Heron Therapeutics, Inc. · NASDAQ:HRTX
Heron Therapeutics — Investor Presentation (November 2017)
65 slides from Heron Therapeutics's investor presentation, November 2017
Slide 1: Company Update November 2017
Company Update November 2017
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: Status of Product Portfolio
Status of Product Portfolio CINV Pain Preclinical Clinical NDA Approved SUSTOL® (granisetron) extended- Approved by U.S. Food and Drug Administration release injection CINVANTI™ (aprepitant) injectable Now Approved by U.S. Food and Drug Administration emulsion HTX-011 bupivacaine + • Fast Track desi
Slide 4: CINV
Heron : Developing Best-in-Class Medicine, Improving Lives.” : CINV
Slide 5: CINVANTI Now Approved
CINVANTI™ Now Approved • CINVANTI™ is the first and only polysorbate 80-free IV NK1 receptor antagonist approved for the prevention of both acute and delayed CINV CINVANTI™ is indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomitin
Slide 6: CINV Prophylaxis Requires Two Complimentary Mechanisms of Action
CINV Prophylaxis Requires Two Complimentary Mechanisms of Action NK1 receptor antagonist NK1 receptor antagonists CINVANTI™ • EMEND® IV (fosaprepitant) has 90% share of the US NK1 market • Infusion site reactions (predominately infusion site pain) observed with EMEND® IV are believed to be caused by
Slide 7: The Goal of Antiemetic Therapy is to Prevent CINV Across Both Acute and Delayed Phases
The Goal of Antiemetic Therapy is to Prevent CINV Across Both Acute and Delayed Phases Patterns of CINV and Neurotransmitters Involved Acute phase Cisplatin Cyclophosphamide/carboplatin Intensity of Emesis Delayed phase 5-HT3 and NK1 pathways are important in both acute and delayed phases of CINV 0
Slide 8: Heron Is the Only Company with Two Single-Agent Products for Acute and Delayed CINV
Heron Therapeutics Is the Only Company with Two Single-Agent Products Approved for Prevention of Acute and Delayed CINV Acute phase Cisplatin Cyclophosphamide/carboplatin Intensity of Emesis Delayed phase 0 1 2 3 4 5 Days 5-HT3 NK1 8
Slide 9: Despite an NCCN Category 1 Recommendation, NK1s are Underutilized
Despite an NCCN Category 1 Recommendation, NK1’s are Underutilized Percent of Patients Receiving NCCN Antiemetic Guidelines NK1 Therapy 100% HEC MEC 80% 60% 5-HT3 5-HT3 dexamethasone dexamethasone 40% 69% NK1 ± NK1 20% ± olanzapine ± olanzapine 17% 0% NCCN 2017 HEC MEC IPSOS “US Tandem Onc
Slide 10: Aprepitant Has Provided Unsurpassed Efficacy for CINV Prevention for Nearly 15 Years
Aprepitant Has Provided Unsurpassed Efficacy for CINV Prevention for Nearly 15 Years Aprepitant is the only single-agent Overview of Aprepitant NK1 that: • Is FDA-approved for prevention of CINV in both acute and delayed FDA approved 2003 phases • Can be administered to patients receiving chemothera
Slide 11: Polysorbate 80 Is a Synthetic Surfactant Associated with Adverse Events
Polysorbate 80 Is a Synthetic Surfactant Associated with Adverse Events • Polysorbate 80 (PS-80) is a synthetic surfactant used to solubilize injectable chemotherapy and supportive care drugs • PS-80 is a pharmacologically active compound and has been linked to adverse events in oncology patients Re
Slide 12: CINVANTI Demonstrated Bioequivalence to Fosaprepitant and Fewer Adverse Events
CINVANTI™ Demonstrated Bioequivalence to Fosaprepitant and Fewer Treatment-Emergent Adverse Events Within 30 Minutes of Infusion Demonstrated Bioequivalence to Fosaprepitant Fewer TEAEs Within 30 Minutes of Infusion Adverse events with >2% of subjects within 30 min. of infusion Fosaprepitant 150 mg
Slide 13: CINVANTI Is the First and Only Polysorbate 80-Free IV NK1
