Heron Therapeutics, Inc. · NASDAQ:HRTX
Heron Therapeutics — Investor Presentation (October 2018)
49 slides from Heron Therapeutics's investor presentation, Oct 1, 2018
Slide 1: Company Update
Company Update October 1, 2018
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 i
Slide 3: Status of Product Portfolio
Status of Product Portfolio CINV Pain Preclinical Clinical NDA Approved SUSTOL® (granisetron) extended- release injection Approved by U.S. FDA for CINV Prevention CINVANTI® (aprepitant) injectable Approved by U.S. FDA for CINV Prevention emulsion HTX-011 bupivacaine • Fast Track and Breakthrough + m
Slide 4: HTX-011 Has Received FDA Breakthrough Therapy Designation
HTX-011 for Postoperative Pain Management Has Received FDA Breakthrough Therapy Designation • Breakthrough Therapy designation (BTD) designed to expedite development and review of drugs: – Intended to treat serious conditions; and – For which preliminary clinical evidence indicates substantial impro
Slide 5: HTX-011's Unique Mechanism of Action
HTX-011’s Unique Mechanism of Action Inflammation Can Reduce the Activity of Local Anesthetics • Surgical insult produces an BUPH+ BUPN + H+ immediate drop in pH Outside membrane • As inflammatory cytokines are Nerve Cell released and inflammation sets in, Membrane the acidic environment is Inside m
Slide 6: Postoperative Opioids Are a Gateway to Addiction
Postoperative Opioids Are a Gateway to Addiction MORE THAN 40 MILLION AS MANY AS 2.6 MILLION UP TO 440,000 patients undergoing surgical procedures are patients that take opioids to manage pain after patients will become addicted to prescribed opioids for pain management surgery may become persistent
Slide 7: HTX-011 Achieved Significant Reductions in Pain and Need for Opioids
HTX-011 ACHIEVED STATISTICALLY SIGNIFICANT REDUCTIONS IN PAIN AND THE NEED FOR OPIOIDS VS. BUPIVACAINE IN EVERY PHASE 2 STUDY AND BOTH PHASE 3 STUDIES 7
Slide 8: Seven Active-Controlled Studies to Be Included in HTX-011 NDA
Seven Active-Controlled Studies to Be Included in HTX-011 NDA NDA, planned in 2018, will request broad label for reduction of postoperative pain for 72 hours and the use of opioid analgesics after surgery Significant for Significant for Significant PK – PD Tissue Study Phase Surgical Model Pain Redu
Slide 9: Phase 3
PHASE 3 9
Slide 10: 301/EPOCH1: Phase 3 Bunionectomy Study Design
Study 301/EPOCH1: Phase 3 Bunionectomy Study Design HTX-011 60 mg Instillation Study 301 Randomization (3:3:2) N = 157 Endpoints Primary: Pain Intensity AUC0-72 vs. placebo Bupivacaine 50 mg Injection 1st Key Secondary: Pain Intensity AUC0-72 vs. N = 155 bupivacaine 2nd Key Secondary: Opioid use vs.
Slide 11: 301: HTX-011 Reduces Pain After Bunionectomy
Study 301: HTX-011 Reduces Pain After Bunionectomy Significantly Better Than Placebo or Bupivacaine (Standard-of-Care) HTX-011 significantly better than Increasing Pain placebo and bupivacaine through 72 hours even without adjustment for opioid use wWOCF, windowed-worst observation carried-forward f
Slide 12: 301: Increases Proportion of Opioid-Free Subjects
Study 301: HTX-011 Significantly Increases Proportion of Opioid-Free Subjects vs Bupivacaine and Placebo Percent of Patients With Severe Pain at Any Time Through 72 hours HTX-011 53.5% 83.0% Saline Placebo p<0.0001 75.5% Bupivacaine p<0.0001 Source: Figure 14.2.3 12
Slide 13: 301: Incidence of Treatment Emergent Adverse Events
