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1 Corporate Update January 7, 2019

2 ties that could cause our the anticipated commercial launch of HTX-011; r the EMA accepts the HTX-011 MAA as ocess for HTX-011; whether the FDA will require law. y on their stated date, and we take no obligation to isks and uncertainties include, but are not limited re based on management’s expectations and chievements to differ significantly from those ned by the Private Securities Litigation Reform Act sults of the studies in the HTX-034 development bstantial risks and uncertain mpany's filings with the Securities and Exchange e for the CINV franchise; whether the FDA approves the potential market opportunity for HTX-011; the timing and re to, those associated with: the full-year 2019 net sales guidanc an advisory committee meeting for HTX-011 in the future; whethe expressed or implied by the forward-looking statements. These r submitted; whether the European Commission authorizes the MAA; clinical development programs, future results, performance or a the HTX-011 NDA as submitted; the timing of the FDA’s review pr update or revise these statements except as may be required by program; and other risks and uncertainties identified in the Co Commission. Forward-looking statements reflect our analysis onl This presentation contains "forward-looking statements" as defi Forward-Looking Statements of 1995. We caution investors that forward-looking statements a assumptions as of the date of this presentation, and involve su 2

3 iated , in combination with other APPROVED APPROVED ) including high-dose cisplatin and nausea and (aprepitant) injectable emulsion ® r the prevention of acute and delayed nausea and vomiting assoc NDA NDA products for patients CINVANTI EU MAA filling by Centralized Procedure in 1H2019 NDA accepted for Priority Review; PDUFA 30 Apr 2019 Fast Track and Breakthrough Therapy designations granted    ogenic cancer chemotherapy (HEC tudied for treatment of established nausea and vomiting. tion chemotherapy regimens. nd repeat courses of highly emet US FDA Approved for CINV Prevention* US FDA Approved for CINV Prevention* t approved by the FDA or other regulatory authority CLINICAL CLINICAL is indicated in combination with other antiemetics in adults fo in validated pig model of postoperative pain Produces complete elimination of pain for 7 days Pain via Local Application  and cyclophosphamide (AC) combina Under Investigation for Postoperative herapy (MEC) or anthracycline (granisetron) extended-release injection ly emetogenic cancer chemotherapy (MEC). CINVANTI has not been s PRECLINICAL PRECLINICAL ® acute and delayed nausea and vomiting associated with initial a Postoperative SUSTOL Under Investigation for Pain via Local Application ® ® Chemotherapy-induced nausea and vomiting. HTX-011 and HTX-034 are an investigational new drugs and are no with initial and repeat courses of moderately emetogenic chemot antiemetic agents, is indicated in adults for the prevention of vomiting associated with initial and repeat courses of moderate CINV: HTX-034 * extended-release injection HTX-011 (granisetron) injectable emulsion SUSTOL (aprepitant) CINVANTI suffering from cancer or postoperative pain: We are currently developing and commercializing pharmaceutical Heron Pipeline PAIN MANAGEMENT CINV* 3

4 ate rity review if in safety or ons valuation of such applications effectiveness of the treatment or prevention of serious conditi supported by clinical data at time of NDA submission – intended to direct overall attention and resources of FDA to e – for drugs that, if approved, would be significant improvements – Fast Track and Breakthrough Therapy products eligible for prio Breakthrough Therapy designation in 2Q 2018 of April 30, 2019 • HTX-011 received Fast Track designation in 4Q 2017 and • Priority Review designation • FDA granted Priority Review to HTX-011 NDA with a PDUFA goal d HTX-011 NDA for Postoperative Pain Management Has Received Priority Review 4

5 Postoperative Pain and its Impact on the Opioid Crisis

6 3 and pain— of the Opioid Crisis. Bates, et al. 2011. 6. Canfield, Marta C., et al. 2010. erdose: U.S. Prescribing Rates Map. 7. 1,3,8 ~500,000 . . 2015;49(3):409-413. users, approximately Am J Prev Med will become addicted to opioids. More than Of these 2.6 million persistent opioid $13 billion management Banta-Green, et al (2009). Opioid use behaviors, mental health to postoperative pain 3. costs associated with The Council of Economic Advisers, 2017. The Underestimated Cost 1 of the annual healthcare 8. . 185 (2): 551 -55. doi:10.1016/j.juro. 2010.09.088. addiction can be attributed ecialty, U.S., 2007-2012.” 265 (4): 709 -714. CDC 2017: Centers for Disease Control and Prevention. Opioid Ov 4. 1 152 (6): e170504. doi:10.1001/jamasurg.2017.0504. g The Journal of Urology .021. 7 Annals of Surgery JAMA Surgery ures.” 6.5% ological Practice.” As many as opioid users. 4,5 That equals about of patients who take 4 (2): 108 -13. doi:10.1097/ADM.0b013e3181b5a713. opioids to manage pain of all opioid addicts 2.9 MILLION PEOPLE after surgery may become persistent through leftover pills. Levy et al. “Trends in Opioid Analgesic-Prescribing Rates by Sp 5. Consumption and Disposal in Ur report first opioid exposure 32% 2 Journal of Addiction Medicine 6 104(1-2), 34-42. _https://-doi.org/10.1016/j.drugalcdep.2009.03 r Minor and Major Surgical Procedures in US Adults.” 1 pioid Dependence:” html. Accessed 8 March 2018. sage of Opioid Prescriptions for Common General Surgical Proced rative Pain Medication Delivery, of these pills surgical patients result in more than 1 billion unused pills. Drug and Alcohol Dependence 90% unsecured locations. 90% remain inside the home in rugoverdose/maps/rxrate-maps. 2 In addition, opioid discharge prescriptions filled by recoverin in the United States. surgical procedures happen www.cdc.gov/d of all these Brummett, Chad M., et al. 2017. “New Persistent Opioid Use Afte go unused. MORE THAN 50 MILLION opioid tablets of patients undergoing a surgical procedure are prescribed opioids for pain management. 70% Hill, Maureen V., et al. 2017. “Wide Variation and Excessive Do “Prescription Opioid Use Among Patients Seeking Treatment for O “Overprescription of Postoperative Narcotics: A Look at Postope Available at https:// Development of a typology of chronic pain patients. 2. References: 1. How Postoperative Opioids Can Be a Doorway to Addiction The Cost of Opioids 6