CINVANTI™ Is the First and Only Polysorbate 80-Free IV NK1 Approved for the Prevention of Both Acute and Delayed CINV CINVANTI™ IV EMEND® IV Varubi® IV aprepitant emulsion fosaprepitant rolapitant Indicated for prevention of both acute and delayed CINV Yes Yes No Can be administered regardless of ch
Slide 14: With CINVANTI, Heron Adds a Second Best-In-Class Therapy
With CINVANTI™, Heron Adds a Second Best-In-Class Therapy to Compete in a Branded CINV Market with ~3.6M Annual Units Leading Branded CINV Products (Annual Units) 1.31M 2.33M Aloxi® Emend IV Source: IMS TTM Q3’17 14
Slide 15: SUSTOL Delivered 28.7K Units in Q3
SUSTOL® Delivered 28.7K Units in Q3 (8% Growth Vs. Q2) SUSTOL Quarterly Unit Performance 35 (Provider Demand) 30 28.7 26.4 25 20 Units (000) 15 10.3 10 5 3.2K - Q4 2016 Q1 2017 Q2 2017 Q3 2017 Net Sales $1.3M $3.6M $8.5M $8.6M Source: Heron 867 data 15
Slide 16: SUSTOL Core Business Steady, Growth Slowed in Anticipation of Generic Aloxi
As Expected, SUSTOL® Core Business was Steady, but Growth Slowed in Anticipation of Generic Aloxi® Active Accounts By Quarter Early Adopter Performance 120 19% 20% 18% 160 Share Thousands of Units 137 100 123 140 119 15% 109 120 80 62 100 60 43 10% 80 74 7% 60 40 74 5% 3% 26 29 40 20 47 38 10 20 19
Slide 17: Market Insights Suggest SUSTOL May Decline Modestly Through Arbitrage
Market Insights Suggest SUSTOL® May Decline Modestly Through the Arbitrage and Grow Thereafter – Consistent with Aloxi® Analogue Recent Market Insights Unit Sales 700,000 • Practices that are converting to SUSTOL are likely to maintain use1 600,000 • ~67% of current “dabblers” likely to stop or redu
Slide 18: SUSTOL Continues to Outperform Recent CINV Brand Launches
Despite Expectations of Generic Aloxi®, SUSTOL® Continues to Outperform Recent CINV New Brand Launches CINV New Brand Launches Since 2008 Administrations in First 12 Months (launch aligned) 80,000 70,000 68,694 60,000 50,000 40,000 30,000 33,530 20,000 10,000 2,756 11,759 0 Sancuso (2008) Akynzeo (2
Slide 19: 2017 CINV Franchise Outlook
2017 CINV Franchise Outlook SUSTOL®: We continue to expect core SUSTOL business to hold firm and with possibility of modest decline during arbitrage and growth thereafter • Maintain guidance of $25M–$30M in SUSTOL net sales in 2017 • Permanent J-code granted by CMS; effective January 1, 2018 CINVANT
Slide 20: Postoperative Pain Program
Postoperative Pain Program HTX-011: Proprietary Extended-Release Combination of Bupivacaine + Meloxicam
Slide 21: Market Is Large, but Long-Acting Anesthetics Have Not Fulfilled the Promise
Market Is Large and Local Anesthetic Use Is Common, but Long-Acting Anesthetics Have Not Fulfilled the Promise Procedures Requiring Postoperative Local Anesthetic Usage Across Key Limiters of Liposomal Pain Relief, 2015-20201 Key Surgeries, 20151* Bupivacaine Market Penetration • Perceived inability
Slide 22: Surgeons Expect to Use More Long-Acting Local Anesthetics
Surgeons Expect to Use More Long-Acting Local Anesthetics as Better Options Become Available Future Pain Market Outlook 72% of surgeons expect to use 62% of surgeons expect to use more Chart Title 73% of surgeons expect to use more fewer opioids local anesthetics long-acting local anesthetics 100% 4
Slide 23: Risk of Chronic Opioid Use After Selected Surgeries
Risk of Chronic Opioid Use After Selected Surgeries Adjusted Odds Ratio for Chronic Opioid Use 0 1 2 3 4 5 6 Total Knee Arthroplasty 5.1 Open Cholecystectomy 3.6 Simple Mastectomy 2.6 Total Hip Arthroplasty 2.5 Open Appendectomy 1.7 Laproscopic Cholecystectomy 1.6 Cesarean Delivery 1.3 Based on data
Slide 24: Opioids Increase Healthcare Costs Due to a High Rate of Side Effects
