2mg 74% v P 0 – 24 hours 20.3mg 15.9mg p<0.0001 v P P<0.0001 v B 67% v B 13.3mg 57% v P 0 – 48 hours 31.1mg 28.5mg p=0.0001 v P p
Slide 23: HTX-011-208: Secondary Endpoints - Time to First Opioid and Opioid-Free Patients
HTX-011-208: Secondary Endpoints -Mean Time to First Opioid Increased by 716% -Significant Increase in Opioid-Free Patients Placebo Bupivacaine HTX-011B (P) Solution (B) 200 mg Mean Time to 31.0hr First Opioid Rescue 3.8hr 11.6hr p<0.0001 vs P Medication p<0.037 vs B Percent of Patients Opioid 32% 0
Slide 24: Preliminary Results HTX-011-202 Phase 2 Herniorrhaphy
PRELIMINARY RESULTS HTX-011-202 PHASE 2 HERNIORRHAPHY 24 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 25: HTX-011 Study 202: Herniorrhaphy Study Design
HTX-011 Study 202: Herniorrhaphy Study Design Part A HTX-011 200mg HTX-011 400mg Saline Injection Instillation Injection Instillation Injection (200 mg) & Instillation (200 mg) Injection Part B HTX-011B 200mg HTX-011B 400mg Saline Injection Instillation Injection Instillation Injection 25 HERON THER
Slide 26: HTX-011-202: Demographics
HTX-011-202: Demographics Characteristic Parameter HTX-011 400mg Saline Part A HTX-011B 400mg Saline Part B Age (Years) n 54 18 24 31 Mean 45.6 46.5 43.9 44.8 Minimum 21 22 19 21 Maximum 67 66 79 62 Gender n (%) Male 52 (96) 18 (100) 23 (96) 30 (97) Female 2 (4) 0 (0) 1 (4) 1 (3) Race n (%) Caucasia
Slide 27: HTX-011-202: Preferable Instillation Route Was Equally Effective to Injection
HTX-011-202: Preferable Instillation Route Was Equally Effective to Injection* Mean SPI 0-24 120 100 80 60 40 20 0 HTX-011 400mg Injection HTX-011 400mg Instillation HTX-011 400mg Injection & Instillation Saline Part A HTX-011B 400mg Injection HTX-011B 400mg Instillation Saline Part B *Based on thes
Slide 28: HTX-011: Instillation Is Easier and Potentially Safer
HTX-011: Instillation Is Easier and Potentially Safer Bupivacaine Solution Bupivacaine Liposome HTX-011 Compared to injection, instillation into the incision site is: Easier to administer and less invasive, avoiding up to 10 or more injections into the skin with large operations Safer, reducing the
Slide 29: HTX-011-202: Mean Pain Intensity Scores, HTX-011 Better Than Placebo
HTX-011-202: Mean Pain Intensity Scores HTX-011 Significantly Better Than Placebo Mean Pain Intensity 7 6 5 4 3 2 1 0 SPI24-48 p=0.274 SPI0-24 p=0.030 SPI0-48 p=0.095 SPI0-72 p=0.325 SPI0-96 p=0.546 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 Hours HTX-011 400mg Saline Placebo *LOCF method used
Slide 30: HTX-011-202: HTX-011B Significantly Better than Placebo through 48 Hours
HTX-011-202: Mean Pain Intensity Scores HTX-011B Significantly Better than Placebo through 48 Hours Mean Pain Intensity 8 7 6 5 4 3 2 1 0 SPI24-48 p=0.145 SPI0-24 p=0.008 SPI0-48 p=0.038 SPI0-72 p=0.142 SPI0-96 p=0.216 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 Hours HTX-011B 400mg Saline Plac
Slide 31: HTX-011-202: Secondary Endpoints Mean Time to First Opioid Increased 110%
HTX-011-202: Secondary Endpoints Mean Time to First Opioid Increased 110% In addition to the significant reductions in pain observed with HTX-011B, opioid use was also reduced: Mean time to first opioid rescue medication increased by 110% (13.3 hours for placebo vs 27.9 hours for HTX-011B; p=0.09) M
Slide 32: HTX-011-203 Phase 2 Abdominoplasty Update
HTX-011-203 PHASE 2 ABDOMINOPLASTY UPDATE 32 HERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives.TM
Slide 33: HTX-011 Study 203: Abdominoplasty Study Design
HTX-011 Study 203: Abdominoplasty Study Design Cohort 1 HTX-011B Cohort 2 HTX-011B Cohort 3 HTX-011B Currently Enrolling 2:1 2:1 2:1 200 mg Injection & Instillation Saline Injection & Instillation 400 mg Injection & Instillation Saline Injection & Instillation 600 mg Injection & Instillation Saline
Slide 34: Comparative Bupivacaine PK: Hernia, Bunion, and Abdominoplasty
Comparative Bupivacaine PK: Hernia, Bunion, and Abdominoplasty Location of Surgery Has Little Impact on HTX-011 Pharmacokinetics 200 mg HTX-011B, Abdominoplasty 200 mg HTX-011B, Bunion 200 mg HTX-011B, Hernia 400 mg HTX-011B, Abdominoplasty 400 mg HTX-011B, Hernia Plasma Bupivacaine (ng/mL) 700 600
Slide 35: Preliminary Safety from Ongoing Phase 2 Studies: HTX-011 Was Well Tolerated
Preliminary Safety from Ongoing Phase 2 Studies: HTX-011 Was Well Tolerated Treatment-Emergent Related Adverse Events with at Least 2% in Either HTX-011 or Control (Saline or Bupivacaine Solution) AE Preferred Term HTX-011 (n=256) Control (n=100) Nausea 3.9% 5.0% Vomiting 0.8% 5.0% Bradycardia 4.3%
Slide 36: Phase 3 Program Designed to Demonstrate HTX-011's Broad Utility
Phase 3 Program Designed to Demonstrate HTX-011’s Broad Utility and Clear Advantage over Standard of Care Heron’s Phase 3 program for HTX-011 will: – Include multiple types of surgical procedures Compare HTX-011 not only to placebo but also to bupivacaine solution, the current standard of care for p
Slide 37: HTX-011's Emerging Profile
HTX-011’s Emerging Profile HTX-011 has been shown to: – Significantly reduce pain for several days after surgery – Significantly reduce opioid use: Reduced total amount of opioids consumed Increased number of patients who NEVER need an opioid – Demonstrate these benefits versus bupivacaine solution,