7 ain regimen, our goal s unnecessary in the f patients ids but should be used as n as close to 100% of a last resort, rather than the first step in pain management experiencing more pain is to: outpatient setting patients as possible, making discharge prescriptions for opioid – Provide better pain control than conventional reliance on opio – Eliminate the need for opioids to control postoperative pain i 2. Reduction in the use of opioids should not come at the cost o 1. Opioids play an important role for reduction of severe pain, 3. Using our technology as part of a multi-modal postoperative p Heron’s Goals For Postoperative Pain Program • Our philosophy is that: 7

8 HTX-011 Mechanism of Action

9 far 1:26–39 2002 Endodontic Topics cell membrane environment bupivacaine is able to penetrate the nerve Inflammation produces an acidic With a one pH unit drop, 10-fold less 53:98–109 2006 Anesth Prog and Reed. ntics: Mechanisms and Management , 1,2 Local Anesthetics Exist in a Balance Between Water- and Lipid-Soluble Forms effects less drug penetrating the nerve membrane and reduced anesthetic With a pKa of 8.1, bupivacaine is sensitive to reduced pH The acidic environment associated with inflammation results in • • 1. Hargreaves, K, Keiser, K, Local anesthetic failure in endodo 2. Local anesthetic nerve penetration model adapted from Becker Inflammation, pH, and Local Anesthetic Failure A Potential Hypothesis: 9

10 st 72 72 1 (n=4 pigs in each arm) 48 e) 24 5 + Meloxicam with 3-day releas Hours 2 3 1 Saline Control HTX-011 (Biochronomer Bupivacaine Biochronomer ER Meloxicam Biochronomer ER Bupivacaine Liposomal Bupivacaine 0 ine with 40% smaller incision gs from Castle et al, 2013 EPJ 0.0 70.0 60.0 50.0 10.0 20.0 40.0 30.0 90.0 80.0 100.0 Tolerated Percentage of Maximal Force (60 gm) Postoperative pain model in pi Human dose of liposomal bupivaca 1 2 Increasing Analgesia Hours After Surgery as Demonstrated in this Preclinical Model HTX-011 is Designed to Produce Marked Analgesia Through the Fir 10

11 FDA p=0.0333 vs. HTX-002* p=0.0090 vs. HTX-009* p=0.0072 vs. HTX-009* p=0.0333 vs. HTX-002* s. HTX-002 or HTX-009 p=0.0208 vs. HTX-002* p=0.0005 vs. HTX-009* p=0.0592 vs. HTX-002* p<0.0042 vs. HTX-009* HTX-011 is an investigational new drug and not approved by the p=0.2041 vs. HTX-002* p<0.0001 vs. HTX-009* p=0.0154 vs. HTX-002* p<0.0035 vs. HTX-009* *p-value from ANOVA, LSMD of area under the curve for HTX-011 v HTX-011 Reduces Pain Better Than the Individual Components in Both Bunionectomy and Herniorrhaphy Phase 2 Studies 11

12 free syringe to directly ring Data on file. Reference: HTX-011 is Applied into the Surgical Site at the End of Surgery Without a Needle coat the affected tissue within the surgical site prior to sutu HTX-011 is a single-dose application administered via a needle- 12 12

13 Significant Opioid Use Reduction in FDA BPV Pain Reduction vs. Significant for        vs. PBO Significant for Pain Reduction Soft Soft Soft Soft hroplasty Type Bony Bony Bony Tissue HTX-011 is an investigational new drug and not approved by the TKA Breast Augmentation Herniorrhaphy Bunionectomy Bunionectomy Herniorrhaphy Abdominoplasty 2 2 3 2 3 2b 2b 211 202 209 208 203 302 301 Study Phase Surgical Model PBO = placebo; BPV = bupivacaine solution; TKA = total knee art Pain Reduction With HTX-011 Than Bupivacaine Included in NDA Seven Active-Controlled Studies Showing Significantly Better 13

14 (Study 301) HTX-011 Clinical Development EPOCH 1: Bunionectomy Results

15 FDA (Day 42) ) End of Study HCl 50 mg) 39 Days Outpatient Follow-up Period ived saline placebo Primary Endpoint 72 Hours HTX-011 is an investigational new drug and not approved by the vacaine HCl but rece HTX-011 60 mg (N=157) Bupivacaine HCl 50 mg (N=155) Saline Placebo 2.1 mL (N=100) Inpatient Period and Surgery Randomization 1018) was randomized to Bupi 412 Dosed 675 Screened 438 Randomized 438 subjects were randomized and 412 were dosed (ITT Population 13 sites in the United States N = 412 (3:2:3 to HTX-011 60 mg, saline placebo, or bupivacaine Screening Period • • • 1 subject (006- EPOCH 1 (Study 301) Bunionectomy: Study Design 15