In Addition to Potential Addiction, Opioids Increase Healthcare Costs Due to a High Rate of Side Effects Cost of Opioid-Related Adverse Drug Events1,2 Moderate to Severe Opioid- Cost per ADE Events in Induced ADE 2013 $ Ileus $6,141 Pruritus $502 Urinary Retention $1,867 Respiratory Depression $1,50
Slide 25: Reducing Pain at the Source Can Eliminate the Need for Opioids
Reducing Pain at the Source Can Eliminate the Need for Opioids and May Decrease the Development of Chronic Pain HTX-011 directly blocks transmission of the pain signal, Acting on opiate receptors in the brain, opioids can reduce the sensation of potentially reducing the chance of chronic pain. pain,
Slide 26: Inflammation Plays a Key Role in Pain Management
Inflammation Plays a Key Role in Pain Management (Current local anesthetics do not address this) BUPH+ BUPN + H+ • Inflammation produces an acidic environment Outside membrane Nerve Cell Membrane • Shifts the balance to Inside membrane ionized form, which is unable to penetrate nerve cell membrane B
Slide 27: Fixed-Dose Combination of Bupivacaine & Meloxicam Produced Complete Analgesia
Unique Fixed-Dose Combination of Bupivacaine & Meloxicam Delivered Into the Incision Produced Complete Analgesia1 Pig Post-Operative Pain Model1 Saline Control Liposomal Bupivacaine 2 Biochronomer Bupivacaine Biochronomer Bupivacaine + Meloxicam 6-Day Release Percentage of Maximal Force (60 gm) 100.
Slide 28: >72 Hour Duration of Action Seen as Ideal
>72 Hour Duration of Action Seen as “Ideal” Ideal Duration of Efficacy for Long- Minimally Acceptable Duration of Acting Local Anesthetic Efficacy for Long-Acting Local Anesthetic >5 days 2% 5 days 4% ≤ 24 hours 72 hours 4 days 11% 12% 9% ≤ 24 48 hours hours 27% 44% 48 hours 72 hours 45% 46% Source:
Slide 29: HTX-011 Designed to Produce Marked Analgesia Through the First 72 Hours
HTX-011 Designed to Produce Marked Analgesia Through the First 72 Hours After Surgery1 Saline Control Liposomal Bupivacaine Biochronomer Bupivacaine 2 Biochronomer Meloxicam HTX-011 (Biochronomer Bupivacaine + Meloxicam with 3-day release) Percentage of Maximal Force (60 gm) 100.0 90.0 80.0 Increasi
Slide 30: Activity of HTX-011 Cannot Be Replicated By Systemic Meloxicam
Activity of HTX-011 Cannot Be Replicated By Systemic Administration of Meloxicam Along With ER Bupivacaine Pig Post-Operative Pain Model Saline Placebo HTX-011 (Bupivacaine + Meloxicam) Biochronomer Bupivacaine With Simultaneous Injectable Meloxicam 100.0 90.0 80.0 Increasing Analgesia Percent of Ma
Slide 31: HTX-011 Clinical Experience Shows Potential to Transform Postoperative Pain Control
HTX-011 Clinical Experience Shows It Has the Potential to Transform Postoperative Pain Control Phase 2 data has demonstrated: Product attributes of HTX-011 optimized in Phase 2 for Phase 3 efficacy studies: Statistically significant reductions in Formulation, where the product has both pain and
Slide 32: End-of-Phase 2 Meeting Agreements with FDA
End-of-Phase 2 Meeting Agreements with FDA • Two Phase 3 adequate and well-controlled efficacy studies and a Phase 3 safety study of approximately 200 subjects in multiple surgical models are adequate to support an NDA for a broad indication for reduction in postoperative pain for 72 hours – Primary
Slide 33: Phase 3 Program Has Been Initiated
PHASE 3 PROGRAM HAS BEEN INITIATED 33
Slide 34: Study 301: Phase 3 Bunionectomy Study Design
Study 301: Phase 3 Bunionectomy Study Design Study 301 HTX-011 60 mg Endpoints Instillation Randomization (3:3:2) Primary: Pain Intensity AUC0-72 vs. placebo N = 150 1st Key Secondary: Pain Intensity AUC0-72 vs. bupivacaine Bupivacaine 50 mg 2nd Key Secondary: Opioid use vs. placebo Injection N = 15
