Company Update. November 2015

Transcription

1 Company Update November 2015

2 Legal Disclaimer This presentation contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of These forward-looking statements involve risks and uncertainties, including uncertainties associated with the development, regulatory approval, manufacture, launch and acceptance of new products, completion of clinical studies and the results thereof, the ability to establish strategic alliances and execute on business alliances or initiatives, progress in research and development programs, intellectual property, thirdparty relationships, regulatory oversight and developments, potential market acceptance of new products, financial results and other risks and uncertainties identified in the Company's filings with the Securities and Exchange Commission. None of the Company s product candidates discussed in this presentation have been approved by the FDA or any other regulatory agency. Actual results may differ materially from the results anticipated in our forwardlooking statements. We caution investors that forward-looking statements reflect our analysis only on their stated date. We do not intend to update them except as required by law. 2

3 Status of Development Programs Preclinical Phase 1 Phase 2 Phase 3 NDA SUSTOL (APF530) Acute and Delayed CINV after MEC and HEC HTX-019 Intravenous NK 1 for CINV 505(b)(2) registration pathway should lead to NDA filing 2H2016 HTX-011 Bupivacaine + meloxicam for post-operative pain Will be evaluated multiple indications HTX Day Buprenorphine for chronic pain and addiction 3

4 4 CINV FRANCHISE

5 CINV Highlights SUSTOL (granisetron) Injection, extended release, is a long-acting, injectable product for the prevention of chemotherapy-induced nausea and vomiting (CINV) 1,341-patient, randomized, controlled, Phase 3 study demonstrated activity in acute and delayed CINV after moderately emetogenic chemotherapy (MEC), and acute CINV after highly emetogenic chemotherapy (HEC) MAGIC: Complete Response in delayed nausea and vomiting in patients receiving HEC was significantly greater with the SUSTOL-based, three-drug regimen compared to standard-of-care. Significantly more patients had no nausea or infrequent nausea with SUSTOL and SUSTOL patients reported a significantly greater satisfaction with therapy NDA resubmitted to FDA July 17, PDUFA goal date January 17, 2016 HTX-019 is a proprietary intravenous (IV) formulation of aprepitant, an NK 1 receptor antagonist and is distinguished from the only IV NK 1 receptor antagonist presently approved in the U.S. in that it does not contain polysorbate 80, which may cause infusion site reactions, hypersensitivity or other adverse reactions in some patients. Rapid development utilizing the 505(b)(2) registration pathway is anticipated to achieve NDA submission in 2H2016 5

6 Aloxi 0.25 mg APF mg Aloxi 0.25 mg APF mg Aloxi 0.25 mg APF mg Aloxi 0.25 mg APF mg Complete Response Rates (%) Complete Response Rates (%) FDA-Requested ASCO 2011 Reanalysis Improves Difference Between SUSTOL and Aloxi in HEC Patients Protocol Specified HEC Population ASCO 2011 Guideline HEC Population Acute Delayed Acute Delayed 6

7 A Delayed-HEC Indication Would Provide Clear Differentiation in an Important Segment of the CINV Market Distribution of Aloxi Sales 1 HEC regimens account for ~20% (500K) of Aloxi (palonosetron) administrations LEC Minimal HEC This is the same segment of the CINV market where NK 1 receptor antagonists are extensively used MEC 1 IntrinsiQ data from July 2012 June

8 MAGIC Study Design The First Three-Drug Regimen Versus Three-Drug Regimen Efficacy Study 942 patients received HEC* randomized 1:1 Standard-of-Care Ondansetron 0.15 mg/kg IV (up to 16 mg IV) d1 + fosaprepitant 150 mg IV d1 + dexamethasone 12 mg IV d1 & 8 mg PO QD d2 + 8 mg PO BID d3-4 + placebo SC d1 SUSTOL (granisetron injection, extended release) SC d1 + fosaprepitant 150 mg IV d1 + dexamethasone 12 mg IV d1 & 8 mg PO QD d2 + 8 mg PO BID d3-4 + placebo IV d1 Prospectively Defined Primary Endpoint: Complete Response in the Delayed Phase 8 *HEC agents as defined in the 2011 ASCO CINV guidelines