16 FDA p < 0.0001 p = 0.0002 p = 0.0022 p < 0.0001 p = 0.0001 (Opioid-Free vs. PBO: p < 0.0001) BPV: bupivacaine HCl HTX-011 is an investigational new drug and not approved by the HTX-011 vs. BPV 0-72 PBO: saline placebo; HTX-011 vs. PBO 0-72 Primary: AUC Key Secondary: AUC st Key Secondary: Opioid-Free HTX-011 vs. BPV 1 rd 3 Key Secondary: Opioid Consumption HTX-011 vs. BPV Key Secondary: Opioid Consumption HTX-011 vs. PBO th nd 4 2 EPOCH 1 Bunionectomy: Results Hierarchy 16

17 Source: Figure 14.2.7 FDA HTX-011 is an investigational new drug and not approved by the wWOCF – window worst observation carried forward EPOCH 1 Bunionectomy: Mean Pain Intensity 17

18 75.5% 83.0% 53.5% p<0.0001 p<0.0001 Percent of Patients With Severe Pain at Any Time Through 72 hours Bupivacaine HTX-011 Saline Placebo FDA HTX-011 is an investigational new drug and not approved by the Key Secondary Endpoint EPOCH 1 Bunionectomy: Percentage of Subjects Who Are Opioid-Free Through 72 hours and Through Days 10 and 28 18

19 measured in (MME) equivalents morphine Opioid consumption is milligram FDA : HTX-011 Opioid-Free Subjects Have HTX-011 is an investigational new drug and not approved by the Bunionectomy the Lowest Rate of Opioid-Related Adverse Events (ORAEs) EPOCH 1 19 N for each bar:

20 FDA → Favors Active Favors Placebo ← HTX-011 is an investigational new drug and not approved by the EPOCH 1 Bunionectomy: Benefit – Risk for HTX-011 20

21 (Study 302) HTX-011 Clinical Development EPOCH 2: Herniorrhaphy Results

22 FDA (Day 28) ) End of Study HCl 75 mg) 25 Days Outpatient Follow-up Period ivacaine HCl Primary Endpoint 72 Hours HTX-011 is an investigational new drug and not approved by the HTX-011 300 mg (N=164) to HTX-011 but received Bup Bupivacaine HCl 75 mg (N=172) Saline Placebo 10.3 mL (N=82) Inpatient Period and Surgery Randomization 446 Randomized 418 Dosed 668 Screened 1 subject (005-2018) was randomized Screening Period N= 418 (2:1:2 to HTX-011 300 mg, saline placebo, or bupivacaine 446 subjects were randomized and 418 were dosed (ITT Population 17 sites in 2 countries (United States, Belgium) • • • EPOCH 2 (Study 302) Herniorrhaphy: Study Design 22

23 FDA p = 0.0240 p = 0.0004 p < 0.0001 p = 0.0486 p = 0.0001 (Opioid-Free vs. PBO: p < 0.0001) HTX-011 is an investigational new drug and not approved by the HTX-011 vs. BPV PBO: saline placebo; BPV: bupivacaine HCl 0-72 HTX-011 vs. PBO 0-72 Primary: AUC Key Secondary: AUC st Key Secondary: Opioid-Free HTX-011 vs. BPV 1 rd 3 Key Secondary: Opioid Consumption HTX-011 vs. PBO Key Secondary: Opioid Consumption HTX-011 vs. BPV th nd 4 2 EPOCH 2 Herniorrhaphy: Results Hierarchy 23

24 FDA HTX-011 is an investigational new drug and not approved by the Source: Figure 14.2.7 EPOCH 2 Herniorrhaphy: Mean Pain Intensity 24

25 60.5% 81.7% 48.8% p=0.0372 p<0.0001 hours Pain at Any Time Through 72 Percent of Patients With Severe Bupivacaine Saline Placebo HTX-011 FDA HTX-011 is an investigational new drug and not approved by the Key Secondary Endpoint EPOCH 2 Herniorrhaphy: Percentage of Subjects Who Are Opioid-Free Through Day 28 25

26 milligram (MME) Opioid consumption is measured in equivalents morphine FDA HTX-011 is an investigational new drug and not approved by the EPOCH 2 Herniorrhaphy: HTX-011 Opioid-Free Subjects Have the Lowest Rate of Opioid-Related Adverse Events (ORAEs) 26 N for each bar:

27 FDA → Favors Active Favors Placebo ← HTX-011 is an investigational new drug and not approved by the EPOCH 2 Herniorrhaphy: Benefit – Risk for HTX-011 27

28 (Study 209) (TKA) Study Phase 2b Total Knee Arthroplasty HTX-011 Clinical Development

29 FDA Pre-op Medication: acetaminophen (IV) 1 g, available Post-op Medication: only opioid rescue medication pregabalin (oral) 150 mg injected into posterior capsule Ropivacaine Administration Technique: 50 mg HTX-011 Administration Technique: needle-free instillation of 100 mg for posterior capsule & 300 mg for remaining tissue HTX-011 is an investigational new drug and not approved by the • • • • N = 56 N = 53 N = 55 N = 58 capsule Injection Injection Instillation Saline Placebo HTX-011 400 mg HTX-011 400 mg Bupivacaine 125 mg 50 mg injected to posterior Instillation, plus ropivacaine Study 209 Phase 2b: Total Knee Arthroplasty 29

30 FDA p < 0.0001 p = 0.0002 p < 0.0001 p = 0.0004 points for reduction in HTX-011 is an investigational new drug and not approved by the HTX-011 400 mg vs. Placebo HTX-011 400 mg vs. Placebo 0-72 0-48 HTX-011 400 mg+ Ropivacaine vs. Placebo HTX-011 400 mg + Ropivacaine vs. Placebo AUC AUC 0-72 0-48 AUC AUC HTX-011 via instillation achieved primary and key secondary end pain intensity scores at rest (NRS-R) Study 209 TKA: Results Hierarchy 30

