Heron Therapeutics, Inc. · NASDAQ:HRTX
Heron Therapeutics — AP Pharma — Investor Presentation (January 2013)
46 slides from Heron Therapeutics's investor presentation, Jan 7, 2013
Slide 1: Company Overview
Exhibit 99.1 Company Overview OTCBB: APPA January 2013
Slide 2: Legal Disclaimer
Legal Disclaimer 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 timely development, approval, launch and acceptance o
Slide 3: Stock Summary
Stock Summary Company: A.P. Pharma, Inc. Ticker: OTCBB: APPA.OB Stock Price: $0.60 (1/4/13) Market Capitalization: $280.3 million 1 Cash: $60.0 million 2 Debt: $4.7 million 2 1 Based on 499.0 million fully diluted, as-converted common shares assuming the full conversion of convertible debt outstandi
Slide 4: Senior Management
Senior Management John B. Whelan President & CEO Raven Biotechnologies Eos Biotechnology Hewlett Packard/Agilent Michael A. Adam, Ph.D. Senior Vice President & Spectrum Pharmaceuticals Chief Operating Officer Pfizer/Agouron Bristol-Myers Squibb Mark Gelder, M.D. Senior Vice President & GE Healthcare
Slide 5: A.P. Pharma Highlights
A.P. Pharma Highlights Lead product candidate, APF530, is long-acting, injectable product for chemotherapy-induced nausea and vomiting (CINV) Incorporates widely used 5-HT3 antagonist - granisetron (Kytril ®) 5-day delivery profile Reduces both acute- and delayed-onset CINV with single injection Pat
Slide 6: Important APF530 Milestones
Important APF530 Milestones Milestone Timing Status Successful End-of-Review Meetings with 1Q 2011 FDA Successful Completion of Thorough QT 1Q 2012 and Metabolism Studies Completed $53.6MM PIPE Financing 3Q 2012 Successful Completion of Human Factors 3Q 2012 Validation Study Successful Completion of
Slide 7: Clinical Summary
Clinical Summary January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 7
Slide 8: APF530 Pivotal Phase 3 Study Overview
APF530 Pivotal Phase 3 Study Overview Randomized, controlled, multi-center study 1,341 patients in primary efficacy population Two doses of APF530 (5 mg and 10 mg granisetron) compared to the approved dose of Aloxi Patients stratified by type of chemotherapy regimen (moderately or highly emetogenic)
Slide 9: 5-Day Profile: APF530 Pharmacokinetics
5-Day Profile: APF530 Pharmacokinetics Granisetron is released rapidly following injection of APF530 and continues to be released over a 5-day period. 20 15 All subjects (n= 18) mean ± SEM 10 5 0 0 24 48 72 96 120 144 168 Time after Dosing (h) January 2013 © 2013. A.P. Pharma, Inc. All rights reserv
Slide 10: Primary Efficacy Results: Complete Response
Primary Efficacy Results: Complete Response Patients Receiving Moderately Emetogenic Chemotherapy 100.0 90.0 75.0 76.9 80.0 70.0 57.2 58.5 60.0 50.0 Acute 40.0 30.0 APF530 10mg Delayed 20.0 10.0 0.0 -15 -10 -5 0 5 10 15 Acute Delayed Difference in Complete Response APF530-Aloxi (97.5% CI) January 20
Slide 11: Primary Efficacy Results: Complete Response
Primary Efficacy Results: Complete Response Patients Receiving Highly Emetogenic Chemotherapy Acute APF530 10mg Delayed -15 -10 -5 0 5 10 15 Acute Delayed Difference in Complete Response APF530-Aloxi (98.33% CI) January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 11
Slide 12: Safety Summary
Safety Summary Reported in Cycle 1 APF530 10 mg Aloxi 0.25 mg N % N % 1 Drug Related Serious Adverse Events 0 0 0 0 Discontinued Due to Adverse Event 1 1 0.2 0 0 Frequent Adverse Events Gastrointestinal Disorders Constipation 72 15.4 62 13.4 Diarrhea 44 9.4 39 8.4 Abdominal pain 13 2.8 28 6.0 Nervou
Slide 13: Efficacy through Multiple Chemotherapy Cycles