9 Complete Response Rate MAGIC Primary Analysis: SUSTOL Regimen Statistically Superior to Standard-of-Care Delayed (24 to 120 Hours) Nausea and Vomiting after HEC 80% 70% 60% 50% 40% 30% 20% 10% 0% 14% Relative Improvement p = % 56.6% SUSTOL Regimen Standard-of-Care 9 Complete Response defined as no emesis episodes and no rescue medications

10 MAGIC Safety Summary No clinically significant differences between arms on safety No significant differences in SAEs No significant differences in discontinuations, or discontinuations due to adverse events Consistent with previous trials, injection site reactions were relatively common, but generally mild and usually resolved prior to the next cycle of chemotherapy Not an impediment to treatment as evidenced by the significant improvement in patient satisfaction with SUSTOL therapy, with over 80% of patients either very satisfied or satisfied with SUSTOL treatment 10

11 SUSTOL Has the Potential to be the Next Generation 5-HT 3 Receptor Antagonist 5-HT 3 RAs 1 st generation 2 nd generation 3 rd generation Products ondansetron granisetron palonosetron SUSTOL Duration of action Short acting ~ 8 hr half-life Longer acting ~40 hr half-life Long acting PK profile 5-7 days Indications Prevention of CINV in emetogenic chemo including high-dose cisplatin MEC acute & delayed CINV HEC acute CINV MEC acute & delayed CINV HEC acute & delayed CINV* *Obtaining an indication for delayed nausea and vomiting after HEC will be based on FDA s assessment of MAGIC trial results 11

12 Conclusion SUSTOL, as part of a three-drug regimen, is the first 5-HT 3 antagonist to demonstrate superiority to a standard-of-care, three-drug regimen in delayed nausea and vomiting in patients receiving HEC NDA resubmitted to FDA July 17, 2015 PDUFA goal date January 17,

13 HTX-019 Potential Tolerability Benefit Fosaprepitant is currently the only injectable NK 1 RA approved in the U.S. Fosaprepitant contains polysorbate 80, which may cause: Hypersensitivity reactions, including flushing, itching or shortness of breath, and has the potential to cause severe anaphylaxis reactions Infusion site reactions, including infusion site pain, erythema, swelling, superficial thrombosis, infusion site hives, and phlebitis/thrombophlebitis In review of cancer drugs containing polysorbate 80, hypersensitivity reactions linked to at least 23 deaths in spite of premedication HTX-019 does not contain polysorbate 80 and may have a lower incidence of certain adverse reactions than reported with fosaprepitant 13 Sources: Leal et al, Support Care Cancer, 22: , 2014; Norris et al, Community Oncology, 7: , 2010

14 Plasma Aprepitant Concentration (ng/ml) HTX-019 Demonstrated Bioequivalence to Fosaprepitant 10,000 HTX-019 Pharmacokinetics of Aprepitant in Rats 1,000 HTX-019 fosaprepitant Time (hours) 14

15 CINV FRANCHISE COMMERCIAL OPPORTUNITY 15

16 3.8 Million Penetrable Units ALOXI & EMEND Current Market Leaders 800,000 Injectable Drugs for the Prevention of CINV Number of Package Units Sold by Quarter 700, ,000 ALOXI 500, , ,000 EMEND 200, ,000 0 Q2'06 Q4'06 Q2'07 Q4'07 Q2'08 Q4'08 Q2'09 Q4'09 Q2'10 Q4'10 Q2'11 Q4'11 Q2'12 Q4'12 Q2'13 Q4'13 Q2'14 Q4'14 Q2'15 ALOXI ANZEMET KYTRIL granisetron ZOFRAN ondansetron EMEND Data is Package Units; ondansetron units reflect only 2 mg/ml and 32mg/50 ml sizes 16 Source: Symphony Health Solutions data, 2015

17 Oncologists Favorably View SUSTOL s Profile of Activity in Acute and Delayed CINV After Both MEC and HEC Attribute Favor IV Aloxi (1-2) No Preference (3) Favor SUSTOL (4-5) Avg. (N=66) Effective for prevention of delayed CINV in assoc. with HEC 6% 33% 61% 3.65 Is long-acting, with an extended PK profile 6% 38% 56% 3.62 Provides consistently durable efficacy for over 5 full days 3% 47% 50% 3.53 Effective for prevention of delayed CINV in assoc. with MEC 8% 41% 52% 3.48 Has low rates of breakthrough CINV 8% 42% 50% 3.47 Minimizes amount of rescue medication required 8% 42% 50% 3.44 Demonstrates sustained efficacy over multiple chemo cycles 5% 50% 45% 3.44 Effective for prevention of acute CINV in assoc. with HEC 6% 55% 39% 3.32 Well tolerated, with a low risk of side effects 8% 59% 33% 3.32 Effective for prevention of acute CINV in assoc. with MEC 11% 52% 38% MD PMR Q29: Please rate the extent to which you favor SUSTOL versus IV Aloxi (palonosetron) on each of the following attributes using a 5- point scale, where 1= Strongly favor IV Aloxi (palonosetron) over SUSTOL and 5 = Strongly favor SUSTOL over IV Aloxi (palonosetron) [SS]