31 FDA pain data HTX-011 is an investigational new drug and not approved by the ue medication and LOCF for missing wWOCF for use of opioid resc Study 209 TKA: Significant Separation between HTX-011 Arms and Placebo through 72 Hours (Primary Endpoint) 31

32 nd e medication Notes: Pain intensity collected at rest LOCF for missing data and no adjustment for use of opioid rescu Study 209 TKA: HTX-011 Significantly Superior to Both Placebo a Bupivacaine Through 72 Hours Without Adjusting for Opioid Use 32

33 milligram (MME) Opioid consumption is measured in equivalents morphine FDA HTX-011 is an investigational new drug and not approved by the Source: Figure 14.2.2.2 Study 209 TKA: HTX-011 Reduces Opioid Use through 72 Hours 33

34 ents each 0.077 0.010 0.243 0.068 0 - 24 FDA HTX-011 400 mg + Ropivacaine 0.022 0.001 0.348 0.055 0 - 12 HTX-011 400 mg proportion of subjects who first achieve an MPADSS score ≥9 at ease Compared to Placebo in Pati t test. Bupivacaine HCl HTX-011 is an investigational new drug and not approved by the 0.007 0.003 0.347 0.185 0 - 8 Saline Placebo 0% 40% 60% 20% 80% 100% timepoint was analyzed cumulatively. P-values from Fisher's exac Source: Table 14.2.13.2 *MPADSS, modified postanaesthetic discharge scoring system. The Achieving “Discharge Ready” MPADDS Criteria* with HTX-011 Study 209 TKA: Significant Incr P-value vs BPV: p-value vs PBO: 34

35 se 3 ents FDA HTX-011 is an investigational new drug and not approved by the HTX-011 was generally well tolerated across all Phase 2 and Pha • Overall adverse events • The incidence of serious adverse events • Premature discontinuations due to adverse events • Potential local anesthetic systemic toxicity (LAST) adverse ev studies with no clinically meaningful differences in: • Potential wound healing related adverse events • No deaths on HTX-011 (one on bupivacaine) Safety Summary 35

36 (Study 215) Herniorrhaphy Phase 2 Opioid Elimination Study in HTX-011 Clinical Development

37 √ 30 Cohort √√ √√ √√ 12 33 FDA HTX-011 is an investigational new drug and not approved by the Pilot study to evaluate use of HTX-011 with a standard + Postoperative acetaminophen q 6h + ibuprofen q6h + Intraoperative IV ketorolac Number of Subjects Dosed HTX-011 300 mg + Preoperative oral acetaminophen (APAP) Treatment Study Design: background multimodal regimen. Study Rationale: Study 215 Herniorrhaphy: Pilot Opioid Elimination Study 37

38 0 to 4 Mild Pain no added benefit and ibuprofen. ketorolac provided Addition of IV beyond oral acetaminophen FDA :Preop oral APAP + Intraoperative IV 1 : Ketorolac + Postop APAP + ibuprofen (N=30) Cohort 2 pain data HTX-011 is an investigational new drug and not approved by the ue medication and LOCF for missing : Preoperative oral APAP + Postop APAP + ibuprofen (N=33) Cohort 1 wWOCF for use of opioid resc Study 215 Herniorrhaphy: HTX-011 Plus Acetaminophen and Ibuprofen Kept Pain in the MiId Range Through 72 Hours 38

39 FDA HTX-011 is an investigational new drug and not approved by the Study 302 and Study 215 Herniorrhaphy: Proportion of Patients Opioid-Free 39

40 milligram (MME) Opioid consumption is measured in equivalents morphine FDA HTX-011 is an investigational new drug and not approved by the Study 302 and Study 215 Herniorrhaphy: Mean Consumption of Opioid Rescue Medication 40

41 from at erienced to the surgeon FDA ease outpatient opioids by >90% hould be given discharge opioids need a discharge prescription HTX-011 is an investigational new drug and not approved by the – 80% of patients would not – 5 pills of oxycodone would have been sufficient to avoid calls procedures/year in US would decr a pain score of 6 or more s the current estimate of approximately 30M pills/year • For discharge 2 hours post surgery, only patients who have exp Proposed Standardized Protocol for Outpatient • Scheduled acetaminophen and ibuprofen for 5 days; PRN after th • HTX-011 at the end of surgery • Use of this protocol in the approximately one million such Open Inguinal Hernia Repair Surgery 41

42 HTX-034 Development Next Generation Product for Postoperative Pain

43 pig model of HTX-009 with HTX-011, observations clinical predictive of pain has been postoperative HTX-002 and This validated 7 Day 6 Day HTX-034 (Cohort 2) 5 Day d by the FDA 4 Day HTX-034 (Cohort 1) 3 Day 2 Day HTX-011 5h 3h Day 1 HTX-011 & HTX-034 are investigational new drugs and not approve Liposomal Bupivacaine 1h -1 Day Saline Placebo 0.0 HTX-034 Produces Complete Elimination of Pain Through 7 Days in Pig Postoperative Pain Model 60.0 50.0 40.0 30.0 20.0 10.0 70.0 Withdrawal Force (g) 43

44 FDA HTX-011 is an investigational new drug and not approved by the The Commercialization of HTX-011 Advancing Pain Management 44