Efficacy through Multiple Chemotherapy Cycles Overall Complete Response Rates1 for APF530 10 mg Moderately Emetogenic Highly Emetogenic Chemotherapy Chemotherapy 100 100 90 90 82.1 80 80 76.9 73.7 70 70 61.7 62.0 63.3 58.8 60 60 53.8 50 50 40 40 30 30 20 20 10 10 0 0 Cycle 1 Cycle 2 Cycle 3 Cycle 4
Slide 14: Overall Complete Response Rates
1 Overall Complete Response Rates First Generation 5-HT3 Antagonists MEC HEC Ondansetron Ondansetron Granisetron Emend Gralla Eisenberg Aapro Emend Label Studies Saito Label 50% 34% 25% 43% 52% 43% 33% 40% Aloxi – Second Generation MEC HEC Eisenberg Gralla Grunberg Hajdenberg APPA Ph 3 Aapro APPA Ph
Slide 15: APF530's Efficacy with Difficult Chemo Regimens
APF530’s Efficacy with Difficult Chemo Regimens1 Treatment Chemotherapeutic Regimen APF530 10 mg Aloxi 0.25 mg Cyclophosphamide/Doxorubicin 70.7% 65.7% Acute Moderately All other regimens 84.4% 85.0% Emetogenic Cyclophosphamide/Doxorubicin 47.4% 46.3% Delayed All other regimens 72.9% 70.0% Cisplatin
Slide 16: Summary of APF530 Phase 3 Results
Summary of APF530 Phase 3 Results One of the largest, randomized, controlled clinical studies conducted in the CINV setting Bioerodible polymer technology releases granisetron to prevent CINV over 5 days Non-inferiority to Aloxi was demonstrated at 10 mg For both acute- and delayed-onset CINV With b
Slide 17: Regulatory Status
Regulatory Status January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 17
Slide 18: APF530 NDA Status
APF530 NDA Status Submitted NDA in May 2009 under 505(b)(2) filing pathway Received Complete Response Letter in March 2010 FDA raised issues in three main areas: Dosing system Two-syringe system Chemistry, Manufacturing, and Controls (CMC) Sterilization Characterization Clinical/statistical Specific
Slide 19: Addressed Complete Response Letter Issues
Addressed Complete Response Letter Issues Dosing System Change to single-syringe system Enhanced dosing instructions Successfully evaluated in a Human Factors study Chemistry, Manufacturing, and Controls Change from bulk to terminal irradiation Additional specifications and assays for raw materials,
Slide 20: Improved Dosing System
Improved Dosing System Original Two-syringe System New Single-syringe System January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 20
Slide 21: Thorough QT Study Background
Thorough QT Study Background The QT interval represents the amount of time the heart’s electrical system takes to repolarize after each beat Prolongation of the QT/QTc interval is associated with increased susceptibility to fatal cardiac tachyarrhythmias Thorough QT studies are intended to determine
Slide 22: Zofran Use in CINV Restricted
Zofran Use in CINV Restricted Most widely used generic 5-HT3 now restricted FDA issued a Drug Safety Communication June 29, 2012 “The use of a single 32 mg intravenous dose of ondansetron should be avoided. New information indicates that QT prolongation occurs in a dose-dependent manner, and specifi
Slide 23: Anzemet in CINV Previously Removed
Anzemet in CINV Previously Removed FDA issued a Drug Safety Communication Dec. 17, 2010 “Anzemet causes a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram (ECG) …” “Anzemet injection should no longer be used to prevent nausea and vomiting associated with initial a
Slide 24: APF530 Thorough QT Study Design
APF530 Thorough QT Study Design Double-blind, single-site Four-way crossover 56 healthy male and female subjects Study Arms SC APF530 1 g (granisetron 20 mg) – 2x therapeutic dose IV Granisetron 50 µg/kg over 3 minutes – 5x therapeutic dose Oral Moxifloxacin 400 mg (Avelox®) – positive control Place