Slide 35: Study 302: Phase 3 Herniorrhaphy Study Design
Study 302: Phase 3 Herniorrhaphy Study Design Study 302 HTX-011 300 mg Endpoints Instillation Randomization (2:2:1) Primary: Pain Intensity AUC0-72 vs. placebo N = 160 1st Key Secondary: Pain Intensity AUC0-72 vs. bupivacaine Bupivacaine 75 mg 2nd Key Secondary: Opioid use vs. placebo Injection 3rd
Slide 36: HTX-011 Study 208: Phase 2 Bunionectomy
HTX-011 STUDY 208: Phase 2 Bunionectomy Updated Results With the Phase 3 Dose Analyzed by the FDA Requested Methodology (wWOCF) (5 Clinical Sites Enrolled Subjects) 36
Slide 37: HTX-011 Reduces Pain Better Than Placebo or Bupivacaine After Bunionectomy
HTX-011 Reduces Pain Significantly Better Than Placebo or Bupivacaine (Standard-of-Care) After Bunionectomy Increasing Pain 37 wWOCF, windowed-worst observation carried-forward for use of opioid rescue medication and LOCF for missing data
Slide 38: HTX-011 Produces 24-Fold Greater Pain Reduction vs Bupivacaine in Bunionectomy
HTX-011 60 mg Produces 24-Fold Greater Reduction in Pain Compared to Bupivacaine 50 mg Through 72 Hours in Bunionectomy Greater Pain Reduction vs. Placebo p-values are from ANOVA using AUC of Pain Intensity with wWOCF for HTX-011 vs. bupivacaine 38 AUC, area under the curve; LSMD, least squares mean
Slide 39: Bunionectomy: HTX-011 Significantly Reduces Total Opioid Use
Bunionectomy Study: HTX-011 Significantly Reduces Total Opioid Use vs Bupivacaine and Placebo Source: Data on File, Heron Therapeutics, Inc. 39
Slide 40: Bunionectomy: HTX-011 Increases Proportion of Opioid-Free Subjects
Bunionectomy Study: HTX-011 Significantly Increases the Proportion of Opioid-Free Subjects vs Placebo 40 Source: Data on File, Heron Therapeutics, Inc.
Slide 41: Bunionectomy Study: Drug-Related Treatment-Emergent Adverse Events
Bunionectomy Study: Drug-Related Treatment-Emergent Adverse Events* Pooled HTX-011 Bupivacaine 50mg Saline Placebo Preferred Term (N = 174) (N = 25) (N = 104) Any Drug-related 28.2% 28.0% 24.0% TEAEs Nausea 12.1% 8.0% 11.5% Erythema 8.0% 8.0% 1.0% Vomiting 3.4% 4.0% 11.5% Hypertransaminasaemia 1.1%
Slide 42: HTX-011 Greater Pain Reduction Than ER Bupivacaine or Meloxicam Alone
HTX-011 Has Demonstrated Significantly Greater Pain Reduction Than Extended-Release Versions of Bupivacaine or Meloxicam Using the Same Formulation Study 208 Greater Pain Reduction vs. Placebo p-value from ANOVA, LSMD of area under the curve for HTX-011 vs. HTX-002 or HTX-009 AUC, area under the cur
Slide 43: HTX-011 Study 202: Phase 2 Hernia Repair
HTX-011 STUDY 202: Phase 2 Hernia Repair Updated Results With the Phase 3 Dose Analyzed by the FDA Requested Methodology (wWOCF) (3 Clinical Sites Enrolled Subjects) 43
Slide 44: HTX-011 Reduces Pain Better Than Placebo or Bupivacaine After Herniorrhaphy
HTX-011 Reduces Pain Significantly Better Than Placebo or Bupivacaine (Standard-of-Care) After Herniorrhaphy Increasing Pain 44 wWOCF, windowed-worst observation carried-forward for use of opioid rescue medication and LOCF for missing data
Slide 45: HTX-011 Produces 4-Fold Greater Pain Reduction vs Bupivacaine in Hernia Repair
HTX-011 300 mg Produces 4-Fold Greater Reduction in Pain Compared to Bupivacaine 75 mg Through 72 Hours in Hernia Repair Greater Pain Reduction vs. Placebo p-values are from ANOVA using AUC of Pain Intensity with wWOCF for HTX-011 vs. bupivacaine 45 AUC, area under the curve; LSMD, least squares mea
Slide 46: Herniorrhaphy: HTX-011 Significantly Reduces Total Opioid Use
Herniorrhaphy Study: HTX-011 Significantly Reduces Total Opioid Use vs Placebo 46 Source: Data on File, Heron Therapeutics, Inc.