45 Successful hospital and pain Robust systems in place and pressure tested for blockbuster launch Proven compliant execution Safety monitoring structure in place 3PL in place* Strong KOL relationships GPO contracts in place* management launch experience IND/hospital/ASC expertise and relationships Reimbursement infrastructure in place Full Line Wholesaler agreements and EXISTING PLATFORM ADVANTAGES Liaisons Backbone Infrastructure Medical Science Our critical teams are already in place, and Regulatory Compliance Management Key Account Leadership Commercial Payer vigilance Pharmaco- Trade and GPO Distribution Established Platform With Experienced Teams in Place We are prepared for the launch of HTX-011. with extensive experience in successful hospital launches. 45 45

46 33% 67% Q4'18 (LE) 78% 22% Q3'18 CINVANTI 13% 87% Q2'18 Emend IV Total Market Share 7% 93% Q1'18 0% 80% 20% 40% 60% 100% 224 249 215 225 192 215 169 197 138 175 114 161 80 152 Hospitals/IDN 60 133 Clinics 42 108 26 82 CINVANTI Ordering Accounts Since Launch 11 41 0 18 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Commercial teams achieved rapid adoption of CINVANTI and captured one-third of the market in the first 12 months of launch 0 50 400 450 500 100 150 200 250 300 350 Source: Heron 867 data December 31 , 2018 46

47 (LE) 76% 24% 226 (est) Q4’18 Q4'18 (LE) 226 Q3’18 89% 11% Q3'18 211 Q2’18 3% 97% Q2'18 Hospital 194 Q1’18 0% Q1'18 100% ) (Jan 3, 2018) LE CINVANTI Launch (LE) ( 68% 32% 391 (est) Q4’18 Q4'18 Q4'17 100% Hospital (000s) NK1 Units 0% 80% 20% 40% 60% 391 78% 22% Q3’18 100% Q3'18 NK1 market flat to Q3’18 ) (LE) LE ( 55% 164 (est) 45% Q4’18 Q4'18 372 13% 87% Q2’18 Q2'18 Total 164 Q3’18 64% 36% Q3'18 334 7% 93% Q1’18 Q1'18 (Jan 3, 2018) CINVANTI Launch 158 Q2’18 nd IV Q Units. Q4’18 Cinvanti share calculated by keeping total 26% 74% Q2'18 Clinic data 100% Q4'17 139 Q1’18 15% 85% Q1'18 Total** (000s) NK1 Units 0% 80% 60% 40% 20% (Jan 3, 2018) 100% CINVANTI Launch Q4'17 100% NK1 Units Clinic (000s) execute across both clinic and hospital Commercial teams demonstrated the ability to 0% 60% 80% 20% 40% 100% CINVANTI EMEND IV Source(s): Heron 867 data. Heron DDD 5HT3, NK1 Data *Share calculation Q1’18 – Q3’18 = Cinvanti Q Units/Cinvanti + Eme ** Total includes units classified as “Other” Class of Trade in 47

48 Merck confidence CINVANTI 80-free NK1 RA affiliated hospitals Reduce / Eliminate Top 200 IDNs, 340B Community Oncology Selected GPOs / IDNs Risk community setting IDN driven pull through at First and only polysorbate Lower Acquisition Cost (-$40) 3- year pass through (C-Code) Leverage Community to create WAC 340B FOCUS PRODUCT SERVICES COMPETITION VALUE ADDED CONTRACTING DIFFERENTIATED REIMBURSEMENT IMPLEMENTATION KEY DRIVERS ACCELERATE SALES ASCs HTX-011 Surgical lines Top 200 IDNs Exparel, On-Q Broad Access Pricing Selected GPOs / IDNs Hospital driven / Multiple for access and confidence Reduce / Eliminate Risk with Ambulatory Surgical Centers 3-year pass through (C-Code) Leverage ASCs and Outpatient MOA, Superior efficacy vs. SOC Key CINVANTI Learnings to Support HTX-011 Launch 48 48

49 CREATE CHANGE DRIVE VALUE AND OPPORTUNITY TO THE LARGEST * 15% NB Only, NB: Nerve Block 85% Any Local, Local Anesthetic Route of Delivery ~15.5M procedures more of these reasons: Secondary Targets Other procedures requiring postoperative pain management but not amongst initial targets for one or • Lower volume per procedure • Non-core specialties • Relatively lower pain scores Local Anesthetics are used in ~70% of procedures * ~13.5M procedures • ~2.6M OB/GYN Initial Targets • ~5.9M Orthopedic 4 major specialties Higher volume procedures across • ~0.8M Plastic Surgery • ~4.2M General Surgery Non-opioid Solution The Market is Large and Waiting for an Effective Theoretical and Target Market ~29M Annual US Surgical Procedures Requiring Postoperative Pain Management 49 49

50 Exparel Bupivacaine NB Ropivacaine NB Others Lidocaine Bupivacaine 4% 4% 14% 15% 10% N = 22M Procedures 53% Local Anesthetic Volume Share CHANGE CREATE VALUE AND THE LARGEST OPPORTUNITY TO DRIVE NB, 15% DRG Foundational Insights Research Dec. 2016 NB: Nerve Block All Local, 85% Local Anesthetic Route of Delivery HTX-011 is focused on the largest market opportunity 50 50