Study 301: Incidence of Treatment Emergent Adverse Events Occurring in ≥ 5% in the HTX-011 Group HTX-011 60 mg Saline Placebo Bupivacaine HCl 50 mg Preferred Term (N=157) (N=101) (N=154) Any TEAE 83.4% 78.2% 85.1% Nausea 37.6% 43.6% 45.5% Dizziness 21.7% 17.8% 23.4% Incision site oedema 17.2% 12.9%
Slide 14: 302/EPOCH2: Phase 3 Herniorrhaphy Study Design
Study 302/EPOCH2: Phase 3 Herniorrhaphy Study Design HTX-011 300 mg Study 302 Instillation Randomization (2:2:1) Endpoints N = 164 Primary: Pain Intensity AUC0-72 vs. placebo Bupivacaine 75 mg 1st Key Secondary: Pain Intensity AUC0-72 vs. Injection bupivacaine N = 172 2nd Key Secondary: Opioid use v
Slide 15: 302: HTX-011 Reduces Pain After Herniorrhaphy
Study 302: HTX-011 Reduces Pain After Herniorrhaphy Significantly Better Than Placebo or Bupivacaine (Standard-of-Care) HTX-011 significantly better than Increasing Pain placebo and bupivacaine through 72 hours even without adjustment for opioid use wWOCF, windowed-worst observation carried-forward
Slide 16: 302: Increases Proportion of Opioid-Free Subjects
Study 302: HTX-011 Significantly Increases Proportion of Opioid-Free Subjects vs Bupivacaine and Placebo Percent of Patients With Severe Pain at Any Time Through 72 hours HTX-011 48.8% 81.7% Saline Placebo p<0.0001 60.5% Bupivacaine p=0.0372 Source: Figure 14.2.3 16
Slide 17: 302: Incidence of Treatment Emergent Adverse Events
Study 302: Incidence of Treatment Emergent Adverse Events Occurring in ≥ 5% in the HTX-011 Group HTX-011 300 mg Saline Placebo Bupivacaine HCl 75 mg Preferred Term (N=163) (N=82) (N=173) Any TEAE 73.0% 74.4% 73.4% Nausea 18.4% 34.1% 21.4% Constipation 17.2% 18.3% 23.7% Dizziness 14.7% 15.9% 24.3% He
Slide 18: Recently Completed Phase 2b Studies
RECENTLY COMPLETED PHASE 2B STUDIES 18
Slide 19: 209: Phase 2b Total Knee Arthroplasty Study Design
Study 209: Phase 2b Total Knee Arthroplasty (TKA) Study Design HTX-011 200 mg HTX-011 400 mg Instillation Instillation N=20 N=58 HTX-011 400 mg HTX-011 200 mg Instillation + Ropivacaine Instillation + Injection Injection N=22 Cohort 2 Cohort 1 N=56 IRC Bupivacaine 125 mg Bupivacaine 125 mg Injection
Slide 20: 209: Separation Between HTX-011 Arms and Placebo for Pain at Rest
Study 209: Significant Separation between HTX-011 Arms and Placebo through 72 Hours for Pain at Rest Notes: Pain intensity collected at rest wWOCF for use of opioid rescue medication and LOCF for missing pain data 20
Slide 21: 209: Separation Without Adjustment for Opioid Use
Study 209: Significant Separation Between HTX-011 Arms and Placebo Through 72 Hours Without Adjustment for Opioid Use – Conservative Comparison Notes: Pain intensity collected at rest LOCF for missing data and no adjustment for use of opioid rescue medication 21
Slide 22: 209: HTX-011 Superior to Placebo and Bupivacaine
Study 209: HTX-011 Significantly Superior to Both Placebo and Bupivacaine Through 72 Hours With Conservative Analysis Not Adjusting for Opioid Use Notes: Pain intensity collected at rest LOCF for missing data and no adjustment for use of opioid rescue medication 22
Slide 23: 209: HTX-011 plus Ropivacaine Reduces Opioid Use
Study 209: HTX-011 plus Ropivacaine Significantly Reduces Opioid Use vs. Placebo through 72 Hours Opioid consumption is presented in mean milligrams of morphine equivalents 23
Slide 24: Can HTX-011 Study 209 and Exparel PILLAR TKA Study be Compared?