Slide 47: Herniorrhaphy: HTX-011 Increases Proportion of Opioid-Free Subjects
Herniorrhaphy Study: HTX-011 Significantly Increases Proportion of Opioid-Free Subjects vs Bupivacaine and Placebo Source: ESRA SEPT 2017. 47
Slide 48: Herniorrhaphy Study: Drug-Related Treatment-Emergent Adverse Events
Herniorrhaphy Study: Drug-Related Treatment-Emergent Adverse Events* HTX-011 300/400 mg Bupivacaine 75 mg Saline Placebo Preferred Term (n = 99) (n = 32) (n = 85) Any Drug-Related 30.3% 28.1% 29.4% TEAEs Hypotension 8.1% 3.1% 3.5% Nausea 7.1% 0% 9.4% Bradycardia 5.1% 6.3% 7.1% Dizziness 5.1% 3.1% 1.
Slide 49: HTX-011 Study 203: Phase 2 Abdominoplasty
HTX-011 STUDY 203: Phase 2 Abdominoplasty Updated Results Using wWOCF (8 Clinical Sites Enrolled Subjects) 49
Slide 50: HTX-011 Reduces Pain Better Than Placebo or Bupivacaine After Abdominoplasty
HTX-011 Reduces Pain Significantly Better Than Placebo or Bupivacaine (Standard-of-Care) After Abdominoplasty Increasing Pain 50 wWOCF, windowed-worst observation carried-forward for use of opioid rescue medication and LOCF for missing data
Slide 51: HTX-011 Produces 5-Fold Greater Pain Reduction vs Bupivacaine in Abdominoplasty
HTX-011 400 mg Produces 5-Fold Greater Reduction in Pain Compared to Bupivacaine 100 mg Through 72 Hours in Abdominoplasty Greater Pain Reduction vs. Placebo p-values are from ANOVA using AUC of Pain Intensity with wWOCF for HTX-011 vs. bupivacaine 51 AUC, area under the curve; LSMD, least squares m
Slide 52: Abdominoplasty: HTX-011 Significantly Reduces Total Opioid Use
Abdominoplasty Study: HTX-011 Significantly Reduces Total Opioid Use vs Bupivacaine and Placebo Source: Data on File, Heron Therapeutics, Inc. 52
Slide 53: More HTX-011 Patients Were Opioid-Free by Day 3
Although Almost All Patients Took Opioids on Day 1, More HTX-011 Patients Were Opioid-Free by Day 3 53
Slide 54: Abdominoplasty Study: Drug-Related Treatment-Emergent Adverse Events
Abdominoplasty Study: Drug-Related Treatment-Emergent Adverse Events* HTX-011 400 mg Bupivacaine 100 mg Saline Placebo Preferred Term (n = 25) (n = 17) (n = 32) Any Drug-Related 44.0% 41.2% 31.3% TEAEs Nausea 20.0% 29.4% 15.6% Headache 12.0% 5.9% 6.3% Vomiting 8.0% 5.9% 6.3% Constipation 4.0% 11.8%
Slide 55: HTX-011 Significantly Better Than Extended-Release Bupivacaine and Unique PK-PD
HTX-011 SIGNIFICANTLY BETTER THAN EXTENDED-RELEASE BUPIVACAINE (002) AND SHOWS A UNIQUE PK-PD RELATIONSHIP 55
Slide 56: PK-PD: 002 ER Bupivacaine Shows No PK-PD Relationship
Pharmacokinetic-Pharmacodynamic (PK-PD) Assessment Bunionectomy Study: 002 ER Bupivacaine 60 mg Was Significantly Better Than Placebo Through 24 hr, but Does Not Demonstrate a PK-PD Relationship 002 ER Bupivacaine No PK-PD Relationship Mean Pain Intensity vs Time 10 3 135 Change in Pain Score 9 002
Slide 57: PK-PD: Exparel Bunionectomy Study