51 56% physicians: 56% knee & hip arthroplasty, C-section, laparoscopic shares than prior market research, notably Raw preference share for HTX-011 from hysterectomy and spine procedures The top procedures where physicians expected to use HTX-011 were knee arthroplasty and hernia repair Several procedures saw higher raw preference Overall Wt. Average Preference Share • • • 67% 67% 67% 63% >1M Procedures in 2035 62% >500K Procedures in 2035 <500K Procedures in 2035 61% 61% 58% 57% 56% 56% 55% 55% 54% 53% 53% 53% 53% 52% 51% 50% 47% 37% 37% 37% 37% 36% - n = 290 physicians; *Less than 100K procedures at peak 20% C-Section Rhinoplasty (%, Raw) Gastrectomy Spinal Fusion Fracture - Hip Mammoplasty Fracture - Leg Fracture - Arm Fracture - Hand Fracture - Foot* Fracture - Ankle Hip Arthroplasty Abdominoplasty Fracture - Pelvis* Knee Arthroplasty Rotator Cuff Repair Hysterectomy - Open Hernia Repair - Open Carpal Tunnel Release Roux-en-Y Gastric Bypass DRG Postoperative Pain Quantitative Research (Nov 2018) Hysterectomy - Laparoscopic Hernia Repair - Laparoscopic Appendectomy - Laparoscopic Cholecystectomy - Laparoscopic Bunionectomy & Phalangectomy Reference: for HTX-011 across the covered procedures Physicians indicated a raw preference share of 56% Preference Share Colon & Small Bowel Resection - Open Laminectomy, Foraminotomy, Discectomy 51 51 Colon & Small Bowel Resection - Laparoscopic

52 er agents e includes a from 2017 for Exparel, oth atic survey & conjoint - Sampl Data from analysis of physician st are based on 2018 Physician Survey Current therapy based on Claims dat n = 330 physicians indicated a willingness to use HTX-011 in ~30% of physicians not using local anesthetics; physicians There is an additional opportunity to convert procedures where they are currently not using local anesthetics HTX-011 is likely to initially convert share from Exparel, as well as the rest of the local anesthetics (bupivacaine & other “caines”) • • share) 6% 36% 44% 14% preference Future Therapy (Applying HTX-011 -5% -6% -32% 11% 64% 25% Current Therapy (Actual) Adjusted Physician Preference Share Distribution HTX-011 Exparel Bupivacaine HCl Other "caines" generic combo, etc.) (e.g. lidocaine, ropivacaine, HTX-011 Enjoyed a Physician Preference Share of 44% 52 52

53 60% found across more valuable than at an equivalent price 60% 68% 71% 88% would grant access and for HTX-011 to be on formulary 68% of Pharmacy Directors 71% of physicians would advocate Aggregated preference share specialties and key surgeries was HTX-011’s profile Exparel ator 11% 14% 17% Weakness 11% oid-free ovel MOA 64% would use in all 87% 85% 81% 80% Neither a Strength Nor Weakness Strength from both physicians and pharmacy directors, search (Nov 2018) - n = 290 physicians; Novel MOA DRG Postoperative Pain Quantitative Re Reduction in severe pain More opioid-free patients endpoints supported by superior pain reduction, opioid reduction, and opi procedures they deemed appropriate 95% preferred bupivacaine (versus placebo) as the Phase 3 compar High preference shares across initial target procedures driven by key differentiators versus bupivacaine, including a n Highly favorable feedback Based on phase 3 and 2b procedures (bunion, hernia, TKA), 72-hour Analgesia Duration Reference: • • • • Customers Value HTX-011’s Superior Product Profile 53 53

54 s than 6% eyed consistently r access to nificant benefit over 20 injections, with no need for ncrease in opioid-free patients extensive training Simple route of administration eliminating the need for up to 1 Unique mechanism of action bupivacaine HCl Superior efficacy profile of HTX-011 through 72 hours, with sig Significant reduction in severe pain resulting in significant i is a small obstacle to HTX-011 uptake as its penetration is les ® • • • • prefer HTX-011 over Exparel for the following reasons: Across product attributes, surgeons and pharmacy directors surv Surveyed pharmacy directors state that they would provide bette HTX-011 than to Exparel DRG Pharmacy Director Surveys • • Reference: Being Second to Market is NOT a Significant Obstacle to Commercial Success Exparel 54 54

55 by and our standing order sets – Pharmacy Director encourage use of [HTX-011] patients contraindicated to Product X.” EMR system, so if we continued to carry We can “ Exparel, we would make it restricted to only or would be entirely removed from that if HTX-011 became available on segment of patients not using HTX-011 be stocked to accommodate a small their institution’s formulary, Exparel would be subject to greater restrictions consolidation, Exparel may continue to formulary making use of Most pharmacy directors indicate on formulary HTX-011 would displace Exparel • For institution’s with less formulary • Over 50% of pharmacy directors report ® Restrictions On Formula, Restrictions No Formulary, On Not on With Formulary ution? 12% 44% 44% 56% 22% 22% Formulary Status of Exparel vs. Expected HTX-011 Status o EXPAREL if Product X was approved on formulary at your instit HTX-011 (Predicted) EXPAREL (Stated) Exparel status would stay the same Exparel formulary status / purchasing would be made more restrictive Exparel would be removed 43% 25% 33% Exparel Formulary Status : DRG Pharmacy Director Survey (2018): Q27. What would happen t Impact of HTX-011 Launch on N = 40 Pharmacy Directors (DRG Survey, 2018) % of Pharmacy Directors Pharmacy Directors Prefer HTX-011 to Exparel Reference 55 55