Slide 25: APF530 Thorough QT Study Results
APF530 Thorough QT Study Results Primary Endpoint Achieved in Both Granisetron Dose Groups Both APF530 and IV granisetron dose groups did not approach or exceed the upperbound of 10 ms at any time point The primary end point was met irrespective of heart-rate correction methodology – QTcF, QTcI, QTc
Slide 26: Granisetron Thorough QT PK/PD Results
Granisetron Thorough QT PK/PD Results ddQTcF vs. Granisetron Plasma Concentration Slope = -0.019 60 50 40 30 20 10 0 -10 -20 -30 -40 ddQTcF vs PlCon LME Regression Line -50 90% Upper Confidence Interval 90% Lower Confidence Interval -60 Corr = 0.02 (p>0.32) 0 20 40 60 80 100 Plasma Concentration (ng
Slide 27: Metabolism/Fate of Polymer Study
Metabolism/Fate of Polymer Study FDA requested study at end-of-review meeting in 1Q 2011 Purpose of study is to demonstrate fate of polymer in human subjects Confirm polymer breaks down into same hydrolytic end-products as seen in animals Confirm lack of other detectable polymer-related metabolites
Slide 28: Human Factors Study
Human Factors Study Assess the Instructions-for-Use and usability of APF530 in simulated oncology setting Follows June 2011 FDA guidance: “Applying Human Factors and Usability Engineering to Optimize Medical Device Design” Initial risk assessment followed by iterative process of formative studies Va
Slide 29: Commercial Opportunity
Commercial Opportunity January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 29
Slide 30: Continuing Unmet Need in CINV
Continuing Unmet Need in CINV NCI Statement On The Existing Need for long-acting antiemetic 1 therapies Unmet Need in CINV Delayed CINV (days 2-5) remains particularly challenging to manage “Despite the use of both first-generation Significant portion of patients fail to and second-generation 5-HT 3
Slide 31: Addressing Debilitating Effects of CINV
Addressing Debilitating Effects of CINV More than 7 million cycles of chemotherapy administered each year ~27% are highly emetogenic ~46% are moderately emetogenic Most chemotherapy patients will undergo 4-15 cycles of chemotherapy 5-HT3 antagonists are standard- of- care for CINV Recommended in ASC
Slide 32: 5-HT3 Antagonists Have Made a Substantial Impact
5-HT3 Antagonists Have Made a Substantial Impact FDA withdrawal of Anzemet and 32 mg dose of ondansetron (Zofran) due to QT prolongation risk Approval of first NK-1 antagonist 2011 Approval of second-generation 5-HT3 antagonist (long-acting) 2006 Introduction of first-generation 5-HT3 antagonists (s
Slide 33: U.S. CINV Market Dynamics
U.S. CINV Market Dynamics Injectable Drugs for the Prevention of CINV Number of Package Units Sold by Quarter 800,000 700,000 600,000 ~40% drop following FDA 32 mg dose warning 500,000 ~35% drop and rebound 400,000 in 6-month period 300,000 ~85% drop following tQT FDA Safety Letter 200,000 100,000 0
Slide 34: Aloxi Market Performance
Aloxi Market Performance Aloxi Sales 450 Pricing Average Selling Price = $175 400 Zofran went Medicare Reimbursement = $186 350 generic Wholesale Acquisition Cost ~ $380 300 250 Orange Book Patent Exclusivity 200 One patent expires April 2015 150 Three patents expire January 2024 100 50 0 2004 2005
Slide 35: ~80% of Aloxi Is Used in Clinics
~80% of Aloxi Is Used in Clinics th U.S. Aloxi Units by Class of Trade – 12 Months Ending June 30 2012 Clinics 2.2 million units Hospital 0.5 million units Other 0.1 million units 0 1 2 3 IMS Health and Source Healthcare Analytics (WKH) data and Eisai Co., Ltd. published sales figures January 2013 ©