Can HTX-011 Study 209 and the Exparel PILLAR* TKA Study be Compared? • Cross-study comparison between these 2 studies is more difficult than other cross-study comparisons due to several factors including different anesthesia and background analgesics: – PILLAR Study used spinal anesthesia and schedu
Slide 25: 211: Phase 2b Breast Augmentation Study Design
Study 211: Phase 2b Breast Augmentation Study Design HTX-011 60 mg HTX-011 120 mg HTX-011 240 mg HTX-011 400 mg Nerve Block Nerve Block Nerve Block Nerve Block N=12 N=27 N=25 N=47 HTX-011 400 mg Instillation N=50 Cohort 1 Cohort 2 Cohort 3 Cohort 4 Bupivacaine 50 mg Bupivacaine 50 mg Bupivacaine 50
Slide 26: 211: Pain Reduction at Rest Triple that of Bupivacaine
Study 211: Pain Reduction from HTX-011 at Rest Approximately Triple that of Bupivacaine HTX-011 achieved primary endpoint for AUC0-24 with activity and at rest 26
Slide 27: 211: Instillation Shows Superior Early Pain Reduction
Study 211: HTX-011 Instillation Shows Superior Reduction in Pain at Rest Intensity Early and HTX-011 Nerve Block Shows Durable Response Notes: Pain intensity collected at rest wWOCF, windowed-worst observation carried-forward for use of opioid rescue medication and LOCF for missing pain data 27
Slide 28: 211: Raw Pain Scores in All Arms Drop Quickly
Study 211: Raw Pain Scores in All Arms Drop Quickly; Difficult to Discriminate between Arms after 24 Hours Notes: Raw pain intensity collected at rest Scores not adjusted for opioid use 28
Slide 29: 211: Both HTX-011 Arms Reduce Opioid Use vs. Placebo
Study 211: Both HTX-011 Arms Significantly Reduce Opioid Use vs. Placebo through 24 Hours Opioid consumption is presented in mean milligrams of morphine equivalents 29
Slide 30: Safety Summary
Safety Summary HTX-011 was generally well tolerated across all Phase 2 and Phase 3 studies with no clinically meaningful differences in: • Overall adverse events • The incidence of serious adverse events • Premature discontinuations due to adverse events • Potential local anesthetic systemic toxicit
Slide 31: Consistent Pharmacokinetics and Strong PK-PD Correlation
CONSISTENT PHARMACOKINETICS AND STRONG CORRELATION BETWEEN PK – PD ACROSS SURGICAL MODELS 31
Slide 32: HTX-011 Pharmacokinetics Dose-Linear Across Surgical Models
HTX-011 Pharmacokinetics Across 5 Diverse Surgical Models Are Dose-Linear Versus Bupivacaine Solution HTX-011 Bupivacaine HCl Bupivacaine Cmax Bupivacaine Cmax 800 700 Bunionectomy Bunionectomy Herniorrhaphy 700 600 Bupivacaine Cmax (ng/mL) Abdominoplasty Bupivacaine Cmax (ng/mL) Herniorrhaphy R² =
Slide 33: Correlation Between Pain Reduction and Pharmacokinetics
Correlation Between Pain Reduction and Pharmacokinetics of HTX-011 Across Surgical Models Bunionectomy Hernia Repair Pain Score Plasma PK 4 50 3.5 45 Bupivacaine Concentation (ng/mL) 40 3 35 (Saline-HTX-011) 2.5 30 ΔPain Score 2 25 1.5 20 15 1 10 0.5 5 0 0 0 24 48 72 Time (hour) Breast Augmentation
Slide 34: HTX-011 NDA Filing Plans
HTX-011 NDA Filing Plans • Goal is to file an NDA in 2018 requesting a broad label for reduction of postoperative pain for 72 hours and use of opioid analgesics after surgery • HTX-011 produced significant reductions in both pain intensity and need for opioids through 72 hours post-surgery compared
Slide 35: 9.7 Million Procedures Will Have ASP+6% Reimbursement At Launch
9.7 Million Out of the 15 Million Initial Target Procedures (65%) Will Have ASP+6% Reimbursement At Launch* Hospitals account for 76% Remaining outpatient facilities account for 24% [11.4 M procedures] [3.6 M procedures] 10% Ambulatory Surgical 14% Other (Physician 35% Inpatient 41% Hospital Outpati
Slide 36: 340b Hospital Summary
340b Hospital Summary • ~2258 hospitals (excluding children’s & psych) • Perform 8.4M outpatient surgeries • 4.4M inpatient surgeries/year • Manufacturers required to provide 23.1% discount off ASP/WAC • Effective January 1, 2018, CMS reimbursement to hospitals for 340B drugs changed significantly f
Slide 37: Being Second to Market is NOT a Significant Obstacle
Being Second to Market is NOT a Significant Obstacle to Commercial Success • First to market is not a guarantee of being the largest seller – Lipitor, Crestor, Eliquis, and Naropin for nerve block are good examples • Penetration of Exparel is low (<6% of the addressable market) providing a significa