56 Lower access barriers procedures Targeted high value Connected to top IDNs Targeted facilities ASP +6% 8% Ambulatory Surgical • account for 8% (1.1M procedures) • Centers (ASCs) • (1.1M procedures) • Ambulatory surgical centers • lends itself to with pharmacy, surgeons, 3-year pass through (C-Code) 340B opportunity High value IDN and procedure focus favorable reimbursement and access 47% of the opportunity 39% • Hospital Outpatient (5.3M procedures) • • 340B hospitals ~50% connected average cost 3 SKUs/lower payment Part of DRG Inpatient 52% • • top 200 IDNs (12.3M procedures) • (7M procedures) Hospitals account for 91%, including Hospital The remaining 1% of procedures are performed at private physician practices 13.5 PROCEDURES INITIAL TARGET MILLION Clearly differentiated strategy supported by building advocacy of Care HTX-011 has Strategic Advantages Across Each Setting and anesthesiologists 56 56

57 ement change rs provide eligible 40B drugs changed ASP – 22.5% Without C-Code 340B Drug Reimbursement ASP + 6% With C-Code Perform 8.4M outpatient surgeries 4.4M inpatient surgeries/year • • hospitals Change enables CMS to capture most of the discounts manufacture Products with pass-through status are exempt from this reimburs significantly from ASP+6% to ASP–22.5% Effective January 1, 2018, CMS reimbursement to hospitals for 3 Discount does not impact ASP or best price calculations Manufacturers required to provide 23.1% discount off ASP/WAC ~2258 hospitals (excluding children’s & psych) 340B Hospital Summary • • • • • • 57 57

58 81% 95% 87% 86% 89% 72% 77% 88% 82% 85% 32% Survey Anesthetic Use Overall % Local Non- 34% 83% 74% 66%* 98%* 37%* 52%* 65%* 59%* 57%* 73%* Medicare lume of procedures occurring in the given setting 6% 2% 9% 16% 47% 33% 25% 43% 35% 41% 27% Medicare 2 5 0 11 19 28 36 73 0.7 106 192 ASC (C-Code) 8 7 92 65 18 6.1 118 343 777 147 249 Annual Volume (‘000s, US, 2015) (C-code) Outpatient vs. non-Medicare breakdown was applied to the total vo 11 96 10 10 29 325 463 721 461 200 1273 Inpatient Completed studies was not available, the overall Medicare 550 160 337 750 483 815 107 504 >300 Total 1,285 1,096 Procedures ic breakdown of Medicare vs. non-Medicare Procedure Knee arthroplasty Rotator cuff repair Spine procedures Shoulder arthroplasty Hip arthroplasty Abdominoplasty resection Colon and small bowel Hemorrhoidectomy Mammoplasty Hernia repair High-Value Procedures in Initial Target Market Ortho Plastic Surgery Surgery Surgery General OB/GYN C-Section *Note: For settings in which procedure-specif 58 58

59 FDA HTX-011 is an investigational new drug and not approved by the Existing robust platform and structure to support launch Unprecedented value proposition Proven track record with hospital launch success Highly focused launch strategy to accelerate sales Significant unmet need and market opportunity Launch for HTX-011 Heron is Well Positioned to Execute a Blockbuster 59 59

60 CINV Commercial Products

61 market, 1 hypersensitivity and infusion IV (fosaprepitant), which has ® serious receptor antagonists 3 receptor antagonists 1 phase and secondary driver in the primary driver for CINV in the acute prophylaxis delayed phase contains the synthetic surfactant with polysorbate 80 that has been associated site reactions failures CINV, but related to ~15% of acute 90% share of the US NK • These are the backbone of CINV • Excessive serotonin release is the NK 5-HT •EMEND • Substance P is primary driver of delayed ® ™ receptor 3 receptor 1 SUSTOL antagonist antagonist CINVANTI 5-HT NK Complimentary Mechanisms of Action CINV Prophylaxis Typically Requires Two 61

62 277,000 68,694 SUSTOL... CINVANTI (2018) Varubi... 11,759 Last 10 Years ates for months 1- to data availability, 2,756 Akynzeo... (distributor 867 reports); due r launch months 3-12 and estim 33,530 First 12 Months of Sales for All CINV Brand Launches in Sancuso (2008) Sancuso data includes actuals fo Sources: IMS DDD; Heron actuals 2; Varubi includes actuals for months 1-12 Heron’s CINV Portfolio Continues to Outperform All CINV Branded Launches in Past 10 Years 62

63 $5.1 $23.0 $28.1 $3.4 $19.8 $16.4 $6.1 $11.2 $17.3 $5.2 $6.4 $11.6 $10.1 $8.6 $8.5 CINV portfolio net sales by quarter SUSTOL CINVANTI $3.6 $1.3 Q4 2016 Q1 2017 Q2 2017 Q3 2017 Q4 2017 Q1 2018 Q2 2018 Q3 2018 Q4 2018 $5 $- $10 $15 $25 $30 $20 Millions in 2018 and Over $100M Since Inception CINV Portfolio Achieved $76.7M in Net Product Sales 63

64 33% 67% Q4'18 (LE) 78% 22% Q3'18 CINVANTI 13% 87% Q2'18 Emend IV Total Market Share 7% 93% Q1'18 0% 80% 40% 60% 20% 100% 224 249 215 225 192 215 169 197 138 175 114 161 80 152 Hospitals/IDN 60 133 Clinics 42 108 26 82 CINVANTI Ordering Accounts Since Launch 11 41 0 18 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec CINVANTI Accounts and Market Share Continue to Grow 0 50 400 450 500 100 150 200 250 300 350 Source: Heron 867 data December 31 , 2018 64