18 Palonosetron Administrations (Annual) HEC Regimens Represent a Significant Market Opportunity for SUSTOL and HTX-019 HEC Regimens Account For ~20% (500K) of Palonosetron Administrations Of All HEC Administrations, ~20% Are Given Without Concomitant IV 5-HT 3 Inconsistent With Clinical Guidelines 1,600,000 1,463,558 1,200,000 1,400,000 1,200,000 1,000,000 1,000, , ,988 Untreated with IV 5HT3 800, , , , , , , , , , , ,256 Treated with generic IV 5HT3 Treated with Aloxi - HEC MEC LEC Minimal - Annual HEC administrations 18 Source: IntrinsiQ data from July 2012 June 2013

19 19 POST-OPERATIVE PAIN PROGRAM

20 Percentage of Maximal Force (60 gm) Tolerated by Animal Biochronomer Bupivacaine Superior to EXPAREL at Hours Pig Post-Operative Pain Model Saline Control (1) Biochronomer Bupivacaine (1) Exparel (2) HOURS 1. Study #1; All studies used the post-operative pain model in pigs from Castle et al, 2013 EPJ 2. Study #2 used the human dose of EXPAREL with 40% smaller incision 20 (n=4 pigs)

21 Local Anesthetics Exist in a Balance Between Water-Soluble and Lipid-Soluble Forms Acidic Environment Shifts the Balance to Ionized Form Unable to Penetrate Nerve Cell Membrane BUPH + BUPN + H + Nerve Cell Membrane BUPH + BUPN + H + The acidic environment associated with inflammation shifts the balance further to the left, resulting in far less drug penetrating the nerve membrane and reduced anesthetic effects. With a pka of 8.1, bupivacaine is very sensitive to reduced ph 21 Local anesthetic nerve penetration model adapted from Becker and Reed, Anesth Prog 53:

22 Percentage of Maximal Force (60 gm) Tolerated by Animal HTX-011 Significantly Superior to EXPAREL at Hours Pig Post-Operative Pain Model Saline Control (1) Biochronomer Bupivacaine (1) HTX-011 (2) Exparel (2) HOURS 1. Study #1; All studies used the post-operative pain model in pigs from Castle et al, 2013 EPJ 2. Study #2 compared <½ expected human dose of Biochronomer bupivacaine/meloxicam formulation to the human dose of EXPAREL (40% smaller incision used with EXPAREL) 22 (n=4 pigs)

23 A Randomized, Placebo- Controlled, Double-Blind, Phase 2 Study of HTX-011 in the Management of Post-Operative Pain in 64 Patients Undergoing Bunionectomy 23

24 HTX-011 Phase 2 Bunionectomy Study Screening Subjects requiring bunionectomy Treatment (96-hour evaluation) Part A - HTX mg bupivacaine (n=20) Placebo - All subjects pooled for endpoint analysis Part A (n=10), Part B (n=10) Part B - HTX mg bupivacaine (n=20) Primary Endpoint SPI 0-24 hrs Secondary Endpoints SPI 0-48 & hrs SPI 0-72 & hrs SPI 0-96 & hrs % of patients pain free Time to first use of opiate rescue medications % of patients who received no opiate rescue medication through 72 hrs SPI = Summed Pain Intensity score Efficacy assessments: Pain intensity scores (NPRS) using 0-10 point scale at 1, 2, 4, 6, 8, 10, 12, 14, 18, 24, 30, 36, 42, 48, 54, 60, 72, 78, 84, and 96 hours after administration of study medication Patient s global assessment of pain control at 24, 48, 72, and 96 hours after administration of study medication Percent of patients who are pain free, use of rescue medication, and nausea assessments (NNRS) at 6, 24, 48 and 72 hours after administration of study medication 24