Slide 38: Pharmacy Directors Would Provide Better Access to HTX-011
Pharmacy Directors State That They Would Provide Better Access to HTX-011 Than Currently Available to EXPAREL Formulary Status of Exparel vs. Expected HTX- 011 Status 22% Not on Formulary 44% On Formula, With Restrictions 56% On Formulary, No Restrictions 44% 22% 12% HTX-011 (Predicted) EXPAREL (Sta
Slide 39: Up to 25% Report Exparel Would be Removed From Formulary
Up to 25% of Pharmacy Directors Report That Exparel Would be Removed From Formulary When HTX-011 Becomes Available Impact of HTX-011 Launch on Exparel Formulary Status Most pharmacy directors indicate HTX-011 would displace Exparel status would stay the Exparel on formulary same 43% § Over 50% of ph
Slide 40: Large US Market Opportunity
Large US Market Opportunity Theoretical and Target Market ~28M Annual US Surgical Procedures Requiring Postoperative Pain Management That Were Considered Potentially Suited For HTX-011 ~15M procedures ~6M procedures ~7M procedures Initial Targets Secondary Targets Tertiary Targets Higher volume proc
Slide 41: High-Value Procedures in Initial Target Market
High-Value Procedures in Initial Target Market Annual Volume Overall % Local (‘000s, US, 2015) Anesthetic Use Procedure Total Outpatient ASC Non- Inpatient Medicare Survey Procedures (C-code) (C-Code) Medicare Knee arthroplasty 815 721 65 28 41% 59%* 87% Hip arthroplasty 337 325 7 5 43% 57%* 81% Ort
Slide 42: Positive Response to HTX-011's Target Product Profile
Overwhelmingly Positive Response by Physicians and Pharmacists to HTX-011’s Target Product Profile HTX-011 Target Product Profile: Strengths Reduction in Opioid Consumption 88% 11% Reduction in Pain Score 87% 13% Reduction in Opioid AEs* 80% 19% Analgesia Duration 79% 20% Mechanism of Action 73% 23%
Slide 43: CINV Commercial Products
ERON THERAPEUTICS Developing Best-in-Class Medicine. Improving Lives” - CINV Commercial Products
Slide 44: CINV Prophylaxis Requires Two Complimentary Mechanisms of Action
CINV Prophylaxis Typically Requires Two Complimentary Mechanisms of Action NK1 receptor antagonists NK1 receptor • Substance P is primary driver of delayed antagonist CINV, but related to ~15% of acute failures CINVANTI™ • EMEND® IV (fosaprepitant), which has 90% share of the US NK1 market, contains
Slide 45: Heron's CINV Portfolio Outperforms Recent CINV Launches
Heron’s CINV Portfolio Continues to Outperform All Recent CINV Branded Launches CINV Brand Launches Since 2008 CINVANTI Ordering Accounts Since Launch Approximate administrations in 250 First 18 Months (launch aligned) 136,000 200 150 CINVANTI administrations in 249 first 6 months: 100 206 58,000 69
Slide 46: CINV Portfolio achieved $17.3M Q2 2018 Net Sales
Heron CINV Portfolio achieved $17.3M Q2 2018 Net Sales $19.0 CINV Franchise Net Sales $17.3 $17.0 SUSTOL CINVANTI $15.0 $13.0 $11.6 Net Sales ($M) $11.0 $10.0 $9.0 $8.5 $8.6 $7.0 $5.0 $10.0 $3.6 $8.5 $8.6 $3.0 $6.41 $6.1 $1.3 $3.6 $1.0 $1.3 $(1.0) Q4 2016 Q1 2017 Q2 2017 Q3 2017 Q4 2017 Q1 2018 Q2 2
Slide 47: 2018 CINV Franchise Outlook
2018 CINV Franchise Outlook SUSTOL®: We continue to expect core SUSTOL business to be weak during the palonosetron arbitrage with growth thereafter CINVANTI® • We believe it has the best overall profile compared to the other available NK1 antagonists • Offers strong strategic and operational fit wit
Slide 48: Financial Summary
Financial Summary Summary Statement of Operations and Net Cash Used in Operations Three Months Ended Six Months Ended (In thousands, except per share data) June 30, 2018 June 30, 2018 Net product sales $ 17,277 $ 28,844 Operating expenses1 56,130 119,687 Other income (expense), net 183 (92) Net loss
Slide 49: Key Catalysts in Pain Management & CINV Franchises
Key Catalysts in Pain Management & CINV Franchises HTX-011 for Postoperative Pain CINVANTI ® and SUSTOL® for CINV 2018 net sales guidance for CINV ü Fast Track designation granted franchise: upper end of $60M - $70M ü Completed enrollment in Phase 3 pivotal trials ü Top-line Pivotal Phase 3 results
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