65 (LE) 76% 24% 226 (est) Q4’18 Q4'18 (LE) 226 Q3’18 89% 11% Q3'18 211 Q2’18 3% 97% Q2'18 Hospital Long tail of use (30-40% of use is in hundreds of smaller practices) is challenging to reach, with minimal contract advantages Unique J code Jan 2019 194   Factors influencing further share growth: Q1’18 0% Q1'18 100% ) (Jan 3, 2018) LE CINVANTI Launch (LE) ( 68% 32% 391 (est) Q4’18 Q4'18 Q4'17 100% Hospital (000s) NK1 Units 0% 60% 20% 80% 40% 391 78% 22% Q3’18 100% Q3'18 NK1 market flat to Q3’18 ) (LE) LE ( 55% 164 (est) 45% Q4’18 Q4'18 372 13% 87% Q2’18 Q2'18 Total 164 Q3’18 64% 36% Q3'18 334 7% 93% Q1’18 Q1'18 (Jan 3, 2018) CINVANTI Launch 158 Q2’18 nd IV Q Units. Q4’18 Cinvanti share calculated by keeping total 26% 74% Q2'18 Clinic data 100% Q4'17 139 Q1’18 15% 85% Q1'18 NK1 Units Total** (000s) 0% 80% 40% 20% 60% (Jan 3, 2018) 100% CINVANTI Launch Q4'17 100% Clinic (000s) NK1 Units All Segments CINVANTI Market Share is Climbing Steadily Across 0% 20% 60% 80% 40% 100% CINVANTI EMEND IV Source(s): Heron 867 data. Heron DDD 5HT3, NK1 Data *Share calculation Q1’18 – Q3’18 = Cinvanti Q Units/Cinvanti + Eme ** Total includes units classified as “Other” Class of Trade in 65

66 020 nd rentiating hospital capturing one-third of the market in Q4 2018 CINVANTI from Emend and generics Strategy to preserve CINVANTI through generic arbitrage • Long term contracts extending beyond September of 2019 • CINVANTI has become an established brand across both clinics a • Leverage favorable 340B pass through status, ASP+ 6% through 2 • Potential Q1 2019 label expansion to include IVP further diffe 66

67 $96 $8 Q4 19 $116 Projections $9 Q3 19 $133 $11 Q2 19 $147 $10 Q1 19 $168 $19 Q4 18 ASP $222 $128 Q3 18 $197 $140 Q2 18 Palo Reimbursement (ASP+4.3%) Analog: Ondansetron ASP* $200 $140 Q1 18 $206 $139 * Ondansetron launch aligned Q4 17 Branded $- $50 $100 $150 $200 $250 $300 slope of the palonosetron ASP decline become more disciplined on pricing to maximize revenue the price of palonosetron has not dropped as quickly as in the past drop in ASP and a longer arbitrage competition between generic manufacturers, we do not expect substantive changes in the SUSTOL sales though most of 2019 • Slower decline in prices leads to a slower Therefore, the arbitrage will continue to impact • Although the DoJ is investigating the lack of • Even with multiple generics on the market, • Generic manufacturers have evolved and Longer Than the Zofran/Ondansetron Arbitrage ALOXI/Palonosetron Arbitrage is Lasting Much 67

68 re etron arbitrage year due to what we believe is de J0185 effective January 1, antagonists 1 we do not expect this arbitrage to have the same during the protracted palonos ® : While we expect to see sales of SUSTOL slowly improve, the co ® 2018 guidance: $60M - 70M raised to $70M - $72M magnitude as the Aloxi arbitrage – – Due to significant sales in 340b hospitals and other factors, the best overall profile compared to the other available NK 2019 2018 net product sales: $76.7M 2019 guidance: $115M - $120M • • • We expect to see steady growth in the marketplace through mid- CINV Franchise SUSTOL • CINVANTI (aprepitant) injectable emulsion received unique J-Co • Generic aprepitant IV is expected in September 2019 CINVANTI business will continue to be weak 2019 CINV Franchise Outlook 68

69 3,342 181,253 $ 53,633 $ 406,808 $ 470,896 $ 364,800 $ (1.81) $ (158,318) $ 48,630 $ (129,281) September 30, 2018 Nine Months Ended September 30, 2018 3,434 61,566 r 30, 2018, respectively. $ (38,346) $ (0.49) $ (35,876) $ 19,786 ember 30, 2018, respectively. September 30, 2018 Three Months Ended llion. shares outstanding for the three and nine months ended Septembe d compensation expense for the three and nine months ended Sept 1 2 1 Based on 77.8 million and 71.5 million weighted-average common Includes $8.1 million and $23.6 million of non-cash, stock-base Financial Summary 1 2 Common shares outstanding at September 30, 2018 totaled 78.0 mi Net loss Other income, net Operating expenses Net product sales Summary Statement of Operations and Net Cash Used in Operations (In thousands, except per share data) Net cash used in operations Net loss per share (In thousands) Condensed Balance Sheet Data Accounts receivable, net Cash, cash equivalents and short-term investments Total stockholders’ equity Total assets 69

70 for CINV ® and SUSTOL ® d by the FDA $60M - $70M raised to $70M - $72M 2018 net sales: $76.7M franchise: $115M - $120M • 2018 net sales guidance for CINV:  • 2019 net sales guidance for CINV HTX-011 & HTX-034 are investigational new drugs and not approve No Advisory Committee planned PDUFA date April 30, 2019 Priority Review Designation    011 as the cornerstone of an opioid-free multimodal pain regimen Additional Phase 2 clinical studies using HTX- FDA accepted NDA HTX-011 & HTX-034 for Postoperative Pain CINVANTI • Publication of Phase 3 and Phase 2b studies • Anticipated launch in 3Q2019 (if approved) • Phase 2 with HTX-034 in 2H2019   Key Catalysts in Pain Management & CINV Franchises 70

71 © 2019 HERON THERAPEUTICS, INC. ALL RIGHTS RESERVED.

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