Slide 36: >90% of Aloxi Units Contracted Through GPOs
>90% of Aloxi Units Contracted Through GPOs th Clinic Units by GPO – 12 Months Ending June 30 2012 USO Onmark ION Misc 8% 21% 48% 23% 2.2 Million Clinic Units IMS Health and Source Healthcare Analytics (WKH) data and Eisai Co., Ltd. published sales figures January 2013 © 2013. A.P. Pharma, Inc. All
Slide 37: Aloxi Clinical Use Is Largely Concentrated
Aloxi Clinical Use Is Largely Concentrated 2,200 80% of units (1.7M) comes from 39% of accounts (904) 2,000 50% of units (1.1M) comes from 15% of accounts (362) 1,800 1,600 1,400 1,200 1,000 800 600 400 200 0 32 87 161 252 362 500 674 904 1246 2305 1% accts 4% accts 7% accts 11% accts 15% accts 22%
Slide 38: No New Injectable 5-HT3 Drug on Horizon
No New Injectable 5-HT3 Drug on Horizon APF530 FDA PDUFA Date FDC P3 Oral FDC Oral Data Expected Q1 2013 FDA Approval 1H 2014 2012 2013 2014 2015 Rolapitant IV Rolapitant IV FDA Approval Study Data 1H 2014 Expected 2H 2015 Rolapitant Oral Rolapitant P3 FDA Approval Oral Data Expected 2H 2013 Expecte
Slide 39: APF530 Proposed Label
APF530 Proposed Label Proposed indication submitted in NDA INDICATIONS AND USAGE 1.1 Chemotherapy-Induced Nausea and Vomiting APF530 is indicated for: • Moderately emetogenic cancer chemotherapy (MEC)- prevention of acute and delayed nausea and vomiting associated with initial and repeat courses • H
Slide 40: APF530 Planned Market Positioning
APF530 Planned Market Positioning If approved by FDA, APF530 and Aloxi would be the only “long acting” 5-HT3 antagonists approved for the prevention of acute and delayed-onset CINV Acute Onset Delayed Onset (0-24 Hours) (24-120 Hours) Moderately Highly Moderately Highly Emetogenic Emetogenic Emetoge
Slide 41: APF530 and Aloxi Profiles
APF530 and Aloxi Profiles Attribute APF530 Aloxi MEC – acute and delayed CINV MEC – acute and delayed CINV Indication HEC – acute CINV HEC – acute CINV MOA 5-HT3 receptor antagonist 5-HT3 receptor antagonist Dosing SC injection once per cycle IV once per cycle Long acting Bioerodible polymer technol
Slide 42: Summary
Summary $900 million market potential for injectable 5-HT3 antagonists* APF530 demonstrated non-inferiority to the market share leader Aloxi APF530 product profile 5-day release PK profile Good response in difficult chemotherapy regimens Efficacy through multiple cycles of chemotherapy Clean QT resu
Slide 43: A.P. Pharma Product Lifecycle Considerations
A.P. Pharma Product Lifecycle Considerations APF530 covered by multiple patents 2 patents covering combination of polymer, excipients and drug expire in 2021 3 patents covering APF530 expire in 2024 Polymer-based injectable products are difficult to copy independent of IP ANDA FDA requirements for i
Slide 44: Financial Summary
Financial Summary Expect cash sufficient to fund commercial launch of APF530 Summary Statement of Operations Year Ended Nine Months Ended (In thousands, except per share data) December 31, 2011 September 30, 2012 Revenue $ 646 $ – Operating expenses 11,708 15,203 Other income (expenses) (752) (408)
Slide 45: A.P. Pharma Highlights
A.P. Pharma Highlights Lead product candidate, APF530, is long-acting, injectable product for chemotherapy-induced nausea and vomiting (CINV) Incorporates widely used 5-HT3 antagonist - granisetron (Kytril) 5-day delivery profile Reduces both acute- and delayed-onset CINV with single injection Paten
Slide 46: Thank You
Thank You A.P. Pharma, Inc. OTCBB: APPA January 2013 January 2013 © 2013. A.P. Pharma, Inc. All rights reserved. 46