25 Mean Pain Intensity Score* Pain Intensity Difference at 200 mg HTX mg Placebo SPID %, p= Hours 25 *Standard LOCF method used to account for use of rescue medications from Golf et al, Adv Ther, 28(9): , 2011

26 Mean Pain Intensity Score* Pain Intensity Difference at 400 mg SPID %, p= HTX mg Placebo SPID %, p< SPID %, p< SPID %, p= Hours *Standard LOCF method used to account for use of rescue medications from Golf et al, Adv Ther, 28(9): , 2011

27 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 mg SPID 0 24 hours hours hours (-69%) p< (-52%) p< (-40%) p=

28 Percent of Patients Pain Free (PI 1) Percent of Patients Pain Free HTX mg Placebo p< Hours 28

29 Mean Time to First Use of Opiate Rescue Medication 488% longer time to first use of rescue medications with 400 mg dose compared to placebo Placebo 8.2 hours HTX mg 20.8 hours p=0.15 HTX mg 48.2 hours p< Cross-study comparison: Mean time with Exparel was 7.2 hours versus 4.3 hours on placebo Source: Golf et al, Adv Ther, 28(9): ,

30 Percent of Patients Who Received No Opiate Rescue Medication Percent of Patients Who Received No Opiate Rescue Medication HTX mg Placebo An additional 20% of HTX-011 patients took only a single pill of oxycodone p< % Hours 5% 30

31 Mean Pain Intensity Scores Pain Intensity NOT Adjusted for Opiate Use: HTX-011 Significantly Better Than Unlimited Opiates* HTX mg Placebo SPID 0-24 p< SPID 0-48 p= SPID 0-72 p= Hours *Patients were permitted to take 5 mg oxycodone every 2 hours as needed for pain; data not adjusted for opiate use

32 Preliminary Safety HTX-011 was generally well tolerated The most commonly reported adverse events were: headache, nausea, vomiting, constipation, erythema, cellulitis, dizziness, and hypoxia, none of which were considered drug-related 32

33 Mean Pain Intensity Scores* Pain Intensity: HTX-011b 200 mg vs. HTX mg HTX-011b 200 mg (n=5) HTX mg (n=22) Hours *Not adjusted for use of rescue medications

34 Phase 2 Bunionectomy Study Summary Phase 2 results establish proof-of-concept, demonstrate unprecedented level of efficacy for a local anesthetic in the management of post-operative pain Major reduction in pain intensity with true opiate-sparing activity Although HTX-011 cannot be diluted with water/saline, we do have the ability to increase volume during manufacturing HTX-011b results demonstrate enhanced profile with the ability to cover surgical procedures requiring volumes of 5-20 ml, which are the majority of soft tissue, orthopedic and nerve block procedures 34

35 HTX-011 Phase 2 Hernia Repair Study Expanded Target Enrollment Screening Subjects requiring hernia surgery Treatment (96 hour evaluation) A) 200 mg of HTX by injection into the surgical wound (n=15 subjects) B) 400 mg of HTX by injection into the surgical wound (n=15 subjects) C) 200 mg of HTX by administration into the surgical wound (n=15 subjects) D) 400 mg of HTX by administration into the surgical wound (n=15 subjects) E) 200 mg of HTX by injection into the surgical wound and 200 mg of HTX by administration into the surgical wound (n=15 subjects) F) saline solution by injection into the surgical wound (n=15 subjects) Primary Endpoint SPI 0-24 hrs Secondary Endpoints SPI 0-48 & hrs SPI 0-72 & hrs SPI 0-96 & hrs First use of rescue medications Amount of opiate used % of pts pain-free PK for bupivacaine and meloxicam Powered for 90% probability of observing a significant difference 35

36 Financial Summary $128.2M raised June 2015 (net proceeds) Summary Statement of Operations (In thousands, except per share data) Nine Months Ended September 30, 2015 Revenue $ Operating expenses 65,865 Other income (expenses) (484) Net loss $ (66,349) Net loss per share 1 $ (2.07) Condensed Balance Sheet Data (In thousands) September 30, 2015 Cash and cash equivalents $ 152,989 Total assets $ 158,151 Total stockholders equity $ 141, Based on 32.1 million weighted average common shares outstanding for the period ended September 30, 2015