PK-PD: Exparel® Bunionectomy Study Exparel Significantly Better Than Placebo Through 24 hr, but Does Not Demonstrate a PK-PD Relationship Exparel® (liposomal bupivacaine) No PK-PD Relationship Mean Pain Intensity vs Time 3 140 ∆ Pain Score Plasma Conc 120 Plasma Bupivacaine (ng/mL) ∆ Pain Score (Sal
Slide 58: HTX-011 Better Than Placebo Through 72 hr With Excellent PK-PD
PK-PD: Bunionectomy Study HTX-011 Significantly Better Than Placebo Through 72 hr With an Excellent PK-PD Relationship HTX-011 (bupivacaine + meloxicam) PK-PD Relationship Mean Pain Intensity vs Time Pain Score Plasma PK 4 50 45 3.5 Bupivacaine Concentation (ng/mL) 40 3 35 (Saline-HTX-011) 2.5 ΔPain
Slide 59: Cross-Study Comparison: HTX-011 Superior Pain Reduction vs ER Bupivacaine
In a Cross-Study Comparison of a Standardized Bunionectomy Model, HTX-011 Demonstrated Superior Pain Reduction vs Two Forms of Extended-Release Bupivacaine Liposomal Extended-Release Bupivacaine (Exparel, 120 mg)* 002 Extended-Release Bupivacaine (60 mg) HTX-011 (60 mg) 10 Greater Pain Reduction vs
Slide 60: On-Going Phase 2b Studies
[EEIROWN THERAPEUTICS Developing Best-in-Class Medicine, Improving Lives.” On-Going Phase 2b Studies
Slide 61: Phase 2b Total Knee Arthroplasty Study Design
Phase 2b Total Knee Arthroplasty Study Design HTX-011 200 mg HTX-011 400 mg Instillation Instillation N = 20 N = 25 HTX-011 200 mg HTX-011 400 mg Instillation + Injection Instillation + Injection Cohort 2 Cohort 1 N = 20 N = 25 IRC Saline Placebo Saline Placebo Injection Injection N = 10 N = 25 Bupi
Slide 62: Phase 2b Nerve Block: Breast Augmentation Study Design
Phase 2b Nerve Block: Breast Augmentation Study Design HTX-011 60 mg HTX-011 120 mg HTX-011 240 mg Nerve Block Nerve Block Nerve Block N = 12 N = 24 N = 24 Cohort 3 Cohort 1 Cohort 2 Saline Placebo Saline Placebo Saline Placebo Nerve Block Nerve Block Nerve Block N=6 N = 12 N = 12 IRC IRC dose decis
Slide 63: Summary: HTX-011 Is Poised to Fulfill the Promise of a Long-Acting Local Anesthetic
Summary: HTX-011 Is Poised to Fulfill the Promise of a Long-Acting Extended-Release Local Anesthetic Large, growing market opportunity Differentiated, synergistic mechanism addresses inflammation – a key inhibitor of both generic and long-acting local anesthetics Demonstrated superiority vs. gen
Slide 64: Financial Summary
Financial Summary Cash, cash equivalents and short-term investments were $74.0 million as of September 30, 2017. Heron also had accounts receivable of $28.9 million, the majority of which it expects to collect in the fourth quarter of 2017 and the first quarter of 2018. Summary Statement of Operatio
Slide 65: Key Catalysts in Pain & CINV Franchises
Key Catalysts in Pain & CINV Franchises HTX-011 for Postoperative CINVANTI™ for CINV SUSTOL® for CINV Pain 2017 net sales guidance: Top-line results abdominoplasty NDA submission $25M - $30M Phase 2 program in nerve block FDA approval initiated Initiated TKA study (local administration)
Heron Therapeutics — Investor Presentation (November 2017) on 6ix